Evidence Table C2. Oral Vardenafil

Author
Funding
N; study design; eligibility Participants characteristics Diagnosis details Intervention Outcomes
Carson (2004) 85 86
Companion Hatzichristou (2005) 86


Funding source: Bayer Corporation and GlaxoSmithKline
N screened = NR
N randomized = 463

IG, n = 233
CG, n = 230

ITT analysis used for primary outcome: yes(N = 454, n = 229 vs. n = 225)

Inclusion: men 18 or older with ED, no response to 100 mg sildenafil indicated by at least 4/ 6 unsuccessful intercourse attempts; in heterosexual relationship for past 6 mo

Exclusion: penile anatomical abnormalities; hypoactive SD; ED due to SCI or radical prostatectomy; retinitis pigmentosa; hepatitis B, C surface antigen or; unstable angina pectoris; MI, stroke, ischemia; DM; hypotension; use of anticoagulants, androgens, trazodone, antiandrogens, alpha1 antagonist, potent HIV protease inhibitor, nitrates, itraconazole, ketokonazole, erythromycin (more in full text)
Age, mean (range):
60 (29–83) vs. 59 (23–88) y

Race, n (%):
White: 404 (87); Asian: 18 (10); Hispanic: 14 (3); Black: 13 (3);
Other: 5 (1)

Co-morbidities: NR

Previous ED treatment: Sildenafil up to 100 mg

BMI, mean (sd): 29 (4) vs. 28 (4) kg/m2

Body weigh: NR
Other: Severity of ED,
Severe: 242 (52); moderate 164 (36); mild to moderate 9 (2); mild 8 (2)

IIEF-EF domain= 9.3 vs. 9.7
Concomitant medications: NR

Duration of ED, mean (sd): 5 (4) y

Underlying disease, n (%):
Hypertension 90 (39) vs. 92 (41)
DM 78 (34) vs. 7 (25); Benign prostatic hyperplasia: 39 (17) vs. 40 (18); CAD 8 (3) vs. 11 (5)

Psychogenic ED, n (%): 8 (3) vs. 20 (9)

Physiologic ED, n (%): 148 (65) vs. 128 (57)

Mixed ED, n (%): 3 (32% vs. 77 (34)
IG: vardenafil
CG: Placebo

IG:
Dose: 10 mg (option to titrated to 5 or 20 mg at 4 and 8 wks)
Duration: 12 wks
Frequency: max 1/d
Compliance: 99% [n=2 (<1%) did not complete]

CG:
Dose: NA
Duration: 12 wks
Frequency: as IG
Compliance: 98%; [n=4 (2%) did not complete]

Run In period: NR
Wash out period: 24 hrs

F/u duration: 12 wks + 24 hrs post final visit.

Note: topical formulas were allowed in this study; investigational drugs within 30 days of screening therapy for ED within 7 d or vardenafil at any time prior to study.
Primary outcome results:
IIEF-EF: baseline=<10 (severe ED); post tx pts with normal scores, n (%)=67 (31) vs. 12 (6)

SEP-Q2, % yes, n (%):
0.25 hr post dosing= 57 (62) vs. 55 (30) >6 hr post dosing= 30 (77) vs. 18 (50)

SEP-Q3, % yes, n (%):
0.25 hr post dosing= 57 (53) vs. 55 (12) >6 hr post dosing=30 (70) vs. 17 (24)

GAQ, % yes: 61.6% vs. 15% 61.8% vs. 14.7% at LOCF, p<0.001)

Other outcomes assessed: intercourse attempts data

Withdrawals/drop-outs/loss to f/u, n (%): 25 (11) vs. 41 (18); including insufficient tx effect in 5 (2) vs. 17 (7)

WDAE, n (%): 5 (2) vs. 3 (2)
TAE, n (%): 40.7% vs. 22.6%; drug related in 2% or more=flushing 16 (7) vs. 2 (1); headache: 15 (6) vs. 4 (2); nasal congestion: 11 (5) vs. 1 (<1); dyspepsia: 8 (3) vs. 0; total mild AE= 55 (24) vs. 20 (9); total moderate AE= 34 (15) vs. 25 (11)
SAE, n (%): 7 (3.0) vs. 3 (0.9)

Outcome ascertainment: IIEF-EF; SEP, Q2 and 3; GAQ
Demir (2006) 87


Funding source: NR
N screened = NR
N randomized = 60

IG, n = 39
CG, n = 21
(n=15 with no ED also served as ctrls, data not shown)

ITT analysis used for primary outcome: NR

Inclusion: men with ED (diagnose with color Doppler Ultrasound and IC injection of 60 mg papaverine) and functioning renal graft (serum creatinine level <2 mg/dL); in a stable relationship with a partner

Exclusion: stroke, DM, MI, CHD, overt heart failure; sing penile anatomical deformities active peptic ulcer, chronic liver disease; sign hypo/hypertension; blood coagulation disorders; nitrate tx
Age, mean (sd):
48 (7.4) vs. 50 (7.1) y

Race: NR

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status: NR

Body weight: NR
Concomitant medications, n (%): immunosuppressant tx: cycloporine (14+8) or JD506 (25+13); low dose prednisolone and ycophenolate mofetil

Duration of ED: NR

Underlying disease, n (%): Renal transplant


Psychogenic ED, n (%): NR

Physiologic ED, n (%): 100%

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

IG:
Dose: 10 mg titrated to 20 mg based on efficacy measures
Duration: 4 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: NR
Wash out period: NR

F/u duration: 4 wks
Primary outcome results:
IIEF-EF, mean (sd):
Baseline 12.8 (3.5) vs. 12.5 (3.7)
Post tx 26.46 (2.4) vs. 13.27 (2.8)
Tx effect, P<0.001

ED Severity, baseline- post tx in IG:
Severe: 3 -0
Moderate 17- 0
Mild to moderate: 9 – 2
Mild 10–4
None 0 – 32

Other outcomes assessed: IIEF individual scores of Q1–5 and 15; serum T, FSH, and LH levels, not sign. between grps (data not provided)

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

WDAE: NR
TAE, n (%): 7 (18), including headache in 3, palpitation in one, flushing in two and dyspepsia in one
SAE: NR

Outcome ascertainment: self administered IIEF on renal transplant pts
Edwards (2006) 88


Funding source: NR
N screened = 288
N randomized = 260

IG, n = 194
CG, n = 66

ITT analysis used for primary outcome: yes (LOCF; n=254)

Inclusion: men 18 or older with ED for at least 6 mo; no prior hx of PDE5i use

Exclusion: unstable medical, psychiatric condition; substance abuse; hypoactive SD; SCI, surgical prostatectomy; hereditary degenerative retinal dx; hepatitis B surface angina, hepatitis C, HIV; liver disease; sign hematologic disease; active peptic ulceration; any cardiovascular condition; MI, stroke, serious arrhythmia within 6 mo of entry; uncontrolled hypo/hypertension; hx of malignancy within 5 y; use of nitrates or nitric oxide donors; androgens or any other investigational drug
Age, mean: 53.6 vs. 54.2

Race: NR

Co-morbidities, %: DM 27; hypertension 35; Hyperlipidemia 10 vs. 6

Previous ED treatment:

Smoking status: NR

Body weight: NR

Other: BMI, mean 27.4 kg/m2
Concomitant medications, n (%): NR

Duration of ED: 2 y

Underlying disease, n (%): NR

Psychogenic ED, %: 16 vs. 23

Physiologic ED, %: 29 vs. 24

Mixed ED, %: 55 vs. 53

Other:
Baseline IIEF score: 13.6
Severity of ED, %:
Severe 29% vs. 39%
IG: Vardenafil
CG: Placebo

IG:
Dose: flexible dose starting dose of 10 mg for 4 wks; adjusted to 5 or 20 mg for the next 8 wks
Duration: 12 wks
Frequency: NR
Compliance: 99%

CG:
Dose: NA
Duration: 12 wks
Frequency: NR
Compliance: 100%

Run In period: 4 wks
Wash out period: NA

F/u duration: 12 wks (excluding the 4 wks run-in period)
Primary outcome results:
IIEF-EF, mean: baseline moderate; post tx 23.5 vs. 15.8; increase on score of 8.8 in IG vs. CG (95% CI 6.4, 11.1; p<0.0001)

SEP-2, %: baseline 48 vs. 46
12 wks: 85 vs. 65

SEP-3, %: Baseline: 21 vs. 22
12 wks: 78 vs. 49

GAQ, % improved: 83% vs. 38%, p<0.0001

Other outcomes assessed: TSS, sign better score in IG vs. CG, p<0.0001

Withdrawals/drop-outs/loss to f/u, n (%): 12 (6.7) vs. 4 (6.1)

WDAE, n (%): 3 (1.5) vs. 1 (1.5); IG included MI, aortic bifurcation graft; CG muscle cramp
TAE, n (%): NR; tx related occurring in 2% or more of pts, %: headache 5.2 vs. 0; flushing 7.3 vs. 0; Influenza 1 vs. 3
SAE, n (%): 2 (1.0) vs. 0; aortic bifurcation graft and MI (MI occurred5 d after last dose of 10 mg); no death occurred

Outcome ascertainment: SEP- 2, 3; GAQ; IIEF-EF; Treatment Satisfaction Scale (TSS)
Goldstein (2003) 89


Funding source: Bayer Corporation
N screened = 452
N randomized = 452

IG1, n = 153 (ITT = 149)
IG2, n = 149 (ITT= 141)
CG, n = 150 (ITT= 140)

ITT analysis used for primary outcome: Yes

Inclusion: men older than 18 y, and clinical diagnosis of type 1 or type 2 DM, Ed of 6 mo or longer. HbA1c ≥12%.

