Evidence Table 1Head-to-head trials in patients with SAR

Author
Year
Country
Trial Name (Quality Score)
Study Design
Setting
Eligibility criteriaInterventionsRun-in/washout periodAllowed other medications/interventionsMethod of outcome assessment and timing of assessmentAge
Gender
Ethnicity
Other population characteristicsNumber screened/eligible/enrolledNumber withdrawn/lost to fu/analyzedOutcomesMethod of adverse effects assessmentAdverse Effects ReportedTotal withdrawals due to adverse eventsComments
Berger
2003
USA (Fair)
Parallel-group, single-blind, RCT MulticenterAdult and adolescents with spring SAR for at least 24 mos.
Positive epicutaneous or intradermal test to one or more of grass or tree pollen and/or outdoor molds TNSS (the sum of discharge, stuffiness, itching, and sneezing scores recorded the morning of randomization visit plus scores from 3 of the 4 previous days were required to equal at least 42 (of a possible 84) points for patients to continue in the study.
TAA AQ 220 mcg daily
FP 200 mcg daily

Study duration: 3 weeks
Wash-out period × 5 days involving discontinuation of all rhinitis medications
Run-in: none
NRPatient reported severity (0=absent to 3=severe of nasal symptoms (nasal drainage, stuffiness, itching, and sneezing) scores twice daily during wash-out period through week 3
Primary outcome: TNSS (sum of individual symptom scores-max=12)
RQLQ (patients >17 years of age) baseline and week 3
SAQ at week 3
Mean age (years): 31.6
% Female: 62
Race (%): White 81.7
Black 10.2
Other 8.1
TAA AQ vs. FP
Years with allergic rhinitis
Mean: 16.6 vs. 19.1
TNSS at baseline
Mean: 8.06 vs. 7.64
NR/NR/2958 (2.7%)/4/INSS n=290, RQLQ n=232

For Kaiser INSS/TNSS= 295, RQLQ=292
TNSS TAA AQ=FP (data NR)
TNSS moderate: TAA AQ (n=69) =39% improvement from baseline vs FP (n=76)=36% improvement from baseline (p=NS)
TNSS severe: TAA AQ (n=79)=38% improvement from baseline vs FP (n=71)=41% improvement from baseline (p=NS)
INSS moderate and severe difference in mean change from baseline was statistically significant TAA AQ=FP (p=NS)
INSS (mean estimated from graph):
Nasal discharge: −0.76 vs −0.76 (p=NS)
Nasal stuffiness: −0.80 vs −0.78 (p=NS)
Sneezing: −0.78 vs −0.80 (p=NS) Nasal itching: −0.85 vs −0.88 (p=NS)

RQLQ: (TAA AQ n=110, FP n=122)
Mean overall score: TAA AQ=FP (data NR)
RQLQ moderate (TAA AQ n=58) vs (FP n=67): −1.9 vs −1.8 (p<0.0001)
RQLQ severe (TAA AQ n=89) vs (FP n=78): −2.4 vs −2.3 (p<0.0001)
SAQ: less odor reported with TAA AQ than FP (P<0.0001)

*Moderate severity: < 8.14 baseline score
Severe: > or equal to 8.14 baseline score
Reported by patient Responses to 2 SAQ items prospectively defined as “treatment-related adverse events” (e.g. nose bleeds, nasal irritation)TAA AQ (n=148) vs FP (n=147) (any causality, (%); possibly related, (%))
Headache: 10 (6.8) vs 6 (4.1); 2 (1.4) vs 1 (0.7)
Epistaxis: 4 (2.7) vs 7 (4.8);3(2) vs 6 (4.1)
Rhinitis: 3 (2) vs 6 (4.1); 3 (2) vs 4 (2.7)
Infection: 2 (1.4) vs 5 (3.4); 0 vs 0
Pain: 4 (2.7) vs 2 (1.4); 0 vs 0
Sinusitis: 3 (2) vs 0; 0 vs 0
Back pain: 1 (0.7) vs 3 (2); 0 vs 0
Pharyngitis: 1 (0.7) vs 4 (2.7); 0 vs 2 (1.4)
Cough increased:1 (0.7) vs 3 (2); 0 vs 1 (0.7)
Accidental injury: 0 vs 3 (2); 0 vs 1 (0.7)
Withdrawals (overall): 8
Withdrawals (adverse events): 0
Kaiser re-analyzed Berger et al data to examine the effects of each drug on symptoms and HRQL in patients stratified into cohorts based on symptom severity.
Kaiser
2004
USA
Moderate severity (<8.14)(n=69 vs n=76)
mean score :6.14 and 6.22
Severe (> or equal to 8.14) (n=79 vs n=71)
mean score:10.03 vs 9.47
Gross
2002
USA (Fair)
Parallel-group, single-blind, RCT MulticenterAdult and adolescents with fall (ragweed) AR for at least 24 months.
Positive skin prick test for ragweed.
TNSS (the sum of discharge, stuffiness, itching, and sneezing scores recorded the morning of randomization visit plus scores from 3 of the 4 previous days were required to equal at least 42 (of a possible 84) points for patients to continue in the study.
TAA AQ 220 mcg daily FP
200 mcg daily

Study duration: 3 weeks
Wash-out period × 5 days involving discontinuation of all rhinitis medications
Run-in: none
NoPatient reported nasal symptom scores (nasal discharge, stuffiness, itching; sneezing; ocular itching/tearing/redness) twice daily during wash-out period through week 3
RQLQ baseline and week 3
Mean age (years): 38.8
Female gender (%): 66.5
Race (%): Caucasian 81.3
Black 4.25
Asian 0.85
Hispanic 12.75
Other 0.85
TAA AQ vs FP
TNSS at baseline
Mean: 8.95 vs 9.01
NR/NR/35210/NR/unclear for INSS, safety n= 352. RQLQ n= 349TAA AQ vs FP
TNSS: 49.4% vs 52.7% change from baseline scores at wk 3 (p=NS)
INSS: TAA AQ=FP (P=NS) in all INSS categories except FP provided greater reduction in sneezing at week 2 (P=0.046)
HRQL: TAA AQ (n=170) vs FP (n=179)
TAA AQ=FP (p=NS)
RQLQ: individual dimensions TAA AQ = FP (p=NS) except emotions in which FP demonstrated significant improvement (P=0.04)
Reported by patient via daily questionnairesTAA AQ (n=172) vs FP (n=180) (possibly related, (%); probably related, (%)):
Body as a whole: 2 (1.2) vs 3 (1.7); 0 vs 2 (1.1)
Headache: 2 (1.2) vs2 (1.1); 0 vs 2 (1.1)
Digestive system: 1 (0.6) vs 1 (0.6); 1 (0.6) vs 1 (0.6)
Dyspepsia:0 vs 1 (0.6); 0 vs 0
Respiratory system:6 (3.5) vs 7 (3.9); 4 (2.3) vs 5 (2.8)
Pharyngitis:1 (0.6) vs 2 (1.1); 0 vs 0
Rhinits:4 (2.3) vs 2 (1.1); 3 (1.7) vs 3 (1.7)
Skin and appendages: 35 (20.3) vs 32 (17.8); 82 (47.6) vs 102 (56.7)
Application (local) reaction
36 (21) vs 32 (17.8); 81 (47) vs 102 (56.7)
Withdrawals (overall): 10
Withdrawals (adverse events): 2

Two patients in the TAA group withdrew from the study, one patient due to nausea and the other due to nasal dryness, sinus dryness, and insomnia
Application reaction included post-dose burning, stinging, sneezing, or blood in mucus.

