Evidence Table C1. Oral Sildenafil

Author FundingN; study design; eligibilityParticipants characteristicsDiagnosis detailsInterventionOutcomes
Abdel-Naser (2004) 1


Funding source: Pfizer
N screened = NR
N randomized = 30

IG1, n = 15
IG2, n = 15
CG, n = 12 (normal men)

Intention to treat (ITT) analysis: NR

Inclusion: men with psychogenic ED (no response to sildenafil citrate of up to 100 mg in more than one occasion within a one mo); also non-sildenafil treated pts with ED served as control

Exclusion: penile anatomical defects, active peptic ulcer, bleeding dx, retinitis pigmentosa, major haematological renal or hepatic abnormalities; hx of stroke or recent MI; loss of libido; use of anihypertensives, nitrates, tranquilizers or drugs known to interfere with sildenafil citrate metabolism (e.g. cimetadine & ketoconazol)
Age, mean (sd): 42.5 (6.7) y, range 34–58 y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: 100% with Sidenafil, 100 mg

Smoking status: NR
Concomitant medications: NR

Duration of ED: NR

Underlying disease: NR

Psychogenic ED: 100%

Physiologic ED: 0

Mixed ED: 0
IG1: sildenafil citrate (night 3) & placebo (nights 1,2 & 4)
IG2: sildenafil citrate (night 4) & placebo (nights 1, 2, & 3)
CG: placebo (all nights)

IG1:
Dose: 50 mg
Duration: 4 nights
Frequency: once, 1 hr before bedtime/night
Compliance (%): NR

IG2:
Dose: as IG
Duration: 4 nights
Frequency: as IG
Compliance (%): NR

CG:
Dose: NA
Duration: 4 nights
Frequency: once/night
Compliance (%): NR

Run In period: NR
Wash out period: NR

F/u duration: NR
Primary outcome results:
NPTR for basal condition, mean (sd) placebo nights vs. sildenafil night
Number of events
IG1 4.7 (1.4) vs. 6.7 (1.6)
IG2: 3.8 (1.2) vs. 7 (1.2)
Total event duration, hr:
IG: 1.4 (0.2) vs. 2.1 (0.4)
IG2: 1.3 (0.2) vs. 2.4 (0.2)
Tip rigidity
IG1: 39.7 (9.5) vs. 47.8 (10.4)
IG2: 44.3 (10.3) vs. 57.6 (10.7)
Base rigidity:
IG1: 45.1 (8.8) vs. 57.3 (10.5)
IG2: 49.4 (10.5) vs. 60.8 (11)

Other outcomes assessed: base, tip RAU, and TAU (result suggestive of possible performance anxiety effect in this population); no result reported for CG

Withdrawals/drop-outs/loss to f/u: NR
WDAE: NR
TAE, n (%): 3 (10), headache in 2 pts (6.7%), GI upset in 1 (3.3%)
SAE: 0

Ascertainment of outcomes assessed: RigiScan nocturnal penile tumescence and rigidity (NPTR); RAU and TAU
Albuquerque (2005) 2


Funding source: Pfizer
N screened = 153
N randomized = 120

IG, n = 61
CG, n = 59

ITT analysis used for primary outcome: yes (n=120)

Inclusion: men 18 y or older, with established ED of at least 6 mo duration, in a stable sexual relationship for 6 mo, and with hypertension that is being treated with at lest 2 drugs. (Diuretics, alpha-blocker, beta blockers, ACE inhibitors or calcium blockers); baseline IIEF score of 25 or less

Exclusion: Concurrent tx with nitrates, presence of genital deformity or sexual disturbance that precluded sexual intercourse, use of any form of ED tx within 4 wks, alcohol or drug abuse, presence of retinitis pigmentosa, major medical condition or inability to fill out log or comply with study
Age, mean (range):
30–81y

Race: Brazilian

Co-morbidities: None

Previous ED treatment: None

Smoking status n (%): 13 (21.3) vs. 15 (25.4)

Body weight: NR
Concomitant medications: None

Duration of ED, median (range): 2.0 (0.6 – 24) vs. 2.3 (0.6 –30)

Underlying disease: hypertension (duration 0.6 –30 y)

Psychogenic ED, n (%): 9 (14.8) vs. 7 (11.9)

Physiologic ED, n (%): 11 (18) vs. 11 (18.6)

Mixed ED, n (%): 41 (67.2) vs. 41 (69.5)

Other, n (%): alcohol use 30 (49.2) vs. 30 (50.2)
IG: Sildenafil
CG: Placebo

IG:
Dose: 50mg (adjusted to 25 or 100mg)
Duration: 8wks
Frequency: 1 hr before sexual intercourse
Compliance n (%): 46 (75.4)

CG:
Dose: NA
Duration: 8 wks
Frequency: 1 hr before sexual intercourse
Compliance n (%): 41 (69.5)

Run In period: None
Wash out period: 4 wks

F/u duration: 2, 4 and 8 wks

Other: % pts taking
25 mg: 6.6 vs. 5.1
50 mg: 39.3 vs. 74.6
100 mg: 54.1 vs. 20.3
Primary outcome results:
IIFE, mean (sd): (mean baseline/Q=2)
Q1: 4.2 (1.3) vs. 2.6 (1.5)
Q3: 4 (1.3) vs. 2.6 (1.6)
Q4: 4 (1.4) vs. 2.2 (1.6)
Q5: 4.2 (1.2) vs. 2.6 (1.5)
Q15: 3.6 (1.0) vs. 2.4 (1.1)
Q6: 4.2 (1.3) vs. 3.4 (1.4)
Q7: 4.2 (1.2) vs. 2.3 (1.4)
GEQ, % improved: (87) vs. (37)
Successful intercourse attempts wks 2, 4 and 8 (%): 54, 61, 73 vs. 13, 20, 29
Other outcomes assessed: EDITS

Withdrawals/drop-outs/loss to f/u, n (%): 22 (18.3)

WDAE: tx interrupted 1 (1.4) vs. 2 (3.4)
TAE, n (%): in 2% or more 35 (57.3) vs. 16 (27.1); including facial flushing 8 (13) vs. 2 (3.4); headache 7 (11.4) vs. 2 (3.4); rhinitis 6 (9.8) vs. 1 (1.7); dyspepsia 4 (6.5) vs. 0; dizziness= abdominal pain 2 (3.2) vs. 1 (1.7); paresthesia 1 (1.6) vs. 0; hypertension 1 (1.6) vs. 3 (5.1); chest pain 1 (1.6) vs. 2 (3.4); flue like syndrome= diarrhea 1 (1.6) vs. 2 (3.); AE in 82% vs. 40% of pts
SAE: 3 (5) vs. 1 (1.7); CVA, pulmonary edema/heart failure, atrial fibrillation/arrhythmia, and one polytrauma due to MVA leading to death)
Ascertainment of outcomes assessed: IIEF, patient logs, EDITIS, GEQ
Althof (2006) 3


Funding source: Pfizer Inc.
N screened = NR
N randomized = 553 (combined from two studies US, n=253; Brazil, Mexico, Australia and Japan n=300)

IG, n = 274
CG, n = 279

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older with documented ED (score of 21 or less on IIEF)

Exclusion: BP of 90 mmHg or less or 170/110 mmHg or more; sign cardiac dx; use of nitrates, nitric oxide donors, or ritonavir; more than 6 dosed of sildenafil within 6 mo prior to study entry
Age, mean (sd): 56 (11) vs. 55 (12) y

Race: White 55.5%; Black 15%; Asian 5.5%; Other 23.5%

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: NR

Body weight, mean (sd): 86 (16) vs. 85 (16) kg
Concomitant medications, n (%):

Duration of ED, mean (sd): 4.4 (4.5) vs. 4.3 (4.4) y

Underlying disease, n (%): Not specific

Psychogenic ED, n (%): 44 (16) vs. 55 (20)

Physiologic ED, n (%): 119 (43) vs. 113 (41)

Mixed ED, n (%): 116 (41) vs. 106 (39)
IG: Sildenafil
CG: Placebo

IG:
Dose: NR
Duration: 12 wks
Frequency: NR
Compliance: NR

CG:
Dose: NA
Duration: NR
Frequency: NR
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: 12 wks (f/u intervals at 2, 4, 6, 8 wks)
Primary outcome results:
IIEF, LS mean change from baseline (SE)
EF: 11.0 (0.5) vs. 4.8 (0.5), p<0.001
OF: 2.5 (0.2) vs. .0 (0.2), p<0.001
SD: 1.3 (0.1) vs. 0.6 (0.1), p<0.001
IcS: 5.2 (0.2) vs. 2.9 (0.2), p<0.001
OS: 3.8 (0.2) vs. 1.7 (0.2), p<0.001
Successful sexual attempts, mean change %(sd): 59 (2.6) vs. 39 (42)

GEQ, frequency of achieved erections at end of tx: 3.9 (1.5) vs. 2.7 (1.6), p<0.001

Other outcomes assessed: SEAR sexual relationship domain (sign more improved in IG)

Withdrawals/drop-outs/loss to f/u, n (%): NR

WDAE, n (%): 3 (1) vs. 1 (0.4)
TAE, n (%): 129 (46) vs. 88 (32); included headache, flushing, dyspepsia, and rhinitis
SAE, n (%): 1 (<1) vs. 1 (<1); one case of coronary artery disease in sildenafil grp and one case of urinary tract infection in placebo

Ascertainment of outcomes assessed: SEAR; self-esteem, confidence and sexual relationship satisfaction; IIEF, GEQ, self reported event log
Bank (2006) 4


Funding source: Pfizer Inc. (educational grant)
N screened = NR
N randomized = NR (n=35 completed the trial)

IG1, n = 12
IG2, n = 10
CG, n = 13

ITT analysis used for primary outcome: NR

Inclusion: men 25–75 y, in a stable relationship, and normal libido, IIEF-5 < 21, with current use of sildenafil (evaluated after the 2–4 wks run in period tx with 100 mg sildenafil); with vasculogenic ED

Exclusion: use of lipid lowering agents, angiotensin converting enzyme inhibitors, anti-depressants or nitrates; hx of prostate cancer or pelvic/ low back surgery
Age, mean (SEM): 59.2 (1.9) vs. 58.7 (3.3) vs. 63.8 (2.1) y

Race: NR

Co-morbidities, n (%): DM type II, 2 (5) only in CG

Previous ED treatment: NR

Smoking status: 3 (9%); one in each grp

Body weight: NR

Other: BMI, mean (SEM) 27.5 (1.5) vs. 29.7 (2.3) vs. 26.1 (0.9) kg/m2
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): vasculogenic

Psychogenic ED, n (%): NR

Physiologic ED, n (%): 100%

Mixed ED, n (%): NR

Other: lipid profiles reported, SBP; CBP; total cholesterol; LDL-c; HDL-c; TG, and CRP
IG1: Sildenafil + Atorvastatin
IG2: Sildenafil + quinapril
CG: Sildenafil + placebo

IG1:
Dose: 100 mg sildenafil + 40 mg atrovastatin
Duration: 3 mo
Frequency: sildenafil as instruction; atrovastatin once/d
Compliance: NR

IG2:
Dose: 100 mg sildenafil + 10 mg quinapril
Duration: 3 mo
Frequency: as IG1
Compliance: NR

CG:
Dose: sildenafil as IG
Duration: 3 mo
Frequency: as IG
Compliance: NR

Run In period: 2–4 wks on 100 mg sildenafil
Wash out period: NA

F/u duration: 3 mo
Primary outcome results:
Mean (SEM) baseline vs. post tx
IIEF-5
IG1: 11.1 (1.5) vs. 16.7 (2.0)
IG2: 9.9 (1.1) vs. 18.7 (2.2)
CG: 10.2 (1.6) vs. 11.3 (2.1)

IIEF-EF domain:
IG1: 14.5 (2.2) vs. 20.8 (2.3)
IG2: 13.8 (1.3) vs. 23.6 (2.3)
CG: 12.8 (2.0) vs. 14.2 (2.5)

N of intercourse attempts/3 mo, mean (SEM): IG1, 37.7 (12) vs. IG2, 22.5 (7.7) vs. IG3, 23.8 (13.9)

Other outcomes assessed:
NS differences between IG1/2 and CG for penile blood flow and vascular function, PSV, EDV, RI, and FMD; no differences for SBP, DBP, HDL-c and CRP, no correlation between IIEF scores and improvement on other measures

Withdrawals/drop-outs/loss to f/u, n (%): NR

WDAE: NR
TAE: NR
SAE: NR

Ascertainment of outcomes assessed: IIEF-5;Penile Doppler studies
Bawa (2004) 5


Funding source: NR
N screened = NR
N randomized = 59 crossover design

IG/ CG, n = 59

ITT analysis used for primary outcome: NR

Inclusion: Indian men with ED for 6 mo or longer

Exclusion: NR
Age, mean (range):
32.8 (18–60) y

Race: Asian (India)

Co-morbidities: NR

Previous ED treatment: NR

Smoking status:
NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range): 23 (6–120) mo

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil
CG: placebo

IG:
Dose: 50 mg
Duration: 3 wks
Frequency: NR
Compliance (%): NR

CG:
Dose: N/A
Duration: 3 wks
Frequency: NR
Compliance (%): NR

Run In period: NR
Wash out period: NR

F/u duration: 1 y
Primary outcome (EF):
IIEF score, mean (SEM)
EF domain
Baseline: 18.5 (0.7)
post tx: 25.6 (0.7) vs. 22.1 (0.7), P<0.05
Intercourse satisfaction:
Baseline 8.2 (0.4)
post tx: 11.9 (0.4) vs. 10 (0.4), not sign
OF:
baseline: 7.3 (0.3)
post tx: 8.8 (0.2) vs. 7.9 (0.3), p<0.05
SD:
Baseline: 6.9 (0.1)
post tx: 7.1 (0.1) vs. 6.9 (0.2), not sign
OS:
pre tx: 5.8 (0.2)
post tx: 7.0 (0.2) vs. 6.4 (0.2), p<0.05
GAQ (% improved): 81.3% vs. 28.8% (P<0.001)

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: NR

WDAE: 0
TAE: 4 (6.8%) vs. 3.4% including Headache 30.2%; Flushing: 43.5%; Dyspepsia: 18.8%; Dizziness: 7.5%
SAE: 0

Ascertainment of outcomes assessed: IIEF; partner questionnaire
Becher (2002) 6


Funding source: Pfizer
N screened = 156
N randomized = 143

IG, n = 72
CG, n = 71

ITT analysis used for primary outcome: NR

Inclusion: Men with ED who were in a stable relationship with a female partner of at least 6 mo

Exclusion: penile anatomical defects, primary diagnosis of another sexual disorder, SCI, any major psychiatric disorder not well controlled, poorly controlled DM, Hx of alcohol or substance abuse, major haematological, renal or hepatic abnormalities, hypotension or malignant hypertension, recent stroke or myocardial infraction or if they were receiving nitrated.
Age, mean (sd);
57.2 (11.5) vs. 56.7 (10.9) y

Race, n (%): White Southern Latin 6 (8.3) vs. 7 (9.8)
Hispanic: 66 (91.7) vs. 64 (90.2)

Co-morbidities: NR

Previous ED treatment: NR

Smoking status, n (%): Current: 32 (44.4) vs.27 (38.0)
Former: 28 (38.9) vs. 26 (36.6)

Body weight, mean (sd): 84.2 (11.8) vs. 83.4 (14.2)
Concomitant medications, n (%):
Any medication 51 (70.8) vs. 51 (71.8), with no sign difference between grps for use of any medication

Duration of ED, mean (range): 3.5 (0.5–22.4) vs. 2.6 (0.5–20.5) y

Underlying disease (diagnosis), n (%):
Diabetes: 12 (16.6) vs. 13 (18.3)
Hypertension: 23 (31.9) vs. 28 (43.6)

Psychogenic ED:
44.3%

Physiologic ED: 39.3%

Mixed ED:
16.4%
IG: Sildenafil
CG: Placebo

IG:
Dose: 25–50 and 100mg tablets
Duration: 12 wks
Frequency: 1h before planned sexual activity, up to once/d
Compliance: 90%

CG:
Dose: NA (14 tablets/bottle as IG)
Duration: 12 wks
Frequency: as IG
Compliance: 89%

Run In period: 4 wks
Wash out period: None

F/u duration: 12 wks (2, 4, 8, and 12 wks)
Primary outcome results: IIEF mean (SE):
% Change, Q3: 3.8 (0.17) (66.2) vs. 2.7 (0.18) (15.1)
% Change Q4: 3.6 (0.18) (77.6) vs. 2.5 (0.18) (21.2)
EF: 20.5 (0.6) vs. 15.9 (0.7)
OF: 8.2 (0.35) vs. 7.0 (0.37)
S-D: 7.68 (0.18) vs. 7.0 (0.19)
GEQ, % with Improved erections: (77.3) vs. (33.8)

Other outcomes assessed: all IIEF questions (1–15)

Withdrawals/drop-outs/loss to f/u, n (%): 3 (2) vs. 2 (3)

WDAE, n (%): 7 (9.7) vs. 6 (8.5) discontinued treatment
TAE, n (%): pts with AE 45 (59.1) vs. 21 (29.6)
Flushing: 16 (22.2) vs. 3 (4.2); Headache: 17 (23.6) vs. 6 (8.4); Hypertension: 1 (1) vs. 3 (4); nasal congestion 2 (2.3) vs. 1 (1); tachycardia 3 (4) vs. 0
SAE: 2 (2.8) vs. 1 (1.4) died in due to MI

Ascertainment of outcomes assessed: RigiScan test (nocturnal penile tumescence NPT), IIEF (q3 and 4) (investigator), GEAQ, self and partner reported event logs
Boolell (1996) 7


Funding source: Pfizer Inc.
N screened = NR
N randomized =12 (phase I: double blind, placebo controlled four way crossover trial; phase II: double blind, randomized placebo controlled two way cross over)

IG1-3/CG (both phases), n = 12

ITT analysis used for primary outcome: NR

Inclusion: men 18–70 y, with penile ED of at least 6 mo, with no known organic cause by clinical examination and blood test

Exclusion: pts with DM, hypertension or alcohol abuse
Age, range: 36–63 y

Race: NR

Co-morbidities: NR

Previous ED treatment, n (%): IC papaverine 4 (30), three responders and one non responder

Smoking status NR

Body weight: NR
Concomitant medications: NR

Duration of ED: NR

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
Phase I
IG: single doesesildenafil + 2 hr visual stimulation 30 min post tx (VS)
CG: placebo + VS
Phase II
IG: sildenafil + VS
CG: placebo

IG (phaseI):
Dose: 10, 25 or 50 mg
Duration: NR
Frequency: once/dose
Compliance: 100%

IG (phase II):
Dose: 25 mg
Duration: 7 d
Frequency: once/d
Compliance: 100%

CG:
Dose: NA
Duration: Phase II= 7 d
Frequency: phase phase II= once/d
Compliance: 100%

Run In period: NR
Wash out period: phase I, 3 d between consecutive tx periods; 3 d between phases, phase II, at least 7 d
F/u duration: 7 d
Primary outcome results:
Phase I
Duration of penile rigidity > 80%, mean (approximate values from figure):
Base: < 4 vs. 8 vs. <12 vs. <2 min
Tip: < 5 vs. <7 vs. < 8 vs. <2 min

Phase II
Erections of grade 3 or 4, mean:
1.6 vs. 0.5
N of erections phase I + phase II, mean (95% CI): IG vs. CG, p=0.005
6 (3.2–11.4) vs. 1.3 (0.5–2.7)

Pts with improved erection, n/N (%):
10/12 (83) vs. 2/12 (16); p = 0.018

Other outcomes assessed: frequency of erection and time of dosing; pulse rate, BP, laboratory safety data

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE, n (%): phase I: 2 (16) vs. 2 (16); phase II: 6 (50) vs. 5 (41) with headache, dyspepsia, pelvic musculoskeletal pain
SAE: 0

Ascertainment of outcomes assessed: RigiScan (phase I); self diary, grading erection from 1=no erection to 4=max rigidity (phase II)
Boulton (2001) 8


Funding source: NR
N screened = NR
N randomized = 219

IG, n = 110
CG, n = 109

ITT analysis used for primary outcome: NR

Inclusion: men 37 or older; with diagnosed ED, and stable type II DM (≥2 y; HbA1c <11%); also in stable heterosexual relationship for longer than 6 mo

Exclusion: genital anatomical deformity; major psychiatric disorder; hx of alcoholism or substance abuse; ED resulting from SCI; MI, stroke, heart failure or unstable angina within previous 6 mo; hx of hypotension; nitrate tx; type I DM; HbA1c ≥11%; recurrent hypoglycemic episodes; severe disabling autonomic neuropathy; diabetes secondary to pancreatic damage; Cushing's syndrome; acromegaly
Age, mean (range):
58 (range 38–80) vs. 59 (45–72) y

Race (%):
White 96; Black 2 vs. 0; Asian 2; other: 1 vs. 2

Co-morbidities, %:
Hypertension
40 vs. 52; Ischemic heart dx 6 v. 3; hypercholesterolemia 8 vs. 7

HbA1c, median, (range): 8.3 (5.1–12.1)

Previous ED treatment: NR

Smoking status (%): smokers 22 vs. 24

Body weigh, mean (range): 88 (60–146) kg
Concomitant medications: Insulin 32 vs. 37

Duration of ED, mean (range): 4.6 (0.4–21) vs. 3.7 (0.7–11)

Underlying disease: DM

Psychogenic ED: NR

Physiologic ED, %: 100

Mixed ED: NR

Other: duration of DM, mean (range) = 10 (1–34) y
IG: sildenafil citrate
CG: placebo

IG:
Dose: 50 mg initially; could adjust to 25 or 100 mg
Duration: 12 wk
Frequency: NR
Compliance: NR

CG:
Dose: placebo
Duration: 12 wk
Frequency: NR
Compliance: NR

Run In period: 4 wk
Wash out period: NA

F/u duration: 12 wk
Primary outcome results:
IIEF- Q3, mean (SEM): pre: 1.8; post 3.4 (0.2) vs. 1.9 (0.2)
IIEF- Q3, mean (SEM): pre: 1.5; post: 3.4 (0.2) vs. 1.8 (0.2)
IIEF- EF: pre: 10.4; post: 20.4 (1.2) vs. 11.5 (1.2)
Successful intercourse, %: pre 13.8; post 58.8 vs. 14.4
GEQ, %: 65 vs. 11

Other outcomes assessed: life satisfaction checklist; partner questionnaire

Withdrawals/drop-outs/loss to f/u: NR

WDAE, %: 0
TAE: 65 vs. 11; pts with AE= 38% vs. 6.4%; including headache 18.2 vs. 4; flushing 15 vs. 0; dyspepsia 2 vs. 0.9; abnormal vision 5 vs. 0
SAE: 0

Ascertainment of outcomes assessed: IIEF, GEQ, life satisfaction checklist
Cappelleri (2000) 9 10

Companion Lewis (2001)


Funding source: Pfizer Inc.
N screened = NR
N randomized = 247

IG, n = 124
CG, n = 123

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older; with documented diagnosis of ED for at least 6 mo; in stable relationship with female partner for longer than 6 mo

Exclusion: hx of retinitis pigmentosa; uncontrolled psychiatric disorder, hyper/hypotension or DM; serious CVD (MI, stroke or arrhythmia within previous 6 mo); evidence of alcoholism or substance abuse within previous 12 mo; current use of nitrates; nitric oxide donor
Age, mean (range):
IG1 58 (range 38–77)
CG 60 (range 31–81)

Race (%): NR

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%):
Anti-inflammatory analgesic 98 (40)
Antihypertensive 93 (38)
Antidiabetic 49 (20)
Vitamins 49 (20)
Analgesic 30 (12)
Diuretic 30 (12)

Duration of ED, mean (range): 4 (0.4–17) y

Underlying disease: Essential hypertension 83 (34)
DM, Type II 49 (20)
Hypercholesterolemia 37 (15)
Hyperlipidemia 22 (9)
Prostatic hyperplasia 30 (12)

Psychogenic ED, n (%): 4 (3) vs. 6 (5)

Physiologic ED, n (%): 102 (82) vs. 99 (81)

Mixed ED, n (%): 36 (15)
IG: sildenafil citrate
CG: placebo

IG:
Dose: 50 mg, with option to titrate to 100 or 25 mg
Duration: 12 wk
Frequency: up to once/d, 1 dose 1 hr before sexual activity
Compliance: NR

CG:
Dose: placebo, titration as IG
Duration: 12 wk
Frequency: as IG
Compliance: NR

Run In period: 4 wk
Wash out period: NA

F/u duration: 12 wk
Primary outcome results:
Mean response scores for questions 3 and 4 of IIEF- total, mean: pre: 9.5 vs. 9.6; post: 20 vs. 11
IIEF-EF, mean: pre: 1.7 vs. 1.6; post: 3.4 vs. 1.8
(Approximate mean values from figure):
IIEF, Q3: pre: 1.8; post 3.7 vs. 2.2
IIEF, Q4: pre: 1.5; post 3.6 vs. 1.9
IIEF, Q7 (ICs): pre: 2.7; post: 3.9 vs. 2.2
GEQ-Q1, 2, %: 70 vs. 17
GEQ-Q3, least square mean: 3.5 vs. 1.8

Other outcomes assessed: EDITS; partner satisfaction; positive correlation between self-assessment and IIEF-EF at baseline and post tx

Withdrawals/drop-outs/loss to f/u: 7 (6) vs. 12 (10)

WDAE, n (%): 2 (1.6) vs. 0
TAE: NR; pts with AE, n (%)=52 (42) vs. 20 (16); including flushing 17 (14) vs. 1 (1); headache 14 (11) vs. 1 (1); dyspepsia 5 (4) vs. 0; abnormal vision (blue tinge to vision, ▴ sensitivity to light, eye pain, & photophobia) 3 (2) vs. 0
SAE, n (%): 3 (2) vs. 3 (2); cause NR

Ascertainment of outcomes assessed: IIEF, GEQ; ED self assessment scoring system
Cavallini (2005) 11


Funding source: Sigma Tau (Industrie Farmaceutiche Riunite)
N screened = 139
N randomized = 110

IG1, n = 37
IG2, n = 40
CG, n = 33

ITT analysis used for primary outcome: No

Inclusion: Pts complaining of ED after having bilateral nerve- sparing radical retro pubic prostatectomy 6 mo or more before the study entry with completely functional erections before the prostatectomy and had not received adjuvant or neoadjuvant tx for prostate cancer or other ED txt, having undetectable PSA levels, involvement in a heterosexual relationship for at least 6 mo before surgery

Exclusion: pts with Peyronie's dx, hormonal abnormalities, Myocardial or cerebral ischemia, major surgery, tobacco/alcohol use, DM, uncompensated hyper/hyoptension
Age, mean (sd):
63 (4) vs. 61 (4) vs. 60 (5) y

Race (%): NR

Co-morbidities, %: compensated hypertension 53 vs. 54 vs. 62; Hypercholesteremia 53 vs. 48 vs. 55 obesity 9 vs. 7 vs. 10

Previous ED treatment: None

Smoking status, %: past smokers (56 vs. 56 vs. 55)

Body weight: NR
Concomitant medications: gemfibrozil, simvastatin, cilazapril, enalapril, nifedipine, quinapril, losartan, lacidipine

Duration of ED (yr): NR (mean time past surgery= 1 y)

Underlying disease: prostate cancer/prostatectomy

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG1: Sildenafil + Carnitines (acetyl- and propionyl)
IG2: Sildenafil + placebo
CG: placebo

IG1:
Dose: 100 mg sildenafil + 2 g/d each carnitine
Duration: 4 mo
Frequency: once/d
Compliance: NR

IG2:
Dose: 100 mg sildenafil
Duration: 4 mo
Frequency: once/d
Compliance: NR

CG:
Dose: NR
Duration: 4 mo
Frequency: once/d
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: 4 mo
Primary outcome results:
IIEF, mean (sd), IG1 vs. IG2 vs. CG:

IIEF, EF: pre: 13 (5) vs. 11 (4); post: 27 (5) vs. 22 (7) vs. 12 (4), p < 0.05
IIEF, ICs: pre: 3 (1); post: 9 (5) vs. 5 (3) vs. 3 (0.6), p < 0.05
IIEF, OF: pre: 3 (1); post: 9 (3) vs. 6 (3) vs. 3 (0.6), p < 0.05
IIEF, SD: pre: 7 (0.7) vs. 6 (0.8); post: 6 (0.6) vs. 7(0.6) vs. 6 (0.7), p => 0.05
General sexual well-being: pre: 3 (0.7) vs. 3 (0.9); post: 8.6 (2.0) vs. 5.4 (2.7) vs. 2.8 (0.7), p < 0.05