Exclusion: ED due to radical prostatectomy, hypoactive SD; SCI. MI, stroke, ischemia; sign arrhythmia; uncontrolled atrial tachyarrhythmia, unstable angina pectoris, liver dx, haematological dx or bleeding disorder, resting hypo/hypertension, retinitis pigmentosa, progressive retinopathy, autonomic neuropathy, migraine headaches; AE or dissatisfaction with Sildenafil; Nitrates, anti androgens, anti coagulant androgens, trazodone hypochloride not allowed
Age, mean (sd): 57 (NR) y

Race n (%): White
350 (80); Black 41 (9); Hispanic 15 (8) Other 13 (3)

Co-morbidities, n (%): Hypertension 231(53); depressive dx 45 (10)

HbA1C levels, n (%): ≤ 6 = 12 (3);
> 6 to < 8= 192 (43)
≥ 8.0 = 231 (53)

Previous ED treatment n (%): Sildenafil 256 (58)

Body weight: NR

Other: Severity of ED n (%): Severe (<11)=240 (55); Moderate (11–16)
102 (23); Mild to Moderate (17–21):
68 (15); Mild (22–25): 26 (9); Normal (≥ 26): 3 (<1), only in IG2 & CG
Concomitant Medications, n (%): Beta Blockers 52 (12); Renin-angiotension system acting agents 210 (50); Calcium-channel blockers 45 (10); Serum lipid-reducing agents 146 (33); Diuretics 71 (16);
Other antihypertensives 40 (9); Insulin 152 (35); Glucose-lowering drugs 318 (72)

Duration of ED: 3.5 y

Underlying disease: 88% type 2 diabetes and poor glycemic control

Psychogenic ED:
2 (<1) only in IG1: 2 (1)

Physiologic (organic) ED, n (%):
358 (81)

Mixed ED: 77 (18)
IG1: vardenafil
IG2: vardenafil
CG: Placebo

IG1:
Dose: 10 mg
Duration: 12 wks
Frequency: as needed, no more than 1/day
Compliance: NR

IG2:
Dose: 20 mg
Duration: 12 wks
Frequency: as needed, no more than 1/d
Compliance: NR

CG:
Dose: NA
Duration: 12 wks
Frequency: as needed, no more than 1/d
Compliance: NR

Run In period: 4 wk unmedicated phase
Wash out period: NR

F/u duration: 12 wk
Primary outcome results:
IG1 vs. IG2 vs. CG
IIEF-EF, mean final score: 17 vs. 19 vs. 13 (change from baseline: 1.4 vs. 6 vs. 8)
SEP-Q2, mean least square success rate (%): 61 vs. 64 vs. 36 (in severe ED= NR vs. 40 vs. 11; in mild ED= NR vs. 75 vs. 47)
SEP-Q3, mean least square per pts (%): 49 vs. 54 vs. 23 (type I diabetes= 48 vs. 65 vs. 10; type II= 49 vs. 52 vs. 25)
GAQ, proportion of men with improved erection: 54% vs. 72% vs. 13%

Other outcomes assessed: Blood chemistries, ECG

Withdrawals/drop-outs/loss to f/u: 73 (17)

WDAE, n (%): 4 (3) vs. 5 (3) vs. 2 (1); headache, cutaneous flushing, rhinitis
TAE, n (%): 7 (5) vs. 9 (6) vs. 6 (4)
SAE, n: 3 (2) vs. 4 (3) vs. 4 (3); including chest pain, dyspnea, larynx edema, asthma (n=1); depression, hypesthesia, or moderate amnesia; no death occurred

Outcome ascertainment: IIEF, SEP, Q2 and 3; GAQ, diary questions
Goldstein (2005) 90 91

Companion study, by Fisher (2005)


Funding source: Bayer HealthCare (conflict of interest for authors paid by Bayer Health Care)
N screened = NR
N randomized = 229

IG, n = 116
CG, n = 113

ITT analysis used for primary outcome: Yes

Inclusion: men with ED of 6 mo or longer, previously treated for ED who had a stable heterosexual relationship for => 6 mo with a female partner without sexual disorder, Female Sexual Function Index (FSFI) > 26.55

Exclusion: pts with unstable medical conditions, sign penile deformities, SCI, hx of prostatectomy, retinitis pigmentosa, unstable angina pectoris, MI, uncontrolled atrial fibrillation, taking nitrates or nitric oxide donors, anticoagulants, androgens, antiandrogens, indinavir, intraconazole, or erythromicyn or any ED drug; female partner's having primary hypoactive sexual disorder measured by Female Sexual Function Index
Age, mean (sd):
58 (28–79) y

Race (%): White: 85%, Black: 8%, Other: 7%

Co-morbidities: NR

Previous ED treatment: prior sildenafil in 81% vs. 91%

BMI, mean: 29 kg/m2

Smoking status: NR

Body weight: NR

Other: Mean sexual intercourse activity: 6 during run in
Concomitant medications: NR

Duration of ED, mean: 4.7 y

Underlying disease: NR

Psychogenic ED, %: 44.5%

Physiologic ED, %: 5%

Mixed ED, %: 50%
IG: vardenafil
CG: placebo

IG:
Dose: starting dose 10 mg with option to titrate to 5 or 20 mg at 4 wks
Duration: 12 wks
Frequency: NR
Compliance: NR

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

Run In period: 4 wks
Wash out period: NR

F/u duration: 12 wks
Primary outcome results:
IIEF-EF, mean score: baseline: 13; post tx 23 vs.13.5, p < 0.0001 (IG vs. CG)

% Success rate of improved least squares mean on Sexual Encounter Profile:
SEP-Q2, % yes: 80 vs. 47, p <0.0001
SEP-Q3, % yes: 68 vs. 28, p < 0.0001

Mean Erection Quality Scale (EQS) score: 37 vs. 16, p < 0.0001 (IG vs. CG)

Other outcomes assessed: Women's sexual function

Withdrawals/drop-outs/loss to f/u: 1 (<1) vs. 0

WDAE, n (%): 1 (<1) in IG; elevated creatinine
TAE, n (%): drug related AEs in at least 2% of pts= 22% vs. 4%; including flushing 13 (11) vs. 0; nasal congestion 9 (8) vs. 0; headache 5 (4) vs. 3 (3); dyspepsia 4 (4) vs. 1 (<1)
SAE, n (%): 1 (<1) vs. 0; unstable angina

Outcome ascertainment: IIEF EF domain (Q1, 5, and 15); SEP Q2 and 3; Erection Quality Scale (EQS)
Hatzichristou (2004) 92 93


Funding source: Bayer Corporation, Bayer AG, GlaxoSmithKline
N screened = NR
N randomized = 323

IG1, n = 157 (ITT, n = 154)
CG, n = 166 (ITT, n = 155)

ITT analysis used for primary outcome: Yes

Inclusion: men 18 or older with ED (NIH consensus), stable heterosexual relationship for 6 mo or longer, at least 50% of 4 or more attempts at sexual intercourse on 4 separate d during the 4 wk baseline period unsuccessful; answer ‘no’ to at least 1 diary question (IIEF)

Exclusion: penile abnormalities, primary hypoactive SD, ED due to SCI; radical prostatectomy, unstable angina, poorly controlled DM, hypertension; liver or hematologic dx; use of organic nitrates, other nitric oxide donors, or potent CYP3A4; sildenafil use permitted except for unresponsiveness or WDAE in last 7 d prior to screening
Age, mean: 54 vs. 53 y

Race (%): NR

Co-morbidities, (%): hypertension 34 vs. 24; DM 16 vs. 20; hyperlipidemia 2 vs. 5; Cardiac dx 9 vs. 6; respiratory, thoracic

Previous ED treatment, (%):
Prior sildenafil use
54 vs. 50

BMI, mean: 27kg/m2

Smoking status:
Non smoker 61 % past smokers

Body weight, mean: 81 vs. 82 kg
Concomitant medications: NR

Duration of ED, mean: 2 y

Underlying disease: NR

Psychogenic ED, %: 21 vs. 22

Physiologic ED, %: 37 vs. 42

Mixed ED, %: 43 vs. 36
IG: Vardendafil (flexible dose)
CG: placebo

IG1:
Dose: 10 mg titrated up or down if desired)
Duration: 12 wks
Frequency: as needed, no more than 1 dose/d
Compliance: NR

CG:
Dose: placebo (titration as IG)
Duration: 12 wks
Frequency: as needed, no more than 1 dose/d
Compliance: NR