Outcomes for INSS and TNSS is not reported. Raw data for INSS and TNSS is only reported in a bar graph which is very small so estimating actual numbers would be difficult.
Ratner
1992
USA (Fair)
Placebo-controlled
Double-blind
RCT
Multicenter
Adult patients with moderate to severe SAR for at least 24 months
Positive skin test to Mountain Cedar, Juniperus ashei
Normal adrenal function
Women of non-childbearing potential
At least 200/400 points on INSS on at least 4 out of 7 days of run-in period
FP 200 mcg in the morning + placebo in the evening
BDP 168 mcg twice daily
Placebo twice daily

Study duration: 2 weeks
Run-in period 4–14 days
Wash-out: none
Chlorpheniramine 4 mg tabletsNasal exam days 1, 8, and 15 and day 22 of post-treatment f/u INSS severity (nasal obstruction, rhinorrhea, sneezing, and itching) scored by clinician at each visit and by pts at the end of each day(scale of 0 (no symptoms) to 100 (severe symptoms))
Pt reported nasal obstruction upon awakening each day
Clinician rated overall effectiveness (7 pt scale) at the end of study
Morning plasma cortisol, exam, lab tests, 12-lead ECGs at screening visit and after 2 wks of treatment.
Mean age (years): 37.1
Female gender (%): 45.3
Race not reported
FP vs BDP vs PL asthma, n (%):
27(25) vs 24 (23) vs 20 (19)
perennial rhinitis, n (%) 72(68) vs 53(51) vs 58(56)
seasonal rhinitis (other than to mountain cedar), n (%)
59(56) vs 61(59) vs 63(61)
NR/NR/NR4/NR/313FP vs BDP vs PL
INSS (clinician-rated, patient-rated):
For all INSS FP=BDP>PL (P<0.05 for both drugs vs placebo)
Nasal obstruction:
−0.32 vs −0.33 vs −0.23
−0.34 vs −0.37 vs −0.26
Rhinorrhea:
−0.46 vs −0.44 vs −0.26
−0.38 vs −0.41 vs −0.20
Sneezing:
−0.36 vs −0.39 vs −0.25
−0.35 vs −0.41 vs −0.19
Nasal Itching:
−0.42 vs −0.43 vs −0.30
−0.35 vs −0.41 vs −0.24
Nasal obstruction upon awakening:
FP=BDP on day 2 (p<0.05) and throughout treatment (p<0.01)
Overall efficacy (clinician rated):
FP=BDP>PL (P<0.001)
Elicited by investigator at each clinic visitFP (n=106) vs BDP (103) vs PL (n=104)
Sore throat: 2(2%) vs 2 (2%) vs 1 (1%)
Blood in nasal mucus: 6(6%) vs 1(1%) vs 2(%)
Nasal burning: 5(5%) vs 2(2%) vs 4(4%)
Epistaxis: 3(3%) vs 2(2%) vs 0
Headache: 0 vs 1(1%) vs 3(3%)
Any event: 19(18%) vs 10(10%) vs 19(18%)
Withdrawals (overall): 4
Withdrawals (adverse events): 2 (placebo group for insomnia, objectionable odor of study drug)
Authors only listed adverse events if reported by 3 or more patients across treatment groups

All centers were in Texas with an allergen specific to that region. Treatment period was 2 weeks.
Graft
1996
USA (Fair)
Placebo-controlled
Double-blind
Parallel group
RCT
Multicenter
Adult and adolescent (at least 12 years old) pts with SAR for at least 24 months
Positive skin prick test to ragweed
Women of non-childbearing status or using acceptable form of birth control Free of nasal and non-nasal symptoms (score less than or equal to 1) and TNSS less than or equal to 2 at screening and baseline.
MF 200 mcg in the morning + placebo in the evening
BDP 168 mcg twice daily
Placebo twice daily

Study duration: 8 weeks
Run-in period: none
Wash-out period: 1 day to stop nasal, oral, or ocular decongestants. Oral antihistamines for a variable amount of time depending on duration of action
Systemic corticosteroids for 1 month (IM or intraarticular for 3 months), nasal or ocular corticosteroid medications or cromolyn for 2 weeks
NoINSS : 4 nasal symptoms (rhinorrhea, nasal stuffiness/congestion, nasal itching, and sneezing) and 4 non-nasal symptoms (eye itching/burning, eye tearing/watering, eye redness, itching of ears/palate) using a 4-point rating scale. MD evaluated INSS on screening, day 1 (baseline), and days 8, 22, 29, 36, 50, 57 and the patient evaluated twice daily in a diary.
Global Evaluation by patient and MD at each visit
Compliance evaluated with phone call day 15 and 43
Adverse events (safety) reviewed with MD at each visit.
Mean age (years): 34.7
Female gender (%):47
Race (%):
Caucasian: 93
Black: 3.3
Other: 2.7
Mean duration of disease (years): 19 for all 3 groups
Patients entered the study an average of 23 days before onset of ragweed season symptoms.
NR/NR/3492/NR/330 for efficacy, 347 for safetyMF (n=114) vs BDP (n=112) vs PL (n=104)
The average proportion of minimal symptom days (am and pm scores averaged < or = 2) from the start of ragweed season to study completion: 0.83 vs 0.77 vs 0.64 MF=BDP>PL (p<0.01)
The average proportion of minimal symptom days from the start of treatment to study completion: MF=BDP>PL (p<0.01) (numbers not reported)
Number of days from start of ragweed season to a non-minimal symptom day (TNSS >/= 3): Median reported in text: 27 vs 27 vs 10.5
Fig.2 % pts with minimal symptoms at day 44: 39 vs 29 vs 29
Number of days to first occurrence of a non-minimal symptom day from start of treatment: 51.5 vs 50 vs 34 MF=BDP>PL (p=<0.01)
TNSS based on diary data (mean change from baseline-start of ragweed season):
Days 1–15 (estimated from graph): 0.4 vs 0.6 vs 1.4
MF=BDP>PL (p>0.01)
Days 16–30 (estimated from graph): 0.8 vs 1.1 vs 2
MF=BDP>PL (p>0.01)
Days 31–45 (estimated from graph): 0.9 vs 1.3 vs 2
MF=BDP>PL (p>0.01)
Investigator NSS change from baseline(all results estimated from graph :)
Day 8: 0.1 vs 0 vs 0.1
MF=BDP=PL
Day 15: 0.4 vs 0.4 vs 0.75
MF=BDP=PL
Day 29: 0.8 vs 0.7 vs 1.2
MF=BDP>PL (p>0.01)
Day 36: 1.2 vs 1.4 vs 2.9
MF=BDP>PL (p>0.01)
Day 50:1.2 vs 1.1 vs 2.4
MF=BDP > PL (p>0.01)
Elicited by investigator at each clinic visitMF (n=116) vs BDP (n=116) vs PL (n=115)
Any adverse event, n (%):
73 (63) vs 59 (51) vs 60 (52)
Headache, n (%):
42 (36) vs 25 (22) vs 27 (23)
Pharyngitis, n (%):
7 (6) vs 12 (10) vs 6 (5)
Upper respiratory tract infection, n (%):
7 (6) vs 3 (3) vs 1 (<1%)
Dysmenorrhea*, n (%):
4 (6) vs 0 vs 4 (8%)

*percents calculated based on total female population
Withdrawals (overall): 27
Withdrawals (adverse events): 10 (MF=1, BDP=5, PL=4)
Authors only listed adverse events if reported by 5% or more patients across treatment groups

Study evaluated the use of MF and BDP as prophylactic agent for SAR

Pollen counts collected from each center

Typos in figure 2 (key) and table IV dose of BDP

Statements in text don’t seem to match text with regard to Fig.2.