Other outcomes assessed: Peak systolic and diastolic velocity

Withdrawals/drop-outs/loss to f/u: 14 (13.5%) discontinued

WDAE: None
TAE, n (%): NR; AEs included headache 8 (25) vs. 9 (28) vs. 0; flushing 7 (22) vs. 8 (23) vs. 0; dizziness 3 (9) vs. 3 (9) vs. 0; nasal congestion 2 (6) vs. 2 (6) vs. 0; nausea 2 (6) vs. 2 (6) vs. 0; euphoria 2 (6) vs. 0 vs. 0; abdominal pain 0 vs. 0 vs. 1 (3)
SAE: NR

Ascertainment of outcomes assessed: IIEF, Doppler effect
Chen (2001) 12


Funding source: Pfizer
N screened = NR
N randomized = 236

IG, n = 119
CG, n = 117

ITT analysis used for primary outcome: Yes

Inclusion: men 26–80 y; well-documented hx of ED for at least 6 mo; in stable heterosexual relationship for at least 6 mo

Exclusion: genital anatomical abnormality or SCI; other coexisting sexual disorder; elevated serum PRL level or low T level; major psychiatric disorder or hx of alcohol or substance abuse; major hematologic, renal or hepatic dx; poorly controlled DM associated with untreated proliferative retinopathy; stroke or MI in last 6 mo; hypotension or any other sign CVD; hx of retinitis pigmentosa; taking drugs known to be causally associated with ED, androgen therapy, trazodone, nitrates or nitric oxide donor compounds; receiving any tx for ED
Age, mean (range): 61 (26–80) y

Race (%): Asian 100%

Co-morbidities:
Benign prostatic hyperplasia
40 (34) vs. 44 (38)
Visual disturbance
46 (39) vs. 37 (32)
Essential hypertension 30 (25) vs. 40 (34)
DM 26 (22) vs. 29 (25)
Arthropathies and related disorders 16 (13) vs. 14 (12)

Previous ED treatment: NR

Smoking status, n (%): current smoker: 27 (23) vs. 28 (24)

Body weight, mean (range): 69 (46–98) kg
Concomitant medications, n (%):
Antihypertensive 30 (25) vs. 43 (37)
Antacid 52 (22)
Antirheumatic/antigout 21 (18)
Antidiabetic 38 (17)
Hypnosedative/anxiolytic 26 (11)
Upper respiratory tract medication 33 (14)
Vitamins 30 (13)
Beta-adrenoceptor blocker 23 (10)
Antibacterial 23 (10)

Duration of ED, mean: 4 y

Underlying disease: NR

Psychogenic ED, n (%): 20 (8)

Physiologic ED, n (%): 193 (82))

Mixed ED, n (%): 23 (10)
IG: Sildenafil citrate
CG: Placebo

IG:
Dose: 50 mg for first 2 wk; option to titrate to 100 mg or 25 mg
Duration: 12 wk
Frequency: once/d; 1 hr before sexual activity
Compliance: NR

CG:
Dose: placebo
Duration: 12 wk
Frequency: as IG
Compliance: NR

Run In period: 4 wk
Wash out period: NA

F/u duration: 12 wk
Primary outcome results:
IIEF, Q3, mean change from baseline: 1.9 vs. 0.7
IIEF, Q4 mean change from baseline: 2.vs. 0.9
IIEF-EF: pre: 14; post: 24 vs. 18
IIEF-ICs: pre: 5.3; post: 10 vs. 8
IIE-OF: pre: 5; post: 8 vs. 6
IIEF-SD: pre: 6; post: 7 vs. 6
IIEF-OS: pre: 4; post: 7 vs. 6
Successful intercourse, %: 62 vs. 30

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: 10 (8) vs. 6 (5)

WDAE, n (%): 1(<1) in IG; skin rash
TAE, n (%): in at least 3 pts= 76 (64) vs. 58 (50); including: CV 34 (29) vs. 14 (12); flushing 30 (25) vs. 11 (9); palpitation 4 (3) vs. 2 (2); body as a whole 22 (19) vs. 11 (10); headache 8 (7) vs. 4 (3); abdominal pain 5 (4) vs. 0; chest pain 3 (2.5) vs. 0; respiratory system 15 (13) vs. 14 (12); nervous system 15 (13) vs. 9 (8); dizziness 9 (8) vs. 6 (5); musculoskeletal events 9 (3 (3); myalgia 3 (3) vs. 0; arthralgia 3 (3) vs. 2 (2); special senses 9 (8) vs. 2 (2); abnormal vision 3 (3) vs. 1 (0.9); skin an appendages 7 (6) vs.12 (10); fungal dermatitis 3 (3) vs. 2 (2)
SAE, n (%): 4 (3) vs. 4 (3)

Ascertainment of outcomes assessed: IIEF, pts filled diary
Choi (2002) 13


Funding source: Pfizer
N screened = 133
N randomized = 133

IG, n = 66
CG, n = 67

ITT analysis used for primary outcome: Yes

Inclusion: men with ED for at least 6 mo, in a stable heterosexual relationship for 6 mo or longer

Exclusion: penile anatomical abnormalities; SCI, other co-existing sexual disorders, serum PRL levels > 3x upper limit to normal, low free T (> 0% below lower limit of normal), major psychiatric disorder, hx of alcohol or substance abuse; hx of haematological, renal, hepatic dx, MI; stroke, hypotension, retinitis pigmentosa, poorly condoled or causing proliferative retinopathy DM, use of drugs associated with androgen therapy, vacuum devices or other tx for ED.
Age, mean (range): 51 (28–78) vs. 51 (32–67) y

Race (%): NR

Co-morbidities, n (%):
Eye disorders 21 (32) vs. 14 (21)
Hypertension: 13 (20) vs. 10 (15)
Hyperplasia of prostate: 11 (17) vs. 12 (18); DM: 10 (15) vs. 8 (12)
GI disorders: 6 (9) vs. 5 (8)

Previous ED treatment: NR

Smoking status, n (%): Smokers 25 (37.9) vs. 30 (44.8)

Body weight, mean (range): 70 (52–102) vs. 71 (50–98)
Concomitant medications: NR

Duration of ED (yr): 5 vs. 5.6 y

Underlying disease: NR

Psychogenic ED n (%): 21 (32) vs. 24 (36)

Physiologic ED: 31 (47) vs. 26 (39)

Mixed ED: 14 (21) vs. 17 (25)
IG: sildenafil
CG: placebo

IG:
Dose: 50 mg, option for titration at 2 wks to 100, or 25 mg
Duration: 8 wks
Frequency: once/d
Compliance (%): 100

CG:
Dose: NA
Duration: 8 wks
Frequency: once/d
Compliance (%): 97

Run In period: 4 wks
Wash out period: NR

F/u duration: NR
Primary outcome results:
IIEF, mean score, IG vs. CG
Q3: baseline=2.5; post tx: 4 vs. 3
Q4: baseline = 2; post tx: 4 vs. 2
EF domain: baseline=13; post tx: 23 vs. 15
IS: baseline= 6; post tx: 11 vs. 8
OF: baseline 5; post tx: 8 vs. 5
SD: baseline=6; post tx: 7 vs. 6
OS: baseline= 4; post tx: 7 vs. 5
GAQ, % yes: 81 vs. 28
Intercourse success, %: 62 vs. 26

Other outcomes assessed: Event logs of sexual activity

Withdrawals/drop-outs/loss to f/u, n (%): 2 (3)

WDAE: 0
TAE, n of events (%): 46 (70) vs. 25 (27); AE in at least 3 pts: CV=flushing 21 (32) vs. 3 (5); body as whole: 21 (32) vs. 9 (13); headache 17 (26) vs. 6 (9);
Upper respiratory tract infection=nasal congestion: 5 (8) vs. 3 (4); digestive system events: 8 (12) vs. 9 (14); dyspepsia 3 (5) vs. 5 (8); special senses events: 10 (15) vs. 3 (5); abnormalities in colour vision: 4 (5) vs. 0; abnormal vision 3 (5) vs. 1 (2)
SAE, n (%): 2 (3), in CG

Ascertainment of outcomes assessed: IIEF, GAQ, also event logs, 12 lead ECG, standard laboratory tests
Choppin (2001) 14


Funding source: Roche Bioscience
N screened = NR
N randomized = 24

IG1/IG2/CG, n = 24 (Latin-Square design)

ITT analysis used for primary outcome: yes

Inclusion: ED of continual duration ≥6 mo with no established organic cause

Exclusion: NR
Age, mean (range): 44 (18–65) y

Race (%): black 41.7%, white 58.3%

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications:

Duration of ED: at least 6 mo

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG1: Ro70-0004 (active alfa1A-adrenoceptor) + VSS
IG2: sildenafil + VSS
CG: placebo + VSS

IG1:
Dose: 5 mg (oral)
Duration: NA
Frequency: single dose
Compliance (%): NR

IG2:
Dose: 50 mg (oral)
Duration: NA
Frequency: as IG1
Compliance (%): NR

CG:
Dose: placebo (oral)
Duration: NA
Frequency: as IG
Compliance (%): NR

Run In period: NR
Wash out period: 7 d

F/u duration: 2.5 hrs post dosing

Note: last tx was repeated at 4th visit
Primary outcome results:
Duration of erection in 26 vs. 27 vs. 25 periods; for total of 20 pts):

Base, >60% rigidity: 8.28 (3.7) vs. 22.64 (3.57) vs. 9.69 (3.71) min
Tip, >60% rigidity: 5.52 (2.84) vs. 9.21 (2.75) vs. 5.33 (2.85) min

Base, >80% rigidity: 0.45 (1.69) vs. 5.26 (1.63) vs. 0.67 (1.69) min
Tip, >80% rigidity: 1.20 (1.20) vs. 3.18 (1.16) vs. 1.23 (1.21) min

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: 4 (20)

WDAE: NR
TAE, n (%): any AE 2 (10) vs. 2 (9.1) vs. 1 (4.8); dizziness, hypotensive episode, GI disorder in IG1; dizziness, sedation and haematoma nose in IG2; an thrombophlebetitis in CG
SAE: NR

Ascertainment of outcomes assessed: RigiScan (30 min pre dose to 2.5 hrs post dose)
Christiansen (2000) 15


Funding source: Pfizer Ltd.
N screened = NR
N randomized = 205

IG, n = 99
CG, n = 106

ITT analysis used for primary outcome: Yes

Inclusion: men 18–70 y with ED of psychogenic or mixed organic/psychogenic etiology for at least 3 mo; at least 1 grade 3 or 4 erection during 4 wk before screening or positive response to IC injection test (papaverine ≤40 mg or PgE1 ≤20 μg)

Exclusion: known vascular, neurological, endocrine or penile anatomical cause for ED; hx of major hematologic, renal or hepatic abnormality; stroke, subarachnoid haemorrhage, bleeding disorder or peptic ulceration; elevated serum PRL level; low serum T level; moderate to severe hyper/ hypotension; regular tx with nitrates, anticoagulants, major tranquillizers, estrogens or antiandrogens
Age, mean (sd): 53 (19–70) vs. 54 (21–70) y

Race (%): NR

Co-morbidities, %: Most frequent:
Hypertension 14
Ischemic heart disease 12
Diabetes 7
Depression 5

Previous ED treatment, n (%):
IC injections 86 (42)

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range): 4.8 (0.3–20) vs.5.3 (0.3–23) y

Underlying disease: NR

Psychogenic ED, %: 38 vs. 40%

Physiologic ED: NR

Mixed ED: 62 vs. 60
IG: sildenafil citrate
CG: placebo

IG1:
Dose: 10 or 25 mg, as determined during 16-wk tx phase prior to double-blind study
Duration: 8 wk
Frequency: up to once/d approximately 1 hr before sexual activity
Compliance: NR

CG:
Dose: placebo
Duration: 8 wk
Frequency: as IG
Compliance: NR

Run In period: 2 wk with placebo
Wash out period: NA

F/u duration (both on and off treatment): 8 wk

Other: 16-wk open-label treatment phase after run-in period to adjust dosage
Primary outcome results:
IIEF frequency of erections when sexually stimulated, mean change in score: ▴ 1.53 vs. ▾ 0.3
Question assessing frequency of erections lasting long enough:
IG1 ▴ 1.72, CG ▾ 0.13
Mean number of grade 3 or 4 erections per wk: 1.5 vs. 0.6

GAQ, % yes: 82 vs. 26

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 3 (3), all in IG1

WDAE, n (%): 4 (3), no grp designation
TAE: NR, most frequent AEs in IG vs. CG/ IG in 1 y open label, n (%): headache 6 (6) vs. 2 (2)/19 (10); dyspepsia. 5 (5) vs. 3 (3)/26 (14); flushing 7 (7) vs. 1 (1)/24 (13); abdominal pain 0 vs. 4 (4)/10 (5); diarrhoea 1 (1) vs. 0; nausea 1 (1) vs. 0/4 (2); back pain 2 (1) vs. 1 (1)/11 (6); asthenia 2 (2) vs. 0/3 (2); abnormal vision including colour hue or brightness perception 2 (2) vs. 0/4 (2); conjunctivitis 2 (2) vs. 0/4 (2)
SAE: 24 no grp designation, including MI in open label phase

Ascertainment of outcomes assessed: IIEF, GAQ, Patient diary of grading erection (1=enlarged but not hard-4=full erection)
DeBusk, (2004) 16


Funding source: Pfizer Inc
N screened = 186
N randomized = 151

IG, n = 75 (ITT=70)
CG, n = 76 (ITT=72)

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older with diagnosed ED (≤ 21 on Sexual Health Inventory), confirmed, and stable CAD for at least 4 wks

Exclusion: currently using prescription for and/or taking nitrates, hypotension, uncontrolled hypertension, high cardiac risk, unstable angina, hypotrophic obstructive cardiomyopathy, moderate/severe aortic stenosis, concomitant TX with drugs that inhibit P450, commercial tx for ED, previously taken sildenafil
Age, mean (range): 61 (39–82) vs. 62 (41–80) y

Race (%): more than 90% White

Co-morbidities: CV conditions 100% (listed in full text); Hyperlipidemia 53 (72) vs. 49 (65); pure hypercholesterolemia 38 (51) vs. 38 (50); other also listed in full text

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): medication taken by more than 50% of pts= anti-inflammatory analgesics 133 (88); hyperlipidemia 131 (87); anti-hypertensives: 113 (75); Beta Blockers: 90 (60)

Duration of ED, mean: 5 y

Underlying disease: NR

Psychogenic ED, n (%): 5 (7) vs. 3 (4)

Physiologic ED, n (%): 36 (49) vs. 34 (45)

Mixed ED, n (%): 33 (45) vs. 39 (51)
IG: sildenafil
CG: placebo

IG:
Dose: 50 mg with option to titrate to 100 or 25 mg
Duration: 12 wks
Frequency: up to once/d (total dose=36)
Compliance (%): 80

CG:
Dose: NA (titration as IG)
Duration: 12 wks
Frequency: up to once/d (total = 40)
Compliance (%): 85

Run In period: 2 wks
Wash out period: NR

F/u duration: 12 wks

Other: final dose, n (%)=
25 mg: 3 (4) v. 0
50 mg: 16 (22) vs. 13 (17)
100 mg: 55 (74) vs. 63 (83)
Primary outcome results:
IIEF- least square mean (SE) score:
Q3, baseline=2; post tx: 3.5 vs. 2.7
Q4, baseline=1.6; post tx: 3.3 vs. 2.3

GEQ, % of pts with improvement on:
Erection: 59 vs. 28
Intercourse: 56 vs. 27
Intercourse success: 51 vs. 25

Other outcomes assessed: IIEF, % of max possible score (all but SD improved in IG vs. CG, p<0.02;); EDITS scores; life satisfaction checklist scores

Withdrawals/drop-outs/loss to f/u: 7 (10) vs. 9 (13); including lack of efficacy in 0 vs. 4 (6)

WDAE, n (%): 1 (1.4) vs. 1 (1.3)
TAE, %: 47 vs. 32; AE in more than 3% of pts, n (%)=headache 6 (8) vs. 1 (1); chest pain 4 (6) vs. 2 (3); hypertension 4 (6) vs. 1 (1); flushing 6 (8) vs. 0; dyspepsia 2 (3) vs. 4 (5); leg cramps 3 (4) vs. 0; respiratory tract infection 4 (5) vs. 2 (3); nasal congestion 2 (3) vs. 0; abnormal vision 1 (1) vs. 1 (1)
SAE, n (%): 1 (1.4) vs. 2 (2.6), One chest pain in IG, and urinary tract infection, severe angina pectoris in CG

Ascertainment of outcomes assessed: IIEF, EDITS; GEQ, and intercourse success rate by diary; life satisfaction check list
Deveci (2004) 17


Funding source: NR
N screened = NR
N randomized = 40

IG, n= 20
CG, n= 20

Intention to treat (ITT) analysis: NR

Inclusion: NR

Exclusion: presence of any contraindication for sildenafil use; hormonal disorders; performance concern; unsteady sexual partnership, past trial/use of oral sildenafil; chronic dx


Data reported as IG vs. CG
Age, mean (range): 55 (25–65) y

Race (%): NR

Co-morbidities, n (%): DM 6 (15); hypertension 5 (12.5); benign prostatic hyperplasia 7(17.5); pts with 2 or more risk factors 4(10)

Previous ED treatment: NR

Smoking status, n (%): current & past smokers 9 (22.5)
Concomitant medications: NR

Duration of ED: more than 3 mo

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil sublingual
CG: placebo

IG:
Dose: 20 mg during sexual stimulation
Duration: NR
Frequency: NR
Compliance (%): NR

CG:
Dose: NR
Duration: as IG
Frequency: as IG
Compliance (%): NR

Run In period: NR
Wash out period: NA

F/u duration: NR
Primary outcome results:
Mean ▴ in IIEF-5: 1.75 (endpoint vs. baseline p=0.02) vs. 0.6 (endpoint vs. baseline p>0.05)

Overall success rates, n (%): 13 (65) vs. 3 (15)

Mean onset of erection: 15.5 vs. 30 min

Mean duration of erection: 40 vs. 20 min

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: NR

WDAE: NR
TAE, n (%): NR; headache 2 (10) vs. 1 (5); flushing 2 (10) vs. 2 (10); sweating 2 (10) vs. 0
SAE: 0

Ascertainment of outcomes assessed: pts self reports; & IIEF-5 (5 item version of IIEF)
Diamond, LE (2005) 18


Funding source: Palatin Technologies, Inc.
N screened = NR
N randomized = 19 (cross over)

IG1/ IG2/CG, n = 19

ITT analysis used for primary outcome: NR

Inclusion: men 40–65 y, with diagnosed ED of at least 6 mo currently using viagra or levitra and having an adequate response to either of them

Exclusion: ED caused by untreated endocrine dx, penile deformity, prostate cancer or prostatectomy, major hepatic, renal, CV, psychiatric or CNS dx, stroke, SCI
Age, mean (sd): 53 (6.7)

Race (%): White 70, Black 10, Hispanic 20

Co-morbidities, %: Diabetes 10, hypertension 20, hyperlipidemia 50, obesity 10

Previous ED treatment: Viagra and levitra

Smoking status: 50% (past/current)

Body weight: 87 (13) kg

Other: Total T level, mean: 436 (168) ng/dl
Concomitant medications:

Duration of ED (yr): 5.0 (SD=5.4)

Underlying disease: NR


Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR

Other: IIEF mean score = 21.2 (6–29)
IG1: Sildenafil + PT141
IG2: Sildenafil + placebo
CG: Placebo

IG1:
Dose: 25 mg+7.5 mg
Duration: NR
Frequency: NR
Compliance: NR

IG2:
Dose: 25 mg
Duration: NR
Frequency: NR
Compliance: NR

CG:
Dose: NA
Duration: NR
Frequency: NR
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: NR

Other: Outcome assessments done on 3 visits 3–10 d apart and continuously monitored until 6 hrs after each dose
Primary outcome results:
IG1 vs. IG2, mean (SE):
Base rigidity => 60%: 112.9 (19.2) vs. 69.9 (14.3) min, p < 0.01

Base rigidity => 80%: 61 (16) vs. 40 (10) min, p=>0.05

Tip rigidity => 60%: 99.5 (16.6) vs. 40.6 (7.5) min, p < 0.001

Tip rigidity => 80%: 48.6 (12.2) vs. 20.7 (4.8) min, p < 0.05

Pts-assessed mean quality score of erection after sexual-visual stimulation (1–10) = 8.2 (0.41) vs. 6.8 (0.52), p < 0.05

Rigidity parameters improved in IG1 vs. placebo (p < 0.05)

Other outcomes assessed: tumescence activity levels

Withdrawals/drop-outs/loss to f/u: NR

WDAE: None
TAE: more and new AE observed with combination tx; flushing one also had nausea 4 (21%) vs. 0 vs. 0; headaches 0 vs. 1 vs. 1
SAE: 0

Ascertainment of outcomes assessed: RigiScan and questionnaire
Dinsmore, W (1999) 19


Funding source: NR
N screened = 127
N randomized = 111

IG, n = 57
CG1, n = 54
CG2, n= 109 (separate parallel study, no treatment, age matched, healthy subjects, single-visit data not included in this table)

ITT analysis used for primary outcome: Yes

Inclusion: men older than 18 with clinical diagnosis of ED of at least 6 mo, participated in a stable, heterosexual relationship for at least 6 mo and to forego self-injection programs

Exclusion: advanced vascular, neurological, endocrine, or anatomic causes for ED, major hematologic, renal, or hepatic abnormalities, regular use of nitrates, hx of stroke in the past 6 mo. or currently active peptic ulceration, tx with any experimented drugs in the 3 mo. preceding the study
Age, mean (range): 56 (30–78) vs. 55 (29–89) y

Race (%): NR

Co-morbidities, %: hypertension IG 9 vs. 11; DM 7 vs. 7; ischemic heart disease 1 vs. 1
Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED (yr): NR

Underlying disease: NR

Psychogenic ED (%): 40 vs. 39 (CG1)

Physiologic ED (%): 21 vs. 20

Mixed ED (%): 39 vs. 37
IG: sildenafil (self-administered)
CG: placebo
CG2: no treatment

IG:
Dose: 25 mg (option to ▴ to 50 mg, max. 100 mg)
Duration: 12 wks Frequency: 1-hr pre sexual activity but not > once daily
Compliance: 87 %

CG:
Dose: NA (option to ▴ to 50 mg, max. 100 mg)
Duration: 12 wks Frequency: 1-hr pre sexual activity but not > once daily
Compliance (%): NR

Run In period: 2–4 wks
Wash out period: NR

F/u duration (both on and off treatment): 12 wks + 2 wks = 14 wks
Primary outcome results:
IIEF-Q1–15, range: pre (except Q11, and 12) </= 2.52; post tx range 2.77–3.92 vs. 1.37–3.10, sign ▴ (p < 0.01)

GEQ, % improved: 81% vs. 18% (p<0.0001)
Grade 3 or 4 erection/mo, mean (event log): 6.9 vs. 2.4 (p<0.0001)

Successful sexual intercourse attempts: 73% vs. vs. 30% (p<0.0001)

Other outcomes assessed: all IIEF items

Withdrawals/drop-outs/loss to f/u, n (%): 14 (13) including 3 in IG, and 11 in CG discontinued tx due to lack of efficacy

WDAE: 0
TAE, n (%): 18 (30) vs. 3 (5.5) headache 7(12%) vs.1 0; flushing 5 (9) vs. 2 (4); dyspepsia 4(7) vs.1 (2); abnormal vision 2 (4) vs. 0
SAE, n: nr

Ascertainment of outcomes assessed: 15-item IIEF; GEQ; event log with of erection using a 5-point scale grading system (0 =no sexual activity; 1=almost never; 5=almost always) (added”)
Dunzendorfer (2002) 20


Funding source: NR
N screened = NR
N randomized = 77 (cross over)

IG1, n = 44
IG2, n = 33
CG, n = NA

ITT analysis used for primary outcome: NR

Inclusion: pts with ED, and low to non-response to 5 PDE inhibitors; with complaint of prostate disease

Exclusion: NR
Age, mean (range): 62 (34–77) y

Race: NR

Co-morbidities: NR
Previous ED treatment: 100% with PDE-5 inhibitors; 4 wks screening drug program for low responders to (n=58), 3 hrs before sildenafil 100 mg intake (dose/ sexual activity): Midodrine 25 mg; Testosterone 250 mg/wk; Ginseng 900 mg; Yohimbine 15 mg; Akatinol 10 mg; Apomorphine4 mg; Hydergin-S 8 mg; Prazosi 4 mg; DHE 5 mg

Body weight: NR
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): DM 4 (5); hypertension 17 (22); prostate dx 77 (100); mixed vasculogenic 77 (100)

Psychogenic ED, n (%): NR

Physiologic ED, n (%): 100%

Mixed ED, n (%): NR
IG1: A: Sildenafil/ B: Sildenafil + Dihydro-ergotamine (DHE)
IG2: A: Sildenafil + DHE/ B: Sildenafil

IG1:
Dose: slidenafil 50 mg, titrated to 100 mg; DHE 5 mg
Duration: NR
Frequency: twice / wk
Compliance: NR

IG2:
Dose: 50 mg (titration as IG1)+ 5 mg DHE
Duration: NR
Frequency: as IG1
Compliance: NR

Run In period: 4 wks (see previous ED tx)

Wash out period: 4 wks

F/u duration: NR

Other: Pts received tx A (IG1) or B (IG2) followed by a wash out period and then crossed over to B (IG1) or A (IG2) respectively
Primary outcome results:
Mean IIEF Q3, 4, 5 and 6, range of mean scores per question, (SD range):

Baseline (run in) = 1.1–1.8 (0.2–0.4)
50 mg sildenafil alone = 1.1–2.1 (0.2–0.4)
100 mg sildenafil =1.5–2.1 (0.3–0.4)
DHE alone = 1.3–2.2 (SD range 0.2–0.5)
Combination 50 mg sildenafil + DHE =2.9–3.2 (0.5–0.7)
100 mg sildenafil + DHE = 3.5–3.8 (.6–0.8)

Other outcomes assessed: NO-cAMP (N1 oxide cyclic adenosine monophosphate), and cGMP (cyclic guanosine monophosphate) levels in corpora cavernosa; urodynamic profile

Withdrawals/drop-outs/loss to f/u, n (%): NR

WDAE: NR
TAE: NR (authors claim that combination tx reduced AE)
SAE: NR

Ascertainment of outcomes assessed: IIEF, lab measures
Eardley (1999) 21


Funding source: NR
N screened = NR
N randomized = 16 (cross over)

IG/CG = 16

ITT analysis used for primary outcome: No

Inclusion: men 18 or older, with ED of no known organic cause

Exclusion: Hx of DM, untreated hypogonadism; tx with nitrates, antidepressants or tranquilizers. Concomitant sign.arterial disease; other tx for ED less than 2 wks prior to start of study
Age, mean (range): 35–68 (57) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range): 1.9 (0.25 – 8) y

Underlying disease: NR
Psychogenic ED: NR

Physiologic ED: 0

Mixed ED: NR
IG: sildenafil
CG: Placebo

IG:
Dose: 100 mg
Duration: 2–5 hrs
Frequency: twice
Compliance (%): 100%

CG:
Dose: NA
Duration: 2–5 hrs
Frequency: twice
Compliance (%): 100%

Run In period: 2 wks
Wash out period: 7 d

F/u duration: f/u assessments at 2 and 4 hrs post dosing
Primary outcome results:
Pts with grade 3 or 4 erection, n (%): IG only 13 (81.25)

Duration of erection 2 hrs post dosing, mean:
RigiScan, erections with > 60% rigidity at base:
At 2 hrs post dosing: IG 2.5 min (responders = 4.1 min)
At 4 hrs post dosing: IG responders = 2.2 min, for IG1 = 1.4 min
Pts rated erection, grade 3 or 4: responders:
At 2 hrs post dosing: 23.8 minutes
At 4 hrs post dosing: IG responders 17.2 min