Run In period: 4 wks
Wash out period: NR

F/u duration: 12 wk

Other: Titration data, n (%)
At wk 4- down to 5 mg: 6 (4) vs. 0
At wk 4-up to 20 mg: 95 (61) vs. 136 (88)
At wk 8- down to 5 or 10 mg: 7 (5) vs. 1 (<1)
At wk 8- up to 20 mg: 20 (13) vs. 4 (3)
Primary outcome results:
IIEF- EF, mean: Baseline=12.8; post tx: 24 vs. 16
SEP-Q2 (% yes): 84 vs. 53
SEP-Q3 (% yes): 74 vs. 34
GAQ; (% yes): 86 vs. 33

Erection hardness mean (%): 63 vs. 23
OS (%): 65 vs. 28
Penis enlargement (%): 92 vs. 75
Successful ejaculation (%): 79 vs. 56
(all p<0.005)

Other outcomes assessed: sub-grp by dose; depression; self confidence

Withdrawals/drop-outs/loss to f/u: 22 (14) vs. 45 (29)

WDAE, n (%): 5 (3) vs. 3 (2); tx emergent AEs only: abdominal pain, headache, dysphagia, pneumonia vs. accidental injury, vascular anomaly, ▴ CPK)
TAE, %: pts with at least one AE = 45 vs. 27 (data provided for AE of 2 or more incidence= flushing, headache, rhinitis, flu syndrome, dyspepsia, back pain, CPK increase, dizziness, accidental injury, hypertension and QT interval prolonged); total n of AE= 94 vs. 50
SAE: 4 (2.5) vs. 5 (3); cause NR

Outcome ascertainment: IIEF, GAQ; SEP question 2 and 3; pts diary
Hellstrom (2002) 94 95 96 97


Funding source: Bayer Pharmaceutical & Bayer Inc.
N screened = 1311
N randomized = 805 (parallel grps)

IG1: n= 193
IG2: n = 199
IG3: n = 188
CG: n = 182

ITT analysis used for primary outcome: Yes (n=749; safety population: n=762)

Inclusion: heterosexual men 18 y or older with ED, > 6 mo in duration; also with 50% or more failure rate in maintaining erection on at least 4 intercourse attempts on 4 separate d before tx

Exclusion: Ed due to SCI, radical prostatectomy, retinitis pigmentosa, angina pectoris or poorly controlled DM; primary hypoactive SD, no response to sildenafil, hx of hepatitis B or C, & concomitant use of nitrates

Note: Data reported as IG1 vs. IG2 vs. IG3 vs. CG
Age, range: 57–78 y (mean range per grp 57–58 y)

Race, %:
Caucasian 77 vs. 80 vs. 82 vs. 77

Co-morbidities: hypertension, prostatic hyperplasia, diabetes type II, depression, prior MI, hyperlipidemia, obesity, all not sign. between grps

Previous ED treatment sildenafil (%): 77 vs. 74 vs. 66 vs. 68
BMI, mean: 29kg/m2

Smoking status: NR

Body weight: NR
Concomitant medications: NR

Duration of ED, mean: 1st diagnosed: 3.6 vs. 3.6 vs. 4.2 vs. 2.9 y
(1st noticed: 5.9 vs. 6 vs. 6.6 vs. 5.1 y)

Underlying disease: NR

Psychogenic ED, %: 7 vs. 7 vs. 7 vs. 9

Physiologic ED, %: 61 vs. 59 vs. 60 vs. 54

Mixed ED, %: 33 vs. 34 vs. 33 vs. 37

Other: baseline IIEF score: 12.6 vs. 13.4 vs. 12.8 vs. 13.7
IG1-3: Vardenafil
CG: placebo

IG1-3:
Dose: IG1 = 5 mg; IG2 = 10 mg; IG3= 20 mg
Duration: 26 wks
Frequency: once/ d
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: 26 wks (1 wk post last tx)
Primary outcomes:
IIEF- mean score (LOCF), IG vs. CG:
EF, Baseline=14; post tx: 18–22 vs. 15
IS (Intercourse satisfaction): 10 vs. 8
OS: 7 vs. 5

SEP-Q2, % yes:
Baseline: 43 vs. 45 vs. 41 vs. 46
Post tx: 66 vs. 76 vs. 81.1 vs. 52
SEP-Q3:
Baseline=15;
Post tx: 52–67 vs. 33

GAQ, % yes: 65 vs. 80 vs. 85 vs. 28

Other outcomes assessed: self reported erection hardness; satisfaction with intercourse, and OS

Drop outs: n=297 (37%): 38% vs. 27% vs. 30% vs. 54% (non compliance, consent withdraw, insufficient tx effect, protocol violation, & lost to F/u)
WDAE, n (%): 8 (4.1) vs. 7 (3.5) vs. 15 (7.9) vs. 4 (2.2) reasons reported only for IG=headache, abnormal liver function, nausea, and kidney calculus
TAE: NR; AEs included headache, rhinitis, flushing, dyspepsia, accidental injury; all numerically more frequent in IG compare to CG
SAE (%): 5 vs. 3 vs. 4 vs. 5 (one MI, no death)

Outcome ascertainment: IIEF, GAQ, diaries, SEP, Q2 and 3
Ishii (2006) 98


Funding source: Bayer Yakuhin Ltd.
N screened = 954 (enrolled)
N randomized = 780

IG1, n = 340
IG2, n = 339
CG, n = 111

ITT analysis used for primary outcome: yes (12 wks LOCF)

Inclusion: men with ED (according to NIH Consensus statement) and DM > 3 y; currently under hypoglycemic drug tx or HbA1c>6.5% at visit 1;

Exclusion: penile deformities; substance abuse; major heart or liver disorders; SCI, MI, hx of hepatitis B, or C, HIV infection; cancer; hypo/hypertension; prostatectomy; retinitis pigmentosa; tx with; non respondent to PDE5i; ED tx within 7 d of trial entry (randomization); low T levels; elevated creatinine levels; tx with nitrates or nitric oxides (other criteria listed in detail in full report)
Age, mean (sd): 53 (7.7); range 26–64

Race: Asian 100% (Japanese)

Co-morbidities, n (%): NR

Previous ED treatment: sildenafil 296 (37)

Smoking status: NR

Body weight, mean: 71.8 kg
Concomitant medications, n (%):
Medication for DM

Duration of ED: 5.4 y

Underlying disease, n (%): DM

Psychogenic ED, n (%): 0

Physiologic ED, n (%): 720 (92.3)

Mixed ED, n (%): 58 (7.7)

Other: ED severity on EF domain score, n (%):
< 11: 275 (35.4)
11–16: 231 (30)
17–21: 184 (23.8)
22–25: 79 (9.8)
IG1-2: Vardenafil
CG: Placebo

IG:
Dose:20 mg (IG1), 10 mg (IG2)
Duration: 12 wks
Frequency: 1 hr prior to sexual activity up to 1/d
Compliance: NR

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

Run In period: 4 wks no ED tx
Wash out period: NA

F/u duration: 12 wks
Primary outcome results:
IIEF-EF, mean baseline: 13.7
12 wks LOCF, mean: 21.8 vs. 22.9 vs. 16.3 (more evident changes in pts, with baseline EF score of <11)

SEP mean % (from graph):
SEP- 2: Baseline 37.5
Post tx: 77 vs. 73 vs. 51

SEP-3, Baseline: 12.5
Post tx: 63 vs. 60 vs. 29

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to F/u, n (%): 28 (8.4) vs. 11 (3.3) vs. 14 (13.2)

WDAE, n (%): 9 (2.7) vs. 2 (0.6) vs. 2 (1.9)
TAE, n (%): NR; AE in 2% or more palpitations in 7 (2) vs. 12 (4) vs. 2 (2); nasopharyngitis 17 (5) vs. 31 (9) vs. 6 (6); blood creatinine phosphokinase ▴ 1(<1) vs. 8 (2) vs. 3 (3); headache 20 (6) vs. 13 (4) vs. 2 (2); nasal congestion 6 (2) vs. 9 (3) vs. 0.; upper respiratory tract inflammation 6 (2) vs. 7 (2) vs. 2(2); hot flush 45 (13) vs. 32 (9) vs. 3 (3)
SAE, %: 1 vs. 1 vs. 0 (detail NR)

Outcome ascertainment: SEP-2, 3; IIEF
Klotz (2001) 99


Funding source: NR
N screened = NR
N randomized = 25 (cross over)

IG1/IG2/CG, n = 25

ITT analysis used for primary outcome: NR

Inclusion: men, able to have an erection with visual stimulation; diagnosed with ED as per Cologne Evaluation Form for Erectile Dysfunction (KEED) and IIEF ≤ 6 mo prior to study

Exclusion: weak or no response to visual stimulation; no prior response to Sildenafil; ED of neurological or endocrine cause; anatomical abnormality (severe penile fibrosis); SCI, radical prostatectomy, retinitis pigmentosa, DM, any relevant comorbidities (not specified); major psychiatric illness; abnormal BP or heart rate or laboratory tests indicating AV-block] use of nitrites or nitrite oxide donors or user of any medication likely to interact with vardenafil.
Age, mean (sd):
34 (9), range 22–52 y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Initial body weight, mean (sd): 77 (7), range 64–89 kg
Broca index: 1 (0.1), range 0.9–1.1 kg
Concomitant medications: NR