MF had less severe symptoms at baseline until the start of
McArthur
1994
UK (Fair)
Single-blind
Parallel group
RCT
Adult pts with a history of at least 2 seasons of SAR
At least 2 defined seasonal allergic rhinitis symptoms (blocked nose, runny nose, itchy nose, or sneezing)
BUD 200 mcg twice daily
BDP AQ 200 mcg twice

Study duration: 3 weeks
Run-in: NR
Wash-out: NR
antazoline-xylometazoline eye dropsINSS: recorded daily by pt: runny nose, blocked nose, sneezing, itchy nose, sore eyes, runny eyes (0-no symptoms to 3-severe symptoms)
INSS: Clinician visit at entry Global assessment of study medication by pt at wk 3
AE reported by pt in diary card
Mean age (years):27
Female gender (%): 51
Race not reported
Mean duration of disease (years):10

Mean symptom score at baseline:
BUD (n=50) vs BDP (n=38)
Blocked nose: 1.6 vs 1.39
Runny nose: 1.96 vs 1.95
Itchy nose: 1.43 vs 1.66
Sneezing: 2.06 vs 2.03
 P=NS for all INSS at baseline
NR/NR/8822/NR/77 for efficacy, 88 for safety,73 for global effectiveness surveyMean symptom score for entire treatment period:
BUD (n=41) vs BDP (n=36)
Blocked nose: 0.39 vs 0.55 (p=NS)
Runny nose: 0.38 vs 0.66 (p= 0.01)
Itchy nose: 0.3 vs 0.60 (p=0.01)
Sneezing: 0.45 vs 0.92 (p<0.001)

For mean total weekly scores during wk 1: BUD=BDP (p=NS)
wk 2: BUD<BDP (p<0.005)
wk 3: BUD<BDP (p<0.005)

Global efficacy at end of treatment
BUD (n=41) vs BDP (n=33)
Noticeably, very or totally effective: 35 (85%) vs 27 (82%)
Reported by ptBUD (n=50) and BDP (n=38)
Adverse event: n (%)
Coughing: 2 (4) vs 0
Headache: 1 (2) vs 0
Nose Bleed: 0 vs 1 (2.6)
Sneezing: 1 (2) vs 0
Peculiar taste: 1 (2) vs 0
Slight wheezing: 2 (4) vs 0
Nausea/sickness: 0 vs 1 (2.6)
Itching: 0 vs 1 (2.6)
Diarrhea: 0 vs 1 (2.6)
Chest tightness: 1(2) vs 0
Itchy nose: 0 vs 1 (2.6)
Sore throat: 1 (2) vs 0
Total: 9 (18) vs 5 (13)
Withdrawals (overall): 22
BUD: 14, (25%) BDP: 8, (21%)
Withdrawals (adverse events): 2 (BUD: sneezing and coughing/wheezing)
No SPT for eligibility

Other withdrawals were due lack of efficacy, unassociated illness, or refusal to cooperate

Withdrawals 22/88 (25%) 11/22 withdrew due to refusal to cooperate.
Langrick
1984
England (Fair)
Single-blind
Parallel group
RCT
Number or Centers: NR
Adult pt with history of moderate to severe hay fever
Agreed to treatment during the same 7-week period (May-July)
Flunisolide 100 mcg twice daily
BDP AQ 200 mcg twice daily

Study duration: 7 weeks
Run-in: NR
Wash-out: NR
NRINSS on a 4 pt scale (0=none to 3=severe) recorded daily by the pt and at admission and weeks 3 and 7 by the clinician (INSS: sneezing, stuffy nose, nose blowing, runny nose, post-nasal drip, epistaxis, eye symptoms)
Overall efficacy: pt and clinician at each visit
Nasal exam at week at admission and wks 3 and 7.
Mean age (years): 66.7
Female gender (%): 37.5
Race not reported
Mean duration of disease (years)=7.3

FN vs BDP
Diagnosis, n (%):
SAR: 32 (94) vs 28 (80)
PAR with seasonal exacerbation: 2 (6) vs 7 (20)
asthma: 8 (23.5) vs 11 (31)
dermatitis: 4 (11.8) vs 5 (14)
Family history of allergies: 12 (35.3) vs 8 (23)
Usual severity:
Moderate: 15 (44) vs 24 (69)
Severe: 19 (56) vs 11 (31)
NR/NR/699/6/60 overall efficacy, 66 at wk 3, 51 at wk 7FN vs BDP
INSS
FN=BDP (p=NS) for all pt reported INSS. Numbers not given, results only in graphical presentation.

Overall efficacy:
FN(n=28)= BDP (n=32)(p=NS) for any of the responses: Physician, Patient n, (%)
Total control: 8 (29) vs 11 (34), 8(29) vs 12 (38)
Good control: 18 (64) vs 15 (47), 18(64) vs 18 (56)
Minor control: 2 (7) vs 6 (19), 2 (7) vs 2 (6)
No Control: No pt reported this outcome
Elicited by investigator via indirect questioningFN vs BDP AQ
Dry throat of moderate severity: 1 (3) vs 0
Tickling sensation inside of nose: 0 vs 1 (3)
Withdrawals (overall): 9
Withdrawals (adverse events):0
No SPT for eligibility

Other withdrawals were due to non-compliance, pregnancy, lack of treatment effect
Ratner
1996
USA (Fair)
Double-blind
Placebo-controlled
Parallel group
Multicenter
RCT
Adult and adolescent pts with a history of SAR of Mountain Cedar allergy for at least 24 months Positive Skin test to Mountain Cedar Total symptom score at baseline/screening within range of 2 to 7.
Stabilized on anti-allergy injection or had not had injection in 1 year proceeding study enrollment
Otherwise healthy
FN (old formulation) 100 mcg twice daily
FN (new formulation) 100 mcg twice daily
Placebo vehicle (new formulation) twice daily
Placebo vehicle (old formulation) twice daily

Study duration: 6 weeks
Run-in period: NR
Wash-out: NR
Chlorpheniramine 4 mg tablets (maximum of 6 tablets per 24 hours)INSS: recorded daily by pt and assessed by the clinician at weekly office visit: Rhinorrhea complex (runny nose, stuffy nose, post-nasal drip), sneezing, nasal itching, and eye symptoms (0-no symptoms to 3- severe symptoms)
TSS: 4 symptom scores (Rhinorrhea complex, sneezing, nasal itching, and eye symptoms) summed
TNSS: The scores for rhinorrhea complex, sneezing, and nasal itching were summed
Mean age (years): 44
Female gender: 134 (62%)
Race not reported
Baseline TNSS: Numbers not reported but text indicates that there were no differences.256/NR/21814/2/136 for efficacy, 216 for safetyFN (new) n=34 vs VH (new) n=35 vs FN (old) n=36 vs VH (old) n=31