Other outcomes assessed: None

Withdrawals/drop-outs/loss to f/u: 0
WDAE: 0
TAE: 0
SAE: 0

Ascertainment of outcomes assessed: RigiScan, self-rating scale
Eardley (2001) 22


Funding source: Pfizer Inc.
N screened = 47
N randomized = 44 (crossover design)

IG/CG, n = 44

ITT analysis used for primary outcome: Yes (n=40)

Inclusion: men18–70 y; clinical diagnosis of ED of no established organic cause for longer than 6 mo; in stable relationship with female partner; have residual ED (at least one grade 3 or 4 erection) or positive response to papaverine or PgE1 injection within 4 wk of study entry

Exclusion: having 2 successive penetrative sexual intercourse acts per wk; hx of alcohol misuse; regular tx with nitrates, anticoagulants or acetylsalicylic acid within 2 wk; tx with antidepressants or major tranquillizers for psychoses or related conditions; continued use of other ED tx
Age, mean (range): grp: 53 (33–69) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range): 3 (0.5–10) y

Underlying disease: NR

Psychogenic ED: 100%

Physiologic ED: 0

Mixed ED: NR
IG1: sildenafil
CG: placebo

IG1:
Dose: 25 mg with option to titrate to 50 mg and then 75 mg if necessary
Duration: median 29 d (two 28 d tx periods)
Frequency: 1 dose 30–60 min before sexual activity; max. 1/d
Compliance: 91% took at least one dose

CG:
Dose: placebo (titration as IG)
Duration: as IG
Frequency: as IG
Compliance: as IG

Run In period: None
Wash out period: None

F/u duration: 10 wk (2 wks post last tx period)

Other: 24 pts received sildenafil first, and 20 received placebo first; each period lasted for 28 d
Primary outcome results:
Geometric mean number of grade 3 or 4 erections per wk: 4.2 vs. 1.4

Erection of grade 3 or 4/ doses: I94 vs. 68

Intercourse success/ dose, %: 62vs. 12

GEQ-Q1 (improved erection), % yes: 34 (94) vs. 9 (25)
GEQ-Q2 (ease of use), %: 33 (94) vs. 13 (37)

Other outcomes assessed: partners' assessment of quality of erections

Withdrawals/drop-outs/loss to f/u: 5 (11)

WDAE, n (%): 0 vs. 1 (<1)
TAE, n (%): all reporting AE 23 (53) vs. 14 (33); tx related AE: headache 11 (26) vs. 0; flushing 4 (9) vs. 0; dyspepsia 3 (7) vs. 1 (2); arthralgia 3 (7) vs. 2 (5)
SAE, n (%): 0 vs. 1 (<1) MI in second period

Ascertainment of outcomes assessed: daily log of erection (grading system 1–4), and intercourse satisfaction
Eardley (2002) 23

Study a


Funding source: NR
N screened = 17
N randomized = 17 (two-way crossover study)

IG, CG, n = 17

ITT analysis used for primary outcome: No

Inclusion: age 35–70 y, clinical diagnosis ED, no organic cause for at least 6 mo

Exclusion: hx of serious medical conditions (DM, untreated hypogonadism, sign arterial dx, migraine headaches, alcohol or substance abuse. Current tx with nitrates, antidepressants, tranquilizers or anticoagulants. Other therapies for ED (e.g. E1 IC) discontinued 2 wks prior to start of study
Age, mean (range):
52yrs (37–70)

Race (%): NR

Co-morbidities: NR

Previous ED treatment: 4 received prostaglandin, 2 yohimbine, 1 an investigational drug

Smoking status: NR

Body Weight: NR

Other: other conditions, n (%); vasectomy 3 (17.6%), 1 unilateral orchidectomy, prostatitis 1 (5.8%), caricosities 1(5.8%)
Concomitant medications: NR

Duration of ED: 3.1 y (0.5–19)

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil + 60 min visual sexual stimulation (VSS)
CG: placebo + 60 min visual sexual stimulation

IG:
Dose: 50 mg
Duration: NR
Frequency: once
Compliance (%): 100%

CG:
Dose: NA
Duration: NR
Frequency: once
Compliance (%): 100%

Run In period: NR
Wash out period: 7 d

F/u duration: NR
Primary outcome results:
Proportion of responders with rigidity > 60%, n (%): 14 (82) vs. 9 (53)

Pts with grade 3 or 4 erection: 12 (71) vs. 6 (35)

Time to onset of erections (median):
27 min (range 12–70) vs. 50 min

The onset of erections occurred only after VSS; 8 (47%) responded to both active and placebo tx

Other outcomes assessed: none

Withdrawals/drop-outs/loss to f/u, n (%): 1

WDAE: 0
TAE: NR
SAE: NR

Ascertainment of outcomes assessed: RigiScan; physical exam, patient report; standard laboratory tests
Eardley (2002) 23

Study b


Funding source: NR
N screened = 16
N randomized = 16 (two-way crossover)

IG/ CG, n = 16

ITT analysis used for primary outcome: No

Inclusion: men 35–70 yrs, clinical diagnosis ED, no organic cause for at least 6 mo

Exclusion: hx of serious medical conditions (DM, untreated hypogonadism, sign arterial dx, migraine headaches, alcohol or substance abuse. Current tx with nitrates, antidepressants, tranquilizers or anticoagulants; other therapies for ED (IC injections) discontinued 2 wks prior to start of study.
Age, mean (range): 57 (35–68) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: none

Smoking status: NR

Body weight NR

Other: pts conditions, n (%) vasectomy 7 (43.8), undescended right testicle 1 (6.3), prostatitis, redundant prepuce 1 (6.3), scrotal cyst 1 (6.3), hyperplasia of the prostate 1 (6.3)
Concomitant medications: NR

Duration of ED (mean yrs, range): 1.9 (3–8.0) y

Underlying disease (diagnosis) (N or % of diseased/ grp): NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil+ 60 min visual sexual stimulation (VSS)
CG: placebo + 60 min VSS

IG1:
Dose: 100 mg
Duration: NR
Frequency: twice
Compliance (%): 100%

CG:
Dose: NA
Duration: NR
Frequency: twice
Compliance (%): 100%

Run In period: NR
Wash out period: NR

F/u duration: four assessment at 3 hrs and 5 hrs

Other: pts received 4 tx (2 active and 2 placebo)
Primary outcome results:
Proportion of responders with rigidity > 60%, n (%):
3 hrs post VSS: 12 (75) vs. 5 (31)
5 hrs post VSS: 13 (81) vs. 5 (31)

Duration of erection, mean (SE):
3 hrs post VSS: 19.4 (4.1) vs. 3.9 (2.1) min
5 hrs post VSS: 17.2 (4.0) vs. 3.6 (2.0)

Other outcomes assessed: none

Withdrawals/drop-outs/loss to f/u, n (%): 1 (6.3)

WDAE: 0
TAE: NR
SAE: NR

Ascertainment of outcomes assessed: RigiScan; physical exam patient report, standard laboratory tests
Eardley (2005) 24


Funding source: Lilly ICOS LLC
N screened = 411
N randomized = 367

IG1, n = 183 (first period)
IG2, n = 184 (first period)
CG, n = NA

ITT analysis used for primary outcome: Yes

Inclusion: Pts aged => 18 yr with documented ED of any aetiology and severity, in a steady relationship with the same female partner naïve to treatment for ED with drugs inhibiting PDE5

Exclusion: Pts with endocrine dx, premature ejaculation, prostatectomy, pelvic surgery, penile deformity, sign renal or hepatic dx, CHF, Within 6 mo, MI, coronary artery bypass surgery, sudden cardiac arrest, SBP (< 90 - > 170 mmHg) or diastolic (< 50 - > 100 mmHg), malignant hypertension, retinitis pigmentosa, current tx with nitrates, cancer chemotherapy, HIV infection, substance/drug abuse in last 6 mo
Age, mean (sd): 54 (12) y

Race (%): Caucasian 92, Black 4, Asian 3, other 1.3

Co-morbidities, (%): Hyperlipidemia 11, coronary artery dx 6.5, hypertension 26.4, DM 9.5, depression 4

Previous ED treatment: NR

Smoking status, (%): current = 24

Body weight: NR

Other: current alcohol use (65%)
Concomitant medications: no other ED treatments

Duration of ED: NR (pts with 1 y or more ED =74%)

Underlying disease: NR

Psychogenic ED: 12%

Physiologic ED: 28%

Mixed ED: 60%

Other: ED defined as consistent change in the quality of erection that adversely affects subject's satisfaction with sexual intercourse

Other: Mean IIEF (EF): 14 (6); Severity of ED: severe (IIEF1–10): 31%, moderate (IIEF 11–16): 30%, mild (IIEF 17–30): 39%
IG1: Sildenafil
IG2: Tadalafil

IG1: Sildenafil
Dose: 25–100 mg
Duration: 12 wks
Frequency: NR
Compliance: NR

IG2: Tadalafil
Dose: 10–20 mg
Duration: 12 wks
Frequency: NR
Compliance: NR

Run In period: 4 wks
Wash out period: 7–10 d

F/u duration: before and after crossover
24 wks (2 periods of 12 wks)

Other: Dose was titrated up and down between 25–100 for Sildenafil and 10–20 mg for Tadalafil
Primary outcome results:
Mean least squares change from baseline for IIEF domains and 95% CI (IG2 vs. IG1):
EF: 0.5 (-0.07, 1.1)
OF: 0.3 (0.02, 0.5)
SD: 0.2 (0.02, 0.6)
Intercourse satisfaction: 0.17 (-0.1, 0.42)
Mean change in IIEF questions: erection firmness, intercourse satisfaction and enjoyment, desire level, OS, erection confidence: tadalafil > sildenafil
OS: 0.3 (0.02, 0.5)
SEP, mean change from baseline:
SEP-Q2: 36 vs. 39
SEP-Q3: 53 vs. 58

Other outcomes assessed: mean scores of IIEF, drug preference

Withdrawals/drop-outs/loss to f/u: IG1 (1st) and IG2 (2nd): n=42
IG1 (2nd) and IG2 (1st): n=39

WDAE: IG1 (1st) and IG2 (2nd): n=4
IG1 (2nd) and IG2 (1st): n=7
TAE, n (%): pts with 1 or more AE=125 (34) vs. 128 (35)
SAE, n: 4 (2) vs.5 (3)

Ascertainment of outcomes assessed: Questionnaires
Fava (2006) 25


Funding source: Pfizer Inc. (conflict of interest for authors; paid by Pfizer, and other sources)
N screened = NR
N randomized = 142

IG1, n = 71
CG, n = 71

ITT analysis used for primary outcome: NR

Inclusion: men 18 or older with ED diagnosed by Sexual Health Inventory for Men (SHIM) score of 21 or less, and diagnosed major depressive disorder (MDD) according to DSM-IV criteria in remission in stable relationship

Exclusion: symptomatic for depression or anxiety despite tx; pts requiring tx with antipsychotics, mood stabilizers, other nonserotonergic antidepressant agents or lithium; use of nitrates or any commercially available for ED
Age, mean (range): 51 (27–74) y

Race, %: White 86 vs. 92%; Black 6 vs. 3%; Asian 3 vs. 0%; other 6% in both grps

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: NR

Body weight, mean (range): 92 (57–191) vs. 92 (60–138) kg
Concomitant medications, n (%): antidepressant therapy, selective SRI 133 (94); serotonin-norepinephrine reuptake inhibitor 10 (7); other antidepressant drugs 10 (7)

Duration of ED, mean (range): 2.7 (0.1–14.2) vs. 2.2 (0.2–11.6) y

Underlying disease, n (%): depression


Psychogenic ED, n (%): 100%

Physiologic ED: NA

Mixed ED: NR
IG: Sildenafil
CG: Placebo

IG:
Dose: 50 mg titrated to up to 100 or down to 25 mg based on efficacy and tolerance
Duration: 6 wks
Frequency: NR
Compliance:

CG:
Dose: NA
Duration: 6 wks
Frequency: NR
Compliance:

Run In period:
Wash out period:

F/u duration:

Other: mean dose taken/ mo= 13.6 vs. 11; 65% on 100 mg 34% on 50 mg and 1% on 25 mg sildenafil at end of study
Primary outcome results:
IIEF mean score:
Q3: baseline 2.4; post tx 3.9 vs. 3.1, p=0.003
Q4: baseline 2.1; post tx 3.7 vs. 2.8, P<0.001
GEQ- Q1, % improved: 70.6 vs. 28.8
GEQ-Q2, % improved: 72.1 vs. 27.7
GEQ-Q3, mean (SE) scale of 1–5: 2.5 (0.2) vs. 1.3 (0.2)

Event log, mean (SE) N of events/ wk:
N of sexual intercourse attempts: 2.6 (0.2) vs. 1.9 (0.2)
N of successful attempts: 1.9 (0.2) vs. 0.6 (0.2)
Successful attempts/ wk, % (95% CI): 71 (60 to 80) vs. 31 (22 to 43)

Other outcomes assessed:
All EDITS questions indicated tx success with sildenafil

Withdrawals/drop-outs/loss to f/u, n (%): 9 (12.7) vs. 4 (5.6)

WDAE: NR
TAE, n (%): NR; all included headache 6 (9) in all; dyspepsia 6 (9) vs. 1 (1); anxiety 4 (6) vs. 3 (4); abnormal/ blurry vision 2 (3) vs. 0
SAE, n (%): 0

Ascertainment of outcomes assessed: IIEF, EDITS, GEQ
Fowler (2004) 26


Funding source: Pfizer Inc.
N screened = 256
N randomized = 218

IG, n = 104/ (102, 98% completed)
CG, n = 113/ (n= 88, 78% completed)

Intention to treat (ITT) analysis: yes

Inclusion: men 18 yr or older, ED of at least 6 mo; diagnosis of multiple sclerosis (MS) of at least 1 yr (criteria not defined/ type of MS not defined), with residual disability level of 2–6 (ambulatory) based on Kurtzke Extended Disability Status Scale (EDSS)

Exclusion: penile deformities; major haematological, renal or hepatic abnormalities, coexistence /sexual dx as primary cause; uncontrolled psychiatric condition; cardiovascular disorder; unknown hx of retinitis pigmentosa; use of nitrates, or corticosteroids (last 2 mo); nitric oxide donors
Age, mean: 46 y

Race (%): NR

Co-morbidities: 100% MS (mean duration 10.4 y)

Previous ED treatment: NR

Smoking status: NR

Note: data reported for IG vs. CG
Concomitant medications: (used by > 10% of pts) analgesics; antibacterial; antidepressants; antihypertensive (> in CG); corticosteroids (> in IG); drugs affecting immune response, muscle relaxants; rheumatic diseases medication; vitamins

Duration of ED: mean (range) 5.2 (0.7–23.1) vs. 6.1 (0.9–29) yr

Underlying disease: NR

Psychogenic ED: NR
Physiologic ED: NR

Mixed ED: NR
IG: Sildenafil
CG: placebo

IG:
Dose: 50 mg (32%); titrated up to 100 (64%), or down to 25 mg (4%) based on patient response & tolerability
Duration: 12 wks
Frequency: max once / d, 1 hr before sexual activity
Compliance (%): NR

CG:
Dose: NA
Duration: as IG
Frequency: as IG
Compliance (%): NR

Run In period: 4 wks
Wash out period: NA

F/u duration: 12 wks
Note: this trial was followed by an open label period of 24–48 wks (n=206) & included those with non tx related AE; (50 mg sildenafil)
Primary outcome results: IIEF-Q1 (improvement in erection), % of pts: 90% vs. 24%, p<0.0001
Q2 (satisfactory erection for intercourse), % of pts: 92% of responders to Q1
Q3/Q4: IG better than CG, p<0.0001
Q9/ Q10: IG better than CG, p< 0.0001
Q11/ Q12: IG better than CG, p=0.0002
GEQ3, mean score: 4 vs. 2

Other outcomes: quality of life, IG did better in 5/8 variables than CG, (sexual life 86% of pts vs. 22%)

Withdrawals/drop-outs/loss to f/u, n (%): 2 (2) vs. 25 (22)

WDAE: 0 vs. 1%
TAE (%): AE in more than 3% of pts in IG vs. CG/IG open label=66.3 vs. 43.4/73; headache 27 vs. 7/23; flushing 13 vs. 2/16; weakness 6 vs. 1/4; MS relapse 7 vs. 2/10; rhinitis 6 vs. 1/7; chromatopsia 4 vs. 0/4; dyspepsia 6 vs. 0/6
SAE, n (%): 3 (3) vs. 3 (3), urinary tract infection, worsening, & exacerbations of MS in IG; weakness, bone disorder, MI in CG

Ascertainment of outcomes assessed: IIEF; GEQ, quality of life questionnaire
Gentile (2004) 27


Funding source: Sigma-Tau, Italy
N screened = NR
N randomized = 40

IG, n = 20
CG, n = 20

ITT analysis used for primary outcome: N

Inclusion: men 18 or older, with ED, in a stable relationship of more than 6 mo; type 1 DM of at least 5 y or type 2 DM of at least 2 y (defined by National Diabetes Data Group), medical management of DM for 6 mo., HbA1C levels < 11%

Exclusion: genital anatomical deformities, a primary dx of a sexual disorder other than ED, a poorly controlled major psychiatric disorder, a recent hx of major haematological, renal or hepatic abnormalities, MI, stroke, heart failure, unstable angina or hypotension, or tx with nitrates, HbA1C levels ≥ 11%
(Complete list in full text article)
Age, mean (range): 64 (45–81) y

Race (%): Caucasian 100 %

Co-morbidities, %: hypertension 31 vs. 34; peripheral vascular dx 4 vs. 3; other 3 vs. 2

HbA1C level, % (range): 8.6 (5.7–11.3) vs. 8.4 (5.6–10.9)

Previous ED treatment: Viagra monotherapy in all

Smoking status: smoker 32 vs. 29

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range): 5.7 (0.7–22) vs. 5.3 (0.6–19.5) y

Underlying disease, %: DM type 1= 18 vs. 16; DM type 2= 82 vs. 84

Organic ED, (%): 65 vs. 66

Mixed ED, %: 35 vs. 34
IG: propionyl-L carnitine (PLC) + sildenafil
CG: placebo PLC + sildenafil

IG:
Dose: 2 g PLC+ 50 mg sildenafil
Duration: 24 wks
Frequency: once/d + twice/wk
Compliance: NR

CG:
Dose: 2 g (placebo) + 50 mg sildenafil
Duration: 24 wks
Frequency: as IG
Compliance: NR

Run In period: 4 wks
Wash out period: NR

F/u duration: 24 wks
Primary outcome results:
IIEF-Q3, mean (sd): 4.3 (0.6) vs. 3 (0.7), p<0.01
IIEF-Q4, mean (sd): 3.9 (1) vs. 2.7(0.9), p<0.01
GEQ, (% yes): 68 vs. 23, p<0.01
Successful attempts of intercourse (Event logs), %: ▴ from 11% to 34% vs. ▴ 10% to 76%, p<0.01

Other outcomes assessed: vascular evaluations [e.g. cavernosal artery; PSV, resistance index (RI)]

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE: gastric pain 2 vs. 0
SAE: 0

Ascertainment of outcomes assessed: IIEF; GEQ
Gingell (2004) 28


Funding source: Pfizer
N screened = 17
N randomized = 16
(four way crossover trial)

IG/ CG, n = 16

ITT analysis used for primary outcome: yes (n=16)

Inclusion: sildenafil naïve men 18 to 70 y and had been diagnosed with ED of no known organic cause for longer than 6 mo

Exclusion: Men who had not experienced at least one erection of sufficient rigidity for penetrative intercourse in the previous 4 wks, or failed to give positive response to IC prostaglandin or papaverine at screening; hx of DM, untreated hypogonadism; sign arterial, renal or hepatic dx or used antidepressants, tranquilizers, nitrates, IC injections or any other tx for ED in 2 wks.
Age, mean (range): 55 (36–68) y

Race, n (%): White 16 (94)

Co-morbidities: NR

Previous ED treatment: None within last 2 wks.

Smoking status:
NR

Body weight, mean (sd): 83 (10) kg
Concomitant medications: None

Duration of ED: ≥ 6 mo

Underlying disease: None

Psychogenic ED: None

Physiologic ED:
None

Mixed ED: None
IG: Sildrnafil
(mix of both given at diff time periods)
CG: Placebo

IG:
Dose: 100 mg
Duration: three 14 hr inpatient stay in 4 wks
Frequency: once/ session (at one of either 12, 8, or 1 hr prior to VSS)
Compliance: 100%

CG:
Dose: 3 tablets
Duration: one14 hr inpatient stay
Frequency: as IG
Compliance: 100%

Run In period: NR
Wash out period: 7 d

F/u duration: 4 wks

Other: pts were randomized into sequence grps (I–IV) and sildenafil or placebo administered test periods (A–D)
Primary outcome results:
Duration of erections of ≥60% rigidity, mean for IG at 1, 8, 12 hr prior to VSS vs. CG: 26, 11, 8 vs. 3.4 min

Duration of grade 3 or 4 erection, (hard enough, completely hard) at 1, 8, 12 hr: 33, 23, 16 vs. 7 min (75% reported grade 3 or 4 after 2 hrs)

Other outcomes assessed: Proportion of sildenafil responders 1,8, 12 hrs, %: 69, 60, 31; 82% after 8 hrs, and 54% after 12 hrs

Withdrawals/drop-outs/loss to f/u: 1 pts excluded (use of IC injection during trial)

WDAE: None
TAE: NR; most common, AEs at 1, 8, and 12 hrs pre VSS 27 vs. 1; AEs included headaches 12 vs. 0; flushing 9 vs. 0; diarrhea 1 vs. 0; dry mouth 1 vs. 0; GI disorder 1 vs. 1; respiratory tract infection 1 vs. 0; visual disturbances (chromatopsia) 2 vs. 0
Most common headache: 12
Facial Flushing: 9
CG n: Gastro 1
SAE: None

Ascertainment of outcomes assessed: RigiScan; self-assessed duration of grade 3 or grade 4 erections:
Glina (2001) 29
Companion Glina (2002) 30


Funding source: Pfizer
N screened = NR
N randomized = 245
(Parallel grp)

IG, n = 124
CG, n = 121

ITT analysis used for primary outcome: Yes

Inclusion: Brazilian and Mexican men 18 or older with ED of broad-spectrum etiology ≥6 mo in a stable, heterosexual relationship for a duration of ≥ 6 mo.

Exclusion: genital anatomical deformities; ED secondary to SCI, primary diagnosis of other sexual disorders; uncontrolled DM; hx of stroke, MI or sign. CV disease within previous 6 mo, hypotension or hypertension; alcoholism or substance abuse; receiving nitrates or nitric oxide
Age, mean (range): 58 (28– 85) vs. 55 (27– 84)

Race, n (%): Hispanic: 60 (48.4) vs. 57 (47.1); White 60 (48.4) vs. 58 (47.9); Other: 4 (3.2) vs. 6 (5)

Co-morbidities: NR

Previous ED treatment: NR

Smoking status:
NR

Body weight: NR
Concomitant medications: antihypertensives, insulin and antidiabetics, beta-adrenoreceptor blockers, hypnotics, sedatives, anxiolytics, anti-inflammatory analgesics, diuretics, hyperlipidemia tx

Duration of ED, mean (range):
3.7 (0.5 – 25.6) vs. 3.4 (0.5 – 21.7) y

Underlying disease (diagnosis); n (%):
Hypertension 36 (29) vs. 29 (24); DM 30 (24) vs. 22 (18); Prostatic hyperplasia 6 (5) vs. 8 (7); Visual disturbance 5 (4) vs. 7 (5.8)

Psychogenic ED; n (%): 25 (20.2) vs. 18 (14.9)

Physiologic ED: Organic: 51 (41.2) vs. 50 (41.3)

Mixed ED; n (%): 48 (38.7) vs. 53 (43.8)
IG: Sildenafil citrate
CG: Placebo

IG:
Dose: 25, 50 or 100mg
Duration: 12 wks
Frequency: once daily 1 hr before sexual activity
Compliance (%): 91

CG:
Dose: NA
Duration: 12 wks
Frequency: once daily 1 hr before sexual activity
Compliance (%): 89

Run In period: 4 wks
Wash out period: NA

F/u duration: 12 wks
Primary outcome results:
IIEF, mean (SE):
Q3 (penetration): 3.93 (0.15) vs.2.56 (0.16)
Q4 (maintained erections after penetration): 3.83 (0.15) vs. 2.33 (0.15)
GEQ, % improved erection: 81% vs. 36%
GEQ, % with successful intercourse: 71% vs. 32%
% maximal domain score from graph 30 : baseline (pre); post intervention IG vs. CG
EF: pre 40; post 75 vs. 50
OF: pre 59; post 84 vs. 68
SD: pre 70; post 79 vs. 70
IS: pre 44; post 69 vs. 55
OS: pre 40; post 76 vs. 50
Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 15 (12.1) vs. 16 (13.2)

WDAE, n (%): 1 (0.8) vs. 0
TAE (%): 35% vs. 20%, flushing 11(8.9), vs. 0; headache 15 (12) vs. 6 (5); dyspepsia 9 (7) vs. 0; rash 5(4) vs. 0; dizziness 4(3) vs. 1(0.8); abnormal vision 4 (3.2) vs. 1 (0.8); rhinitis 3(2.4) vs. 1(0.8)
SAE: 1 (<1) vs. 5 (4), no reasons provided

Ascertainment of outcomes assessed: Q3 and Q4 and GEQ 29 15 item IIEF questionnaire, and event log
Goldstein (1998) 31
Companion 32

Study a


Funding source: Pfizer
N screened = NR
N randomized = 532 (dose response)

IG, n = 316 (completers: IG1, n = 96; IG2, n = 105; IG3, n= 101)
CG, n = 216 (completers =199)

ITT analysis used for primary outcome: yes

Inclusion: men in stable relationship 6 mo or longer, with ED confirmed by clinical exam and IC injection of vasoactive drug (31% of men), normal NPT, penile duplex ultrasonography, and endocrine testing

Exclusion: penile deformities, another sexual disorder; SCI, major psychiatric dx; poorly controlled DM; peptic ulcer dx, hx or alcohol or substance abuse; hematologic, renal or hepatic abnormalities, recent stroke or MI in last 6 mo; nitrate therapy
Age, mean (range): 58 (24–87) vs. 57 (20–79) y

Race: NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean: 3.2 y

Underlying disease (% of pts): hypertension 30 vs. 26; ischemic heart dx 8; hyperlipidemia 19 vs. 16; hx or radical prostatectomy 12 vs. 10; DM 13 vs. 15


Psychogenic ED (%): 9 vs. 10

Physiologic ED (%): 78 vs. 77

Mixed ED (%): 13 (both grps)
IG1/3: Sildenafil- oral
CG: placebo- oral

IG1-3:
Dose: 25 mg (IG1), 50 mg (IG2), 100 mg (IG3)
Duration: 24 wk
Frequency: once/d (one hr prior to sexual activity)
Compliance: 97%

CG:
Dose: NA
Duration: 24 wk
Frequency: as IG
Compliance: 99%

Run In period: NR
Wash out period: NR

F/u duration: 24 wks
Primary outcome results:
IIEF, Q3/ Q4 (similar values for both), mean (sd) score:
Baseline: IG=CG 2 (0.2);
Post tx: 3–4 (0.2) vs. 2 (0.2)
IIEF-EF: increase in score with dose escalation, IG vs. CG p<0.001
Grade 3 or 4 erection, (%): 72, 80, 85 vs. 50% (80% of grade 3 and 94% of grade 4 erections resulted in intercourse; positive dose response)
Improved erection (% of pts): 56, 77, 84 vs. 25, p< 0.001

Other outcomes assessed: IIEF, Q6, 7, 8, 13 and 14 (> in IG); SD (no change)

Withdrawals/drop-outs/loss to f/u, n (%): IG=31 (10) [15 (15), 8 (7), 8 (7)] vs. CG =36 (17)

WDAE: 4 (1) vs. 1 (<1)
TAE, n (%): in 5% of pts or more IG 15 (15)/ 8 (7)/ 8 (7) vs. CG 36 (17); AE included headache 14–32 (14–30) vs. 14 (6); flushing 13–29 (13–27) vs. 3 (1); dyspepsia 3–17 (3–16) vs. 3 (1); rhinitis 1–12 (1–11) vs. 4 (2); visual disturbance 2–10 (2–9) vs. 1 (<1)
SAE: NR

Ascertainment of outcomes assessed: IIEF; ED validated questionnaire; self report event log (grading system)
Goldstein (1998) 31

Study b

Funding source: Pfizer
N screened = NR
N randomized = 329; (dose escalation + open label extension)

IG, n = 163
CG, n = 166

ITT analysis used for primary outcome: yes

Inclusion: men in stable relationship 6 mo or longer, with ED confirmed by clinical exam and IC injection of vasoactive drug (31% of men), normal NPT, penile duplex ultrasonography, and endocrine testing

Exclusion: penile deformities, another sexual disorder; SCI, major psychiatric dx; poorly controlled DM; peptic ulcer dx, hx or alcohol or substance abuse; hematologic, renal or hepatic abnormalities, recent stroke or MI in last 6 mo; nitrate therapy
Age, mean (range): 60 (26–79) vs. 59 (31–81) y
Race: NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean: 5 y

Underlying disease (% of pts): hypertension 24 vs. 28; ischemic heart dx 15 vs. 8; hyperlipidemia 15 vs. 14; hx or radical prostatectomy 9 vs. 11; DM 8 vs. 11


Psychogenic ED, n (%): 14 vs. 16

Physiologic ED, n (%): 55 vs. 63)

Mixed ED, n (%): 31 vs. 22
IG: Sildenafil -oral
CG: placebo- oral

IG:
Dose: 50 mg (titrated at each f/u visit to double or 50% less based on the therapeutic response and AE)
Duration: 12 wk
Frequency: once/ d (one hr before sexual activity)
Compliance: 94

CG:
Dose: NA
Duration: 12 wks
Frequency: as IG
Compliance: 92

Run In period:
Wash out period:

F/u duration: 12 wk (also at end of open label study of 32 wks)
Primary outcome results:
IIEF, Q3/ Q4 mean (sd) score:
Baseline (IG=CG): 2 (0.1)/ < 2 (0.1)
post tx: 4 (0.1) vs. 2 (0.1)/ 4 (0.1) vs. 1.8 (0.1)
IIEF-EF, mean score: 22 vs. 12, p<0.001
Successful attempts of sexual intercourse (%): 69 vs. 22
Mean n of successful attempts in last 4 wks: 6 vs. 1.5

Improved erection, n (%): 101 (74) vs. 23 (19), p< 0.001

Other outcomes assessed: IIEF, Q6, 7, 8, 13 and 14 (> in IG); SD (no change)

Withdrawals/drop-outs/loss to f/u, n (%): 9 (6) vs. 13 (8), open label (n=225)= 18 (8)

WDAE, n (%):
TAE, n (%): in 5% or more of all IG vs. CG/ IG open label: headache 30(18) vs. 14 (6)/ 28 (12); flushing 30 (18) vs. 1 (1)/ 22 (10); dyspepsia 9 (6) vs. 4 (2)/ 12 (5); rhinitis 8 (5) vs. 1(1)/ 4 (2); visual disturbance 4(2) vs. 1 (1)/ 9 (4)
SAE: NR

Ascertainment of outcomes assessed: IIEF; questionnaire for clinical assessment of ED, & tx outcomes; self report by event log; GAQ
Goldstein (1998) 33


Funding source: Pfizer
N screened = NR
N randomized = 861

Study I dose-response
IG1, n = 316
CG1, n = 216

Study II dose-escalation
IG2, n = 163
CG2, n = 166

ITT analysis used for primary outcome: yes

Inclusion: men with ED of 6 mo or longer, in a stable relationship with a female partner for at least 6 mo

Exclusion: penile anatomical defects, another sexual disorder; SCI; major psychiatric disorder, poorly controlled DM; peptic ulcer disease, hx of alcohol or substance abuse, major systemic abnormalities, recent stroke or MI; nitrate therapy
Age, mean: 58 (NR)

Race: NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: (n/grp) NR

Duration of ED: NR, at least ≥ 6 mos.