Duration of ED (yr): NR
Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG1/ IG2: Vardenafil oral drinking solution + 20 min VS. (20 min post tx × 3)
CG: placebo + 20 min VS. (20 min post tx × 3)

IG1/IG2:
Dose: 10 mg (IG1); 20 mg (IG2)
Duration: N/A
Frequency: once
Compliance: 100%

CG: Placebo
Dose: NR
Duration: N/A
Frequency: once
Compliance: 100%

Run In period: NR
Wash out period: 5 d
Fasting overnight and 4 hr post initial dose

F/u duration: immediately post tx
Primary outcome (EF):
Duration of erection with 60% rigidity:
Base: 54 (27) vs. 67 (39) vs. 31 (24) min
Tip: 39 (26) vs. 45 (36) vs. 17 (20) min

Duration of erection with >80% rigidity
Base: 25 (25) vs. 31 (33) vs. 16 (19) min
Tip: 9 (13) vs. 22 (30) vs. 7 (14) min

Average event rigidity (%):
Base: 64 (24) vs. 66 (20) vs. 53 (29)
Tip: 47 (27) vs. 45 (23) vs. 32 (26)

Circumference, mean (sd): Base= 8 (1); Tip = 7 (1) cm (similar in all 3 grps)

Other outcomes assessed: duration of erection; pharmacokinetics; plasma concentration of vardenafil

Withdrawals/drop-outs/loss to F/u: 5 (20); 3 not included in safety analysis

WDAE: 0
TAE, n (%): 4 (18.2) vs. 2 (9.1) vs. 1 (4.5); including haematoma at the site of sampling IV cannlua; headaches, moderate tiredness, nasal congestion, flush and nasal congestion
SAE: 0

Outcome ascertainment: RigiScan (15 s); measuring event rigidity of >20%
Martin-Morales (2006) 100


Funding source: Químia Farmacéutica Bayer
N screened = 159
N randomized = 121 (12 centres in Spain)

IG, n = 64
CG, n = 65

ITT analysis used for primary outcome: yes (n=61 vs. n=60)

Inclusion: men 18–64 y with ED of at least 6 mo duration

Exclusion: successful intercourse on more than 50% of attempts during the run in; T value lower than permitted (NR); IC injection of PgE1 in a few days before visit 1 with diagnostic intention; elevated liver enzymes and abnormal ECG
Age, mean (sd): 52.5 (8.6) y (age in severe ED pts 52.8 vs. 52.1 y)

Race: White 100%

Co-morbidities, n (%): NR

Previous ED treatment: NR

Smoking status, n (%): past or present smoker 89 (71.2); pack per y hx 44.9 (26.9) vs. 33.7 (21.0), p=0.019

Body weight: 82.6 (12.1) kg

BMI, man (sd): kg/m2

Other: heavy alcohol consumption in 3 (2.4%)
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): NR


Psychogenic ED, n (%): NR

Physiologic ED, n (%): NR

Mixed ED, n (%): NR

ED severity, n (%): by IIEF score,
no ED 3 (2.5)
Mild 52 (43)
Moderate 36 (29.8)
Sever 30 (24.8)
IG: Vardenafil
CG: Placebo

IG:
Dose: starting dose 10 mg, adjusted to 5 or 20 mg based on efficacy and tolerability
Duration: 12 wks
Frequency: NR
Compliance: NR

CG:
Dose: NA
Duration: 12 wks
Frequency: NR
Compliance: NR

Run In period: 4 wks
Wash out period: NR

F/u duration: 12 wks (in addition to 4 wks run in)
Primary outcome results:
Change in score from baseline to 12 wks, LS mean (sd):
IIEF-EF: 10.9 (6.4) vs. 1.6 (7.7); difference -8.8 [95% CI -11.4; -6.1], p<0.001
IIEF-Q3, mean at 12 wks: 4.6 vs. 3.02
IIEF-Q4, mean at 12 wks: 4.34 vs. 2.69

SEP,% of pts with positive response:
SEP-Q2: 64.8% vs. 10.0%
SEP-Q3: 62.7% vs. 0.7%

GAQ, % improved: 73.8 vs. 25

Other outcomes assessed: individual IIEF question scores

Withdrawals/drop-outs/loss to F/u, n (%): 3 (4.7) vs. 5(7.7)

WDAE, n (%): NR
TAE, n (%): 18 (29.5) vs. 11 (17.2), p=0.138; including headache 8.2% vs. 0, flushing (IG only), nasopharyngitis 4.9% vs. 4.7%, flushing 8.2% vs. 0
SAE, n (%): 1 (1.6) vs. 1 (1.5); one case of intestinal obstruction in IG prior to randomization; non-cardiac chest pain in CG

Outcome ascertainment: IIEF-EF; GAQ, SEP, 2–3; Rosenberg Self-Esteem scale, Johnson and McCoy scale Medical Outcome Short Form (SF-36) scale
Mazo (2006) 101


Funding source: NR
N screened = NR
N randomized = 135 (study also included n=30 healthy men, data not shown)

IG, n = NR
CG, n = NR

ITT analysis used for primary outcome: NR

Inclusion: men with ED of at least 6 mo confirmed by pts hx and IIEF-EF domain; tx naïve; in a stable relationship

Exclusion: tx with nitrates

Note: all pts were examined with Doppler ultrasound of the penile arteries after IC injection of PgE1
Age, mean (sd): 51 (14.2)

Race: NR

Co-morbidities, n (%): DM 10 (6); hypertension 48 (29); CAD 20 (12.2), 10% vs. 14.5%; hyperlipidemia 56 (34.2); radical prostatectomy 15 (9)

Previous ED treatment: none

Smoking status: 27 (32.5) vs. 24 (29.3)

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

Duration of ED: NR

Underlying disease, n (%): no specific cause


Psychogenic ED, n (%): 42 (25.5)

Physiologic ED, n (%): non-arterial 20 (12.1); arteriogenic 73 (44.3)

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

IG:
Dose: 20 mg
Duration: NA
Frequency: single doese
Compliance: 100%

CG:
Dose: NA
Duration: NA
Frequency: once
Compliance: 100%

Run In period: NR
Wash out period: NA

F/u duration: NA (outcomes measured 1 hr post dosing)
Primary outcome results:
No data assessed and reported

Other outcomes assessed: % Increase of cavernosal arteries diameter, mean (sd)
baseline 51 (26.5) vs. 51.1 (26.7)
post tx 71.8 (22.1) vs. 51.6)(27.2)

Brachial artery flow mediated dilation:
Baseline 9.7 (5.4) vs. 10.6 (5.6)
Post tx 13 (4.4) vs. 10.7(5.6);
Also reported analysis of outcomes for ED etiology subgroup with greater FMD values in pts with arteriogenic ED, non-sign

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

WDAE, n (%): NR
TAE, n (%): NR
SAE, n (%): NR

Outcome ascertainment: no ED outcome measures used; FMD by Ultrasound
Montorsi, F (2004) 102


Funding source: Bayer Corporation, Pharmaceutical Division
N screened = NR
N randomized = 732

IG1, n = 237
IG2, n = 248
CG, n = 247

ITT analysis used for primary outcome: yes (ITT: n=708; safety: n=724)

Inclusion: men 18 or older, with ED of 6 mo or longer; with 50% or more failure in 4 attempts of intercourse during the run in period

Exclusion: penile abnormality; hypoactive SD; uncontrolled DM; radical prostatectomy or malignancy; SCI; chronic haematological, liver dx; retinitis pigmentosa; unstable angina pectoris; atrial tachyarrhythmia; MI, or stroke ≤ 6 mo; use of nitrates, anticoagulants, androgens, anti-androgens, trazodone, selected CYP3A4 inhibitors, alpha blockers/ other ED; hx of unresponsiveness/AE to other PDE5 inhibitors
Age, mean (range): 56 (22–81) y

Race, n (%):
Caucasian: 603 (83); Black: 22 (3);
Hispanic: 13 (2); Asian: 9 (1)

Co-morbidities: NR

Previous ED treatment, n (%): Sildenafil 521 (72)

BMI, mean: 27 kg/m2

Smoking status, n (%): 385 (53)

Body weight: NR

Other: Severity of ED, n (%): Normal (≥26)= 9 (2%); Mild (22–25)= 63 (9%); Mild-moderate (17–21)= 149 (21); Moderate (11–16)= 205 (28); Severe (≤ 10) =280 (39)
Concomitant medications: Drugs acting on renin-angiotensin system: 22%
Lipid reducing agents: 17%
Calcium channel blockers: 9%
Beta-blockers: 9%

Duration of ED, mean: 4 y

Underlying disease, %: hypertension 30; lipid disorders 17; DM 17; prostatic neoplasms/hypertrophy 13

Psychogenic ED: 310 (43%)

Physiologic ED: 118 (16%)