INSS (mean score):
Rhinorrea complex: 1.64 vs 2.53 vs 1.38 vs 2.36
FN (new) = FN (old) (p=NS) Each active drug > VH (old) and VH (new) respectively (p=0.0003, 0.0001)
Sneezing: 0.6 vs 1.24 vs 0.64 vs 1.28
FN (new) =FN (old) (p=NS) Each active drug > VH (old) and VH (new) respectively (p<0.0001, <0.0001)
Nasal Itching: 0.54 vs 1.13 vs 0.53 vs 1.08
FN (new) =FN (old) (p=NS) Each active drug > VH (old) and VH (new) respectively (p=0.0004, 0.001)
Eye symptoms: 1.02 vs 1.20 vs 1 vs 1.26
FN (new)=FN (old)=VH (new)=VH (old) (p=NS)
Combined Scores on Peak Pollen days (mean score):
TSS: 3.81 vs 6.11 vs 3.55 vs 5.97
FN (new) = FN (old) (p=NS) Each active drug > VH (old) and VH (new) respectively (p<0.0001, <0.0001)
TNSS: 2.79 vs 4.90 vs 2.54 vs 4.73
FN (new) = FN (old) (p=NS) Each active drug > VH (old) and VH (new) respectively (p<0.0001, <0.0001)
Global Assessment:
Would you use this product again? FN (new) n=34) vs VH (new) n=−32 vs FN (old) n=36 vs VH (old) n=29
Yes: 31 (91) vs 21 (66) vs 32 (89) vs 18 (62)
No: 3 (9) vs 11 (34) vs 4 (11) vs 11 (38)
FN (new) = FN (old) (p=NS) Each active drug > VH (old) and VH (new) respectively (p=0.012, 0.012)
Would you prescribe this medication again? FN (new) n=34) vs VH (new) n=−33 vs FN (old) n=36 vs VH (old) n=29
Yes: 31 (91) vs 20 (61) vs 33 (92) vs 16 (55)
No: 3 (9) vs 13 (39) vs 3 (9) vs 13 (45)
FN (new) = FN (old) (p=NS) Each active drug > VH (old) and VH (new) respectively (p=0.004, <0.001)
Reported by ptRhinitis (34%) and headache (8%) were the most frequently reported drug-related AE, and the most severe.
FN (new) vs VH (new) vs FN (old) vs VH (old)
Burning/stinging, n (%):
none: 44 (80) vs 47 (87) vs 32 (58) vs 21 (60)
Present: 11 (20) vs 7 (13) vs 23 (42) vs 21 (40)
FN (new)>FN(old) (p=0.006)
FN (new)=VH (new) (p=NS)
FN (old) =VH (old) (p=NS)
Sneezing, n (%): 2 (4) vs 3 (6) vs 0 vs 1 (2)
Rhinorrhea, n (%): 4 (7) vs 1 (2) vs 1 (2) vs 0
Dry nose n, (%): 2 (4) vs 0 vs 6 (11) vs 1 (2)
Irritation/tenderness, n (%): 2 (4) vs 3 (6) vs 2 (4) vs 3 (6)
Other, n (%): 1 (2) vs 4 (7) vs 2 (4) vs 3 (6)
Aftertaste: none, n (%): 23 (42) vs 34 (63) vs 34 (62) vs 37 (71)
less than 10 mins, n (%):17 (31) vs 13 (24) vs 15 (27) vs 13 (25)
10 mins or more, n (%):15 (27) vs 7 (13) vs 6 (11) vs 2 (4)
FN (new) > FN (old) (p=0.006)
FN (new) > VH (new) (p=0.005)
(FN (old) = VH (old) (p=NS)
Withdrawals (overall):14 Withdrawals (adverse events): 0
One withdrawal was a death from myocardial infarction pt was on FN (old) and his death was deemed unrelated to the study medication.

68 patients excluded due to low pollen count at one center.
68 pt excluded from one center due to low pollen cnt and inability to demonstrate superior efficacy

All centers in Texas and pts only SPT for Mountain cedar

NS difference for eye symptoms b/n VH and active drug
Welsh
1987
USA (Fair)
Single-Blind (Cromolyn vs FN)
Double-Blind (BDP AQ vs PL)
RCT
Adult and adolescent pt with a history of ragweed SAR for 24 mos. (With symptoms in Aug and Sept.)
No ragweed hyposensitization for at least 2 years
Positive SPT to ragweed
Increase in pre-seasonal level of serum IgE antibody to ragweed
Patent nasal airway without polyps
Not pregnant or lactating
Good general health without illness that would interfere with study
DB: BDP AQ 168 mcg twice daily vs PL twice daily

SB: FN 100 mcg twice daily vs Cromolyn Sodium 4% 1 spray each nostril four times daily

Study duration: 6 weeks

Cromolyn and FN (Nasalide) were commercially available. BDP AQ and PL were delivered in metered-dose, manual pump nasal spray containing microcrystalline cellulose, carboxymethylcellulose sodium, dextrose, benzalkonium chloride, polysorbate 80, and 0.25% (weight/volume) phenylethyl alcohol as vehicle. Beconase AQ consists of a microcrystalline suspension of beclomethasone dipropionate monohydrate in this aqueous medium.
Run-in: Yes × 14 days in which pts recorded symptoms of hay fever/asthma, supplemental antihistamine use, no. of hours spent in air conditioningsupplemental antihistamines, pseudoephedrine (or other equivalents), bronchodilators, theophylline for asthmatic ptsINSS: Pt kept daily record of symptoms beginning July 11 to Sept 18th. Pt diary included record of time spent in air conditioning as well as use of supplemental antihistamines.
Global assessment of efficacy by pts at the final visit
Mean age (years): 28
Female gender: 33 (27.5%)
Race not reported
Hay fever score (mean out of possible max score of 24): 15.4
Asthma score (mean out of possible max score of 12): 1.89
Pre-seasonal IgEAR (mean ng/mL): 218
Current smokers (mean number of pts): 5
Past ragweed hyposensitization (mean number of pts): 9.5
NR/NR/120FN vs CR vs BDP AQ vs PL 22/1/analyzed at baseline: 30 vs 30 vs 29 vs 29
pre-peak: 29 vs 30 vs 28 vs 28
peak: 27 vs 24 vs 27 vs 22
post peak: 23 vs 21 vs 24 vs 22
FN vs BDP AQ
Total hay fever scores:
Baseline (FN n=30 vs BDP AQ n=29): 3.8 vs 2.8
Pre-peak (FN n=29 vs BDP AQ n=28): 2.9 vs 2.7
Peak (FN n=27 vs BDP AQ n=27): 4.3 vs 5.5
Post-peak (FN n=23 vs BDP AQ n=24): 3.1 vs 2.8
FN=BDP AQ (p=ns)
Eye symptoms:
FN vs BDP AQ vs PL
8.02 vs 12.63 vs 15.93 (FN=BDP AQ and FN>PL (p<0.05)
Mean scores were augmented for use of antihistamines (chlorpheniramine 4 mg and pseudoephedrine 30 mg added a score of 1 and longer-acting medications or larger doses added a score of 2 or 3 accordingly.)
Global assessment of efficacy: FN=BDP AQ for substantial reduction in hay fever symptoms when compared with previous years.
Not reportedFN vs CR vs BDP AQ vs PL
Nasal burning: 10 (33%) vs. 0 vs 0 vs 0
Sore nose: 1 (3.3) vs 1 (3.3) BDP AQ 1 (3.3) vs 0
Headache: 0 vs 5 (16.7) vs 5 (16.7) vs 1 (3.3)
Nosebleeds: 0 vs 1 (3.3) vs 0 vs 1 (3.3)
Bad taste: 0 vs 1 (3.3) vs 1 (3.3) vs 0
Canker sores: 1 (3.3) vs 0 vs 0 vs 1 (3.3)
Dry nose: 1 (3.3) vs 0 vs 0 vs 2 (6.7)
Upper respiratory tract infections
“common cold” during post-peak period: 6 (20) vs 7 (23) vs 15 (50) vs 9 (30)
Withdrawals (overall): 22
Withdrawals (adverse events): 2 (burning and stinging FN)
FN is Nasalide

AE 50% common cold with BDP AQ

Pollen count included
Stern
1997
UK, Denmark (Fair)
Placebo-controlled
Double-blind (BUD vs PL)
Single-blind (BUD vs FP)
Multicenter
RCT
Adult pts with a history of at least 24 mos. Of SAR provoked by grass pollen
Positive SPT or RAST to grass pollen
BUD AQ 64 mcg in one bottle and placebo in the other bottle (one spray in each nostril from each bottle daily=128 mcg once daily)

BUD AQ 64 mcg in both bottles (one spray in each nostril from each bottle daily=256 mcg once daily)

FP 50 mcg in both bottles (one spray in each nostril from each bottle once daily=200 mcg once daily)