Underlying disease (%): 100 ED

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
Study I dose-response
IG: oral sildenafil
CG: oral placebo

IG:
Dose: 25 or 50 or 100 mg
Duration: 12 wks
Frequency: NR Compliance: NR

CG: placebo (same as IG1)

Study II dose-escalation:
IG1: oral sildenafil
CG: oral placebo

IG1:
Dose: 50 mg (dose could be doubled or reduced by 50% at f/u)
Duration: 24 wks
Frequency: NR Compliance: NR

CG: placebo (same as IG1)

Run In period: NR
Wash out period: NR

F/u duration: dose-response 12 wks dose-escalation 24 wks
Primary outcome results:
IIEF, % increase from baseline in IG vs. CG:
Q3, successful penetration
Study I: 60 (25 mg), 84 (50 mg), 100 (100 mg) vs. CG 5 (p < 0.001);
Study II, 95 vs. 10 (p< 0.001)

Q4, maintaining erection
Study I: 121 (25 mg), 133 (50 mg), 130 (100 mg) vs. 24 (p < 0.001);
Study II: 140 vs. 13 (p< 0.001)

All domains
Study I & II: IG sign. higher with each dose vs. CG (p< 0.001)

GEQ, % increase from baseline
Study I: 56 (25 mg), 77 (50 mg), 84 (100 mg) vs. CG 25 (p<0.001)
Study II: 74 vs. 19 (p< 0.001)

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: NR

WDAE: NR
TAE: NR (AE in IG included headache, flushing, dyspepsia, transient visual disturbances)
SAE: NR

Ascertainment of outcomes assessed: IIEF; GEQ
Gómez (2002) 34


Funding source: Pfizer Inc.
N screened = NR
N randomized = 159

IG, n = 76
CG, n = 82

ITT analysis used for primary outcome: Y

Inclusion: men 18 or older; with ED for 6 mo or longer; in stable relationship with female partner for at least 6 mo

Exclusion: genital anatomic deformity; hyperprolactinemia; low free T level; uncontrolled psychiatric disorders; alcoholism or substance abuse; hx of major hematological, renal or hepatic abnormality; uncontrolled DM; untreated proliferative diabetic retinopathy; hx of stroke, MI or CVD in last 6 mo; hypotension; known hx of retinitis pigmentosa; medication causally associated with ED; taking androgens, trazodone, nitrates (or nitric oxide donors); used vacuum devices, IC injection or any other ED tx
Age, mean (sd): 58 (11) vs. 55 (12) y

Race, n (%):
White 20 (13)
Black 4 (2.5)
Hispanic (mistizo) 123 (77)
Other 11 (7)

Co-morbidities:
Hypotension
25 (33) vs. 17 (21)
DM 13 (17) vs. 9 (11)

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range):
3 (0.4–12) y

Underlying disease: NR

Psychogenic ED, n (%): 10 (13) vs. 16 (20)

Physiologic ED, n (%):
IG1 48 (63) vs. 44 (54)

Mixed ED, n (%): 18 (24) vs. 22 (27)
IG: Sidenafil
CG: placebo

IG:
Dose: 50 mg; titration to 25 or 100 mg
Duration: 12 wk
Frequency: NR
Compliance (%): NR

CG:
Dose: placebo
Duration: 12 wk
Frequency: NR
Compliance (%): NR

Run In period: 4 wk
Wash out period: NA

F/u duration: 12 wk
Primary outcome results:
IIEF, change in mean score (approximate values from figure):
Q3: 1.6 vs. 0.8
Q4: 1.8 vs. 0.8
EF: pre=13.6; post 22.1 vs. 18.4
OF: pre=6.9; post: 8.4 vs. 7.7
SD: pre=7; post 7.3 vs. 7.1
IC s: pre=7.4; post 10.8 vs. 9.4
OS: pre=4.6; post: 7.5 vs. 6.3
GAQ, % yes: 77 vs. 46
Successful intercourse attempts (last 4 wks), %: 65 vs. 35

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: 12 (16) vs. 10 (12)

WDAE, n (%): 1 syncope (1) vs. 0
TAE: pts with at least one AE=39 (51) vs. 27 (33); including headache 19 (25) vs. 10 (12); flushing 9 (12) vs. 6 (7); dyspepsia 5 (7) vs. 0; rhinitis 5 (7) vs. 1 (1); abnormal vision 5 (7) vs. 4 (5); conjuctivities 3 (4) vs. 0; diarrhea 3 (4) vs. 2 (2); chromatopsia 2 (3) vs. 0; palpitation 1 (1) vs. 2 (2); dizziness 0 vs. 3 (4); gastritis 0 vs. 2 (2); also laboratory abnormalities elevated blood urea nitrogen level in 4 (10) vs. 1 (1), elevated creatinine level in 3 (8) vs. 0;
SAE: 0

Ascertainment of outcomes assessed: IIEF (EF=1–5,15), event log on sexual function
Gopalakrishnan (2006) 35


Funding source: Christian Medical College grant; Sun Pharmaceuticals provided the medication
N screened = 150 (40 were identified with ED)
N randomized = 32 (randomized two way cross over)

IG/CG, n = 32

ITT analysis used for primary outcome: yes


Inclusion: married men with schizophrenia or delusional disorder on current tx; with ED

Exclusion: regular use of nitrates, anticoagulants, or aspirin 2 wks prior to study entry; comorbid depressive syndrome; tx with antidepressants; alcohol or other substance dependence; hx of use of sildenafil citrated and continued use of other measures to improve ED
Age, mean (sd): 35.1 (5.5), range 24–45 y

Race: NR

Co-morbidities, n (%): paranoid schizophrenia 20 (62.5); catatonic schizophrenia 1 (3), undifferentiated schizophrenia 5 (16), delusional disorder 3 (9.3),

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: all pts on chlorpromazine equivalents dose 556.3 (198.6) range 200–1000 mg; mean dose of trihezyphenidyl 1.2 mg/d; 3 pts also on diazepam

Duration of ED: NR

Underlying disease, n (%): as in comorbid conditions


Psychogenic ED, n (%): 10%

Physiologic ED, n (%): 0

Mixed ED, n (%): NR
IG: Sildenafil
CG: Placebo

IG:
Dose: 25 mg titrated to 50 mg based on efficacy outcomes at 1st wk
Duration: 2 wks
Frequency: up to 1/d
Compliance: 100%

CG:
Dose: NA
Duration: 2 wks
Frequency: as IG
Compliance: 100%

Run In period: NR
Wash out period: none

F/u duration: end of each 2 wks period
Primary outcome results:
N of grade 3 or 4 erections, mean (sd) combined for two wks of tx:
6.52 (3.92) vs. 3.32 (3.5); P< 0.001

duration of erection, mean (sd): 3.38 (2.25) vs. 2.20 (2.14) min, P<0.055

Combined N of satisfactory intercourse attempts, mean (sd): 5.29 (3.84) vs. 2.45 (3.33); P<0.001

Other outcomes assessed: tx interaction effects (NS)

Withdrawals/drop-outs/loss to f/u, n (%): 1(3)

WDAE, n (%): 0
TAE: 13 (41) vs. 3 (9.3)
AEs, n (%): nasal congestion 4 (12.5) vs. 0; headache 3 (9.4) vs. 1 (3.1); loss of appetite 1 (3.1) vs. 0; retarded ejaculation 2 (6.3) vs. 1 (3.1); dyspeptic symptoms 1 (3.1) vs. 1 (3.1); giddiness 1 (3.1) vs. 0; rash 1 (3.1) vs. 0
SAE, n (%): NR

Ascertainment of outcomes assessed: pts log
Hartmann (1999) 36


Funding source: NR
N screened = NR
N randomized = 315

IG, n = 159
CG, n = 156

ITT analysis used for primary outcome: NR

Inclusion: men 18 or older with documented diagnosis of ED for 6 mo or longer

Exclusion: other sexual disorders, high serum PRL levels, low levels of free testosterone. Hx of renal, hepatic, haematological or bleeding disorders. Stroke or myocardial infarction ≤ 6 mons, poorly controlled diabetes, retinitis pigmentosa, treatment with androgens, trazadone, nitrates, nitrogen oxide donors
Age, mean:
IG1: 54
CG: 55

Race (%): NR

Co-morbidities (unrelated to disease): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED (yr):
IG1: 5
CG: 5

Underlying disease: NR

Psychogenic ED: 50

Physiologic ED, %: 46

Mixed ED, %:
54
Unknown: 3 vs. 6%
IG: sildenafil
CG: oral placebo

IG1:
Dose: 25 mg option to titration to 50 or 100 mg Duration: 26 wks
Frequency: as needed
Compliance (%): NR

CG:
Dose: NA
Duration: 26 wks
Frequency: as IG
Compliance (%): NR

Run In period: NR
Wash out period: NR

F/u duration (both on and off treatment): NR

Other: Final doses:
25 m: in 25%
50 mg in26%
100 mg in 49%
Primary outcome results:
IIEF, Q7, mean: pre= 2.0; post tx: 3.6 vs. 2
IIEF, Q3, and 4: as Q7
GEQ, % improved: 79% vs. 23%

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 13 (8) vs. 0

WDAE, n (%): 8 (5) vs. 0
TAE: NR; most common AE reported headache, flushing, dyspepsia, rhinitis, respiratory tract infection (could not be extracted from table, bad scan); visual disturbances NR (1) vs. 0
SAE: NR

Ascertainment of outcomes assessed:
IIEF Q3, 4, 7, 13, and GEQ, Patient logbook
Heiman (2007) 37


Funding source: Pfizer Inc.
N screened = NR
N randomized = 180

IG, n = 86
CG, n = 94

ITT analysis used for primary outcome: yes (n=85 vs. n=91)

Inclusion: men 21 y or older with ED (score of 21 or less on Sexual Health Inventory for Men) and in stable relationship with female partner; with satisfactory sexual intercourse of 50% or less as reported by their female sexual partner

Exclusion: couple with sign. dyspareunia or lifelong sexual dysfunction or men with more than six doses of any ED tx including PDE-5 inhibitor within 6 mo; use of nitrates, nitric oxide donors; medical or psychological conditions (i.e. CV, arthritis, hx of retinitis pigmentosa)
Age, mean (range): 58 (30–86) y

Race: White 79%; Black 7%; Asian 2%; other 12.5%

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: current smokers 15% vs. 19% (43% never smoked)

Body weight: NR
Concomitant medications, n (%): NR

Duration of ED, mean (range): 4.7 (0.2–21.6) vs. 6.1 (0.1–34.7) y

Underlying disease, n (%): NR


Psychogenic ED (%): 16 vs. 12

Physiologic ED (%): 59 vs. 62

Mixed ED (%): 24 vs. 27

Other: IIEF baseline score, mean= 46.3 vs. 48.8; EF domain=13.2 vs. 12.6; OF domain= 5.6 vs. 5.5; SD domain=6.3 in both grps; IcS=6.7 vs. 6.1; OS=5; Q7=2.3 vs. 2.1
IG: Sildenafil
CG: Placebo

IG:
Dose: flexible dose 25, 50, and 100 mg
Duration: 12 wks
Frequency: as needed, 30 min to 1 hr prior to sexual activity
Compliance: NR

CG:
Dose: NA
Duration: as IG
Frequency: as IG
Compliance: NR

Run In period: 2 wks
Wash out period: NA

F/u duration: 12 wks
Primary outcome results:
IIEF, change from baseline mean (SE):
EF domain: 8.9 (1) vs. 3.4 (1)
OF domain: 1.5 (0.4) vs. 0.9 (0.4)
SD domain: 0.4 (0.2) vs. 0.1 (0.2)
ICS domain: 2.1 (0.3) vs. 0.8 (0.3)
OS domain: 2.1 (0.3) vs. 0.8 (0.3)
Q7: 1.5 (0.2) vs. 0.3 (0.2)
GEQ, % improved (95% CI):
GEQ-1: 69 (57–79) vs. 25 (16–36)
GEQ-2: 71 (60–80) vs. 30 (20–41)

Other outcomes assessed: responses in partner; EDIT scores, SEAR

Withdrawals/drop-outs/loss to f/u, n (%): 21 (12)

WDAE, n (%): 0
TAE, n (%): reported as tx related AE: 29 in 18 (21%) vs. 11 in 10 (11%) of pts; including one severe case of rhinitis in IG, and one severe headache in CG
Most common AE: headache, vasodilatation, rhinitis, dyspepsia, and abnormal vision or chromatopsia (n=3 vs. 1)
SAE, n (%): 0

Ascertainment of outcomes assessed: EDITS; IIEF; Self-Esteem And Relationship (SEAR)
Herrmann (2006) 38


Funding source: Pfizer Inc.
N screened = 16 (recruitment stopped; difficult recruitment due to concurrent release of vardenafil and tadalafil)
N randomized = 12

IG, n = 8
CG, n = 4

ITT analysis used for primary outcome: NR


Inclusion: men with moderate to severe ED despite an adequate sildenafil trial, of max 100 mg (ED defined as IIEF score of 16 or less); with serum low density lipoprotein (LDL) cholesterol 100 mg/dL or higher

Exclusion: hx of Psychogenic ED; severe endocrinopathy including diabetics with neuropathy, recent suregery including prostatatectomy; acute
Age, mean (sd): 58 (13) y

Race: NR

Co-morbidities, n (%): DM 12% vs. 25%; elevated cholesterol 10 (83); hypertension 4 (33)

Previous ED treatment:

Smoking status: 38% vs. 75%

Body weight: NR

Other: LDL cholesterol 139 (19) vs. 146 (10) mg/dL;
N of pts with DM is not consistently reported (text: n=2, 17% in total)
Concomitant medications, n (%):

Duration of ED: 4.2 (4.8) vs. 2.6 (2.9) y

Underlying disease, n (%): as co-morbidities


Psychogenic ED, n (%): NR

Physiologic ED, n (%): all

Mixed ED, n (%): NR

Other: IIEF- EF domain at baseline, mean (sd) 10.2 (7.4) vs. 4 (3.6)
IG: Sildenafil + Atoravastatin
CG: Sildenafil + placebo

IG:
Dose: Sildeanfil 100 mg up to once/d; Atorvastatin 80 mg/d
Duration: 12 wks
Frequency: once /d (each medication)
Compliance:

CG:
Dose: sildenafil as IG + Atorvastatin placebo tablets
Duration: 12 wks
Frequency: as IG
Compliance:

Run In period: NR
Wash out period: NR

F/u duration: 12 wks
Primary outcome results:
IIEF, Q-15, mean (sd):
Baseline 10.3 (7.4) vs. 4 (3.6)
Post tx (12 wks): 18 (10.6) vs. 12.3 (12.4); influenced by single outlier increasing from 9 to 29; increase in post tx score excluding this pts = 4.3 (sildenafil grp ▴ by 7.8)

IIEF-Q6: improved in 100% vs. 25%

GAQ-1, % improved: 62.5% vs. 25%
GAQ-2, % improved: 62.5% vs. 25%
GAQ, % improved: 62.5% vs. 25%

Other outcomes assessed: LDL cholesterol levels ▾ from 135 (19) to 78 (20) mg/dL, or 43% with Atorvastatin vs. from 146 (10) to 139 (24) in placebo

Withdrawals/drop-outs/loss to f/u, n (%): 0

WDAE: NR
TAE: NR
SAE: NR

Ascertainment of outcomes assessed: IIEF; Blood analysis for lipid profile
Hussain (2001) 39


Funding source: Pfizer
N screened = 24
N randomized = 17 (crossover design)

IG/CG, n = 24

ITT analysis used for primary outcome: N

Inclusion: Parkinson's (PD) disease or multiple system atrophy (MSA); resting and standing SBP 90–180 mm hg, and DBP 50–110 mm Hg, on tx if necessary

Exclusion: no stable sexual partner; penile deformity; other sexual or psychological disorder; known hx of alcohol or drug dependence; DM; retinitis pigmentosa; hx of stroke or MI; sign cardiac hx; nitrate therapy; lipid abnormality; thyroid, renal, hepatic or hematologic dx
Age, median (range):
PD 61 (48–68)
MSA 54 (46–61) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED (yr): NR

Underlying disease, n (%):
PD 12 (97)
MSA 6 (33)

Psychogenic ED: 0

Physiologic ED, %: 100

Mixed ED: 0
IG: sildenafil citrate
CG: placebo

IG:
Dose: 50 mg with option ot titrate to100 or 25 mg
Duration: 10 wks
Frequency: up to once/d, 1 hr before sexual activity
Compliance: NR

CG:
Dose: placebo, titration option as IG
Duration: 10 wks
Frequency: as IG
Compliance: NR

Run In period: 4 wk
Wash out period: None

F/u duration: 20 wk (cross over at 10 wks without washout)
Primary outcome results:
(CG, n=16; IG n=14)
IIEF-Q3, mean: 3 vs. 2
IIEF-Q4, mean: 4 vs. 1.4

Quality of life questionnaire:
Whole life, mean: 4.9 vs. 4.7
Sex life, mean: 4.2 vs. 2.2

Other outcomes assessed: Partner questionnaire

Withdrawals/drop-outs/loss to f/u, n (%): 8 (27) including one pts in PD due to lack of efficacy, pt chose to return to IC injections.

WDAE: 3 (12.5) in (50% of MSA pts)
TAE: NR; 3 events of orthostatic hypotension (fall in standing BP), feeling unwell and unable to stand in IG (MSA)
SAE: NR

Ascertainment of outcomes assessed: IIEF, quality of life (0–5 for each questions)
Incrocci (2001) 40


Funding source: Pfizer B.V., The Netherlands
N screened = 82
N randomized = 60 (cross-over)

IG/ CG = 30

ITT analysis used for primary outcome: No

Inclusion: men with progressive ED after 3-dimensional conformal external beam radiotherapy (3D-CRT) for prostate who agreed to perform sexual activity at least once/ wk; in a stable relationship

Exclusion: hx of MI or CVA, prior radical prostatectomy; post-radiotherapy rise in PSA; use of nitrates or hormone therapy
Age, mean: 68 y

Race (%): NR

Co-morbidities (unrelated to disease): NR

Previous ED treatment: None

Smoking status: NR

Body weight: NR

Other: PSA/micrograms, mean (range): 8.5 (1–227) litre
Concomitant medications: NR

Duration of ED, mean (range): time from radiation to trial 39 (15–55) mo

Underlying disease (%): Hypertension: 10%; DM 3%; Transurethral resection of the prostate: 18%

Psychogenic ED: NA

Physiologic ED: 100%

Mixed ED: NA
IG: sildenafil
CG: placebo

IG1:
Dose: 50 mg with option to increase to 100 at 2 wks, or decrease to 25 mg in case of AE
Duration: 6 wks
Frequency: at least 1/wk, up to 1/d
Compliance (%): 100%

CG:
Dose: NA
Duration: 6 wks
Frequency: at least 1/wk, up to 1/d
Compliance (%): 100%

Run In period: 4 wks
Wash out period: NR

F/u duration: 12 wks (assessments at end of each 6 wks period)

Other: 90% patients ▴ dose to 100 milligrams, 0% ▾ to 25 mg
Primary outcome results:
IIEF baseline mean; post tx mean (sd) IG vs. CG
Q1: 1.7; post 2.9 (1.6) vs. 1.8 (1.1)
Q2: 1.5; post 2.8 (1.8) vs. 1.5 (1.1)
Q3: 1.5; post 2.8 (1.7) vs. 1.6 (1.1)
Q4: 1.3; post 2.6 (1.7) vs. 1.5 (1.0)
Q5: 1.6; post 2.8 (1.1) vs. 1.8 (1.4)
Q6: 1.2; post 2.8 (1.1) vs. 2.4 (1.0)
Q7: 1.9; post 2.7 (1.6) vs. 1.9 (1.3)
Q8: 1.6; post 2.8 (1.4) vs. 1.9 (1.1)
Q10: 2.1; post 3.0 (1.6) vs. 2.4 (1.6)
Q11: 2.8; post 3.0 (1.1) vs. 2.8 (1.2)
Q12: 2.7; post 3.0 (1.0) vs. 2.6 (1.0)
Q13: 2.3; post 3.0 (1.4) vs. 2.3 (1.2)
Q14: 2.7; post 3.2 (1.4) vs. 2.8 (1.4)
Q15: 2.1; post 3.0(1.1) vs. 2.4 (1.3)
GEQ, % with improved: 45 vs. 8
Successful intercourse %: 55 vs. 18

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE:
AEs (%)= headache: 42 vs. 15; flushing: 13 vs. 2; myalgia 15 vs. 13; nasal congestion 22 vs. 12; dyspepsia 32 vs. 8; dizziness 17 vs. 10
SAE: 0

Ascertainment of outcomes assessed: IIEF; GEQ
Incrocci (2003) 41


Funding source: Pfizer B.V.
N screened = NR
N randomized = 60 (6 wk cross over); also open label phase

IG, n = 30
CG, n = 30

ITT analysis used for primary outcome: No

Inclusion: progressive ED after 3 dimensional external beam radiotherapy for prostate cancer; normal EF before radiotherapy; in stable relationship

Exclusion: use of nitrates
Age, mean (range): 68 (56–79) y

Race (%): NR

Co-morbidities: diabetes and/or hypertension 13%

Previous ED treatment: NR

Smoking status: NR

Body weight: NR

Other:
Mean interval between completion of radiotherapy and study initiation = 39 mo (range 15–55)
Concomitant medications: NR

Duration of ED (yr): NR

Underlying disease (diagnosis) (N or % of diseased/ grp): NA

Psychogenic ED: NR

Physiologic ED: N

Mixed ED: NR
IG: sildenafil citrate orally
CG: placebo orally

IG:
Dose: 50 mg for first 2 wk; option to increase to 100 mg for next 4 wk
Duration: 6 wk
Frequency: up to once/ d, 1 hr before sexual activity at least once/ wk
Compliance: NR

CG:
Dose: placebo
Duration: 6 wk
Frequency: as IG
Compliance: NR

Run In period: 4 wk
Wash out period: None

F/u duration: 6 and 12 wks (last fu at 2 y)
Primary outcome results: Mean IIEF mean score (sd), IG vs. CG:
Q1- pre: 2 (2); post: 3 (2) vs. 2 (1)
Q2- pre: 2 (2); post: 3 (2) vs. 2 (1)
Q3=Q4=Q5=Q7: pre: 2 (1); post: 3 (2) vs. 2 (1)
Q6- pre: 1 (1); post: 3 (1) vs. 2 (1)
Q9- pre: 2 (2); post 3 (2) vs. 2 (1)
Q10- pre: 2 (2); post: 3 (2) vs. 2.5 (2)
Q11- pre: 3 (1); post: 3 (2) vs. 3 (1)
Q12- pre: 3 (1); post: 3 (1) vs.2.6 (1)
Q13- pre: 2 (1); post: 3 (1) vs. 2 (1)
Q14- pre: 3 (1); post: 3 (1) vs. 2.8 (1)
Q15- pre: 2 (1); post: 3 (1) vs. 2.3 (1)
GAQ1, %: 61 vs. NR
GAQ2, %: 65 vs. NR

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE: NR; % with AE (IG vs. CG/ IG open label): headache 42 vs. 15/17; flushing 13 vs. 2/11; myalgia 15 vs. 13/6; nasal congestion 22 vs. 12/11; dyspepsia 32 vs. 8/24; vision disturbances 17 vs. 8/13; dizziness 17 vs.10/6
SAE: 0

Ascertainment of outcomes assessed: IIEF, GEQ, 1 and 2
Kaplan (2007) 42


Funding source: Pfizer (conflict of interest reported)
N screened =
N randomized = 62 (single center; open label)

IG1, n = 21
IG2, n = 20
CG, n = 21

ITT analysis used for primary outcome: yes


Inclusion: men with self reported ED and untreated LUTS

Exclusion: criteria complied with contraindication of both drugs
Age, mean (sd): 63.4 (7.6) y

Race: NR

Co-morbidities, %: DM 27.4; hypertension 25.8%; Ischemic heart disease 14.5

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): NR

Duration of ED: 24.8 (4.3) mo

Underlying disease, n (%):


Psychogenic ED, n (%): NR

Physiologic ED, n (%): 100%

Mixed ED, n (%): NR
IG1: Sildenafil
IG2: Alfuzosin
CG: Sildenafil + Alfuzosin

IG1:
Dose: 25 mg
Duration: 12 wks
Frequency: one/d
Compliance:

IG2:
Dose: 10 mg
Duration: 12 wks
Frequency: one/d
Compliance: NR

CG:
Dose: combination of IG1 and IG2 doses
Duration: 12 wks
Frequency: one of each/ d
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: 12 wks
Primary outcome results:
IIEF mean (sd)
Q3: baseline 2.2 (0.9); % improvement from baseline 41.7% vs. 27.3% vs. 65.2%
Q4: baseline 2.3 (1.1); % improvement from baseline 59.1% vs. 33.3% vs. 68.2%

EF domain: baseline 15.9 (3.2); post tx
IG= 21.4 (5.7) vs. IG2=20.3 (5.2) vs. IG3=25.7 (4.9); % change from baseline: 49.7% vs. 16.7% vs. 58.6%

Other outcomes assessed: IPSS; PVRU volume

Withdrawals/drop-outs/loss to f/u, n (%): 7 (11)

WDAE, n (%): total 7 (11); 2 (10) vs. 2 (10) vs. 3 (14)
TAE: NR; AE flushing and dyspepsia in sildenafil grp vs. dizziness in Alfuzosin vs. dizziness in combination grp
SAE: 0

Ascertainment of outcomes assessed: IIEF-EF; International Prostate Symptom Score (IPSS); post-void residual urine (PVRU) volume
Katz (2005) 43


Funding source: Pfizer
N screened = 202
N randomized = 137 (parallel design)

IG, n = 63
CG, n = 74

Intention to Treat (ITT): Yes (IG, n=60; CG n=72)

Inclusion: men 18 y or older, with ED, (Sexual Health Inventory for Men score of 21 or greater), & documented evidence of stable coronary heart failure (CHF); naïve to sildenafil (discontinue at least by screening visit)

Exclusion: hypotension, high cardiac risk, CHF secondary to hypertrophic cardiomyopathy; hx or myocarditis or implantable defibrillator firing 6 mo prior to entry; use of organic nitrates, drugs that inhibit cytochrome P450 (i.g. ritonavir)
Data reported as IG vs. CG (unless otherwise indicated)
Age, mean (range): all, 60 (38–83) y

Race (%): NR

Co-morbidities: all pts had one or more conditions including diabetes, hypercholestrrolemia, hypertension, ischemic heart dx, past coronary bypass

Previous ED treatment: NR

Smoking status: 22% in both grps; 19% vs. 33% were ex-smokers
Concomitant medications: ACE inhibitors; angiotension II receptor antagonist (29% vs. 15%); β blockers; loop diuretics, cardiac glycosides, oral anticoagulants, analgesics fro mild to moderate pain (11% vs. 22%)

Duration of ED, mean (range): 5 (0.1–22) y

Underlying disease: CHF, duration of 6 (0.27–31.7) vs. 4.8 (0.03–22.2) y

Psychogenic ED, %: 2 vs. 1

Physiologic ED, %: 57 vs. 56

Mixed ED, %: 41 vs. 43
IG1: Sildenafil
CG: placebo

IG1:
Dose: 50 mg, adjusted to 25 or 100 mg based on pts tolerability & efficacy
Duration: 12 wk
Frequency: NR
Compliance (%): NR

CG:
Dose: NR
Duration: as IG
Frequency: NR
Compliance (%): NR

Run In period: 2 wks
Wash out period: NA

F/u duration: 12 wks
Primary outcome results:
Baseline (mean); post tx (least square mean) scores:
Q3 (improved erections): pre=1.7; post: 3.7 vs. 2.8 (p=0.0003); [74% of pts vs. 18% improved, (<0.002)]
Q4 (improved intercourse), mean score: pre=1.4 post: 3.3 vs. 2.4 (p = 0.0012); [68% vs. 16% improved (p<0.002)]
IIEF, EF: pre=33; post 71 vs. 53
IIEF Q9, 10: pre=45; post 77 vs. 67
IIEF Q11, 12: pre=61; post 69 vs. 63
IIEF, Q6, 8: pre= 35; post 69 vs. 55
IIEF, Q13, 14: pre=39; post: 79 vs. 58
Intercourse success (%): 53 vs. 20,
Improved erection, %: 74 vs. 18
Improved intercourse, %: 68 vs. 16
Other outcomes assessed: IIEF Q 5–12; GEQ; life satisfaction check list; EDITS

Withdrawals/drop-outs/loss to f/u: 20 (16) vs. 10 (14)

WDAE: 2 (3) vs. 2 (3)
TAE: (% of pts) 60% vs. 48% (headache 13% vs. 3%, also respiratory tract infection, asthenia, peripheral edema, rhinitis, back pain, rash, pain in both grps; vasodilatation; ▴ cough, neoplasm, chromatopsia only in IG)
SAE: 3% vs. 5%

Ascertainment of outcomes assessed: self administered IIEF; GEQ, EDITS
Kongkanand (2003) 44


Funding source: Pfizer
N screened = NR
N randomized = 125

IG, n = 63
CG, n = 62

ITT analysis used for primary outcome: yes (n=125)

Inclusion: men ED ≥ 6 mo, stable heterosexual relationship ≥ 6 mo.

Exclusion: Genital deformities, SCI, co-existing sexual disorders, raised serum PRL levels or low free T level, major psychiatric disorder, hx of alcohol or substance abuse; major haematological, renal or hepatic dx, DM; poorly controlled or associated with untreated proliferative retinopathy; hx of stroke or MI≤ 6 mo; hypotension or other sign CV dx, hx of retinitis pigmentosa; taking drugs associated with ED; use of vacuum devices or other tx for ED.
Age, mean (range): 54 (31–76) vs. 56 (26–77)

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status, n (%):
Smokers: 11 (18) vs. 9 (15)

Body weight, mean: 68 vs. 69, range 54–90 kg
Concomitant medications: NR

Duration of ED, n (%):
≤ 2 y: 42 (67) vs. 35 (57);
>2 to ≤ 5 y: 15 (24) vs. 20 (32)
> 5 y: 6 (10) vs. 7 (11)

Underlying disease: NR

Psychogenic ED: 7 (11) vs. 6 (10)

Physiologic ED, n (%): 41 (65) vs. 39 (63)

Mixed ED, n (%): 15 (24) vs. 17 (27)
IG: sildenafil citrate
CG: placebo

IG:
Dose: initially 50 mg for 2 wks, then option to titrate up to 100 mg or down to 25 mg
Duration: 12 wks (median= 84 d)
Frequency: as needed
Compliance (%): 92

CG:
Dose: NA
Duration: 12 wks (median=83 d)
Frequency: as needed
Compliance (%): 84

Run In period: 4 wks
Wash out period: NR

F/u duration: NR
Primary outcome results:
IIEF, Q3 frequency of penetrate, mean: baseline= 2; post tx: 4 vs. 3
IIEF, Q4, frequency of maintaining erection after penetration, mean: baseline=2; post tx: 4 vs. 3
IIEF, EF, mean: baseline=13; post tx: 22 vs. 17
IIEF, OF, mean: baseline=5, post tx: 8 vs. 5
IIEF, SD, mean: baseline=5, post tx: 7 vs. 6
IIEF, intercourse satisfaction, mean: baseline=6; post tx 11 vs. 9
Intercourse success, %: 66 vs. 32
GAQ, % yes: 82 vs. 36

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 1 (2) in CG

WDAE: 0
TAE, n (%): 19 (30) vs. 7 (11); including: flushing = 14%; headache = 6%; dizziness = 6%; laboratory abnormalities: included raised levels of eosinophils, total bilirubin, and blood urea nitrogen 1 (2) in IG; 4 sign laboratory abnormalities in n=2 in CG
SAE: 0

Ascertainment of outcomes assessed: IIEF, pts event log, GAQ, physical exam
Koulikov (2007) 45


Funding source: Pfizer Inc.
N screened = 82
N randomized = 60 (crossover)

IG, n = 30
CG, n = 30

ITT analysis used for primary outcome: NR

Inclusion: men between 45 and 75 y and older with ED and various urological complaints (LUTS, ED and nephrolithiasis), and diagnosis of ADAM (direct Tb less than 0.7 gm/l were defined as hypogonadal)

Exclusion: penile anatomical defects; uncontrolled medical illness or psychological disorders; pts with high cardiac risk (according to Princeton guideline); or regular or intermittently use of drugs that alter androgen metabolism or hx of PDE-5i
Age, mean (SEM): 63.3 (7.85), range 47–75 y

Race: NR

Co-morbidities, n (%): hypogonadal 27 (48), low total T in 13/27

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): various urological reasons

Psychogenic ED, n (%): NR

Physiologic ED, n (%): 100%

Mixed ED, n (%): NR
IG: Sildenafil
CG: Placebo

IG:
Dose: 50 mg, titrated to 100 mg after 2 wks (if no improvement in EF with at least 3 pills)
Duration: 1 mo
Frequency: one pill 30–60 min before planned sexual activity up to once/d
Compliance: NR

CG:
Dose: NA
Duration: 1mo
Frequency: as IG
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: at end of each tx period (each study period was 3 mo; washout and run in is not reported).
Primary outcome results:
Improvement in EF, mean (SEM): 39 (1.9) vs. 52.7 (2)

Improvement in IIEF-EF from baseline, mean (SEM):
Normal men: 18.4 (3.6)
Hypogonadal men: 6.7 (2.7)
(no difference in baseline scores of EF between normal and hypogonadal men)

Other outcomes assessed: FSH, LH, Total T, and Tb (numerical data NR)

Withdrawals/drop-outs/loss to f/u, n (%): 19 (63.3) vs. 12 (40)

WDAE, n (%): 1 (3.3) vs. 1 (3.3)
TAE, n (%): difficulty in controlling BP 0 vs. 1 (3.3); non-Q MI 1(3.3) before ingestion of first tablet vs. 0
SAE, n (%): NR

Ascertainment of outcomes assessed: serum hormone analysis
Levinson (2003) 46


Funding source: Pfizer
N screened = 279
N randomized = 279

IG, n = 128
CG, n = 126

ITT analysis used for primary outcome: Yes

Inclusion: men 18 or older with ED of at least mo in duration; in a stable relationship

Exclusion: penile abnormalities; SCI, concomitant tx with nitrates, endocrine anomalies; major haematological, renal, or hepatic dx, CV dx for less than 6 mo, poorly controlled DM, concomitant use of other ED therapies, hx of alcohol or substance abuse, major psychiatric disorder
Age, mean (range): 52 (26–75) vs. 52 (28–76)

Race (%):
Asian: 6 vs. 7; Black: 2 vs. 2
Mediterranean: 52, vs. 48
White: 40, vs. 42 (all from Egypt and South Africa)

Co-morbidities (%): DM: 27; hypertension: 24; unspecified visual disorders: 14; hypercholesterolemia: 6

Previous ED treatment: NR

Smoking status (%): 20 vs. 29

Body weight: NR
Concomitant medications, %:
Antihypertensives: 24%
Anitdiabetic drugs: 24%
Anti-inflamatory agents: 15%
Antibiotics: 11%
Diuretics: 10%
Drugs for hyperlipidemia: 8%

Duration of ED, mean: 3.7 vs. 4.4 y

Underlying disease: NR

Psychogenic ED (%): 26 vs. 29

Physiologic ED (%): 38 vs. 43

Mixed ED (%): 37 vs. 29
IG: sildenafil citrate
CG: placebo

IG:
Dose: 50 mg, titrated to 100 or 25 mg
Duration: 12 wks
Frequency: up to once/d (total dose=41)
Compliance (%): NR

CG:
Dose: NA
Duration: 12 wks
Frequency: up to once/d (total dose=33)
Compliance (%): NR

Run In period: 4 wks
Wash out period: NR

F/u duration: NR

Other: pts information regarding dose of sildenafil used at the end of tx period, n:
25 mg: 7 vs. 1
50 mg: 32 vs. 5
100 mg: 86 vs. 114
Primary outcome results:
Values are approximate (extracted from figure), mean:
IIEF, Q3: baseline =2; post tx: 4 vs. 2.5
IIEF, Q4: baseline =2; post tx: 4 vs. 2
IIEF- Q7: baseline= 2; post tx: 4 vs. 2.3
GAQ, % yes: 74 vs. 27
Intercourse success, %: 69 vs. 28

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 15 (12) vs. 13 (10); including 0 vs. 4 (3) due to insufficient tx response

WDAE, n (%): 3 (2) vs. 0
TAE, n (%): in at least 5%of pts= 63 (49) vs. 45 (36); including headache 26 (20) vs. 10 (8); dyspepsia 12 (9) vs. 1 (0.8); abnormal vision (chromotopsia) 10 (8) vs. 4 (3); flushing 8 (6) vs. 2 (2); rhinitis 7 (6) vs. 3 (2); flu syndrome) 5 (4) vs. 9 (7); CV events (including one re-infarction, and three pts with palpitations in IG and one hypertension in CG) 4 (3) vs. 1 (0.8)
SAE: 3 (2) vs. 0; MI, accidental vertebral fracture, diverticulitis

Ascertainment of outcomes assessed: physical exam, laboratory tests, questionnaires
Lindsey (2002) 47


Funding sources: Colorectal research fund,
Pfizer
N screened = 43
N randomized = 32

IG, n = 14
CG, n = 18
(n=10 crossed over to open label sildenafil after placebo)

ITT analysis used for primary outcome: No

Inclusion: male, postoperative with ED and colorectal cancer

Exclusion: pre-operative ED, medical contraindication to sildenafil
Age, median (interquartile range): 59.5 (51.1–64.9) vs. 58.7 (49.4–67.5) y

Race (%): NR

Co-morbidities (unrelated to disease): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR

Other: 18 pts with total ED, 14 with partial
Concomitant medications: NR

Duration of ED: NR [time since surgery, median (IQR)= 5.6 (3.3–7.7) y]

Underlying disease, n (%): proctectomy for rectal cancer 12 (37.5); proctectomy for Inflammatory Bowel Diseases 20 (62.5); stoma 11 (34.3)

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil
CG: placebo

IG:
Dose: < age 65 50 mg; ≥ 65 y old pts 25 mg, max dose of 100 mg.
Duration: 4 wks
Frequency: NR
Compliance (%): 100%

CG:
Dose: NA
Duration: 4 wks
Frequency: NR
Compliance (%): 100%

Run In period: NR
Wash out period: NR

F/u duration: 4 wks (duration of open label trial NR)

Other: n=13, and n=11 were dosed up to 50, and 100 mg sildenafil respectively
Primary outcome results:
IIEF total score, mean:
Baseline: 26.7 vs. 29.5
Post tx: 57.4 vs. 34.5
(post open label: 67 vs. 39.7)

GEQ, % with improved erection: 78.6% vs. 16.7%

Other outcomes assessed: Subanalysis by disease grp and severity of impotence was performed on n=24 who receive sildenafil either as primary or crossover tx

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE, n (%): 7 (50) vs. 4 (22), most common AE facial flushing followed by headache (46%, and 64% of pts on 50 and 100 mg respectively experienced AE at end of open label)
SAE: 0

Ascertainment of outcomes assessed: GEQ, IIEF
Mahon (2005) 48


Funding source: Pfizer Inc. (study medication & placebo)
N screened = 41
N randomized = 16

IG/CG, n = 16 (cross over)

ITT analysis used for primary outcome: NR (analysis for n=13)

Inclusion: men 18 y or older with ED and renal failure (on peritoneal dialysis)

Exclusion: cerebro-vascular event within the last 6 mo, severe hepatic impairment, presence of penile anatomic deformities, severe cardiac dx, or concomitant nitrate therapy
Age, mean (range): 53 (26–74) y

Race (%): White 46%; Black 46%; Indian 8%

Co-morbidities: NR

Smoking: 8% smoked

Previous ED treatment: NR

Other: n=1 heavy drinker; n=8 social drinker (<3 to 4 units/d)
Concomitant medications: NR

Duration of ED: 6 mo to 7 y

Underlying disease: diabetes n=6 (46%); hypertensive (hypertensive nephropatny, diabetic nephropathy, focal segmental glomerulosclerosis, polycystic kidney disease) n=10 (77%)

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil (1st then swithced to placebo)
CG: placebo (1st then switched to sildenafil)

IG:
Dose: 50 mg, titrated to 100 mg at wk 2 if no response was attained with the initial dose
Duration: 4 wks
Frequency: once/ d
Compliance (%): 100%

CG:
Dose: 50 mg
Duration: as IG
Frequency: as IG
Compliance (%): 100%

Run In period: 4 wks
Wash out period: none

F/u duration: 12 wks (including the no treatment run-in period)
Primary outcome assessed: (some values extracted from figure and are approximate)
IIEF-EF, mean score: pre: 6.7; post 20 vs. 12
IIEF-OF: pre: 3; post 6.5 vs. 3.8
IIEF- SD: pre: 5; post: 6.3 vs. 5.3
IIEF, ICs: pre: 2.8; post 9.8 vs. 5.7
OS: IG= 7
Q3 (ability to penetrate): post: 3.4 vs. 1.7
Q4 (maintaining erection): post: 3.2 vs. 1.6
GEQ, % improved: 75% vs. 28%
PSV (20 min post PgE1 injection), median (range): 29.5 (7–66) m/s
EDV (15 min post injection), median (range): 5 (0–13) m/s

Other outcomes assessed: T levels, sex hormone binding globulin, PRL, luteinizing hormone, follicle stimulating hormone, HbA1C

Withdrawals/drop-outs/loss to f/u: n=3 (1 died, reported unrelated to intervention)

WDAE: 0
TAE: 1 headache in IG (no titration in this pts)
SAE, n (%): 0

Ascertainment of outcomes assessed: self administered IIEF; GEQ; Doppler ultrasound
McVary (2007) 49


Funding source: Pfizer Inc. (two of the authors declare financial interest /relationship with Pfizer/ Lilly ICOS)
N screened = 683
N randomized = 370 (from 41 centres in US)

IG, n = 189
CG, n = 181

ITT analysis used for primary outcome: yes

Inclusion: men at least 45 y with ED, score of 25 or less on IIEF-EF domain, and lower urinary tract syndromes (LUTS) associated with prostatic hyperplasia, I-PSS score of 12 or greater

Exclusion: confirmed or suspected prostate malignancy; urinary tract dx; hypotension, hypertension, orthostatic hypotension or sign CV dx, use of nitrates; pts with hepatic or renal dysfunction, poorly controlled DM or hx of retinitis pigmentosa, use of antimuscarinics was prohibited
Age, mean (sd): 60 (8.7) vs. 60 (8.5) y

Race: White 82%; Black 11.5%; Asian 2%; other 4%

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): NR

Duration of ED: 5.7 (<1–25) vs. 5.6 (<1–35) y

Underlying disease %: LUTS, 100%


Psychogenic ED, n (%): 5 (3) vs. 8 (4)

Physiologic ED, n (%): 113 (60) vs. 97 (54)

Mixed ED, n (%): 71 (38) vs. 75 (42)

Other: baseline IIEF-EF score, mean (sd): 13.4 (6.8) vs. 13.2 (6.6)
IG: Sildenafil
CG: Placebo

IG:
Dose: 50 mg, titrated to 100 mg at 2 wks based on tolerability and efficacy (down to 50 mg if 100 mg was not toleated, and discountinued if 50 mg was not tolarable)
Duration: 12 wks
Frequency: once/d
Compliance: NR

CG:
Dose: NA
Duration: as IG
Frequency: as IG
Compliance: NR

Run In period:
Wash out period:

F/u duration: 12 wks
Primary outcome results:
IIEF-EF, mean IG vs. CG:
Baseline= 13.4 vs. 13.2
12 wks: 23.5 vs. 15.9
IIEF-EF, LS mean change (95% CI): 9.17 (7.25, 11.09) vs. 1.86 (-0.03, 3.74)

Other outcomes assessed: EDITS and SEAR questionnaire

Withdrawals/drop-outs/loss to f/u, n (%): 21 (11) vs. 25 (13.8)

WDAE, n (%): 10 (5) vs. 6 (3)
TAE, n (%): 100 (53) vs. 78 (43); included headache, flushing dyspepsia and rhinitis in both grps
SAE, n (%): 2 (1) vs. 3 (2); SAE included one case of moderated worsening of right knee arthralgia while on 100 mg sildenafil; and one case of severe acute cerebro-vascular stroke also on 100 mg sildenafil; no pts discontinued as result of SAE

Ascertainment of outcomes assessed: IIEF; I-PSS; Qmax; SEAR; EDIT; BPHII and QOL
Melnik (2005) 50


Funding source: NR
N screened = 287
N randomized = 30

IG1, n = 10
IG2, n = 10
CG, n = 10

ITT analysis used for primary outcome: No

Inclusion: men 25–50 y, with exclusive diagnosis of non-organic, psychogenic (according to IDC-10) mild to moderate ED for at least 6 mo in duration; in a heterosexual relationship for at least 1 y

Exclusion: clinical or psychiatric disease, primary sexual disorder, penile anatomic defects; use of medication known to interfere with sexual function; physical limitations for use of sildenafil citrate; patients with drug or alcohol use; smoking

Data reported as IG1 n=8 vs. IG2 n=6 vs. CG n=8
Age, mean: 40 vs. 66 vs. 43 y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED (yr): NR

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR

Other: baseline IIEF
IG1: Sildenafil + grp psychotherapy
IG2: Sildenafil
CG: grp psychotherapy

IG1/IG2:
Dose: 50 mg
Duration: 6 mo
Frequency: on demand
Compliance: NR

CG:
Dose: NA
Duration: 6 mo
Frequency: time limited
Compliance: NR

Run In period:
Wash out period: NR

F/u duration: immediately after tx at 6 mo, and 3 mo post intervention at 9 mo
Primary outcome results:
IIEF (ED severity) at baseline, % of pts:
Score 11–16: n: 5 vs. 4 vs. 5
Score 17–26: (mild ED) 3 vs. 2 vs. 3

IIEF (ED severity) at 3 mo post tx, %:
Score 11–16: 0 vs. 1 vs. 0
Score 17–26: 2 vs. 2 vs. 2
Score 26–30: 6 vs. 2 vs. 6
Severity of ED based on IIEF at 6 mo tx, %:
Score 11–16: 0 vs. 1 vs. 0
Score 17–26: 4 vs. 3 vs. 2
Score 26–30: 4 vs. 2 vs. 6

IIEF total score, mean:
Pre: 41 vs. 46 vs. 43
Post (6 mo): 58 vs. 49 vs. 62
9 mo post: 62 vs. 53 vs. 63, sign.higher mean scores in IG2 vs. CG, p<0.05
Sign.differences between IG1 and CG in remission of symptoms (EF 26 or higher), p= 0.0002

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, %: 20 vs. 40 vs. 20

WDAE: NR
TAE: NR
SAE: NR

Ascertainment of outcomes assessed: IIEF; clinical interview
Meuleman (2001) 51
Companion study 36


Funding source: NR
N screened = NR
N randomized = 315

IG, n = 159
CG, n = 156

ITT analysis used for primary outcome: Yes

Inclusion: men 18 or older, with clinical diagnosis of ED for at least mo; in stable relationship with female partner for more than 6 mo

Exclusion: sign genital anatomical deformities (e.g. Peyronie's dx); primary diagnosis of other sexual disorders; hyperprolactinemia; hx of major haematological, renal or hepatic abnormalities; poorly controlled major psychiatric disorder; ED attributable to SCI; poorly controlled diabetes or untreated proliferative diabetic retinopathy; occurrence of CVD, stroke or MI within 6 mo before study; tx with anticoagulants, androgens, trazodone or nitrates
Age, mean (range): 55 (24–77) vs. 54 (23–82) y

Race (%): NR

Co-morbidities, n (%):
Diabetes: 25 (16) vs. 24 (15); hypertension: 33 (21) vs. 30 (19); Ischemic heart dx 21 (13) vs. 10 (6); pelvic surgery 33 (21) vs. 27 (17)

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range): 4.8 (1–35) vs. 5 (1–27) y

Underlying disease: NR

Psychogenic ED:
50 (32)

Physiologic ED, n (%): 46 (29)

Mixed ED, n (%):
60 (38) vs. 54 (35)

Other types of ED, n (%): 0 vs. 3 (2)
IG: Sildenafil citrate
CG: Placebo

IG1:
Dose: 25 mg titrated to 50 mg 100 mg at any of 5 times during tx period
Duration: 28 wk
Frequency: once daily, one hr before sexual activity
Compliance: NR

CG:
Dose: Placebo
Duration: 28 wk
Frequency: once daily, one hr before sexual activity
Compliance: NR

Run In period: 4 wk
Wash out period: NA

F/u duration: 12 wks and 26 wks post tx
Primary outcome results:IIEF- at 12 wks (values very close to 26 wks result), mean (SEM)
IIEF, Q3=Q4: pre=2 (2); Post 2 (0.2) vs. 4 (0.2)
IIEF, EF: pre=12 (0.7); Post tx: 13 (0.7) vs. 21 (0.7)
IIEF, OF: pre=6 (0.3); Post 6 (0.3) vs. 8 (0.3)
IIEF, IS: pre=7 (0.4); Post: 8 (0.3) vs. 11 (0.4)
IIEF, OS: pre=5 (0.2); post: 5 (0.2) vs. 7 (0.2)
IIEF, SD: pre=6 (0.2); Post: 6 (0.2) vs. 7 (0.1)

Other outcomes assessed: event log reports; partner satisfaction

Withdrawals/drop-outs/loss to f/u: 35 (22) vs.77 (49) stopped tx

WDAE, n (%): 5 (3) vs. 1 (<1); headache (3) and colour tinge to vision, dizziness, diarrhoea, nausea, and intermittent stomach ache in IG, one headache in CG
TAE, n (%): NR; most common: flushing, headache, dyspepsia, and rhinitis; abnormal vision in IG 2 (1), star vision, colour perception
SAE, n (%): 8 (5) vs. 6 (4); two death in IG, one due to accident and one cardiac arrest 1 mo post last dose

Ascertainment of outcomes assessed: IIEF; GAQ; diary log
Montorsi (1999) 52


Funding source: Pfizer Inc.
N screened = NR
N randomized = 514

IG1, n = 128
IG2, n = 132
IG3, n = 127
CG, n = 127

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older, with at least 6 mo primary clinical diagnosis of ED

Exclusion: SCI, hx of stroke or MI in the last 6 mo or longer, major hematologic, renal or hepatic abnormalities, receiving regular tx with nitrates; poorly controlled DM
Age, mean (range): 56 (19–77) y (slightly older in IG3, range 30–76)

Race (%): NR

Co-morbidities, n (range %):
Genitourinary procedures: 57 (12–19%); Essential hypertension: 74 (11–17%); DM: 45 (7–10%); Genitourinary disease:
IG1 = 3 (2%)
IG2 = 6 (5%)
IG3 = 13 (10%)
CG = 5 (4%)
Depression: 1–2%; Ischemic heart disease: 1–2%

Previous ED treatment: NR

Smoking status: NR

Initial body weight: NR
Concomitant medications: NR

Duration of ED (yr) mean (range): 5 (0.5–30) y

Underlying disease (diagnosis) (N or % of diseased/ grp): NR


Psychogenic ED, n (%): 129 (25)

Physiologic ED: n (%): 166 (32)

Mixed ED: 219 (42.5)
IG1/IG2/IG3: sildenafil
CG: placebo

IG1:
Dose: 25 mg (IG1); 50 mg (IG2); 100 mg (IG3)
Duration: 12 wks
Frequency: up to once/d
Compliance (%): NR

CG:
Dose: NA
Duration: 12 wks
Frequency: up to 1x/day
Compliance (%): NR

Run In period: 4 wks
Wash out period: NA

F/u duration (both on and off treatment): mean 85 d
Primary outcome results:
IIEF- EF, mean (values approximate extracted from graph): pre 13;
Post IG 19 vs. 21 vs. 23 vs. CG 13
IEF- Q3, mean score:
IG1= 3.18; IG2= 3.65; IG3= 3.79 vs. CG= 2.17 (IG vs. CG p<0.0001)
IIEF- Q4, mean score:
IG1= 2.99; IG2= 3.40; IG3= 3.63 vs. CG= 1.96 (IG vs. CG p<0.0001)
GEQ, % improved: IG1=67%; IG2=78%; IG3=86%; vs. CG=24%
Successful intercourse attempt, mean/mo: range 4.4–5.8 vs. 1.6

Other outcomes assessed: OF, intercourse satisfaction, OS (values NR; IG vs. CG p<0.0001; partner satisfaction

Withdrawals/drop-outs/loss to f/u: 6 (2) vs. 1 (<1%)