Mixed ED: 295 (41%)
IG1: Vardenafil oral
IG2: Vardenafil oral
CG: Placebo oral

IG1:
Dose: 10 mg
Duration: 4 wks
Frequency: 1/d
Compliance: NR

IG2:
Dose: 20 mg
Duration: 4 wks
Frequency: 1/d
Compliance: NR

CG: Placebo
Dose: NA
Duration: 4 wks
Frequency: 1/d
Compliance: NR

Run In period: 4 wks
Wash out period: NR

F/u duration: 4 wks
Primary outcome results:
Onset of adequate erections
At ≥ 25 min, (% yes): 50 vs. 53 vs. 26
At 10 min post intake in subgrps, %:
Mild/moderate ED: 40 vs. 34 vs. 23
Moderate ED: 21 vs. 20 vs. 10
Severe ED: 6 vs. 12 vs. 8
IIEF, mean (sd) score, IG vs. CG:
IIEF- EF: baseline= 13.4 (NR); post tx: 21 (8) vs. 14 (0.6)
IIEF-IS: 10 (3) vs. 7 (0.4)
IIEF-OS: 7 (3) vs. 5 (0.4)
SEP-Q2, % yes: 71 vs. 73 vs. 46
SEP-Q3, % yes: IG 75–77 vs. CG 45–47

Other outcomes assessed: SEP-3 in various time intervals post tx; elapsed time to adequate erection

Withdrawals/drop-outs/loss to F/u, n (%): 9 (4) vs. 6 (2) vs. 14 (6)
WDAE, n (%): 0 vs. 0 vs. 1 (<1)
TAE (%): NR; most common AE in ≥ 2% of pts = headache 7 vs. 12 vs. 1; flushing 6 vs. 9 vs. < 1; nasal congestion 2 vs. 4 vs. < 1; nausea <1 vs. 2 vs. 0; dyspepsia 2 vs. 1 vs. 0; abdominal pain <1 vs. 2 vs. 0
SAE, n: 0 vs. 5 (2) vs. 1 (<1); one patient in IG2 experienced two SAEs; IG included 1 skin ulcer, 1 reflux dx, 1 MI, 1 syncope + encephalitis; CG one pneumonia

Outcome ascertainment: IIEF domains; SEP-Q2 and 3
Nagao (2004) 103


Funding source:
Bayer Yakuhin Ltd
N screened = 375
N randomized = 283

IG1, n = 67
IG2, n = 75
IG3, n = 66
CG, n = 71

ITT analysis used for primary outcome: Yes

Inclusion: men 20–70 y, with ED for 6 mo or longer, willing to attempt at least 4 sexual intercourse during 4 wk run-in period, with no sign cardiac dx

Exclusion: any medical, psychiatric, substance abuse disorder; any major clinically sign dx or condition; abnormal hormone profile; use of nitrates or nitric oxide donors, beta blockers; erythromycin, ketoconazole, anti-coagulants; antiandrogens, traxodone, investigational drugs in the previous 3 mo; sildenafil or other ED tx within 7 d; hypersensitivity to sildenafil or to ≥ 3 other drugs; unresponsiveness to sildenafil
Age, mean (range): 52 (21–70) y

Race (%): all Asian (Japanese)

Co-morbidities: NR

Previous ED treatment, n (%): Sildenafil IG= 25 (12) vs. CG=4 (6)

Smoking status: NR

Body weight, mean: 68 kg

Other:
IIEF-EF Baseline score: mean (sd)
13.7 (5)
Concomitant medications: NR

Duration of ED, mean range: 2–3 y

Underlying disease: NR

Psychogenic ED, n (%): 183 (88) vs. 62 (87)

Physiologic ED, n (%): 10 (5) vs. 4 (6)

Mixed ED, n (%):
10 (5) vs. 5 (7)

IG1-IG3: Oral vardenafil
CG: Placebo

IG1-3:
Dose: 5 mg (IG1); 10 mg (IG2); 20 mg (IG3)
Duration: 12 wks
Frequency: as required, no more than once/d
Compliance (%): NR

CG:
Dose: 20 mg
Duration: 12 wks
Frequency: as required, no more than once/d
Compliance (%): NR

Run In period: 4 wk unmedicated
Wash out period: NR

F/u duration: 12 wks, every 4 wks for AE
Primary outcome results:
Least square mean IG1-2–3 vs. CG:
IIEF Q3: baseline= 3; post: 4.1–4.5–4.6 vs. 3.2
IIEF Q4: baseline = 2; post: 3.5–4.2–4.3 vs. 2.3
IIEF EF: baseline= 13.7; post: 22.4–25.6–25.9 vs. 16.7
GAQ, % yes: 73, 85.3, 86.4 vs. 35.2
Successful intercourse, % yes, baseline vs. tx grp= IG1: 64 vs. 13; IG2: 79 vs. 8; IG3: 80 vs. 10; CG: 33 vs. 9

Other outcomes assessed: Fugl-Meyer quality of life questionnaire

Withdrawals/drop-outs/loss to F/u: 7 (10) vs. 9 (12) vs. 6 (9) vs. 15 (21)

WDAE, n (%): 2 (3) vs. 2 (2.7) vs. 3 (4.5) vs. 4 (6)
TAE, n (%): Per-patient incidence 39 (57) vs. 47 (63) vs. 49 (74) vs. 37 (52); most frequently reported IG vs. CG: flushing 60 (28) vs. 6 (4); headache 21 (10) vs. 6 (4); rhinitis 14 (7) vs. 0
SAE: NR

Outcome ascertainment: IIEF- Q3 & 4; GAQ; pts diary of sexual intercourse; Fugl-Meyer quality of life questionnaire
Nehra (2005) 104 105

Companion Brock (2003) 105


Funding source: Bayer Pharmaceuticals Corp & Bayer Inc.
N screened = 567
N randomized = 440

IG1, n = 146 (ITT, n = 135)
IG2, n = 149 (ITT, n = 145)
CG, n = 145 (ITT, n = 134)

ITT analysis for primary outcome: Yes

Inclusion: men 18 or older, with ED due to nerve sparing-radical retro pubic prostatectomy, between 0.5 and 5 y prior to screening; localized tumours allowed; 4 attempts at sexual intercourse on 4 separate d with a 50% or higher chance of failure

Exclusion: unstable CV; Gleason tumour score ≥ 8, hx of unresponsiveness to sildenafil due to lack of efficacy or sign. side effects leading to discontinuation, hypoactive SD, low serum T, DM; prostate cancer.
Age, mean: 60 y

Race, (%): White 99 vs. 87 vs. 93

Co-morbidities, n (%): depressive disorder1 (<1) vs. 8 (6) vs. 10 (7); acute MI 12 (3); hypertension 130 (30); prostate hyperplasia 11 (3); hypercholesterolemia 91 (21); vasectomy 44 (10)

Previous ED treatment, n (%): 338 (77)

BMI, mean: 28 kg/m2

Smoking status, (%): 46–55% previously smoked

Body weight: NR

Other: IIEF EF score, mean:
pre-operation =23; baseline =9
Concomitant medications: NR

Duration of ED, mean: 1.7 y (post surgery)

Underlying disease: nerve sparing radial retro pubic prostatectomy (Mean Gleason tumour=6)

Psychogenic ED: NR

Physiologic ED: 100%

Mixed ED: NR

Other: neurovascular bundle sparing: n (% bilateral): 112 (76) vs. 101 (72) vs. 99 (71)
IG1: Oral Vardenafil
IG2: Oral Vardenafil
CG: placebo

IG1/IG2:
Dose: 10 mg (IG1), 20 mg (IG2)
Duration: 12 wks
Frequency: as needed but no more than 1×/day
Compliance: NR

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

Run In period: 4 wk tx free
Wash out period: NA

F/u duration: 12 wks
Primary outcome results:
Last observation carried forward, mean
IIEF- -Intercourse satisfaction, mean:
Baseline, all =5; post tx: 8 vs. 7 vs. 5
IIEF-OF, mean:
Baseline, all=5; post tx: 6 vs. 6 vs. 5
IIEF-OS:
Baseline, all=5; post tx: 6 vs. 6 vs. 5
Hardness of erection, (mean per pts satisfaction rate %): 28 vs. 24 vs. 8
IIEF-EF score:
Baseline, all =9; post tx 15 vs. 15 vs. 9
Mild-moderate ED: 26 vs. 25 vs. 16
Moderate ED: 23 vs. 19 vs. 13
Severe ED: 11 vs. 13 vs. 7
SEP-Q2, mean per pts success rate (%): baseline 21 vs. 18 vs. 14
Post tx: 47 vs. 48 vs. 22
SEP-Q3, mean per pts success rates (%): baseline 7 vs. 7 vs. 6;
post tx 37 vs. 34 vs. 10
GAQ, % yes: 59 vs. 65 vs. 13
Other outcomes assessed: NA
Withdrawals/drop-outs/loss to f/u: NR
WDAE, (%): 4 vs. 3 vs. < 1%
TAE, (%): Tx emergent AEs 57 vs. 65 vs. 40; including headache 16 vs. 22 vs. 4; Vasodilation 19 vs. 21 vs. 0; Rhinitis 16 vs. 20 vs. 6; Sinusitis 6 vs. 7 vs. 1; dyspepsia 4 vs. 5 vs. 0; nausea 1 vs. 5 vs. <1
SAE: 1 (<1%) vs. 3 (2%) vs. 1 (<1%) cause NR