Study duration: 4–6 weeks
Run-in: NR
Wash-out: NR
terfenadine 60 mg tablets (60–120 mg daily) disodium cromoglycate (20 mg/mL) 1–8 drops to be instilled into each eye dailyINSS: daily diary records kept by pts with a 4 pt scale (0=none, 3=severe)
Blocked nose, runny nose, sneezing, and eye symptoms
Combined NSS: Addition of INSS scores
Global assessment of efficacy: At visit 5 using a 5-pt scale
Safety: Standard questions from investigators at each visit
Mean age not given
Age range: 18–72
Female gender: 266 (44%)
Caucasian, n (%) 595 (99)
Asian, n (%): 2 (0.33)
Black, n (%): 4 (0.66)
Other, n (%): 1 (0.1)
Mean disease duration (years): 18.85

Baseline Combined nasal symptoms:
PL vs BUD 128 vs BUD
256 vs FP
UK/DK: 3.25/1.93 vs 3.24/2.38 vs 2.95/2.25 vs 3.13/2.21
NR/NR/63584/NR/583 “per protocol analysis” 602 “all pts treated” analysis

(out of 602 pt 19 were considered protocol violators and the data was analyzed with and without data from those individuals)
INSS
PL (n=59) vs BUD 128 (n=181)* vs BUD 256 (n=182) vs FP (n=178)
Blocked nose: +0.26 vs −0.35 vs −0.33 vs −0.28
Runny nose: +0.46 vs −0.47 vs −0.46 vs −0.44
Sneezing: +0.31 vs −0.48 vs −0.54 vs −0.45 BUD 256 > FP (p=0.04)
Eye symptoms: +0.25 vs −0.02 vs −0.06 vs 0
TNSS (combined nasal symptoms score):
+1.02 vs −1.29 vs −1.31 vs −1.18
FP=BUD 128/256 > PL (p<0.001)

On days in which pollen cnt > 10 grains/m^3
BUD 256> BUD 128=FP for TNSS (p=0.04), runny nose (p=0.04) and sneezing (p=0.02)

*n=180 for blocked nose and combined nasal symptoms

Global assessment:
PL (n=51) vs BUD 128 (n=177) vs BUD 256 (n=173) vs FP (n=171)
Total control of symptoms
31% vs 85% vs 88% vs 82%
Elicited by investigator and reported by pt33% of individuals reported adverse events during the study. Most frequently reported adverse events were aggravation of asthma (not significantly different between the three treatment groups), followed by flu-like disorder, and headache.Withdrawals (overall): 84
33 at baseline and 51 during the treatment period
Withdrawals (adverse events): 6 (PL=1, BUD 128=1, BUD 256=1, FP=3)
Greenbaum
1988
Canada (Fair)
Double-blind
Cross-over
Multicenter
RCT
Adult and adolescent pts with a 12 month history of SAR associated with tree and/or grass pollen
Positive SPT to tree and/or grass pollen
Sufficiently severe rhinitis to require therapy with NCS (okay if pt had FL (old) in the past)
FN (new) 100 mcg twice daily × 2 weeks
FN(old) 100 mcg twice daily × 2 weeks
Then cross-over to whichever one pt hadn’t used for another 2 weeks
Run-in: NR
Wash-out: NR
Chlorpheniramine 4mg tablets
If chlorpheniramine was ineffective and/or if side effects occurred with the medication, other marketed antihistamines or decongestants were allowed to be taken concomitantly
Pt recorded SE profile daily and reported at 2 and 4 wk visits
Pt and investigator subjective evaluation of control of pt’s nasal symptoms at 2 and 4 wk visits
Pt global assessment of efficacy wk 4
Demographics not reported24/122 pts had secondary diagnosis of asthma, allergic conjunctivitis, atopic dermatitis
Two times as many patients had SAR>5 yrs compared to those who had rhinitis for <5 yrs (numbers not reported) 120/122 pts described their nasal symptoms during the past pollen season as either moderate or severe
NR/NR/12218/10/FN(new) (n=110), FN (old) (n=112) for nasal burning/stinging n=110 for throat irritation
Overall comparisons of medications (efficacy/safety) (n=107)
Overall comparison of medications:
(n=107)
Nasal burning and throat irritation: FN (new)<FN (old) (p<0.001 and p=0.009) (less severe SE with New formulation)
Overall efficacy:
No difference reported between formulations: 58 (54%)
Pts who did not perceive a difference in control of nasal symptoms between the two medications: 21 pts preferred FN (old) and 28 pts preferred FN (new)
Overall acceptability: 73 pts preferred FN (new), 22 preferred FN (old) (p<0.001)

Relief of nasal symptoms reported at the end of each treatment period (2 wks)
Pt reported:FN (new)> FN (old) (p=0.43)
Investigator evaluation: FN (new) =FN (old) (p=0.399)
Antihistamine use (mean number of days used):
FN (new)=4.37
FN (old)= 4.39
Reported by ptFN (old) (n=112) vs FN (new) (n=110)
Nasal burning/stinging:
None: 13 (11) vs 52 (47)
Just noticeable: 12 (31) vs 36 (33)
Mild: 38 (34) vs 15 (14)
Moderate: 25 (22) vs 7 (6%)
Severe: 15 (13) vs 0
Throat irritation (n=110 for both groups):
None: 59 (54) vs 65 (59)
Just noticeable: 24 (22) vs 26 (24)
Mild: 15 (14) vs 11 (10)
Moderate: 12 (11) vs 6 (5)
Severe: 0 vs 2 (2)
Duration of nasal stinging/burning
(Median) (n=97):
FN (new): 0.1 min
FN (old): 1 min
FN(new)<FN (old) (p<0.001)
Duration of throat irritation (median) (n=57)
FN (new): 1 min
FN (old): 0.5 min
FN(new)=FN(old) (p=ns)
80 pts reported a difference on duration of nasal burning/stinging between the two products FL (new)<FL (old) (p<0.001)
Nausea: < 5% of pts
Headache: < 12% of pts
Withdrawals (overall): 18
Withdrawals (adverse events): 8 (5 pt in FN (old), 3 pts FN (new))
Pts didn’t record symptom control daily only at the end of each 2 wk treatment period.
Hebert
1996
Canada and Europe (Fair)
Double-blind
Parallel group
Double-dummy
Placebo-controlled
Multicenter
RCT
Adult pts with history of moderate to severe SAR for at least 24 months
Positive skin test to at least one aeroallergen (i.e. tree and/or grass)
TSS (nasal and non-nasal symptoms) of at least 6 and INSS scores of at least 2 (moderate severity) for nasal congestion plus one other nasal symptom
MF 100 mcg once daily + PL
BDP AQ twice daily and PL
MF in the evening

MF 200 mcg once daily
+ PL BDP AQ twice daily and PL MF in the evening

BDP AQ 200 mcg twice daily
+ PL MF twice daily

PL BDP AQ and PL MF twice daily

(Each pt received a total of 16 sprays per day--double dummy)

Treatment duration: 4 weeks
Run-in: No
Wash-out: No
Loratadine 10 mg tablets (maximum permitted one tablet per day)Efficacy and safety assessed at 4,8, 15, 22, and 29 days
Rating scale (0=no symptoms to 3=severe symptoms)
INSS: pt recorded score in diary twice daily, physician evaluated/scored at each visit
TNSS: combined total score of 4 nasal symptoms
TSS: combined total score of nasal and non-nasal symptoms
Global evaluation of overall efficacy (5-point scale) at each visit by pt and physician(referred to pt diary cards to determine score)
Mean age (years): 32
Female gender (%): 8.5
Race not reported
MF 100 mcg (n=126) vs MF 200 mcg (n=125) vs BDP AQ (n=125) vs PL (n=121)
Disease severity (%)
Moderate: 72 vs 83 vs 80 vs 77
Severity: 28 vs 17 vs 20 vs 23