WDAE, n (%): 6 (1.6) vs. 1(0.8)
TAE, n (%): 63 (49), 80 (61), 92 (72) vs. 42 (33); most common AE (range % in IG vs. CG)= headache 17–20% vs. 4%; flushing 13–20% vs. 2%; dyspepsia 2–11% vs. 2%; altered vision 0–11% (n 15 pts) vs. 2%; back pain 0–8% vs. 2%; nausea 1–6% vs. 1%
SAE: NR (one case of MI in IG2)

Ascertainment of outcomes assessed: IIEF, GEQ, partner questions
Montorsi (2000) 53


Funding source: NR
N screened = 129
N randomized = 30 (cross-over design)

IG/ CG, n = 30

ITT analysis used for primary outcome: No

Inclusion: men with ED

Exclusion: Depression; hx of sleep disorder; use of drugs affecting quality of sleep; hypogonadism; hx of low serum T, or hyperprolactinemia; MS; SCI; Parkinson's disease; hx of radical pelvic surgery; use of nitrates, complex (≥3 drugs) antihypertensive regimens, or drugs interfering with metabolic pathway of sildenafil; renal or hepatic failure
Age, mean (range): 58 (range 40–68) y

Race (%): NR

Co-morbidities, n (%): hypertension 12 (40)
CAD 10 (33)
DM 10 (33)
Hyperlipidemia 10 (33)

Previous ED treatment: NR

Smoking status, n (%): Current smoker 15 (50)

Body weight: NR
Concomitant medications: NR

Duration of ED: NR

Underlying disease: NR

Psychogenic ED, n (%): 8 (27)

Physiologic ED, n (%): 22 (73)

Mixed ED: NR
IG: sildenafil
CG: placebo

IG1:
Dose: 100 mg
Duration: one night
Frequency: once
Compliance (%): 100


CG:
Dose: placebo
Duration: one night
Frequency: once
Compliance (%): 100

Run In period: 1 night adaptation with RigiScan™ attached but turned off

Wash out period: none

F/u duration: 3 d
Primary outcome results:
Number of erectile episodes/ night, mean (SE): 3.8 (0.8) vs. 3.0 (0.5)

Duration of erectile episodes, mean (sd): 46.1 (4.4) vs. 33.2 (5.2) min

Duration of tip rigidity >60%: 17.5 (1.5) vs. 10.8 (1.7)

RAU
Tip: 90.5 (8.1) vs. 44.1 (7.8)
Base: 101.8 (5.3) vs. 50.2 (4.2)

TAU
Tip: 55.8 (2.2) vs. 27.2 (1.8)
Base: IG1 54.2 (3.1), CG 36.9 (2.2)

Other outcomes assessed: None

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE, n (%): 2 (7) vs. 1(3) slight self resolving headache upon awakening
SAE: 0

Ascertainment of outcomes assessed: RigiScan™ Rigidity Assessment System
Nurnberg (2003) 54


Funding source: Pfizer Inc.
N screened = 117
N randomized = 90

IG, n = 45
CG, n = 45

ITT analysis used for primary outcome: No

Inclusion: men 18–55; wit major depressive disorder in remission and tx with antidepressant for more than 12 wk (on stable dose for ≥4 wk);

Exclusion: other than antidepressant-associated sexual dysfunction; SCI; uncontrolled psychiatric disorder or DM; proliferative retinopathy; alcohol or substance abuse; sign hematologic, renal or hepatic abnormality; stroke or MI within previous 6 mo; cardiac failure; unstable cardiac condition or arrhythmia; use of nitrates; BP lower than 90/50 or higher than 170/100 mm Hg; hyperprolactinemia, retinitis pigmentosa; investigational drug use within 3 mo; sexual dysfunction tx
Age, mean (sd):
45 (8) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: Antidepressant 100%

Duration of ED: NR; pts with, n (%) ED= 37 (82) vs. 41 (91)

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil citrate
CG: placebo

IG1:
Dose: initially 50 mg; could increase to 100 mg
Duration: 6 wk
Frequency: once/d approximately 1 hr before sexual activity
Compliance: NR

CG:
Dose: NA (titrated as IG)
Duration: 6 wk
Frequency: as IG
Compliance: NR

Run In period: None
Wash out period: NA

F/u duration: 6 wk
Primary outcome results:
IIEF, mean score IG vs. CG (baseline IG-CG where different)
IIEF, total: pre: 69–40; post 60 vs. 41
IIEF, Q3=Q4: pre: 3; post 4 vs. 3
IIEF, EF, pre: 18–17; post: 27 vs. 17
IIEF, OF: pre 6; post: 8 vs. 6
IIEF, SD: pre: 6; post: 7 vs. 6
IIEF, ICs pre: 6–7; post: 11 vs. 7
IIEF, OS: pre: 4–5; post: 7 vs. 5
ASEX, EF: pre 4; post 3 vs. 4
MGH-SFQ- EF: pre 4; post 3 vs. 5
Other outcomes assessed: see below

Withdrawals/drop-outs/loss to f/u: 3 (7) vs. 10 (23)

WDAE, n (%): 1 (2) vs. 1 (2), one acute panic and chest pain in IG, one suicidal gesture in CG
TAE, %: NR; most common=40.5 vs. 10; AE in headache: 17 (41) vs. 4 (10); dyspepsia 2 (7) vs. 0; flushing 7 (17) vs. 1 (2); visual disturbances 5 (12) vs. 2 (5); nasal congestion 5 (12) vs. 1 (2); palpitations 2 (5) vs. 0; restlessness/anxiety 0 vs. 8 (20); insomnia 4 (10) vs. 2 (5)
SAE: 0

Ascertainment of outcomes assessed: Clinical Global Impression Scale -Sexual Function adapted (CGI-SF); Arizona Sexual Experience Scale (ASEX), Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ)
O'Leary (2006) 55


Funding source: Pfizer Inc. (financial interest and/ or other relationships with Pfizer existed for all authors)
N screened = 326
N randomized = 256

IG, n = 129
CG, n = 127

ITT analysis used for primary outcome: efficacy for all who took at least one dose and presented outcome data; safety for all who took at least one dose

Inclusion: men 18 or older with documented ED (score of 21 or less on IIEF) with low self esteem determined by Self-Esteem subscale of the SEAR

Exclusion: BP of 90 mmHg or less or 170/110 mmHg or more; sign cardiac dx; use of nitrates, nitric oxide donors, or ritonavir; more than 6 dosed of sildenafil within 6 mo prior to study entry
Age, mean (sd): 56 (12) vs. 55 (13) y

Race: White 62%; Black 25%; Asian 2%; Other 11% (16 vs. 6)

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: NR

Body weight, mean (sd): 92 (16) vs. 93 (18) kg

Other: overall relationship subscale score, mean (sd)=44.4 (33.1) vs. 53.8 (29.8)
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): not specific cause

Psychogenic ED, n (%): 18 (14) vs. 15 (12)

Physiologic ED, n (%): 61 (48) vs. 62 (50)

Mixed ED, n (%): 49 (38) vs. 48 (38)
IG: Sildenafil
CG: Placebo

IG:
Dose: flexible 25–100 mg
Duration: 12 wks
Frequency: up to once/d, 1 hr prior to sexual activity
Compliance: NR

CG:
Dose: NA
Duration: as IG
Frequency: as IG
Compliance: NR

Run In period: 2 wks
Wash out period: NA

F/u duration: 12 wks post dosing
Primary outcome results:
IIEF, LS mean change from baseline:
EF: 9.3 vs. 3.6, p<0.001
OF: 2.4 vs. 0.8, p<0.001
SD: 1.2 vs. 0.6, p<0.001
IcS: 4.0 vs. 2.2, p<0.001
OS: 2.1 vs. 3.1, p<0.001
Successful sexual attempts, mean change %(95% CI): 52% (44–60%) vs. 19% (11–27%)p<0.0001
GEQ, % (95% CI) more frequent erections allowing satisfactory intercourse: 3.6 (3.3–3.9) vs. 2.4 (2.1–2.7) p<0.0001

Other outcomes assessed: sign correlation between SEAR component scores and IIER-EF domain scores, r range 0.34–0.69, p<0.0001; and other IIEF domain scores

Withdrawals/drop-outs/loss to f/u, n (%): 23 (18) vs. 18 (14.4)

WDAE, n (%): 0
TAE, n (%): NR; most common %: headache 10 vs. 2; rhinitis 6 vs. 0; vasodilatation 6 vs. 0; dyspepsia 6 vs. 1; chromatopsia, photophobia, dry mouth, and nausea 2 vs. 0;
SAE, n (%): 0 vs. 1 death

Ascertainment of outcomes assessed: IIEF domains; SEAR
Olsson (2000) 56


Funding source: NR
N screened = NR
N randomized = 351

IG1, n = 90
IG2, n = 85
IG3, n = 81
CG, n = 95

ITT analysis used for primary outcome: NR

Inclusion: men 18–70 y with diagnosis of ED of at least 3 mo duration, who had at least a grade 3–4 (hard enough for penetration-fully rigid) erection at any time during 4 wks before entering the trial or positive response to papaverine (at least 40 mg) or PGE1 (at least 20 mg)

Exclusion: Men with ED of organic causes; tx with nitrates, resting hypotension, uncontrolled hypertension, stroke, bleeding disorder, active peptic ulceration, taking anticoagulants, and a hx of a major haematological, renal, hepatic disorders
Age, mean (range): 52 (24–70) y


Race (%): NR

Co-morbidities: NR

Previous ED treatment, n (%):
IG: 102 (40)
CG: 41 (43)

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (range): 5 (0.2–40) y

Underlying disease: NR

Psychogenic ED, n (%): 153 (60) vs. 51 (54)

Physiologic ED: 2 (1) vs. 0

Mixed ED, n (%): 101 (39) vs. 44 (46)
IG1-3: sildenafil
CG: placebo

IG1-IG3:
Dose: 10 mg (IG1), 25 mg (IG2), 50 mg (IG3)
Duration: 4 wks
Frequency: once/d
Compliance: NR

CG:
Dose: NR
Duration: 4 wks
Frequency: once/d
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: 6 wks
Primary outcome results:
IG (1-2-3) vs. CG
Mean N of grade 3–4 erections at wk 4, mean n: baseline: 2.1; post tx: 2.8 –3.0 –3.6 vs. 1.8, p < 0.001 (IG vs. CG)
GAQ, %: 64 –79 – 88 vs. 38, p < 0.001

Mean Sexual Function Questionnaire (SFQ) scores =improved in IG vs. CG

% Partners reporting improved erection: 64 –78 – 83 vs. 39, p < 0.001

Other outcomes assessed: NR

Withdrawals/drop-outs/loss to f/u, n (%): 7.8 – 8.2% vs. 13.6% vs. 9.5%

WDAE, %: 2.2 –4.7– 8.6 vs. 4.2
TAE, %: 24.3 – 58.8 – 45 vs. 15%
AE in at least 5% of pts, n (%): headache 12-20-16 (13-24-20) vs. 7 (7); dyspepsia 4-9-5 (4-11-6) vs. 3 (3); flushing 4-7-7 (4-8-9) vs. 0; myalgia 1-3-6 (1-4-7) vs. 1 (1); arthralgia 1-6-0 (1-7-0) vs. 1 (1); flue syndromes 0-5-2 (0-6-3) vs. 2 (2); other (NR) 1-0-2 (1-0-3) vs. 0
SAE, n (%): n=3 (MI, renal cell carcinoma, epileptic crisis)

Ascertainment of outcomes assessed: Questionnaire; GAQ; SFQ (15 question, of 14 d diary)
Olsson (2001) 57


Funding source: Pfizer
N screened = NR
N randomized = 224

IG, n = 136
CC, n = 88

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older, with ED of at least 6 mo duration, in a stable relationship for more than 6 mo, clinical diagnosis of stable CVD treated for more than 6 mo with beta blockers and/or ACE inhibitors and/or calcium-channel blockers, written informed consent

Exclusion: concomitant tx with nitrates in any form, genital anatomical deformities, any major psychiatric disorder, known hx of alcoholism or substance abuse, SCI, sign CV event (hx of stroke or MI, cardiac failure, unstable angina, life threatening arrhythmia) within 6 mo, major haematological, renal or hepatic abnormalities, poorly controlled DM; BP < 90/50 mmHg or >180/ 110 mmHg
Age, mean (range): 62 (42–77) vs. 62 (41–76) y

Race (%): NR

Co-morbidities (unrelated to disease): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: no sign differences between grps

Duration of ED, mean: 4.6 y

Underlying disease, n (%): hypertension: 109 (80) vs.78 (89); Previous MI 25 (18) vs. 18 (20); chronic ischemic heart disease 27 (20) vs. 13 (15); angina 24 (18) vs. 14 (16), Previous coronary bypass 21 (15) vs. 12 (14)
Peripheral vascular disease 19 (14) vs. 8 (9)

Psychogenic ED:

Physiologic ED, %: 63 vs. 60

Mixed ED: 36 vs. 40
IG: sildenafil
CG: placebo

IG:
Dose: 50 mg with option to titration to 100 or 25 mg based on efficacy and tolerability
Duration 12 wks
Frequency: up to 1/d
Compliance (%): 93%

CG:
Dose: NA
Duration 12 wks
Frequency: up to 1/d
Compliance (%): 91%

Run In period: 4 wks
Wash out period: NR

F/u duration (both on and off treatment): 12 wks

Other: final doses, n (%): 25 mg: 2 (1) vs. 0
50 mg: 51 (38) vs. 9 (10)
100 mg: 83 (61) vs. 79 (90)
Primary outcome results:
GEQ, % with improved erection: 71 vs. 24
IIEF, mean (SE):
Q3: pre=2; post 3.7 vs. 2.2
Q4: pre=1.5; post 3.3 vs. 1.9

IIEF Q3, and Q4: sign higher in IG than CG (p=0.0001)

Other outcomes assessed: partner sexual satisfaction

Withdrawals/drop-outs/loss to f/u, (%): 4 vs. 3, due to insufficient clinical response

WDAE, n (%): 0 vs. 1 (1)
TAE: flushing17 vs. 2; headache 15 vs. 1; dyspepsia 5 vs. 0
SAE: 0

Ascertainment of outcomes assessed: IIEF; GEQ; partner satisfaction questionnaire
Orr (2006) 58


Funding source: Pfizer Inc. Israel
N screened = 28
N randomized = 21 (cross over)

IG/ CG, n = 21

ITT analysis used for primary outcome:

Inclusion: men age 18–60 y, with diagnosis of chronic post traumatic stress disorder (PTSD), and ED (score of less than 50 in IIEF, and les than 20 in IIEF-EF domain), in a stable relationship

Exclusion: hx of alcoholism or substance dependence within the last 12 mo; genital or anatomical deformities; SCI; poorly controlled DM; hx of malignant hypertension, resting SBP > 180 mm Hg, hx of stroke or MI within the last 6 mo prior to study entry; predisposing to priapism; any other unstable medical conditions; use of nitrates, or nitric oxide in any form use of sildenafil more than once; tx with T; current use of any ED tx
Age, mean (sd): 44.5 (9.69) y, range 22–55 y

Race: NR

Co-morbidities, n (%): psychiatric conditions: current major depressive episode 47% (past episodes 29%); dysthyia 7%; current maniac or hyomanid episode 4%; anxiety disorder: social phobia 39%; general anxiety disorder 61%, agoraphobia 61%; obsessive compulsive disorder 4%, psychotic symptoms reported in 38%

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): SSRIs 71%, tri-cyclic antidepressants 21%, other antidepressants 14%, anti-psychotics 25%, mood stabilizer 25%, and benzodiazepine 89%

Duration of ED, mean (sd): 19.71 (10.21)

Underlying disease, n (%): as in co-morbidities

Psychogenic ED, n (%): 100%

Physiologic ED, n (%): NR

Mixed ED, n (%): NR
IG: Sildenafil
CG: Placebo

IG1:
Dose: 50–100 mg
Duration: 4 wks
Frequency: one pill 1 hr before sexual activity; total of 6 pills
Compliance: NR

CG:
Dose: NA
Duration: 4 wks
Frequency: as IG
Compliance: NR

Run In period: NR
Wash out period: no washout included

F/u duration:
Other: (pts were randomized to 2 grps, 1st grp started with 4 wks placebo, and 2nd grp started with 4 wks sildenafil)
Primary outcome results:
IIEF, mean (sd)
Total score: baseline 20 (12.32); post 45.19 (15.05) vs. 33.04 (12.99)
EF: baseline 7.42 (5.3); post tx 18.57 (7.7) vs. 13.8 (5.3)
SD: baseline 4.58 (2.23); post tx 4.95 (2.03) vs. 4.58 (1.8)
OF: baseline 4.45 (3.74); post tx 5.59 (2.44) vs. 4.04 (2.15)
IcS: baseline 4.39 (3.75); post tx 7.22 (1.92) vs. 6.20 (2.37)
OS: baseline 3.37 (1.96); post tx 5.18 (2.55) vs. 4.20 (2.48)
Other outcomes assessed: depression, subjective well being and PTSD symptoms score

Withdrawals/drop-outs/loss to f/u, n (%): 6/27 (22) in placebo phase; 1/23 (4.3%) in sildenafil phase

WDAE, n (%): NR
TAE, n (%): NR, AEs included heartburn, decrease in appetite, constipation, diarrhea, nausea, vision blur, tinnitus, dizziness, headache, tiredness, backache, stomach ache, chest pain, hot flushes, rash, palpitation, sweating; no sign.between grps
SAE, n (%): NR

Ascertainment of outcomes assessed: IIEF domains; depression, subjective well being by SAS and ABS); PTSD symptom scores
Padam-Nathan (1998) 59


Funding source: Pfizer
N screened = NR
N randomized =


IG, n = 163
CG, n = 166

ITT analysis used for primary outcome: yes (last observation carried forward)

Inclusion: men 18 or older, with ED of more than 6 mo, ED (ED aetiology determined at screening by medical hx, penile tumescence test, IC injection test, endocrine testing, and penile duplex ultrasonography)

Exclusion: penile anatomical defects; SCI; other sexual disorders; low T; poorly controlled DM or untreated proliferative diabetic retinopathy; psychiatric dx; active peptic ulcer dx; hx of major haematological, renal, or hepatic abnormalities; recent hx of CV dx, stroke, or MI, or alcoholism; or substance abuse; tx with nitrates, androgens or trazodone
Age, mean (range): 60 (26–79) vs. 59 (31–81) y

Race: NR

Co-morbidities, (%): hypertension 24 vs. 28; Hyperlipidemia 15 vs. 15; ischemic heart dx 15 vs. 8; DM (any type) 8 vs. 11; depression 3 vs. 3; radical prostatectomy 9 vs. 11

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): NR

Duration of ED, mean (range): 5 (0.5–26) y

Underlying disease, n (%): NR

Psychogenic ED, n (%): NR

Physiologic ED, n (%): NR

Mixed ED, n (%): NR
IG: Sildenafil
CG: Placebo

IG:
Dose: 50 mg (titrated to 100 mg, or 25 mg at 2 wks based on effecacy and tolerability); total 32 doses
Duration: 12 wks (median=87 d)
Frequency: up to one/d (approximately 1 hr before sexual activity)
Compliance: NR

CG:
Dose: NA/ total of 29 doses
Duration: 12 wks (median = 86 d)
Frequency: as IG
Compliance: NR

Run In period: 4 wks no tx
Wash out period: NR

F/u duration: 12 wks

Other: 23% of pts were on 50 mg; 74% on 100 mg at the end
Primary outcome results:
GEQ, (% yes): 101/136 (74%) vs. 23/118 (16%), p<0.0001
Erection sufficient for intercourse, n (%): 94/137 (69) vs. 32/138 (23)
Maintaining erection after penetration, n (%): 85/137 (62) vs. 22/138 (16)
Maintaining erection on most occasions, n (%): 81/137 (59) vs. 21/138 (15)
Successful intercourse, (%): 65% vs. 20%, p < 0.001
Frequency of successful intercourse attempts (n/mo): 5.9 vs. 1.5, p <0.0001

Other outcomes assessed: partner assessment of sexual performance

Withdrawals/drop-outs/loss to f/u, n (%): 9 (8) vs. 13 (6)

WDAE, n (%): 1 (<1) vs. 2 (1)
TAE, n (%): AE in at least 5% of pts= headache 30 (18) vs. 6 (4); flushing 30 (18) vs. 1 (1); dyspepsia 9 (6) vs. 4 (2); abnormal vision (▴ sensitivity or light or blurred vision) NR (3) vs. NR (1)
SAE, n (%): NR

Ascertainment of outcomes assessed: GEQ; pts log (sexual stimulation, and successful intercourse); optional two item partner questionnaire; IIEF (15 item version); AE by examiner
Padma-Nathan (2003) 60


Funding source: Pfizer Inc.
N screened = NR
N randomized = 228

IG, n = 115
CG, n = 113

ITT analysis used for primary outcome: No

Inclusion: pts 18 or older with clinically documented ED at least 6 mo duration who had previously responded successfully to sildenafil treated minimum. of 2 mo, in a stable 100-mg sildenafil dose, established single-partner relationship; had to discontinue all medications for ED

Exclusion: tx with nitrates or nitric oxide donors and those with hypotension (BP less than 90/50 mmHg), hypertension (PB more than 170/110 mmHg), MI, unstable angina, stroke, or symptomatic or clinically sign cardiac abnormalities in the past 3 mo
Age, mean (sd): 61(10) vs. 59(11)

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Initial body weight: NR
Concomitant medications: NR

Duration of ED (yr, SD): 6.8(4.6) vs.7.2 (5.4)

Underlying disease: NR


Psychogenic ED n (%): 3 (3) vs. 4 (4)

Organic ED, n (%): IG 61 (53) vs. 66 (58)

Mixed ED, n (%): 36 (31) vs. 29 (26)
IG: sildenafil
CG: placebo

IG:
Dose: 100 mg
Duration: 4 wks
Frequency: up to once/d; as need
Compliance: NR

CG:
Dose: NA
Duration: 4 wks
Frequency: as IG
Compliance: NR

Run In period: NR
Wash out period: 2 wks

F/u duration: 4 wks
Primary outcome results:
IIEF: IG sign higher scores vs. CG for all domains p<0.001 (results provided in Figure 2)
Sexual activity event log, mean time to onset of erection (min): 36.3 vs. 140.7 min. (sign, p<0.0001)

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 4 (3.5) vs. 5 (4.4)

WDAE: 2 (2) vs. 0
TAE: 41 vs. 18 in 29 (25%) vs. 15 (13%) of pts, most common AE, %: headache 6 vs.0; flushing 3.5 vs.0.9; respiratory tract infection 4.3 vs. 4.4; sinusitis 0 vs. 5
SAE: NR

Ascertainment of outcomes assessed:
Sexual activity event log: recorded at home time duration of sexual activity using a stopwatch. Other question: whether erection lasted long enough for successful intercourse.
IIEF: questionnaire.
Padma-Nathan, (1999) 32


Funding source: NR
N screened = NR
N randomized = 532

IG, n = 316
CG, n = 216

ITT analysis used for primary outcome: No

Inclusion: ED

Exclusion: penile anatomical deformities, hyperprolactinaemia or testosterone deficiency, stroke, MI, or sign. CVD in the previous 6 mo, poorly controlled DM or major psychiatric disorder, untreated proliferative diabetic retinopathy, major haematological, renal or hepatic abnormalities, active peptic ulcer dx, retinitis pigmentosa, concomitant tx with nitrates, nitric oxide donors, androgens or trazodone, hx of alcoholism or substance abuse
Age, mean (range): 58 (20–87)

Race: NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean: 3.2 y

Underlying disease (%): NR

Psychogenic ED (%): 9

Organic ED (%): 77

Mixed ED (%): 13
IG: sildenafil
CG: placebo

IG1:
Dose: 25, 50 or 100 mg
Duration: 6 mo
Frequency: as need before sexual activity
Compliance: NR

CG:
Dose: placebo
Duration: 6 mo
Frequency: as need before sexual Compliance: NR

Run In period: 4 wks
Wash out period: NR

F/u duration: 6 mo
Primary outcome results:
Erections hard enough for sexual intercourse, mean %: 72 (25mg), 80 (50 mg), 85 (100mg) vs. CG 50 (p < 0.001)
Number of erections, mean/mo:
Grade 3= 2.1(25 mg), 2.4 (50 mg), 3.1 (100 mg) vs. CG 2.4 (p < 0.001);
Grade 4=2.2 (25 mg), 4.2 (50 mg), 3.4 (100 mg) vs. CG 0.7 (p < 0.001)
Successful intercourse (%, grade 3,4): grade 3 = 80 vs. NR
grade 4 = 94 vs. NR

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: NR

WDAE, n (%): 25 mg =1(1), 50 mg= 1 (1), 100 mg =2 (2) vs. CG= 1 (4)
TAE, n (%): headache 25 mg =14(14), 50 mg= 23 (21), 100 mg= 32(30) vs. CG= 14 (6); flushing 25 mg= 13 (13), 50 mg= 29 (27), 100 mg 21 (20) vs. CG= 3 (1); Dyspepsia 25 mg= 3 (3), 50 mg= 12 (11), 100 mg= 17(16) vs. CG= 3 (1)
Abnormal vision, 25 mg= 2(2), 50 mg =6 (6), 100 mg =10(9), CG= 1 (1)
Rhinitis, 25 mg= 1(10), 50 mg =3 (3), 100 mg= 12(11), CG= 4 (2)
SAE: NR

Ascertainment of outcomes assessed: event log (4-point erection hardness scale and successful sexual intercourse attempts)
Palmer (1999) 61


Funding source: Pfizer Inc.
N screened = NR
N randomized = 8 (crossover study)

ITT analysis used for primary outcome: No

IG/CG, n = 8

Inclusion: men with ED and spina bifida

Exclusion: NR
Age, range: 19–35 y

Race (%): NR

Co-morbidities (unrelated to disease): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED (yr): NR

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: sildenafil
CG: placebo

IGa/ IGb:
Dose: a=25 mg; b=50 mg (one set for each dose; 5 tablets/ set)
Duration: NR
Frequency: 1/d
Compliance (%): 100%

CGa/ CGb:
Dose: NA (two sets of tablets)
Duration: NR
Frequency: 1/d
Compliance (%): 100%

Run In period: NR
Wash out period: NR

F/u duration: NR
Primary outcome results:
Duration of erection, mean
Baseline: 8.9 min
Low dose: 17.9 vs. 10.4 min
High dose: 25.6 vs. 13.5 min
(improvement of 101% and 188% for IG a and b respectively)

IIEF, high dose; low dose IG vs. CG mean score:
Q1 baseline 2.1; post: 3.3; 4.4 vs. 2.5
(improvement of 57% and 110% for IG grps)

Q15 baseline 2.3; post 3.0; 3.8 vs. 2.6 (improvement of 30% and 65% for IGa and b respectively)

Erectile score: baseline 3.4; post 5.8, 6.9 vs. 3.7 (improvement of 71% and 103% for IG a and b respectively)

Other outcomes assessed: None

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE: 0
SAE: 0

Ascertainment of outcomes assessed: IIEF
Palmer (2000) 62


Funding source: Pfizer, Inc
N screened = 17
N randomized = 17 (cross over)

IG/CG, n = 17

ITT analysis used for primary outcome: No

Inclusion: men 18–35 with diagnosed spina bifida, and ED, medical clearance from primary care physician

Exclusion: abnormal haematological evaluation, medical contraindications
Age, range:
19–35 y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED (yr): NR

Underlying disease: Spina Bifida 100%

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG1/2: sildenafil- oral
CG: placebo- oral

IG1/ IG2:
Dose: 25 mg (IG1), 50 mg (IG2)
Duration: NR
Frequency: up to once/d, one hr before sexual activity; pts were given 4 sets of tablets (sildenafil 25 mg, 50 mg and two identical looking placebo tablet), 5 tablets/ set in a random order)
Compliance: 88%

CG1:
Dose: NA
Duration: NR
Frequency: as IG
Compliance: 88%

Run In period: NR
Wash out period: NR

F/u duration: NR
Primary outcome results:
IIEF, mean score (values approximate from figure):
Q3- baseline= <2.5 vs. <3; 12 wks: <3 vs. >3.5, p=0.001 (improvement in 35.7% vs. 19.9% of pts)
Q4- baseline: <2; 12 wks: <2.5 vs. >3, p=0.001 (improvement in 68.4% vs. 26.5% of pts)
Number of successful intercourse attempts (event log), %- baseline: 20; 12 wks 40 vs. >65, p=0.001 (improvement in 63% vs. 33% of pts)
EF domain- baseline: <14; 12 wks: 15 vs. 20, p=0.001
GEQ, % improved: 66.6 vs. 28.6