Outcome ascertainment: IIEF; GAQ; SEP-Q2, and 2
Porst (2001) 106 107

Companion study 107


Funding source: Bayer
N screened = NR
N randomized = 601 (data reported for n=590, pts who took at least one dose of study medication)

IG1, n = 147
IG2, n = 141
IG3, n = 150
CG, n = 152

ITT analysis used for primary outcome: Y (n=580)

Inclusion: age 21–70 y; in stable heterosexual relationship with ED for at least 6 mo;

Exclusion: DM; SCI; radical prostatectomy; sign CAD; hx of hepatitis B and/or C; hypogonadal T levels; thyroid stimulating hormone level <0.28 mU/L; prior nonresponse to sildenafil
No other ED tx, or nitrates were permitted

Companion study reports on additional analysis in ITT population (n=580), for subgroups of various age and prior sildenafil use
Age, mean (sd): 53 (11) vs. 52 (11) vs. 52 (12) vs. 52 (11) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment, n (%): Sildenafil 74 (51) vs. 67 (50) vs. 72 (49) vs.72 (49)

Smoking status: NR

Body weight (sd): 83 (16) vs. 85 (14) vs. 84 (14) vs. 85 (15) kg
Concomitant medications: NR

Duration of ED, mean (sd): 3 (3) vs. 3 (4) vs. 3 (4) vs. 3 (3) y

Underlying disease: NR

Psychogenic ED, n (%): 163 (27)

Physiologic ED, n (%): 178 (30)

Mixed ED, n (%): 245 (41)

Other: Severity IIEF domain score, n (%): >25 (none)= 21 (4); 18–25 (mild)= 156 (26); 11–17 (moderate)= 204 (34); <11 (severe)= 195 (32)
IG1-3: vardenafil hydrochloride orally
CG: placebo orally

IG1-3:
Dose: 5 (IG1), 10 (IG2) or 20 (IG3) mg
Duration: 12 wk
Frequency: once 1 hr before intercourse; max 1/d
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: 13 wk
Other: 11 (2%) did not take medication
Primary outcome results:
Mean change from baseline (sd):
IIEF-Q3: 1.2 (1.7) vs. 1.3 (1.5) vs. 1.5 (1.7) vs. 0.2 (1.7)
IIEF-Q4: 1.4 (1.7) vs. 1.5 (2.0) vs. 1.7 (2.0) vs. 0.5 (1.7)
IIEF- EF: 5.7 vs. 8 vs. 9 vs. 1.6
IIEF-IcS: 2.9 vs. 3.5 vs. 3.6 vs. 1
IIEF-OF: 1.9 vs. 1.6 vs. 1.8 vs. 0
IIEF-OS: 2.1 vs. 2.6 vs. 2.8 vs. 0.8
IIEF-SD: 0.5 vs. 0.4 vs. 0.6 vs. 0

GAQ, % improved: 66 vs. 76 vs. 80 vs. 30, IG vs. CG p<0.001

% of successful intercourse, mean %: baseline: 28.9 vs. 26.1 vs. 24.2 vs. 23.7
post tx: 71.1 vs. 70.9 vs. 74.6 vs. 39.5, IG vs. CG p<0.001

Other outcomes assessed: Fugl-Meyer Quality of Life Questionnaire

Withdrawals/drop-outs/loss to f/u: 10 (0.2)

WDAE: 7 (5) vs. 2 (1) vs. 1 (0.7) vs. 2 (1) (Not specified)
TAE, n (%): pts with one or more AE
40 (27) vs. 38 (27) vs. 62 (41) vs. 14 (9); including headache, flushing, dyspepsia, rhinitis
SAE, n (%): 4 (3) vs. 1 (<1) vs. 2 (1) vs. 4 (3) Not specified

Outcome ascertainment: IIEF; SEP; GAQ; Fugl-Meyer QoL; pts diary
Porst (2006) 108


Funding source: NR
N screened = 483
N randomized = 383 (International 31 centres)

IG, n = 194
CG, n = 189

ITT analysis used for primary outcome: yes

Inclusion: men 18 or older, with ED > 6 mo IIEF-EF score >5 or lower than 26, who failed on at least 50% of intercourse attempts

Exclusion: penile abnormalities; hypoactive sexual dysfunction; surgical prostatectomy; retinitis pigmentosa; hx of hepatitis B surface antigen, hepatitis C, hepatic impairment, haematological disease; MI, stroke or serious arrhythmia in last 6 mo; uncontrolled atrial fibrillation, or DM; hypo/hypertension; heart failure; use of nitrates or nitric acid donors, antiandrogens, androgens, alpha blockers, anticoagulants; vardenafil in last 30 d; ED tx within 7 d
Age, mean (sd): 54.8 (9.3) vs. 56.6 (10.1) y

Race: White 75%; Hispanic 11%; Black 8%; Asian 7%; other <1%

Co-morbidities, n (%): NR

Previous ED treatment, %: sildenafil 33%; tadalafil 28%; vardenafil 10%

Smoking status: NR

Body weight: NR

Other: BMI, mean (sd): 28 (4.7) kg/m2
Concomitant medications, n (%):
NR

Duration of ED, mean (sd): since diagnosed 4.0 (3.2) vs. 3.9 (3.1) y

Underlying disease, n (%): no specific cause

Psychogenic ED, n (%): 42 (11)

Physiologic ED, n (%): 165 (44)

Mixed ED, n (%): 168 (45)

Other:
-ED severity, n (%):
Mild 32 (9)
Mild/moderate: 90 (24)
Severe 134 (36)
-IIEF-EF at baseline, mean (sd): 13.3 (5.5)
IG: Vardenafil
CG: Placebo

IG:
Dose: starting dose 10 mg adjusted to 5, 10, or 20 mg; initial dose of 10 mg, titrated to 5 or 20 mg at wk 2
Duration: 10 wks
Frequency: 8 hr before sexual activity
Compliance:

CG:
Dose: NA
Duration: 10 wks
Frequency: as IG
Compliance:

Run In period: 4 wks
Wash out period: NA

F/u duration: 10 wks

Other:
Dose titration to 20 mg, %: 75 vs. 94
Primary outcome results:
IIEF-EF, LS mean at 10 wks:
22.8 vs. 14.9

Success rate wk 2–6/ wk 0–10, LS mean, %:
SEP-2: 81 vs. 51/ 79 vs. 50
SEP-3: 69 vs. 34/ 65 vs. 31

GAQ, %: 77 vs. 27

Other outcomes assessed: EQS superior scores IG vs. CG, p<0.001; primary efficacy data analysed for wk 2–10 (after dose titration)

Withdrawals/drop-outs/loss to f/u, n (%): 17 (9) vs. 30 (16)

WDAE, n (%): 1 (<1) vs. 1 (<1)
TAE, %: pts with any tx emergent AE 39% vs. 22%
SAE, n (%): 8 (4) vs. 0; inincluded flushing, headache, hypoaesthesia, hypotension, muscle cramp, arthralgia, back pain, diarrhoea, intervertebral disc protrusion and lethargy

Outcome ascertainment: IIEF-EF; GAQ; SEP,2/3;Global Confidence Question (GCQ); Erection Quality Scale (EQS); SEP2, 3
Rosen (2006) 109


Funding source: Bayer, and GlaxoSmithKline
N screened = 488
N randomized = 280

IG1, n = 137
CG, n = 143

ITT analysis used for primary outcome: yes (also LOCF)

Inclusion: men 18 or older with ED for 6 mo or longer; with diagnosed but untreated mild major depressive disorder; who were not in psychotherapy or taking antidepressants; in a stable heterosexual relationship for more than 6 mo with 50% or more failure rate on at least 4 attempts of sexual intercourse

Exclusion: men medically unstable; hx of substance abuse, serious suicidal or homicidal risk, bipolar, schizophrenia, delusional, panic, or personality disorder, posttraumatic stress; penile anatomical abnormalities, primary hypoactive SD; SCI; or prior non-response to sildenafil.
Age, mean (sd); 54 (10) vs. 52 (12)

Race, (%): Caucasian 75; Black 8; Asian 2; Hispanic <1; American Indian <1

Co-morbidities: NR

Previous ED treatment, %: Sidenafil 59

BMI, mean (sd):
28 (4) vs. 27 (4) kg/m2

Smoking status, %: 51

Body weight mean (sd): 85 (15) kg (overweight)
Concomitant medications: None

Duration of ED, mean (sd): ≥6mo 3.5 (4)

Underlying disease, %: Depression 100; DM 15; vvascular hypertensive 29; elevated cholesterol 12

Psychogenic ED, n (%); 32 (24) vs. 49 (37)

Physiologic ED: 25 (19) vs. 15 (11)

Mixed ED, n (%): 75 (57) vs. 69 (52)

Other, n (%): 12% with elevated cholesterol
IG: Vardenafil
CG: Placebo

IG1:
Dose: 10 mg (titrated to 5 or 20 mg at 4, or 8 wks)
Duration: 12 wks
Frequency: once/d
Compliance, n (%): 118 (86)