Mean TNNS: 8.1 vs 8.1 vs 7.9 vs 8
Mean TSS: 12.7 vs 12.2 vs 12.4 vs 12.8
NR/NR/50167/NR/497 for safety and 477 for efficacyMF 100 mcg vs MF 200 mcg vs BDP AQ vs PL
physician evaluated INSS (mean percentage change from baseline:)
Rhinorrhea:
Day 4: 32 vs 44 vs 47 vs 30
Day 8: 51 vs 55 vs 58 vs 26
End point: 71 vs 75 vs 73 vs 49
MF 100=MF 200=BDP AQ > PL (for all days except day 4 in which baseline percentage change for MF 100 was not statistically significant when compared with PL)
Nasal stuffiness/congestion:
Day 4: 27 vs 36 vs 43 vs 27
Day 8: 41 vs 35 vs 45 vs 28
End point: 62 vs 67 vs 61 vs 45
MF 100=MF 200=BDP AQ> PL (p<0.01 or p<0.05) except for MF 100 and MF 200 on Day 4 were not statistically significant when compared to PL
Nasal itching:
Day 4: 35 vs 38 vs 41 vs 23
Day 8: 56 vs 59 vs 58 vs 31
End point: 76 vs 77 vs 74 vs 52
All treatments>PL except MF 100 and 200 at day 4
Sneezing:
Day 4: 45 vs 49 vs 52 vs 20
Day 8: 63 vs 64 vs 71 vs 32
End point: 80 vs 77 vs 80 vs 58
All treatments>PL (p<0.01) at all time points
TNSS physician evaluated (percentage change from baseline) (estimated from graph:)
Day 4:35 vs 43 vs 45 vs 29
Day 8: 53 vs 59 vs 59 vs 34
Day 15: 60 vs 73 vs 64 vs 43
Day 22: 68 vs 85 vs 66 vs 50
Day 29: 78 vs 85 vs 75 vs 59
The only value not statistically superior to placebo was MF 100 at day 4.
Reported by pt and observed by physiciann=497
MF 100 vs MF 200 vs BDP AQ vs PL
Any adverse event n, (%): 32 (25) vs 32 (26) vs 38 (30) vs 34 (28)
Headache: 10 (8) vs 12 (10) vs 10 (8) vs 8 (7)
Epistaxis 4 (3) vs 8 (6) vs 6 (5) vs 4 (3)
Nasal burning: 8 (6) vs 4 (3) vs 5 (4) vs 6 (5)
Pharyngitis: 4 (3) vs 3 (2) vs 5 (4) vs 5 (4)
Sneezing: 3 (2) vs 1 (<1) vs 5 (4) vs 6 (5)

AE reported by at least 4% of pts in any treatment group
Withdrawal (overall): 67
Withdrawals (adverse events): 15
(MF 100=4 (3%), MF 200=5 (4%), BDP=0, PL=6 (5%))
0 pts withdrew from BDP AQ grp due to AE
Women excluded if of child- bearing age
Sprays were given directly after one another (double dummy--16 sprays)
MF 100 - diluted by spray of PL would explain day 4 inferiority to MF 200.
Lumry
2003
USA (Fair)
Single-blind
parallel group
Multicenter
RCT
Adult pts with a history of Fall ragweed pollen season during the preceding 24 mos. requiring medication use and were considered candidates for treatment with NCS Positive SPT for ragweed allergen 4 day baseline monitoring of nasal symptoms (discharge, stuffiness, itching, and sneezing) had to be at least 24 out of 48 pointsTAA AQ 220 mcg once daily

BDP AQ 168 mcg twice daily

Treatment duration: 3 weeks
Run-in: No
Wash-out: Yes no rhinitis medication was allowed 6 days preceding the baseline visit until the end of the study.
Ophthalmic vasoconstrictor/deconge stant to relieve eye symptomsEfficacy: pt diary card every evening (rating scale 0=none to 3 = severe) evaluating nasal discharge, stuffiness, itching, sneezing, and total eye symptoms (itchiness, tearing, and redness)
A nasal index scorecombined score of nasal discharge, stuffiness, and sneezing (0–9)

Global evaluation of efficacy by pt and physician at final clinic visit. Pt reported SAR (daily comfort scores) every morning
RQLQ-prior to treatment, wk 1, 2, and 3 (final visit)
Mean age (years): 37
Female gender (%): 51
White (%): 86.5
Other (%): 13.5
TAA AQ (n=75) vs BDP (n=77)
Baseline scores:
Nasal stuffiness: 2.5 vs 2.4
Nasal discharge: 2.4 vs 2.4
Sneezing: 2 vs 2.3
Nasal itching: 2.1 vs 2.2
Nasal index: 6.8 vs 7.1
Total eye symptoms: 2 vs 2
NR/NR/1526/1/147 efficacy at wk 3, 152 for safety, 114 for QOLTAA AQ (n=74 wk 1, 2 and overall, n=72 wk 3) vs BDP AQ (n=77 wk 1, 2 and overall, n=76 wk 2)Reported by ptTAA AQ (n=75) vs BDP AQ (n=77)
Number of pts reporting adverse event, n (%): 26 (35) vs 27 (35)
Number of adverse events: 39 vs 34
Body as a whole, n (%) 16 (21) vs 10 (13)
Respiratory system, n (%):11 (15) vs 8(10)
Skin and appendages, n (%): 1 (1) vs 7(9)
Digestive system, n (%): 4 (5) vs 4 (5)
Nervous system, n (%): 3 (4) vs 0
Withdrawals (overall): 6
Withdrawals (adverse events): 0
Nasal stuffiness:Nasal itching:
WK 1: −0.81 vs −0.84WK 1: −0.75 vs −0.90
WK 2: −1.05 vs −0.94WK 2: −0.97 vs −1.01
WK 3: −1.21 vs −1.09WK −1.21 vs −1.09
Overall: −1.01 vs −0.97Overall: −1.01 vs −0.97
Nasal discharge:Nasal Index:
WK 1: −0.77 vs −0.92WK 1: −2.23 vs −2.76
WK 2: −1.04 vs −1.14WK 2: −3.01 vs −3.31
WK 3: −1.26 vs −1.27WK 3: −3.63 vs −3.70
Overall: −1.01 vs −1.11Overall: −2.92 vs −3.26
Sneezing:Total eye symptoms:
WK 1: −0.65 vs −1.01WK 1: −0.56 vs −0.53
WK 2: −0.92 vs −1.23WK 2: −0.70 vs −0.56
WK 3: −1.15 vs −1.35WK 3: −0.86 vs −0.72
Overall: −0.90 vs −1.18Overall: −0.70 vs −0.61
Global assessment of efficacy:
(numbers not reported)
Overall 82.4% of pts and 78.4% of physicians felt that symptoms of rhinitis had greatly or somewhat improved following following treatment with TAA AQ compared with 89.6% of pts and 87% of physicians following treatment with BDP AQ

TAA AQ (n=59) vs BDP (n=55)
RQLQ:
Overall change from baseline: −1.71 vs −1.79
No significant differences between treatments in QOL variables (sleep index, non-hay fever symptoms, practical problems, nasal symptoms, eye symptoms, and activities).
SAR TAA AQ was statistically significantly preferred (p<0.05) by pt when compared to BDP AQ for both medication odor and taste.
Small
1997
Canada (Fair)
Single-blind
Parallel group
Multicenter
RCT
Adult and adolescent pts with a history of Spring SAR for at least 24 months
A positive SPT to one or more spring pollen allergens
At least 2 or more nasal symptoms including rhinorrhea, congestion, sneezing, and itching upon screening Rhinitis Index score (combined score of the aforementioned symptoms) of at least 24 out of 48 on the 4 highest score of the last 5 days of the drug-free baseline period. Any pt who did not reach the limit of 24 points within 14 days was discontinued from the study.
TAA (aerosol) 220 mcg once daily