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 4 (24)

WDAE: 0
TAE, n (%): 5 (33) only with 25 mg including dyspepsia 1 (7); nausea 1 (7); headache, flushing and nasal congestion 1(7); urinary tract infection 1 (7), and haematological changes 1 (7)
SAE: 0

Ascertainment of outcomes assessed: IIEF, Q1 and 15, patient ratings of erection
Perimenis (2004) 63


Funding source: NR
N screened = NR
N randomized = 30

IG1, n = 15
IG2, n = 15
CG, n = NA

ITT analysis used for primary outcome: Yes

Inclusion: Men with clinically diagnosed ED and obstructive sleep apnea syndrome (OSAS)

Exclusion: deformity in external genitals, taking nitrates, being treated for ED, hormonal deficiency, had not had a stable relationship for at least 6 mo
Age, mean (sd): 55.7 (3.6) vs. 56.4 (3.3)

Race (%): NR

Co-morbidities: DM (NR), atherosclerosis (NR), CAD (NR), hypertension (NR)

% Pts with => 1 disease: n=11 (73%), in each arm

Previous ED treatment: NR

Smoking status, n (%): smokers 23 (77)

Body weight: most pts were overweight
Concomitant medications: NR

Duration of ED: 16.7 (7.6) vs. 15.7 (6.1) mo

Underlying disease: OSAS (100%)

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG1: Continuous Positive Air Pressure (CPAP)
IG2: Sildenafil

IG1:
Dose: NA
Duration: 12 wks
Frequency: nightly
Compliance (%): NR

IG2:
Dose: 100 mg
Duration: 12 wks
Frequency: NR
Compliance (%): NR

Run In period: NR
Wash out period: NR

F/u duration: 12 wks
Primary outcome results:
Mean (sd) scores IG1 vs. IG2:
IIEF total: pre=21.7 vs. 23.3; post = 27.3 (8.6) vs. 37.7 (10.5), p = 0.0025
IIEF-EF: pre=7 vs. 8; post 9 (3) vs. 13 (4)
IIEF-OF: pre=3; post: 3 (1.6) vs. 5.5 (1.9)
IIEF-SD: pre=7; post: 7 (1.4) vs. 7.7 (0.8)
IIEF ICs: pre=3.3 vs. 3.7; post: 4.6 (1.7) vs. 6.4 (2)
IIEF-OS: pre=2; post 2.9 (1.6) vs. 4.5 (2.3)

pts satisfied with the treatment, n/N (%) = 3/15 (20) vs. 8/15 (53.3), p = 0.13
Successful attempts for intercourse, n/N (%) = 33/138 (23.9) vs. 97/180 (53.9), p = 0.001
Mean N of attempts per patient = 9.2 vs. 12, p = 0.005

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: None

WDAE: 0
TAE: NR
SAE: 0

Ascertainment of outcomes assessed: RigiScan, IIEF; pts diary questionnaire
Perimenis (2007) 64


Funding source: NR
N screened =
N randomized = 40

IG1, n = 20
IG2, n = 20
CG, n = NA


ITT analysis used for primary outcome: NR


Inclusion: men with ED and sleep apnea (complete cessation of airflow for at least 10 s and hypopnea as the reduction in airflow by at least 50% for 10 s or more)

Exclusion: genital deformity, use of nitrates; on tx with ED; hormonal deficiency, not in a stable relationship for at least 6 mo
Age, mean (range): 55.3 (42–64) vs. 55.5 (48–62) y

Race: NR

Co-morbidities, n (%): NR

Previous ED treatment: None

Smoking status: NR

Body weight: NR

Other: respiratory disturbance index (RDI) 9.9 (6–24) vs. 8.9 (6–25)
Concomitant medications, n (%): NR

Duration of ED: 17.5 (6–36) vs. 18.7 (8–36) mo

Underlying disease, n (%): NR


Psychogenic ED, n (%): NR

Physiologic ED, n (%): NR

Mixed ED, n (%): NR
IG1: Sildenafil
IG2: Continous Positive Airway Pressure (CPAP)
CG:

IG1:
Dose: 100 mg on demand, 1 hr prior to sexual activity
Duration: 12 wks
Frequency: once/d
Compliance: NR

IG2:
Dose: NA
Duration: 12 wks
Frequency: during night time sleep
Compliance: NR

Run In period: 4 wks
Wash out period: NA

F/u duration: 12 wks (every 4 wks)
Primary outcome results:
Rate of successful intercourse attempts, per pts: 128/249 (51.4%) vs. 51/193 (26.9%)
IIEF-EF, mean (sd):
Baseline: 7.8 (1.2) vs. 7 (1.9)
Post tx: 14.3 (5.0) vs. 10.8 (4.4), p = 0.025

Other outcomes assessed: satisfaction with tx (better with sildenafil, 50% vs. 25%, p=0.007)


Withdrawals/drop-outs/loss to f/u, n (%): 0

WDAE, n (%): 0
TAE, n (%): NR
SAE, n (%): 0

Ascertainment of outcomes assessed: pts diary; IIEF, EDITS
Pickering (2004) 65


Funding source: Pfizer
N screened = 670
N randomized = 568

IG, n = 281
CG, n = 287

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older with ED and hx of arterial hypertension treated with 2 or more different antihypertensive drugs, with stable dose for at least 4 wks; in stable relationship

Exclusion: hypotension or uncontrolled hypertension, sign CV dx in previous 6 mo; current use of nitrates; past tx with sildenafil
Age, mean (sd): 59 (8) vs. 59 (9)

Race: NR

Co-morbidities: None

Previous ED treatment: None

Smoking status:
NR

Body weight: NR
Concomitant medications: None

Duration of ED, mean (sd): 4.6 (4.1) vs. 4.5 (4.6) y

Underlying disease: Arterial hypertension

Psychogenic ED, n (%): 23 (8.2) vs. 24 (8.5)

Physiologic ED, (%): 145 (52) vs. 142 (50.2)

Mixed ED, n (%): 111 (39.8) vs. 117 (41.3)
IG: Sildenafil
CG: Placebo

IG:
Dose: 50mg (after2 wks adjusted to 25 or 100 mg)
Duration: 6 wks
Frequency: before sexual intercourse
Compliance (%): (94)

CG:
Dose: 1 tablet
Duration: 6 wks
Frequency: before sexual intercourse
Compliance (%): (95)

Run In period: 2 wks screening period
Wash out period: None

F/u duration (on and off treatment): Trial followed up by 6 wks open label phase where all participants received Sildenafil.
Primary outcome results:
IIEF mean (sd) IG1 vs. CG
Q3: pre= 3.6 (0.1) vs. 2.7 (0.1)
Q4 (penetration): 3.6 (0.1) vs. 2.5 (0.1)
GEA-Q1, % improved: 71 vs. 18
1: Improved erections: (71) vs. (18)
GEA-Q2, %: 69 vs. 20
Intercourse success rate, %: 62 vs. 26

Other outcomes assessed: EDITS: Patients who took sildenafil score higher mean scores on EDITS

Withdrawals/drop-outs/loss to f/u, n (%): 7 (2.5) vs. 5 (2)

WDAE, n (%): 4 (1.4) vs. 4 (1.4)
TAE, n (%): 111 (39.9) vs. 73 (26) including headache 28 (10.1) vs. 10 (3.6); flushing 17 (6.1) vs. 1 (0.4); dyspepsia 15 (5.4) vs. 3 (1.1); dizziness 11 (4) vs. 1 (0.4); nasal congestion 7 (20.5) vs. 1 (0.4); abnormal vision 7 (2.5) vs. 0
SAE: 2 (0.7) vs. 2 (0.7); including one due to MVA in CG

Ascertainment of outcomes assessed: IIEF-Q3, and 4; GEA-Q1 and 2; pts event log
Price (1998) 66


Funding source: Pfizer
N screened = NR
N randomized = 21 (3 way cross over; two periods)

IG1/IG2/CG, n = 21

ITT analysis used for primary outcome: NR

Inclusion: men 18–70 y with hx of DM type 1 or 2, for 5 y or more, ED of at least 6 mo (ED definition and diagnosis is described)

Exclusion: sign ischemic heart dx or peripheral vascular dx, tx with antidepressants/tranquillizer, nitrates, anticoagulants, or salicylates in last 2 wks prior to study, hx of bleeding dx, severe untreated proliferative diabetic retinopathy, no ED tx in past 2 wks
Age, mean (range): 51 (42–65) y

Race: NR

Co-morbidities:

Blood glucose (or HbA1C): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, median (range): 3 (1–14) y

Underlying disease: 100% DM, with mean duration of 11 (range 3–32) y; evidence of peripheral or autonomic neuropathy n=6 (28%)

Psychogenic ED: NR

Physiologic ED: 100%

Mixed ED: NR
Phase I
IG: single dose sildenafil + 90 min visual sexual stimualtion (VS)
CG: placebo
Phase II
IG: sildenafil
CG: placebo

IG phase I:
Dose: 25 mg (IG1), 50 mg (IG2)
Duration: NA
Frequency: single dose
Compliance: NR

IG phase II:
Dose: 25 mg (IG1), 50 mg (IG2)
Duration: 10 d
Frequency: once/d
Compliance: NR

CG phase I & phase II:
Dose: NA
Duration: as IG in respective phase
Frequency: as IG
Compliance: NR

Run In period: 2 wks
Wash out period: NR

F/u duration: immediately post tx
Primary outcome results:
Phase I, duration of erection with > 60% rigidity, mean (95% CI):
Base: 5 (1.9–12.4) vs. 10.1 (4.2–23.1) vs. 2.8 (0.7–8.4) min
Tip: 1.2 (0.2–3.8) vs. 2.2 (0.7–6) vs. 0.4 (-0.2–2.1) min

Phase II (home study)
N of erection sufficient for intercourse (grade 3 or 4), mean (95% CI):
1.3 (0.9–1.8) vs. 1.6 (1.1 –2.1) vs. 0.6 (0.4–0.9)
% of pts with improved erection, n (%): 10 (50) in 25 mg vs. 2 (10) in placebo
11 (52%) in 50 mg vs. 2 (10) in placebo

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u: NR

WDAE: NR
TAE: NR; tx related AEs= 8 vs. 8 vs. 3 including headache 4 vs. 0, myalgia 3 vs. 2, nausea 2 vs. 1, and dyspepsia 5 vs. 0
SAE: 1 (4.7) vs. 0; pneumococcal pneumonia with 25 mg dose

Ascertainment of outcomes assessed: RigiScan (phase I); self report on grading system (phase II)
Randell (1999) 67


Funding source: study medications by Pfizer (author has served as paid consultant for Pfizer)
N screened = NR
N randomized = 268

IG, n = 136
CG, n = 132

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older, medically documented ED for at least 6 mo, managed and stable DM (type 1at least 5 y, type 2 at least 2 y); in a stable relationship for at least 6 mo

Exclusion: penile anatomical deformities, primary diagnosis of sexual disorder other than ED; sign psychiatric dx; SCI, hx of major haematological, renal, or hepatic abnormalities; stroke or MI, in past 6 mo; active peptic ulcer; hypo/hypertension, diabetic retinopathy or severe autonomic neuropathy; hx of ketoacidosis in last 3 y; tx with nitrates or androgens
Age, mean (range): 57 (27–79) y

Race: NR

Co-morbidities, n (%): hypertension 139 (51); ischemic heart dx 70 (26)

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): antihypertensive agents 141 (53); diuretics 33 (12); beta blockers 19 (7); antidepressant agents 13 (5)

Duration of ED: NR

Underlying disease, n (%): DM type I= 50 (18); type II = 136 (50);

Psychogenic ED: NR

Physiologic ED, (%): 256 (96)

Mixed ED, n (%): 12 (4)
IG: Sildenafil
CG: Placebo

IG:
Dose: 50 mg (titrated up to 100, or down to 25 mg according to pts tolerability and efficacy)
Duration: 12 wks
Frequency: up to once/d (1 hr prior to sexual activity)
Compliance: NR

CG:
Dose: NA
Duration: 12 wks
Frequency: as IG
Compliance: NR

Run In period: 4 wk (no tx)
Wash out period: NA

F/u duration: 12 wks

Other: pts receiving sildenafil 100 mg (high for placebo)= 126 (93%) vs. 127 (96%); 50 mg (medium) = 10 (7%) vs. 5 (4%); 25 mg (low) = 0 vs. 0
Primary outcome results:
IIEF, Q1, 2, 3, 4 (baseline = 2), at 12 wk, mean (SE) for individual questions: 3 (0.2) vs. 2 (0.2); increase of 78% vs. 25%, P<0.001
IIEF, EF (Q5, 15): pre=1, post: individual questions, mean (SE): 3 (0.2) vs. 2 (0.2)

Pts with at least 1 successful attempt at sexual intercourse: 61 (71/117) vs. 22 (25/114), p<0.001

Other outcomes assessed: sexual satisfaction and OF; IIEF 11 & 12 (no change); efficacy variables for subgrp of DM pts

Withdrawals/drop-outs/loss to f/u, n (%): 16 (6); IG 11 (8), vs. CG 5 (4)

WDAE: 1 (<1) vs. 1 (<1); no detail
TAE: AE in at least 3% of pts= 22 (16) vs. 5 (5); including: headache 15 (11) vs. 2 (2); dyspepsia 12 (9) vs. 0; respiratory tract disorder 8 (6) vs. 2 (2); CV 4 (3) vs. 6 (5); flushing 5 (4) vs. 0; abnormal vision 5 (4) vs. 1 (1)
SAE: NR

Ascertainment of outcomes assessed: IIEF Q1, 2, 5–15 self report ability to achieve and maintain erection for sexual intercourse
Safarinejad (2004) 68


Funding source: NR
N screened = 373
N randomized = 282

IG, n = 144
CG, n = 138

ITT analysis used for primary outcome: Yes

Inclusion: pts 18 or older, with ED (NIH consensus), and DM longer than 6 mo; in a heterosexual stable relationship for at least 6 mo, and no tx for ED 4 wks prior to trial

Exclusion: anatomaical defects, another sexual disorder, major haematological, renal, hepatic, uncontrolled psychiatric disorder, tx with nitrates, androgens, CAD, hx of MI or stroke, peptic ulcer dx, poorly controlled DM, hx of drug/alcohol abuse, SCI, hypotension (resting < 90/50 mmHg) or hypertension (resting > 100 mmHg), proliferative retinopathy or autonomic neuropathy and hx of ketoacidosis
Age, mean (range): 46 (36–68) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR (none in 4 wks prior to trial)

Smoking status: NR

Body weight: NR

Other:
HbA1C, % = < 0.12
Concomitant medications, %: ACE inhibitors without diuretics 22; ACE inhibitors with diuretics 22.5, diuretics 12; β-blockers 4

Duration of ED (yr): 3.6 (2.5–12)

Underlying disease, %: DM type I =17; type II= 83

Psychogenic ED: None

Physiologic ED: 96%

Mixed ED: 4%
IG: Sildenafil
CG: Placebo

IG:
Dose: 100 mg
Duration: 16 wks
Frequency: once/d
Compliance: NR

CG:
Dose: NR
Duration: 16 wks
Frequency: as IG
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: 16 wks
Primary outcome results: IIEF-Q3, mean (SE): pre: 1.8 (0.2); post: 2.8 (0.2) vs. 2.2 (0.2), p < 0.002 (vs. baseline)

IIEF-Q4, mean (SE): pre 1.7 (0.2); post: 2.9 (0.2) vs. 2.0 (0.2), p < 0.002 (vs. baseline)

GEQ, n (%) with positive response: 68 (51) vs. 14 (11), p < 0.003

Other outcomes assessed: Mean scores of IIEF 1,2,5–10,13–15 (improved with sildenafil, p <0.05)

Withdrawals/drop-outs/loss to f/u, n (%): 10 (7) vs. 10 (7)

WDAE, n (%): 8 (6) vs. 0
TAE: NR; most common AEs=22 vs. 1.4 (p < 0.001); AE included headache 29 (20) vs. 3 (2), flushing 27 (19) vs. 0; dyspnea 13 (9) vs. 3 (2); rhinitis 9 (6) vs. 0; CV events 10 (7) vs. 0; prolonged erection 1 (1.4)
SAE: NR [CV events in sildenafil grp = four chest pain (two MI), two heart failures and four hypertensions]

Ascertainment of outcomes assessed: Questionnaire
Safarinejad (2006) 69


Funding source: not sponsored
N screened = 430 (486 entered a preliminary phase to emphasize the timing and instruction of sildenafil; responders were excluded)
N randomized = 402

IG1, n = 205
IG2, n = 197

ITT analysis used for primary outcome: yes

Inclusion: men 18 y or older with ED; in a stable relationship, non-responders to sildenafil, and no tx of ED within the last 4 wks prior to entering the study

Exclusion: penile anatomical defects, primary dx of another sexual disorder, use of psychotropic and antidepressant medications, poorly controlled DM, uncontrolled congestive or ischemic heart dx or renal or liver impairment, hx of alcohol or drug abuse, SCI, hx of prostate cancer, neurological dx causing ED
Age, mean (range): 41.5 (21–59) y

Race: NR

Co-morbidities, n (%): DM 44 (12); hypercholesterolemia 91 (24.6); hypertension 87 (23.5);
Ischemic heart dx 52 (14)

Previous ED treatment: NR

Smoking status: smokers 192 (52)

Body weight: NR
Concomitant medications, n (%):

Duration of ED, mean (range): 2.8 (1.9-7) y

Underlying disease, n (%): NS between grps: arteriogenic132 (32.8); mixed vasculogenic 105 (26); veno-occulsive dysfunction 97 (24); corporeal fibrosis 8 (2)

Psychogenic ED, n (%): 15 (7.3) vs. 13 (6.6)

Physiologic ED, n (%): 374 (93)

Mixed ED: NR
IG1: Sildenafil + Cabergoline
IG2: Sildenafil + placebo

IG1:
Dose: sildenafil= 50 ▴ rapidly to 100 if not results were observed with the attempt; cabergoline= 0.5 mg ▴ by 0.25 biwkly up to 1 mg/wk
Duration: 6 mo
Frequency: sildenafil: pkg instruciton up to 1/d; cabergoline: wkly
Compliance: NR

IG2:
Dose: sildenafil as IG1+ placebo
Duration: 6 mo
Frequency: as cabergoline
Compliance: NR

Run In period: NR
Wash out period: NR

F/u duration: 6 mo
Primary outcome results:
IIEF, LS mean (SE) scores:
Q3: baseline 1.8 (0.2); post tx 3.3 (0.2) vs. 2 (0.2)
Q4: baseline 1.7 (0.2); post tx 3.7 (0.2) vs. 2 (0.2)
All other IIEF individual questions sign improved with cabergoline, p=0.04
IIEF- IcS domain mean score: baseline 10 vs. 11; post tx 15 vs. 10
Successful intercourse attempts (% with at least one success): 36% vs. 6%

Other outcomes assessed: IVELT sign difference between tx grps (p=0.001)

Withdrawals/drop-outs/loss to f/u, n (%): 19 (9.3) vs. 13 (6.6)

WDAE, n (%): 12 (5.9) vs. 2 (1)
TAE, n (%): pts with AE 25 (12.2) vs. 4 (2) including nausea, headache, dizziness, somnolence
SAE, n (%): NR

Ascertainment of outcomes assessed: IIEF, Intra-vaginal ejaculatory latency time (IVELT) evaluation, serum T, and PRL levels
Seibel (2002) 70


Funding source: NR
N screened = 226
N randomized = 48

IG, n = 24
CG, n = 24

ITT analysis used for primary outcome: NR

Inclusion: men aged <70 yr; on hemodialysis for ≥6 mo; in stable relationship with female partner

Exclusion: penile anatomic abnormality; cirrhosis; diabetes; angina; severe anemia; nitrate treatment; hx of recent (within previous 6 mo) stroke or myocardial infarction; illiteracy; current ED treatment
Age, mean (sd):
49 (10) vs. 46 (9)

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Initial body weight: NR

Other:
Duration of hemodialysis, mean (sd):
42 (31) vs. 36 (26) mo
Concomitant medications: NR

Duration of ED: NR

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: Nr

Mixed ED: NR

Other: ED severity, n:
Severe 2 vs. 3
Moderate 11 vs. 10
Mild-moderate 5 vs. 6
Mild 2 vs. 2
IG: sildenafil orally
CG: placebo orally

IG:
Dose: 50 mg
Duration: 1 mo
Frequency: 1 dose 1 hr before sexual intercourse; max. 1/d; no drug when on hemodialysis
Compliance (%): NR

CG:
Dose: placebo
Duration: 1 mo
Frequency: as IG
Compliance (%): NR

Run In period: NR
Wash out period: NA

F/u duration: 1 mo
Primary outcome results:
IIEF -change from baseline (mean):
Q3: 1.2 vs. 0.05
Q4: 1.4 vs. no change
EF: 7.0 vs. 0.2
OF: 1.7 vs. 0.4
SD: 0.5 vs. 0.4
ICs: 2.6 vs. 0.7
OS: 2.3 vs. 0.6

Other outcomes assessed: change in severity of ED;

Withdrawals/drop-outs/loss to f/u: 4 (17) vs. 3 (13)

WDAE: 0
TAW: 5 vs. 3; pts with AE =3 (13) vs. 3 (13); including headaches, facial flushing, dyspepsia vs. headaches and facial flushing
SAE: 2 deaths in CG (neither associated with placebo ingestion or sexual intercourse)

Ascertainment of outcomes assessed: IIEF
Seidman (2001) 71 72


Funding source: Pfizer Inc.
N screened = 300
N randomized = 152

IG, n = 74
CG, n = 78

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older, with ED of at least 6 mo in duration, and in stable heterosexual relationship for > 6 mo, ED, DSM-IV (not defined) criteria for depressive disorder, 24-item Hamilton depression scale score ≥ 12 at both screening interviews.

Exclusion: other psychiatric disorder, substance abuse or dependence, current use of nitrates or antidepressant medication, abnormal serum hormone levels, hx of major hematologic renal or hepatic abnormalities, poorly controlled diabetes, retinitis pigmentosa, spinal cord injury, serious CV dx
Age, mean (sd):
57 (10) vs. 55 (12); range 25–81 y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR

Other: baseline depression scores:
Beck Depression inventory, mean, (sd): 15 (8) vs. 16 (7)
Concomitant medications: NR

Duration of ED (yr (sd): 6 (6) vs. 5 (5) range 0.3–33 y

Underlying disease: 1 radical prostatectomy

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: oral sildenafil
CG: oral placebo

IG:
Dose: 50 mg with option to titrate up to 100 mg or down to 25 mg Duration: 12 wks
Frequency: once/d
Compliance (%): 87.8

CG:
Dose: NA
Duration: 12 wks
Frequency: once/d
Compliance (%): 76.9

Run In period: NR
Wash out period: NR

F/u duration: 12 wks

Other: pts in dose grps at 12 wks, n (%):
100 mg: 57 (79)
50 mg: 14 (19)
25 mg: 1 () in IG, 73 (97) in CG.
Primary outcome results:
Overall IIEF mean (SE) score: 23 (1.5) vs. 12 (1), p < 0.001
Ability to achieve erection; mean (SE):
4 (0.3) vs. 2 (0.2)
Maintaining erection: 4 (0.3) vs.2 (0.2)
CGI, improved erections, n (%):
60/66 (91) vs. 8/70 (11)
Successful sexual intercourse, n (%): 59/66 (89) vs. 9/70 (13)
% Pts responders = 73% vs. 14%

Other outcomes assessed:
Depressive symptoms, quality of life

Withdrawals/drop-outs/loss to f/u: 0

WDAE: 0
TAE, n (%): 43 (58) vs. 7 (9); AE in at least 5% of pts: headache 15 (20) vs. 5 (6); dyspepsia 11 (15) vs. 0; flushing 11 (15) vs. 1 (1); abnormal vision 6 (8) vs. 1 (1)
SAE: NR

Ascertainment of outcomes assessed: Clinical Global Impression Improvement (CGI); Self report questionnaires, Hamilton depression scale, Clinical Global Improvement scale, Beck Depression Inventory, IIEF, Life Satisfaction Checklist, physical exam
Shabsigh (1999) 73


Funding source: NR
N screened = NR
N randomized = 329

IG, n = 163
CG, n =166

ITT analysis used for primary outcome: NR

Inclusion: men with ED of 6 mo or longer

Exclusion: NR
Age, mean: NR

Race: NR

Co-morbidities: NR

Previous ED treatment: NR, all had tx for at least 6 mo prior to trial

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED: NR

Underlying disease (%): ED 100

Psychogenic ED (%): 15

Organic ED (%): 59

Mixed ED (%): 26
IG: sildenafil
CG: placebo

IG:
Dose: 5 mg
Duration: 12 wks
Frequency: 1 hr before sexual activity
Compliance: NR

CG:
Dose: placebo 5 mg
Duration: 12 wks
Frequency: 1 hr before sexual activity
Compliance: NR

Run In period: 2 wks (efficacy and toleration)

Wash out period: NR

F/u duration: 12 wk
Primary outcome results:
IIEF, mean score:
Q3: 3.9 vs. 2.3 (p < 0.001)
Q4: 3.6 vs. 1.8 (p < 0.001)

Other outcomes assessed: NA; aetiology of ED had no sign effect on outcome

Withdrawals/drop-outs/loss to f/u: NR

WDAE: NR
TAE: NR
SAE: NR

Ascertainment of outcomes assessed: IIEF question 3 and 4 (/5)
Sharma (2006) 74


Funding source: Zydus Cadila
N screened = NR
N randomized = 32 (randomized cross over)

IG/ CG, n = 32

ITT analysis used for primary outcome: NR

Inclusion: men 18 or older and medically documented ED, who were renal transplant recipients with stable graft function in the last 6 mo; also in a stable relationship

Exclusion: penile anatomic deformities, hx of recent stroke, MI, in last 6 mo, proliferative diabetic retinopathy, sever autonomic neuropathy, regular tx with nitrates/ androgens; SCI
Age, mean (sd): 40 (8)

Race: NR

Co-morbidities, n (%): chronic glomerulonephritis 14 (43); chronic interstitial nephritis 8 (25); diabetic nephropathy 7 (22); other basic diseases 3 (9.4)

Previous ED treatment: NR

Smoking status: NR

Body weight: NR

Other: blood levels of hemoglobin, nitrogen, creatinine was reported
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): renal allograft

Psychogenic ED, n (%): NR

Physiologic ED, n (%): 100%

Mixed ED, n (%): NR
IG: Sildenafil
CG: Placebo

IG:
Dose: 50 mg titreated up to 100 mg or down to 25 mg based on investigator's judgment of efficacy/ tolerability
Duration: 8 wks
Frequency: up to once/d
Compliance: NR

CG:
Dose: NA
Duration: 8 wks
Frequency: as IG
Compliance: NR

Run In period: NR
Wash out period: 2 wks

F/u duration: end of each 8 wks study period

Other: mean number of tablets= sildenafil 24.3 (3.3); placebo 23.8 (2.6)
Primary outcome results:
IIEF, mean (sd):
Q3: baseline 2.28 (0.72); post tx 3.9 (0.85) vs. 2.28 (0.73), P<0.001
Q4: baseline 2.09 (0.92); post 3.80 (0.66) vs. 2.15 (0.98), P<0.001
EF: baseline: 13 (3.3); post tx 22.3 (3.3) vs. 13.3 (3.43), P<0.001
OF: baseline 5.4 (1.8); post 10.4 (2.0) vs. 5.4 (1.77), P<0.001
SD: baseline 6.3 (1.4); post 6.65 (1.0) vs. 5.9 (1.99), P<0.32
IcS:baseline 5.1 (5.4); post 7.7 (1.4) vs. 5.4 (1.99), P<0.001
OS: baseline 4.8 (0.97); post 7.31 (0.9) vs. 5.1 (1.31), P<0.001
GEQ-1, % improved: 81.3% vs. 18.7%

Other outcomes assessed: individual IIEF questions (Q13 placebo effect)

Withdrawals/drop-outs/loss to f/u, n (%): 1 (<1)