CG:
Dose: NA (titration as IG)
Duration: 12 wks
Frequency: Once/d
Compliance n, (%): 111 (78)

Run In period: 4wk
Wash out period: None

F/u duration (on and off treatment): wk 4, 8 12
Primary outcome results:
IIEF Score, least square mean (LSM):
IIEF-EF LS mean improved from baseline: 10 vs. 2, p<0.0001
Intercourse satisfaction: 10.9 vs. 7.8
OF: 7.7 vs. 5.9
OS: 7.1 vs. 4.9
SD: 7.3 vs. 6.4
Erectile hardness: 55.2 vs. 25

SEP-Q2: 76.7 vs. 52.4, p<0.0001
SEP-3: 66.4 vs. 38.1, p<0.0001

GAQ, % improved: (LOCF): 83% vs. 30%; p<0.0001

Other outcomes assessed: Remission of depressive symptoms

Withdrawals/drop-outs/loss to f/u, n (%): 10 (7) vs. 29(20); including Insufficient therapeutic effect: 2 (1) vs. 10 (7)

WDAE, n (%): 4 (3) vs. 2 (1); reason NR
TAE, n (%): NR; AE in at least 2% of pts included headache: 15 (11) vs. 1 (1); flushing: 9 (7) vs. 1 (1); nasal congestion: 4 (3) vs. 0; insomnia: 0 vs. 4 (3)
SAE: NR (no death occurred)

Outcome ascertainment: IIEF domains, SEP-2/3;GAQ; Hamilton Depression rating scale (HAM-D) score, Rosenberg self-esteem scale.
Stark (2001) 110


Funding source: NR
N screened = NR
N randomized = 21 (3 way cross over)

IG1, n = 21
IG2 randomized = 21
CG randomized = 21

ITT analysis used for primary outcome: NR/ or no

Inclusion: men 18–60 y, normal body weight, mild to moderate ED for ≥ 6 mo or longer. Able to respond positively to visual sexual stimuli 4 wks.

Exclusion: penile anatomical deformity, SCI, prostatectomy, neurological or endocrine causes of ED, major psychiatric illness, retinitis pigmentosa, DM, extreme hypo or hypertension, medications that might interact with PDE5 inhibitiors (nitrates), intolerance to medications, hypersensitivity and/or allergic reactions, excessive alcohol consumption, past failure to respond to Sildenafil
Age, mean (sd):
45 (10) y

Race (%): 100% Caucasian

Co-morbidities: NR

Previous ED treatment: NR

Smoking status: NR

Body weight, mean (sd): 83 (10) kg


Other: Mean Broca Index = 1 (0.09)
Concomitant medications: NR

Duration of ED: NR

Underlying disease: NR

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR:
IG1: oral vardenafil hydrochloride solution
IG2: oral vardenafil hydrochloride solution
CG: oral placebo solution

IG1/ IG2:
Dose: 20 mg (IG1); 40 mg (IG2)
Duration: 24 hrs
Frequency: once
Compliance: 100%

CG:
Dose: NR
Duration: 24hrs
Frequency: 1×
Compliance: 99%

Run In period: NR
Wash out period: 5 d

F/u duration: NR
Primary outcome (EF):
Base, % event rigidity, mean (sd):
59 (26) vs. 70 (17) vs. 42 (24)
Base, average event tumescence, mean (sd): 10 (4) vs. 11 (3) vs. 8 (4)
Tip, % Event rigidity, mean (sd):
50 (24) vs. 58 (19) vs. 34 (23)
Tip, average event tumescence, mean (sd): 9 (4) vs. 9 (2) vs. 7 (4)

Duration of erections with Rigidity >60%
58 vs. 64 vs. 14 min
Mean individual ▴ in duration: 43 vs. 49 vs. NR (IG vs. CG, p <0.001)
Duration of erections with Rigidity >80%
30 vs. 40 vs. 6 min
pts with at least one erection: 18 (86) vs. 20 (95) vs. 16 (76)

Other outcomes assessed: pharmacokinetic results

Withdrawals/drop-outs/loss to f/u, n: 3 withdrew and were replaced

WDAE: 0
TAE, n (%): 10 (48) vs. 14 (61) vs. 10 (48); including headache, flushing, nasal congestion, visual disturbance (1 event, 35 min post tx with 40 mg), in total 66 AE in 18 (85%) of patients
SAE: 0

Outcome ascertainment: RigiScan device, venous blood samples, pts interview/self report
Stief (2004) 111


Funding source: Bayer Vital GmbH, Leverkusen
N screened = NR
N randomized = 1020 (n=755 completed 1st 12 mo; data provided for n=566 who continued 2nd 12 mo extension period)

IG1, n = 272
IG2, n = 294
CG, n = NA

ITT analysis used for primary outcome: Yes

Inclusion: men 18 or older with ED (NIH Consensus Statement definition) in a steady heterosexual relationship for 6 mo or longer, had to complete the 1st 12-mo tx to be eligible to enter 2nd 12-mo tx period

Exclusion: penile abnormalities, primary hypoactive SD, SCI-related ED, retinitis pigmentosa, angina pectoris, uncontrolled DM, resting hypo/hypertension, prior radical prostatectomy, prior use of vardenafil/sildenafil with poor tolerance or unresponsiveness within 6 mo
Age, mean (sd): 55 (22–89) y

Race (%): While (91), Black (4), others (5)

Co-morbidities: hypertension (33%), diabetes (16%), prostate hyperplasia (18%)

Previous ED treatment: Previous viagra use % = 56 vs. 65

BMI, mean (sd): 27 (4) vs. 28 (4) kg/m2

Body weight: NR
Concomitant medications: NR

Duration of ED, mean (sd): 2 (3) vs. 2 (4) y

Underlying disease: NR

Psychogenic ED: 17%

Physiologic ED: 45%

Mixed ED: 36%
IG1: Vardenafil
IG2: Vardenafil

IG1:
Dose: 10 mg
Duration: 24 mo
Frequency: once/d
Compliance: 85%

IG2:
Dose: 20 mg
Duration: 24 mo
Frequency: once/d
Compliance: 84%

Run In period: NR
Wash out period: NR

F/u duration: 2 y
Primary outcome results:
Last observation carried forward (IG1 vs. IG2)
IIEF-EF score, mean (sd):
Baseline: 13 (5) vs. 14 (6)
Post tx: 25 (7) vs. 26 (6)

SEP-Q2, mean % with yes response:
Baseline: 48 vs. 43; Post tx: 92 vs. 94
SEP-Q3 mean % with yes response:
Baseline: 16 vs. 17; Post tx: 87 vs. 89

GAQ, % yes: 90 vs. 92% (sildenafil naïve 90.9 vs. 89.3; Sildenafil experienced 90.1 vs. 93.7)

Other outcomes assessed: The Fugl-Meyer Life Satisfaction Checklist items ‘sexual life’ and ‘sexual satisfaction’

Withdrawals/drop-outs/loss to f/u, n (%): 41 (15) vs. 46 (16)

WDAE, n (%): 5 (2) vs. 6 (2)
TAE, n (%): NR; AEs=headache in 16 vs. 20%; flushing in 14 vs. 20%; rhinitis in 10 vs. 14%; nausea 2 vs. 2%; dyspepsia 4 vs. 9%; sinusitis 1 vs. 2%; conjunctivitis 2 vs. 1%; visual symptoms 5 (2) vs. 8 (3)
SAE, n (%): 21 (8) vs. 13 (4); death 1 (0.4) vs. 3 (1) (unknown if the deaths are included in the 34 SAE)

Outcome ascertainment: IIEF; SEP question 2, 3, Fugl-Meyer Life Satisfaction Checklist; and CESD scale
Valiquette, (2005) 112 113


Funding source: GlaxoSmithKline, King of Prussia, Pa, and Bayer Healthcare Pharmaceutical Division
N screened = 600 (773 originally approached for 4 wk run-in)
N randomized = 523

IG1, n = 260 (ITT, n = 255)
CG, n = 263 (ITT, n = 254)

ITT analysis used for primary outcome: Yes

Inclusion: men 18 or older, heterosexual relationship, ED of 6 mo or longer (NIH Consensus Statement), no prior use of Vardenafil. At least 50% of sexual intercourse attempts during the 4 wk run in phase; IIEF-EF score ≤ 26 and ≥5, positive 1st time response to 10 mg challenge.