FP 200 mcg once daily

Study duration: 3 weeks
Run-in: No
Wash-out: Yes 5–14 days before randomization.
All nonsteroidal medications required by the pt to manage acute or chronic illness unrelated to rhinitis were permitted exception medications that would interfere with the assessment of study drugs.Pt recorded nasal symptoms (0=none, 3=severe) daily every morning before randomization and throughout the 3 week period Pt rated acceptance on 10 different aspects using a 5 pt scale every day Global assessment of efficacy from Pt and Investigator at wk 1 and 3 (0=no effect on nasal symptoms, 3=AR symptoms and overall discomfort greatly reduced)Mean age (years): 28
Female gender (%): 52
Race not reported
TAA (n=117) vs FP (n=116)
Mean duration of allergy (mo): 162
TAA (n=111) vs FP (n=112)
RIS: 7.66 vs 7.9
Congestion: 2.16 vs 2.14
Rhinorrhea: 1.88 vs 2
Sneezing: 1.81 vs 1.78
Nasal itch:1.8 vs 1.76
NR/NR/23310/0/233 for safety and 223 for efficacyTAA (n=111) vs FP (n=112)
Mean change from baseline, n (%)
Congestion: −1.06 (−49) vs −1.19 (−56) (p=0.58)
Rhinorrhea: −1.1 (−59) vs −1.24 (−62) (p=0.08)
Sneezing: −1.05 (−58) vs −1.09 (−61) (p=0.51)
Nasal itch: −0.99 (−55) vs −1.07 (−61) (p=0.64)
RIS: −4.2 (−55) vs −4.6 (−60)
Global efficacy: No statistically significant differences between the two treatments for both pt and physician assessments (numbers not reported)
Total daily scores for pt acceptance (0= not bothersome, 4=bothersome)
Medication runs down throat: 0.7 vs 6.77 (p<0.01)
Medication runs out of nose: 1.19 vs 6.26 (p<0.01)
Medication tastes bad 2.84 vs 5.33 (p=NS)
Medication causes sore throat: 1.36 vs 0.77 (p=NS)
Medication causes bleeding nose: 0.37 vs 0.14 (p=NS)
Medication causes dry nostril: 4.88 vs 2.15 (p<0.01)
Medication causes bloody mucus: 0.86 vs 0.65 (p=NS)
Medication causes stuff-up nose: 10.67 vs 5.31 (p<0.01)
Reported by ptTAA (n=117) vs FP (n=116)
Overall AE, no pts (%): 31 (26) vs 25 (22)
Only reported AE reported by more than 2% of pts
Headache, %: 5 vs 9
Epistaxis, %: 3 vs 4
Withdrawals (overall): 10
Withdrawals (adverse events): 1 (TAA group for severe headache)
TAA on market as aerosol using HFA propellant (Nasacort HFA) unclear how to interpret AE for this CFC formulation

Pt acceptance scores included due to likeness with AE (eg. Dry nose, sore throat, etc.) Hard to interpret clinically in single blind study.
LaForce
1994
USA (Fair-good)
Double-blind
Placebo-controlled
Parallel group
Multicenter
RCT
Adult and adolescent patients (12–67 years old) with history of SAR for 2 spring seasons
A positive SPT to at least one spring allergen present in geographical area
Moderate to severe SAR symptoms
TNSS of 200/400 on 4 out of 7 days of Run-in
FP 100 mcg twice daily
FP 200 mcg once daily
BDP AQ 168 mcg twice daily
PL twice daily

Study duration: 4 weeks
Run-in: yes x 4–14 days
Wash-out: No
Chlorpheniramine 4 mg tabletsPt recorded nasal symptoms (0=none, 3=severe) daily every morning (nasal obstruction, rhinorrhea, sneezing and itching) and through-out the entire day x 4 wks Clinician rated nasal symptom severity at weekly clinic visits
Global assessment by clinician at end of trial
Monitoring of HPA axis function pre-treatment and on the final study day.
Mean age (years): 24
Female gender (%): 29
Race not reported

Adolescents (n=110) 10% female
Adults (n=128) 45% female (see exclusion criteria)
PL (n=58) vs FP 100 (n=64) vs FP 200 (n=55) vs BDP AQ (n=61)
asthma: 22 (38) vs 28(44) vs 29(53) vs 21(34)
perennial rhinitis: 41(71) vs 46(72) vs 46(84) vs 46(75)
+ SPT to grass, n:48 vs 50 vs 44 vs 55
+ SPT to tree, n: 40 vs 36 vs 36 vs 30
NR/NR/2383/0/Number analyzed not totally clear but was either 238 or 235Patient-rated nasal scores
FP 100 mcg > BDP AQ in reducing nasal obstruction and rhinorrhea throughout the 4 weeks(p<0.05)
Improvement in obstruction, rhinorrhea, sneezing, and itching throughout the trial with FP vs PL
Improvement in sneezing and nasal itching throughout the trial with BDP AQ vs PL
Rhinorrhea and obstruction (and obstruction upon awakening) were reduced more quickly when compared to BDP and PL.
Within the first 12 hours FP 100 mcg had less nasal obstruction than BDP
Overall patient-rated nasal symptoms for the entire trial: FP 100 mcg >BDP AQ
Overall patient-rated nasal symtpoms for the second and third weeks: FP 200 mcg>BDP (p<0.05)
Clinician-rated mean total nasal symptoms scores:
Week 1: FP 100 and FP 200 (−0.48) vs BDP AQ (−0.35)
Final: decrease with acitve treatements ranged from (−0.55 to −0.67)
improvements were significantly greater for the FP 100 mcg group compared with PL (p<0.01) For FP 200 mcg
improvements reached significance vs PL only on days 8 and 15.
For BDP significantly greater improvements vs PL occured on days 15, 22, and 29 (p<0.05)
Global assessment of efficacy:
FP 100 and 200> PL and BDP >PL (p<or equal to 0.02)
Unclear who reported but authors state all events were reported and followed to resolutionPL (n=58) vs FP 100 (n=64) vs FP 200 (n=55) vs BDP AQ (n=61)
Any adverse event, n (%): 11(19) vs 8(13) vs 7(13) vs 13(21)
Sore throat: 1(2) vs 2 (3) vs 0 vs 2(3)
Nasal burning: 2(3) vs 1(2) vs 1(2) vs 4(7)
Nosebleed: 2 (3) vs 0 vs 1(2) vs 3(5)
Headache: 2(3) vs 3(5) vs 2(4) vs 3(5)

HPA monitoring: FP 100 and 200 and BDP: no differences in free cortisol
Statistically significant differences in urinary 17-ketogenic steroid levels were observed with FP 100 mcg bid group (9.6 to 11.7 mg) and decreases in the BDP AQ and PL groups (9 to 7.3 mg and 9.4 to 8.6, respectively)
For FP 200 mcg--no change (8.5 mg)
Authors state not clinically significant and mean values are within normal range.
Withdrawals (overall): 3
Withdrawals (adverse events): 1 (BDP AQ pt with exacerbation of asthma)
110 adults and 128 adolescents

AE reported only if more than 3 patients across groups had experienced

10% female in adolescent group

Nasal sx recorded throughout entire day

~70% of pts also had perennial rhinitis

Raw data in the form of graphs with Y-axis scale such that lines are very close together and meaningful data would be difficult to estimate.
Bronsky
1987
USA (Fair)
Single-blind
Multicenter
RCT
Adult and adolescent pts
Autumn AR x 24 mos (including seasonal exacerbations of perennial rhinitis
+ SPT to one or more allergens indigenous to the area and season Showed signs of rhinitis
> or equal to 8 on EENT evaluation
BDP AQ 84 mcg twice daily
BDP AQ 168 mcg twice daily
FN (orig. formulation) 100 mcg twice daily
FN (orig. formulation) 100 mcg three times daily