WDAE, n (%): 1 (<1)
TAE, n (%): NR (AE included headache, flushing, generalized body ache, and typical bluish visual hallucination in IG)
SAE: NR

Ascertainment of outcomes assessed: IIEF; diary card; laboratory blood analysis
Sharma (2006) 75


Funding source: NR
N screened = NR
N randomized = 32 (cross over)

IG/ CG, n = 32

ITT analysis used for primary outcome: NR

Inclusion: renal transplant men with confirmed ED, and stable allograft function for the preceding 6 mo; in a stable relationship

Exclusion: proliferative diabetic retinopathy or penile anatomic deformity; recent stroke
Age, mean: 40 y

Race: NR

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): NR

Duration of ED, mean: 17 mo

Underlying disease, n (%): renal surgery

Psychogenic ED, n (%): NR

Physiologic ED, n (%): NR

Mixed ED, n (%): NR
IG: Sildenafil
CG: Placebo

IG:
Dose: 50 mg
Duration: 8 wks
Frequency: 1 hr before sexual activity
Compliance: NR

CG:
Dose: NA
Duration: 8 wks
Frequency: as IG
Compliance: NR

Run In period: NA
Wash out period: 2 wks

F/u duration: 18 wks; evaluation at end of each 8 wks tx period
Primary outcome results:
IIEF, scores: NR
IG: improved in all questions (except SD domain), p<0.001
CG: ▴ only for Q13 (relationship satisfaction), p=0.03

GAQ, % improved: 81.3% vs. 18.7%, p</=0.01

Other outcomes assessed: concentration of ciclosporin assessed in n=5; serum creatinine level; blood urea nitrogen

Withdrawals/drop-outs/loss to f/u, n (%): NR

WDAE, n (%): NR
TAE, n (%): 8 (25) vs. 2 (6.3)
Headache 5 (15.6) vs. 2 (6.3); rhinorrhea and flushing 2 (6.3) vs. 0; blush visual hallucination 1(3.1) vs. 0
SAE, n (%): NR

Ascertainment of outcomes assessed: IIEF; GAQ
Sommer (2007) 76


Funding source: No outside support
N screened = NR
N randomized = 112 (open label; also reported on n=18 non randomized who refused treatment)

IG, n = 56
CG, n = 56

ITT analysis used for primary outcome: yes

Inclusion: men 20–70 y with ED defined by IIEF -EF score of <26 for at least 6 mo in duration with mild to moderate, arteriogenic aetiology and responsive to ED treatments (PDE-5 or IC injection)

Exclusion: penile anatomical abnormalities, primary hypoactive SD, ED of endocrine origin, radical pelvic surgery without erection, poorly controlled DM, or clinically sign. liver kidney, CV, or CNS disorders. Non responders to ED treatment (8 trials of sildenafil 100 mg, or 40 μg IC injection of PgE1), also pts with concurrent tx with nitrates, androgens or anticoagulants
Age, mean (range): 44.7 vs. 46.1 y

Race: NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR

Other: BMI, mean (kg/m2)= 26.9 vs. 27.7

ED severity at baseline, IIEF-EF:
Severe=0
Moderate (11–16), 16 (29) vs. 20 (36)
Mild to moderate (17–21) 28 (50) vs. 28 (50)
Mild (22–25) 12 (21) vs. 8 (14)

Peak flow velocity, men (sd): 25.8 (7.5) vs. 23.1 (6.9) cm/s
Concomitant medications: NR

Duration of ED, mean: 4.3 vs. 5.5 y

Underlying disease (% of pts): NR

Psychogenic ED (%): NR

Physiologic ED (%): NR

Mixed ED (%): NR
IG1: sildenafil
IG2: sildenafil

IG1-3:
Dose: 50 mg
Duration: 12 mo
Frequency: every evening at bedtime
Compliance: NR

IG:
Dose: 50 or 100 mg on demand for anticipated sexual activity
Duration: 12 mo
Frequency:
Compliance: NR

Run In period: 4 wk
Wash out period: NR

F/u duration: 18 mo
Primary outcome results: % of pts with normal (at least 26) IIEF-EF at 12 mo: 32/48 (66.7%) [95% CI 51.6–79.6] vs. 33/49 (67.3%) [95% CI 52.5–80%]

28/48 (58.3%) [95% CI 43.2–72.4%] vs. 4/49 (8.2%) [95% CI 2.3–19.6%] had normal EF domain scores 6 mo after completing the course of study

Other outcomes assessed: PSV of cavernous arteries improved by 11.2 cm/s (95% CI 4.7–21.4; p=0.012) from 25.8 (7.5) to 37 (10.4) after 4 wks washout period (IG1); improved by 3.4 cm/s (95% CI -5.1–14.7; p=0.435)

Withdrawals/drop-outs/loss to f/u, n (%): 8 (14.3) vs. 7 (12.5)

WDAE, n (%): 4 (7) vs. 4 (7)
TAE, n (%): NR (AE included rhinitis in one man (IG1) vs. headache in 5, flushing in four, dyspepsia in four, and rhinitis in two (IG2)
SAE: 0

Ascertainment of outcomes assessed: IIEF
Stuckey (2003) 77


Funding source: Pfizer Inc, New York
N screened = 244
N randomized = 191

IG, n = 97
CG, n = 94

ITT analysis used for primary outcome: NR

Inclusion: men 18 or older with clinical dx of ED for at least 6 mo and controlled type 1 diabetes for longer than 1 y (HbA1c levels < 11%); in a stable heterosexual relationship

Exclusion: penile anatomical deformities, major psychiatric disorder, hx of alcoholism, substance abuse, SCI, MI, stroke, heart failure, unstable angina, nitrate use; severe autonomic neuropathy, diabetes secondary to pancreatic damage; cushings syndrome or acromegaly
Age, mean (range): 47(25–69) y

Race (%): White: 96 vs. 91;
Black: 0 vs. 2;
Asian: 4 vs. 7

Co-morbidities: unspecified GI 6 (9) vs. 5 (8); unspecified disorders of eye: 21 (32) vs. 14 (21)

HbA1C, % (range): 9 (6–13)

Previous ED treatment, %: 28.4 vs. 20.4 including IC, and IU injections; pump; and sildenafil (reported dose only in IG, =28% used 50 mg, and 72% used 100 mg)
Smoking status:
Current 40 vs. 29

Body weight, mean (range):
80 (56–118) vs. 77 (53–139) kg
Concomitant medications, %:
Insulin: 100 (all pts)
Oral antidiabetic: 3.2 vs. 2.1

Duration of ED, mean (range):
5 (0.6–19) vs. 6 (0.7–27)

Underlying disease, %: CVD=34 vs. 39; hypertension= 30 vs. 33; Peripheral vascular dx: 1 vs. 5; DM 10 (15) vs. 8 (12)

Psychogenic ED, %: 0 vs. 1

Physiologic ED, %:
79 vs. 66

Mixed ED, %: 21 vs. 33
IG: sildenafil citrate
CG: placebo solution

IG:
Dose: 50 mg, option to titrate to 100 mg or 25 mg
Duration: 12 wks
Frequency: once/d
Compliance (%): 88

CG:
Dose: NA (titration as IG)
Duration: 12 wks
Frequency: once/d
Compliance (%): 82

Run In period: 4 wks
Wash out period: NR

F/u duration: 12 wks
Primary outcome results:
IIEF Q3, improvement in mean scores from baseline, %: 36 vs. 20; post tx, mean (sd): 4 (0.5) vs. 3 (0.5)

IIEF, Q4, improvement in mean score from baseline, %: 68 vs. 27; post tx, mean (sd): post tx: 3 (0.5) vs. 2 (0.5)

GAQ, % yes: 66 vs. 29
Successful intercourse, %: 63 vs. 33

Other outcomes assessed: subgroup analysis based on severity of ED for IIEF- OF; SD, intercourse satisfaction and OS (all values in figures); all sign better in IG vs. CG

Withdrawals/drop-outs/loss to f/u: 8 (8) vs. 7 (7); including lack of efficacy: 2 (2) vs. 3 (3)

WDAE, n (%): 1 (1) vs. 2 (2)
TAE: 48.4vs. 14 (n of AEs); including headache 20% vs. 7.5%; flushing 18% vs. 3%; dyspepsia 8% vs. 1%; visual disturbances 2% vs. 2% (headache, flushing and dyspepsia in >5% of pts)
SAE, n (%): 0 vs. 1 (1)

Ascertainment of outcomes assessed: IIEF, GAQ; Questionnaires, personal diary logs
Tan (2000) 78
Tan (2002) 79


Funding source: Pfizer pharmaceuticals group (South East Asia Region)
N screened = NR
N randomized = 254

IG, n = 127 (final n=119)
CG, n = 127 (final n=119)

ITT analysis used for primary outcome: yes (n=16, 8 in each grp were excluded from analysis)

Inclusion: men 26–78 with ED of at least 6 mo, in a stable heterosexual relationship for at least 6 mo

Exclusion: genital anatomic abnormalities, SCI, co-existing sexual disorders, PRL levels 3 times higher than ULT, free T 20% below lower limit of normal in morning; hx of major psychiatric disorders, alcoholism, substance abuse, major hematologic, renal or hepatic abnormalities, stroke, MI, sign CVD for under 6 mo; hypotension, poorly controlled DM, retinopathy, retinitis pigmentosa, androgens, trazodone, nitrates or nitric oxide donor agents
Age, mean (range): 52 (31–78) vs. 51 (26–70)

Race (%): 100 Asian

Co-morbidities: NR

Previous ED treatment: NR

Smoking status, n (%): 36 (28) vs. 34 (27)

Initial body weight, mean: 72 vs. 71 kg
Concomitant medications: Antidiabetic drugs 87 (34); antihypertensives 67 (26); lipid-lowering drugs 23 (9)

Duration of ED, mean: 3.6 y

Underlying disease, n (%): DM 91 (36); hypertension 61 (24); visual disturbance: 47 (19)

Psychogenic ED, n (%): 15 (12) vs. 18 (14)

Physiologic ED, n (%): 82 (65) vs. 78 (61)

Mixed ED, n (%): 30 (24) vs. 31 (24)
IG: oral sildenafil
CG: oral placebo

IG1:
Dose: 50 mg with option to titrate to 100 or 25 mg
Duration: 12 wks
Frequency: up to once/d
Compliance (%): NR

CG:
Dose: NA
Duration: 12 wks
Frequency: up to once/d
Compliance (%): NR

Run In period: 4 wks
Wash out period: NR

F/u duration: NR
Primary outcome results:
IIEF mean scores IG vs. CG:
IIEF-Q3: 4.2 vs. 2.6
IIEF-Q4: 4.2 vs. 2.4
IIEF-EF: pre=13.3; post: 25 vs. 15.5
IIEF-OF: pre=5.6; post: 8.6 vs. 3.4
IIEF-SD: pre=7; post: 8 vs. 7
IIEF-IS: pre=6.7; post: 10.7 vs. 8.4
IIEF-OS: pre =4.5; post: 8.4 vs. 5.1
GAQ, % yes: 87 vs. 33
Intercourse success, %: 78 vs. 29.6

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 11 (4)

WDAE, n (%): 1 (<1) vs. 1 (<1)
TAE, n (%): 42 (33) vs. 29 (23), AE reported in at least 2 pts=body as a whole 18 (14) vs. 21 (17); CV events 13 (10) vs. 6 (5); respiratory system = nervous system events 7 (6) vs. 5 (4); digestive system events 5 (4) vs. 1 (0.8); special senses 5 (4) vs. 0; musculoskeletal events 4 (3) vs. 3 (2); laboratory abnormalities 2 vs. 3
SAE, n (%): 1 (<1) vs. 1 (<1); one severe angina pectoris 4 hr post medication with 100 mg sildenafil; one accidental hand injury in CG

Ascertainment of outcomes assessed: IIEF, sexual activity & medication logs, GEQ, physical exam
Tignol (2004) 80


Funding source: Pfizer Inc. (authors also supported by Pfizer)
N screened = 170
N randomized = 168

IG, n = 83
CG, n = 85

ITT analysis used for primary outcome: Yes

Inclusion: men 18 or older, with ED, and in a stable relationship with a female partner for at least 6 mo

Exclusion: major psychiatric disorder other than depression, ongoing major depressive disorder, reactive depression, hypotension, hypertension, stroke, MI, CVD, taking nitrates within 2 wks of entry
Age, mean (sd): 53 (10) y

Race (%): White (100%)

Co-morbidities, %: hypertension 10.8 vs. 16.5; DM 8.4 vs. 7.1

Previous ED treatment: median duration: 89 (4–133) d vs. 86 (13–154) d

Smoking status, %: present smoker 31.3 vs. 34.1

Body weight: NR

Other: mean (range) depression duration 4.8 (0–28.5) vs. 3.1 (0.2–20.5) y
Concomitant medications, %: antihypertensives = 13 vs. 14; diabetes drugs= 10 vs. 6

Duration of ED: 4.3 (0.4–20.8) vs. 4.2 (0.3–32.9) y

Underlying disease: NR

Psychogenic ED, n (%): 51 (61) vs. 64 (75)

Physiologic ED, n (%): 5 (6) vs. 2 (2.)

Mixed ED, n (%): 27 (33) vs. 19 (22)
IG: sildenafil
CG: placebo

IG: sildenafil
Dose: 50 mg (flexible dosing)
Duration: 12 wks
Frequency: once/d
Compliance (%): NR

CG: placebo
Dose: NR
Duration: 12 wks
Frequency: once/d
Compliance (%): NR

Run In period: 4 wks
Wash out period: NR

F/u duration: 12 wks
Primary outcome results:
IIEF Q3: IG: NR vs. CG: NR, p < 0.0001 (improved in IG)

IIEF Q3: IG: NR vs. CG: NR, p < 0.0001 (improved in IG)
Successful intercourse attempts, % = 74 vs. 29, p = 0.0001
GAQ, % yes: 83 vs. 34

Other outcomes assessed: mean IIEF scores for 5 other functional domains demonstrated in figures, mean Life Satisfaction Checklist (LSC) score

Withdrawals/drop-outs/loss to f/u: 9 (11) vs. 10 (12)

WDAE, n (%): 1 (1) vs. 0; also 3 (4) vs. 2 (2) temporarily discontinued or reduced dose
TAE, n (%): 34 (41) vs. 14 (17); most common AEs were headache and flushing; abnormal vision in 2 (2) vs. 1 (1) including a change in colour vision (bluish tinge) in placebo
SAE: NR

Ascertainment of outcomes assessed: Questionnaires (IIEF, LSC, GEA)
Ugarte (2002) 81


Funding source: Pfizer Inc.
N screened = 249
N randomized = 242

IG1, n = 123
IG2, n = 119
CG, n = NA

ITT analysis used for primary outcome: Y

Inclusion: men 18 or older, with mild to moderate ED for at least 6 mo; in stable sexual relationship with female partner

Exclusion: psychological or social risk factor for entering the trial; genital /anatomic deformity impairing erection; ED due to another primary sexual disorder, SCI or radical prostatectomy, marked liver function abnormality, hx of gastroduodenal ulceration, retinitis pigmentosa); use of investigational drugs in last 6 wk; or medications associated with ED unless prescribed 2 wk before study entry and no dosage adjustments anticipated; use of nitrates, nitric oxide donors or alpha blockers
Age, mean (range): 53.6 (25–75) vs. 55.2 (28–80) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight, mean (range): 79.9 (43–115) vs. 77.1 (51–155) kg
Concomitant medications: NR

Duration of ED (range): 6 mo - 34 y

Underlying disease: NR

Psychogenic ED, n (%): 19 (15.4) vs. 17 (14)

Physiologic ED, n (%): 42 (34) vs. 41 (34.5)

Mixed ED, n (%): 62 (50) vs. 61 (51)
IG1: sildenafil citrate
IG2: phentolamine

IG1:
Dose: 50 mg, titration option to 25 or 100 mg
Duration: 8 wk
Frequency: up to 1 dose/ d; 1 hr before sexual activity; max. 1/day
Compliance (%): NR

IG2:
Dose: 40 mg
Duration: 8 wk
Frequency: up to 1 dose/ d; 30 minutes before sexual activity
Compliance (%): NR

Run In period: 4 wk
Wash out period: NA

F/u duration: 13 wk
Primary outcome results:
IIEF domain scores, Least square mean score (sd):
EF: pre= 16.3 vs. 15.4; post: (1–5,15): 27.2 (0.6) vs. 19.4 (0.7)
OF (9,10): pre= 6.6 vs. 6; post: 9.3 (0.2) vs. 7.5 (0.2)
SD (11,12): pre=6.8; post: 7.9 (0.1) vs. 7 (0.1)
IC s (6–8): pre=8.2 vs. 7.9; post: 13.7 (0.3) vs. 1.3(0.3)
OS (13,14): pre= 4.8 vs. 4.6; post: 8.5 (0.2) vs. 5.7 (0.2)
GEQ, improved erection % yes: 95 vs. 51
GEQ, improved sexual ability % yes: 94.4 vs.46.4

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 29 (12)

WDAE, n (%): 1 (<1) vs. 4 (3.4)
TAE, n (%): 41 (33) vs. 49 (41), pts with at least 3% incidence of AE including headache 14 (11.4) vs. 6 (5); rhinitis 6 (5) vs. 15 (12.6); flushing 5 (4) vs. 3 (<1); tachycardia 1 (0.8) vs. 7 (5.9); nausea 1 (0.8) vs. 6 (5)
SAE: 1 (0.8) vs.3 (2.5)

Ascertainment of outcomes assessed: IIEF; EF and other domains; GEQ (two questions); event log of sexual function
Webster (2004) 82


Funding source: Grant from University of Alberta Hospital Foundation
N screened = 41
N randomized = 35 (cross over)

IG/ CG, n = 35

ITT analysis used for primary outcome: Yes

Inclusion: pts with moderate to severe heart failure who had documented ED

Exclusion: Pts with hypotension or SBP less than 80 mmHg; hx of myocardial ischemia, receiving psychotropic tx, hx of drug/alcohol abuse, abnormal ECG
Age, mean (SEM): 60 (2) y

Race (%): NR

Co-morbidities, %: ischemia 60; idiopathic 26; hypertension 69; DM 26

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, %: ACE inhibitors=β-blockers 94; diuretics 89; aspirin 66, coumadin= digoxin 63; Ca channel blocker 11

Duration of ED: NR

Underlying disease: CHF

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR

Other: Mean (SEM) IIEF score = 9(1)
IG: Sildenafil
CG: Placebo

IG1: Sildenafil
Dose: 50 mg
Duration: 6 wks
Frequency: once/d
Compliance: 100%

CG: Placebo
Dose: NR
Duration: 6 wks
Frequency: as IG
Compliance: 100%

Run In period: NR
Wash out period: NR

F/u duration: before and after crossover
12 wks
Primary outcome results:
Mean (SE) IIEF score (IG1 vs. CG) before crossover at 6 wks = improved in IG1 (p < 0.001)

Mean (SE) IIEF score (IG1 vs. CG) after crossover = improved in IG1 (p < 0.001)

Overall response on IIEF scores before and after crossover (IG1-CG vs. CG-IG1) = NS (p=0.98)

Other outcomes assessed: Mean scores of IIEF (shown in figure); no sign reduction of BP, or HR in IG

Withdrawals/drop-outs/loss to f/u: 0

WDAE: NR
TAE: NR; arterial fibrillation in 2 (5.7); heart failure/dyspnea 1 (2.8), all during placebo phase
SAE: 2 deaths (study personnel)

Ascertainment of outcomes assessed: IIEF Questionnaire
Young (2002) 83


Funding source: Pfizer Inc.
N screened = blacks (B) 310, Hispanics (H) 257
N randomized = 443 (B, n =246, H, n = 197); open label, n = 191 (B=211; H=144)

IG, n =223 (B= 124, H = 99)
CG, n =220 (B= 122, H =98)

ITT analysis used for primary outcome: Yes

Inclusion: black American or Hispanic American, 18 or older; documented clinical diagnosis of ED for longer than 6 mo; in stable relationship

Exclusion: previous txt with sildenafil for ED; other sexual disorders as primary dx; ▴ PRL levels or low free-T levels; uncontrolled DM; hx of stroke or MI within previous 6 mo; ED as consequence of SCI; concomitant use of nitrates, androgens or trazodone
Age, mean (sd):
B= 53 (25–73) vs. 54 (23–81)
H=55 (31–84) vs. 53 (22–75) y

Race, n (%): black 246 (56), Hispanic 195 (44)

Co-morbidities:
% with ≥1 current medical condition
B= 90; H= 90 vs. 86

Previous ED treatment: NR

Smoking status (%): current
B= 38 vs. 31;
H= 18 vs. 26

Body weight, mean (range):
B=95 (50–182) kg
H= 85 (56–133) kg
Concomitant medications: % with any
B= 86 vs. 87
H =80 vs. 75

Duration of ED, mean (range):
B= 4 (0.3–33) vs. 5.2 (0.3–30)
H= 4 (0.2–43) vs.3 (0.2–20) y

Underlying disease: NR

Psychogenic ED (%): B=13; H 10 vs. 11

Physiologic ED (%): B =56 vs. 54; H= 66 vs. 60

Mixed ED (%): B 32 vs. 33; H 24 vs. 29

Other:
Severity of ED (%)
Mild to moderate: B= 61 vs. 60, H= 46 vs. 62; Severe, B =31 vs. 30, H =39 vs. 26
IG: sildenafil
CG: placebo

IG:
Dose: 50 mg, option to titrate to 100 or 25 mg
Duration: 12 wk
Frequency: up to. 1/d, one hr before sexual intercourse
Compliance (%): NR

CG:
Dose: placebo
Duration: 12 wk
Frequency: as IG
Compliance (%): NR

Run In period: None
Wash out period: None

F/u duration: 12 wk parallel (option to switch to opposite arm during the 12 wk parallel period)+ 12 wk of open-label tx extension (safety results shown)

Other: results reported for 6 wks post intervention; n of pts who switched also reported
Primary outcome results:
IG vs. CG, (B-H where not equal), mean score at 6 wks:
IIEF, Q3: pre: 2.6–2.4; post: 4 vs. 3
IIEF, Q4: pre: 2; post 4 vs. 3
IIEF, EF: pre 14; post 23 vs. 18–16
IIEF, OF: pre 6; post: 8 vs. 6–7
IIEF, SD: pre 7; post 7 vs. 7–6
IIEF, ICs: pre: 6–7; post 11 vs. 9–8
IIEF, OS: pre 4–5; post 8 vs. 6
GEQ-Q1, %: B: 79 vs. 38; H: 82 vs. 30
GEQ-Q2, %: B: 81 vs. 36; H: 80 vs. 29
GEQ-Q3: B: 4 vs. 3; H: 3.5 vs. 2.5

Other outcomes assessed: barriers to tx; subgrp ED severity; EDITS, EPQ

Withdrawals/drop-outs/loss to f/u: B: 6 (5) vs. 10 (10); H: 13 (11) vs. 9 (9)
Open label phase, B: 20 (9), H: 19 (13)

WDAE, n (%): B=0; H: 2 (2) vs. 0
TAE, n (%): 12 wks, B: 18 (15) vs. 3 (3); H: 27 (22) vs. 11 (11); most common, % in IG/ pts switched to IG vs. CG: headache B: 11 vs. 2; H: 16/12 vs. 7; vasodilation B: 2 vs. 0; H: 7/9 vs. 2; rhinitis B: 2 vs. 0; H: 2/4 vs. 0; nausea B: 1 vs. 0, H: 2/1 vs. 0; dizziness B: 0; H: 3/1 vs. 0; abnormal vision B: 2 vs. 0, H: 2/1 vs. 0
SAE, n (%): 1 (<1) in IG (H)

Ascertainment of outcomes assessed: IIEF, GAQ; EDITS; erection problem question (EPQ)
Zinner (2007) 84


Funding source: Pfizer Inc. (conflict of interest: author has spoken for Pfizer)
N screened =
N randomized = 48 (double cross over design- impact of food)

IG/CG 1&2, n = 24
IG/CG 3&4, n = 24

ITT analysis used for primary outcome: NR

Inclusion: men 18 or older in a stable relationship or 6 mo or longer taking 50 or100 mg sildenafil; with IIEF of 25 or less and minimum 4 sexual attempts/ mo

Exclusion: no response to sildenafil 100 mg; CVD in last 3 mo; current use or likely prescription of nitric oxide donors; use of an alpha-blocker; use of other ED tx; hx of retinitis pigmentosa; tx with ritonavir, or an investigational drug within 6 wks of screening; any known medical or psychological conditions; blood donation within 4 wks; drug or alcohol abuse; potential non-compliance
Age, mean (range): 57 (29–79) y

Race: NR

Co-morbidities, n (%): heart disease
IG1&2= 4 (16.7)
IG3&4 =1 (4.2)

Previous ED treatment: 100% had been treated with sildenafil 50 or 100 mg

Smoking status: NR

Body weight: NR

Other: recreational drug use, n (%)
IG1-2= 14 (58.3)
IG3–4= 19 (79.2)
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): NR


Psychogenic ED, n (%): NR

Physiologic ED, n (%): NR

Mixed ED, n (%): NR
IG1-4: Sildenafil
CG1–4: placebo


IG1-4 (sildenafil):
Dose: 100 mg
Duration: 16 wks (4 wk s/ tx period)
Frequency: 1 hr berore meal (IG1); 30–60 min before sexual activity (IG2&4); during meal (IG3)
Compliance:

CG1–4 (placebo):
Dose: NA
Duration: 16 wks as IG
Frequency: 30–60 min berore coitus (IG1&3); 1 hr before meal (IG2); during meal (IG4)
Compliance:

Run In period: 1–2 wks (stopped sildenafil dosing)
Wash out period: NR

F/u duration: end of each tx period
Primary outcome results:
IG1 vs. IG2 & IG3 vs. IG4
IIEF-EF change from baseline, mean:
11.4 vs. 11.4 & 11.2 vs. 11.2

SEP-Q2 intercourse attempts:
93.9% vs. 91.8% & 91.4% vs. 92.6%
SEP-Q3: 84.7% vs. 85.9% & 83.4% vs. 87.5%

Time between dosing and intercourse attempt ▾ responses to SEP-3 (from max 92.8% at 1.5–2 hr to 81.6% when taken >10 hrs prior to coitus)

Other outcomes assessed: mean interval between dosing and coitus in IG2 & IG4 =1.3 (0.6) & 1.1 (0.5) hr
Intervals between dosing and coitus in IG1 & IG4= 4.8 (1.8) & 3.6 (1.9) hr
No sign differences for EDITS responses or preference and satisfaction for any of the regiments

Withdrawals/drop-outs/loss to f/u, n (%): NR

WDAE, n (%): NR
TAE: NR
SAE, n (%): NR

Ascertainment of outcomes assessed: IIEF; SEP- Q2 & 3; EDITS

List of abbreviations: %=percent, ▴=increased, ▾=decreased, AE=adverse event, SAE=serious adverse event, BMI=body mass index, CC=controlled clinical trials, CG=comparator/control group, ctrls=controls, DM=diabetes mellitus, E1 IC=intracavernosal injection, ECG=electrocardiograms, ED=erectile dysfunction, EDV=end-diastolic velocity, f/u=follow-up, FMD=flow mediated dilation, GAQ=global assessment question, GEQ=global efficacy question, grp=group/s, HbA1C=haemoglobin, hr=hour(s), hx=history, IG=intervention group, IIEF= international index of erectile function (EF=erectile function, OF=orgasmic function, OS=overall satisfaction, SD=sexual desire), ITT=intent-to-treat (Y = yes, N = no, NR = not reported), IU=intraurethral, kg=kilograms, lbs=pounds, LUTS=lower urinary tract symptoms, M=male, max=maximum, mo=month(s), NA=not applicable, PADAM=partial androgen deficiency of the aging male, PgE1=Prostagladin, PRL=prolactin, PSA=prostate-specific antigen, RAU=rigidity activity unit, RCT=randomized control trial, SBP=systolic blood pressure, sign.=significant; TAE=total adverse events, TAU=tumescence activity unit, vs.=versus, WDAE=withdrawals resulting from adverse events, wk=week(s), yr=year(s).

From: Appendix C. Evidence Tables

Cover of Diagnosis and Treatment of Erectile Dysfunction
Diagnosis and Treatment of Erectile Dysfunction.
Evidence Reports/Technology Assessments, No. 171.
Tsertsvadze A, Yazdi F, Fink HA, et al.

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