Exclusion: evidence of unstable or chronic medical, psychiatric or substance abuse, penile abnormality, primary hypoactive SD, SCI, hx of radical prostatectomy, retinitis pigmentosa, unstable angina pectoris, hx of MI, stroke or life-threatening arrhythmia in last 6 mo (complete list can be found in full text article)
Age, mean (sd):
53.2 (11) vs. 54.5 (11) y

Race (%): White 75; Asian 12; Black 5; Hispanic 4; Other <1

Co-morbidities: Hypertension: 155 (30); DM 72 (14); Benign prostatic hyperplasia 69 (14); Dyslipidemia 82 (16)

Previous ED treatment, n (%): sildenafil 337 (64); tadalafil 104 (20)

BMI mean (sd): 27 (4) kg/m2

Body Weight: NR
Other: IIEF-EF score, mean (sd)=
15 (5); severity of ED (%): no attempts (≤5)= 1; severe 23; moderate 35; mild-moderate 30; mild 7; no ED (>25) < 1
Concomitant medications: NR

Duration of ED, mean (sd): 6 (5); range 1–29 vs. 1–41 y

Underlying disease: NR

Psychogenic ED: n (%): 82 (16)

Physiologic ED: n (%): 219 (42)

Mixed ED: n (%): 208 (40)
IG: Vardenafil
CG: placebo

IG:
Dose: 10 mg
Duration: 12 wks
Frequency: as needed, no more than once/ d
Compliance: NR

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

Run In period: 4 wk run in period followed by 1 wk open label challenge phase
Wash out period: NR

F/u duration: 12 wks
Primary outcome results:
IIEF-EF score, least square mean (se): 24 (0.4) vs. 16 (0.4)
IIEF-EF score equal or more than 26, (% of pts): 50 vs. 16

SEP2-, (% yes):
Baseline: 56 vs. 53
Post tx: 83 vs. 56

SEP-Q3, (% yes):
Baseline: 22 vs. 21
Post tx: 77 vs. 42

GAQ, (% yes) according to last observation carried forward: 81 vs. 32

Other outcomes assessed: median # of doses/ pts= 32 vs. 20

Withdrawals/drop-outs/lo to f/u, n (%): 76 (30) vs. 43 (17)

WDAE, n: 2 (0.8) vs. 4 (2)
TAE, n (%): any event 72 (28) vs. 40 (15); including headache 13 (5) vs. 5 (2); flushing 14 (5) vs. 2 (0.8), dyspepsia 6 (2) vs. 1 (0.4)
SAE, n: 2 (0.8) vs. 0; facial palsy, appendicitis

Outcome ascertainment: SEP, Question 2 and 3; IIEF-EF, and GAQ
van Ahlen (2005) 114


Funding source: NR(5/6 authors are employees of Galxo-SmithKline/Bayer producers of vardenafil)
N screened = NR
N randomized = 388 (98 primary care sites in Germany)

IG, n = 193 (ITT=178)
CG, n = 195 (ITT= 176)

ITT analysis used: yes (last observation carried forward)

Inclusion: men 18 or older with ED of 6 mo or longer; arterial hypertension controlled with 1 or more medication; able to maintain 4 wk ED tx free (at least 4 intercourses)

Exclusion: prior use of PED5 inhibitors; penile anatomical abnormalities; hypoactive SD; ED due to SCI or radical prostatectomy; retinitis pigmentosa; hepatitis B, C surface antigen or; unstable angina pectoris; MI, stroke, ischemia; DM; hypotension; use of anticoagulants, androgens, trazodone, antiandrogens, alpha1 antagonist, potent HIV protease inhibitor, nitrates, ketokonazole, erythromycin (more in full text)
Age, mean (range): IG1: mean 56 (range 22–78) y

Race (%): NR

Co-morbidities: NR

Previous ED treatment: NR

BMI, mean: 28 vs. 27kg/m2

Smoking status: NR

Body weight, mean (sd): 88 (14) vs. 86 (12) kg
Concomitant medications, n (%): Antihypertensive medications:
Diuretics: 24 (13) vs. 15 (8); Beta-blockers: 81 (42) vs. 82 (43); Calcium channel blockers: 36 (19) vs. 28 (15); Reninangiotensin acting agents: 136 (71) vs. 133 (70)
Mean number of antihypertensives per patient: 1.5 vs. 1.4

Duration of ED (yr): NR

Underlying disease, (%): Hypertension 100 vs. 99

Psychogenic ED: NR

Physiologic ED: NR

Mixed ED: NR
IG: Vardenafil
CG: placebo

IG:
Dose: starting 10 mg (5 mg in pts 65 or older) one step titration to 5 or 20 mg at 4 & 8 wks
Duration: 12 wks
Frequency: 1/ d
Compliance: NR

CG:
Dose: NA
Duration: 12 wks
Frequency: 1/ d
Compliance: NR

Run In period: 4 wks tx free
Wash out period: 4 wks ED tx free

F/u duration: 12 wks (4, 8, and 12 wks measures)

Other: Allowed a single dose per day (No use of nitrate or concurrent ED therapy ≤ 7 d of study or any investigational drugs < 30 d prior to screening; no use of alpha-blockers permitted)
Primary outcome results:
SEP-Q2, % yes: 83 vs. 58, p< 0.0001
SEP- Q3, % yes: 67 vs. 35, p < 0.0001

IEEF-EF, mean score: baseline = 14 vs. 14.5; post tx= 25 vs. 18, p< 0.0001 (unaffected by the class of antihypertensive used)

GAQ, % yes: 80 vs. 40, p < 0.0001

Other outcomes assessed: association of tx with clinical measures of BP, or HR

Withdrawals/drop-outs/loss to f/u: 34 (8.7)

WDAE, n (%): 4 (2) vs. 2 (1)
TAE, (%): 21.2% vs. 16.4%; including headache: 6 (3) vs. 1 (0.5); flushing: 3 (2) vs. 1 (0.5)
SAE, n (%): 6 (3) vs. 2 (1); no detail provided

Outcome ascertainment: IIEF-EF, sum score of Q 1, 5 and 15, SEP question 2 and 3; and GAQ
Ziegler (2006) 115 N screened = NR
N randomized = 318 (82 sites in Germany)

IG, n = 163
CG, n = 155
ITT analysis used for primary outcome: yes (IG n=153, CG n=149)

Inclusion: men 18 or older with ED (by NIH Consensus statement); established DM type I; PDE5i naïve
Exclusion: penile abnormalities; hx or SCI, hepatitis B, C; MI; heart or liver conditions (explicitly reported); hypo/hypertension; uncontrolled DM; hx of malignancy within past 5 y or serum creatinine levels > 2.5 mg/dL (pts were prohibited to take nitrates while in the trial); tx with anticoagulant drugs (except anti-platelets); androgens, alpha1-antagonists, potent HIV protease inhibitors, anti mycotic agents itraconazole and ketoconazole, and erythromycin; other ED tx within 7 d of trial entry
Age, mean (sd): 50.3 (9.7) y

Race: NR

Co-morbidities (%): CV 157 (51.8); nervous system 94 (31); eyes 90 (29.7); endocrine/metabolic 83 (27.4); musculoskeletal system 49 (16.2); urinary tract 46 (15.2); other including allergies 28 (9.3)

Previous ED treatment: NR
Smoking status: NR

Body weight, mean (sd): 85.8 (13.4) kg

Other: BMI, mean (sd): 27.2 (3.8) vs. 26.9 (3.4) kg/m2
Concomitant medications, n (%): NR

Duration of ED: NR

Underlying disease, n (%): DM

Psychogenic ED, n (%): NA

Physiologic ED, n (%): all, 100%

Mixed ED, n (%): NR

Other: Glycemic control, good (HbA1c 7% or less) in 43 vs. 51%; moderate (HbA1c 7–8%) in 58 vs. 47%; poor (HbA1c >8%) 53 vs. 51%
IG: Vardenafil
CG: Placebo

IG:
Dose: flexible dose starting with 10 mg (5 mg for pts 65 or older) titrated to 20 mg
Duration: 12 wks
Frequency: on demand 1 hr prior to intercourse, up to 1/d
Compliance: NR

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

Run In period: 4 wks no tx
Wash out period: NA

F/u duration: 12 wks

Dosing at 12 wks: 87.7% on 20 mg vardenafil; 10.8% on 10 mg, and 1.5% on 5 mg
Primary outcome results:
IIEF domains change in score from baseline, mean (sd):
EF: 7.79 (7.9) vs. 2.05 (5.8); improvements unaffected by level of glycemic control
IcS: 3.43 (3.6) vs. 0.72(2.45)
OF: 1.99 (2.6) vs. 0.30 (2.7)
SD: 0.67 (1.5) vs. 0.09 (1.4)
OS: 2.32 (2.6) vs. 0.52 (2.0)
SEP-2, mean % (sd);
Baseline: 41 (38) vs. 47 (40)
Post tx: 71 (35) vs. 52 (38)
SEP-2, mean % (from graph):
Baseline: 13 vs. 18
Post tx: 50 vs. 28

Other outcomes assessed: NA

Withdrawals/drop-outs/loss to f/u, n (%): 16 (5.3) with no efficacy evaluation at baseline or post tx

WDAE, n (%): 3 (1.8) vs. 2 (1.3)
TAE, n (%): 29.4 vs. 20.6; AE in 2% or more pts n= 14 vs. n= 8; headache 5 (3.1) vs. 0; flushing 4 (2.5) vs. 0; bronchitis 3 (1.84) vs. 4 (2.6); nasopharyngitis 2 (1.2) vs. 4 (2.96)
SAE, n (%): 7 (4.6) vs. 3 (2), cause NR

Outcome ascertainment: IIEF-EF; SEP2, and 3

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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