Study duration: 4 weeks
Run-in:No
Wash-out: No
Chlorpheniramine 4 mg tabletsPt recorded nasal symptoms daily (stuffy or runny nose, sneezing or itching, post-nasal drip, puffy itchy or red eyes and sore throat and chlorpheniramine use.)
F/U visit (visit 2) 12–16 days after initial visit: EENT repeated by clinician, diary cards collected, AE reported
F/U visit (final visit) 26–30 days
Mean age (years): 29
Female gender (%): 52
White n, (%):91
Black n, (%):6
Other n, (%):3
BDP 168 vs BDP 336 vs FN 200 vs FN 300
Mean baseline EENT score: 14.4 vs 15.3 vs 14.2 vs 14
NR/NR/161NR/NR/Number analyzed not clear because only number of appts totally missed or off-schedule were reported not number of patientsBDP 168 vs BDP 336 vs FN 200 vs FN 300
EENT evaluation scores (0=none, 3=severe)
Changes in mean score after 4 weeks
Rhinitis (physical symptoms)
turbinate swelling: −0.8 vs −1 vs −0.8 vs −0.8
nasal discharge: −0.8 vs −0.1 vs −0.8 vs −0.8
pharyngeal discharge: −0.6 vs −0.6 vs −0.6 vs −0.5
discoloration: −0.9 vs −0.8 vs −0.7 vs −0.7
Rhinitis-symptoms
sneezing/itching: −1.6* vs −1.4 vs −1.2 vs −1.1*
nasal congestion: −1.5 vs −1.4 vs −1.1 vs −1.3
Postnasal drip/snoring: −1 vs −0.7 vs −0.9 vs −0.7
Runny nose/sniffling: −1.3 vs −1.4 vs −1 vs −0.9
*p<0.05; BDP 168 vs FN 200 mcg
Pt reportedBDP 168 vs BDP 336 vs FN 200 vs FN 300
Nasal stinging burning n, (%): 4(10) vs 4(10) vs 12(30) vs 13(33)
Headache n, (%): 5(12) vs 4(10) vs 4(10) vs 4(10)
Epistaxis n, (%): 3(7) vs 3(8) vs 3(8) vs 3(8)
Post-nasal drip n, (%): 1(2) vs 4(10) vs 1(3) vs 3(8)
Sore throat n, (%): 0 vs 2(5) vs 3(8) vs 2(5)
Nausea n, (%): 0 vs 0 vs 3(8) vs 2(5)
Nasal congestion n, (%): 1(2) vs 2(5) vs 1(3) vs 0
Others, n (%): 9 (22) vs 13(33) vs 11(28) vs 6(13)
Withdrawals (overall): NR
Withdrawal (due to adverse events): NR
Unclear when pts recorded nasal symptoms

No report of attrition

Compliance was also recorded in diaries and it is unclear who reviewed the diaries on treatment was three times daily blinding could be broken depending on who is reviewing the diary.
Meltzer
1999
USA
Double-blind
Parallel group
Multicenter
RCT
Pediatric pts (6 to 11 years of age)
Positive SPT or intradermal testing
Positive history of SAR (length unspecified)
TNS > or equal to 6 out of possible 12 and nasal congestion > or equal to 2 out of 3 at screening and baseline
MF 25 mcg daily
MF 100 mcg daily
MF 200 mcg daily
BDP 84 mcg twice daily Placebo

Duration: 4 wks
Run-in: yes (2–7 days)
Wash-out: yes (lengths varied depending on medication)
Chlorpheniramine syrupPt and parents/guardians recorded nasal and non-nasal symptoms in diary twice daily (5 point-scale 1= complete relief to 5=treatment failure)
Scores were averaged over day 1 to 15 and 16 to 29
MD completed a physical evaluation days 4, 8, 15 and 29 and scored nasal and non-nasal symptoms over the past 24 hours and the overall condition of SAR since previous visit (response to treatment compared to baseline)
Mean age (years): 9
Female gender (%):38
White n, (%): 84
Black n, (%): 7
Other n, (%): 9
~70% of pts had PAR
~40% of pts had asthma
SAR 5 to 6 years “most patients”
NR/NR/67933/0/679MF 25 vs MF 100 vs MF 200 vs BDP
TNSS (MD evaluated-change from baseline estimated from graph):
Day 4: 2.2 vs 2 vs 2 vs 2.4
Day 8: 2.8 for all
Day 15: 2.9 vs 3 vs 3.1 vs 3.5
Day 29: 3 vs 3.7 vs 3.8 vs 3.7
MF 25=MF 100=MF 200=BDP > PL (p </= 0.2) for days 1–15
MF 100=MF 200 >MF 25 and PL days 15–29
TNSS (pt evaluated-change from baseline estimated from graph)
Days 115: 1.5 vs 1.9 vs 1.8 vs 1.9
Days 1629: 2 vs 2.7 vs 2.6 vs 2.5
MF 100 and 200=BDP > MF 25=PL
MF 200 did not offer any benefit over MF 100 at any time point
TSS (nasal and non-nasal-MD evaluated-mean changed from baseline estimated from graph):
Day 4: 2.7 vs 3 vs 2.7 vs 3.1
Day 8: 3.7 vs 4.2 vs 3.7 vs 4.2
Day 15: 3.8 vs 4.4 vs 4.1 vs 4.5
Day 29: 4.8 vs 5.5 vs 5 vs 5.2
Endpoint: 4.1 vs 5.5 vs 5 vs 5
MF 100 = BDP > PL on days 4 and 8
MF 100 > MF 25 on Day 29.
Pt or parent/guardian reported in diaryMF 25 (n=137) vs MF 100 (n=135) vs MF 200 (n=133) vs BDP (n=138) vs PL (n=136)
Any adverse event, n (%): 24 (18) vs 27(20) vs 19(14) vs 21(15) vs 31(23)
Headache, n (%): 4(3) vs 4 (3) vs 9 (7) vs 8(6) vs 8(6)
Epistaxis, n (%): 10 (7) vs 8 (6) vs 3 (2) vs 6 (4) vs 9 (7)
Pharyngitis, n (%): 2 (1) vs 1 (1) vs 2 (2) vs 4(3) vs 3 (2)
Sneezing, n (%): 6(4) vs 4(3) vs 0 vs 1(1) vs 6(4)
Coughing, n (%): 1 (1) vs 2 (1) vs 2 (2) vs 2 (1) vs 1 (1)
Nasal irritation, n (%): 0 vs 3 (2) vs 0 vs 0 vs 0
Withdrawals (overall): 33 (5%)
Withdrawals (due to adverse events): 14 (2%)
Female pts were pre-menarchal

Abbreviations: (TAA AQ)= triamcinolone acetate aqueous (FP) = fluticasone propionate (RQLQ) = rhinoconjunctivitis Quality of Life Questionnaire (SAQ) = sensory attributes questionnaire (TNSS) = total nasal symptom score (INSS) = Individual nasal symptom score (NR)= not reported (SAR)= seasonal allergic rhinitis (HRQL) = Health- Related Quality of Life (BUD)=Budesonide (PL0=placebo (FN)=flunisolide, (BDP AQ)=beclomethasone dipropionate aqueous (MF) = mometasone furoate

From: Evidence Tables

Cover of Drug Class Review: Nasal Corticosteroids
Drug Class Review: Nasal Corticosteroids: Final Report Update 1 [Internet].
Selover D, Dana T, Smith C, et al.
Portland (OR): Oregon Health & Science University; 2008 Jun.
Copyright © 2008, Oregon Health & Science University, Portland, Oregon.

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