Table 24aDescription of trials in the therapy review: Tachyphylaxis to LABA

Author Year
Country
Source
Publication status
Funding
Trial design
Randomized [R]
Analyzed [A]
Withdrawals [W]
Treatment Groups: drug; dose; delivery device; time pre-ECTECT: type; duration; predicted HR; temp; RH; %
Study days; challenges/day [N]; time between challenges
Withheld asthma med; class; time
Definition EIB/EIA (% fall FEV1)
Outcomes:
Primary
Secondary
Adverse events
Formoterol vs. placebo
Garcia54 2001
Spain
Clinic
Journal article
Fondo de Investigación Sanitaria
Parallel
F: 10; P: 9
F: 10; P: 9
0
F: 12 μg/bid x 28 d; MDI; no pre-Tx and 30 min
P: 2 puffs bid x 28 d; MDI; 30 min
Bicycle ergometer; 6 min; 85%
21.2oC; 48.30% RH
4 [1 screen then days 1, 14, 28]
2; 3 hr
SABA, NCS, SCG, calcium antagonists, antihistamines, ipratropium bromide and study medication x 12 hr
≥15%
Primary: max % fall FEV 1; change bronchoprotection index
Secondary: complete protection; clinical protection
FEV1 measured at 1, 3, 5, 8, 10, 15, 20, 30, 40, 60 min post ECT
NR
Salmeterol vs. placebo
Nelson55 1998
U.S.
Clinic
Journal article
National Heart, Lung, and Blood Institute; NIH; Glaxo Wellcome Corp.
Crossover
20
20
0
Salm: 50 μg bid x 30 d; MDI; 30 and 9.5 hr
P: 2 puffs bid x 30 d; MDI; 30 min and 9.5 hr
Bicycle ergometer; 4 min; 740±246 kilopond meters/min
cold air (−8.5±1.3oC); NR
7 [1 screen then 1, 14 and 29 d of each study mo]
2; 9 hr
ICS, methylxanthines, SABA, NS x 12 hr; methylxanthines x 24 hr
≥15%
Primary: mean % fall FEV1 10 min post-ECT; duration of action
Secondary: FEV1 L; complete protection
FEV1 measured at 10 min post ECT
NR
Ramage57 1994
United Kingdom
Clinic
Journal article
NR
Crossover
12
12
0
Salm: 50 μg bid x 4 wk; MDI; 6 and 12 hr
P: 1 puff bid x 4 wk; MDI; 6 and 12 hr
Treadmill; 6 min; 85%
dry air; NR
5 [1 screen, and first and last day of each Tx period]
2; 6 hr
SABA, SCG, methylxanthines x 8 hr; 24 hr and 24 hr
≥20%
Primary: max % fall FEV 1; difference between 1 and 4 wk dosing
Secondary: Pre-exercise FEV1 L; complete protection; clinical protection
FEV1 measured at 5, 10, 20, 30, 60 min post ECT
NR
Selvaggio58 2003
Italy
NR
Abstract
NR
Crossover
9
9
0
Salm: 50 μg every other d x 21 d; diskus; 9 hr
P: 1 puff every other d x 21 d; diskus; 9 hr
NR
4 [day 1 and 21 of each Tx period]; 1
20 d
NR
NR
Primary: max % fall FEV1
Secondary: bronchoprotective effect
NR
Simons59 1997
Canada
Clinic
Journal article
Glaxo Wellcome Inc.
Crossover
16
14
2
Salm: 50 μg/d x 28 d; MDI with nebulizer; chronolog; 1 and 9 hr
P: 2 puffs/d x 28 d; MDI with nebulizer chronolog; 1 and 9 hr
Treadmill; 8 min; 90%
21.7–22.4oC; 46.5–53.9% RH
4; 2
8 hr
SABA, pseudoephedrine x 8 hr
NR
Primary: max % fall FEV1; duration of action
Secondary: PEF L/min
P: exacerbation=1, chest tightness=1. Salm: headache=3
Salmeterol vs. montelukast
Edelman53 2000
U.S. [17 sites]
Clinic
Journal article
Merck
Parallel
Salm: 94; M: 97
Salm: 86; M: 91
Salm: 8; M: 6
Salm: 50 μg/bid x 8 wk; MDI; 9 hr
M:10 mg/d x 8 wk; tablet; 21 hr
Treadmill; 6 min; 80–90%
room temp; dry air
3; 1
day 1–3, wk 4, wk 8
SABA x 6 hr
≥20%
Primary: max % fall FEV1
Secondary: change in max % fall; FEV1 L; complete protection
FEV1 measured at 0, 5, 10, 15, 30, 45, 60 min post ECT
Salm vs. M: asthma 7% vs. 3%; headache 6% vs. 5%; URTI 10% vs. 14%; total AE Salm vs. M: 40% vs. 41%
Villaran60 1999
25 centers in 12 countries
Clinic
Journal article
Merck
Parallel
R=Salm: 95; M: 102;
A=Salm: 88; M: 100
W=Salm: 7; M: 2
Salm: 50 μg bid x 8 wk; MDI; 8–12 hr
M: 10 mg OD; tablet; 20–24 hr
Treadmill; 8 min; 80–90% room temp; compressed dry air 5 [2 screen, 3rd d, wk 4 and 8]; 1 in evening
25–28 d
SABA; antihistamines x 8 hr; 48 hr; all others 1–2 wk
≥18%
Primary: max % fall FEV 1 at 8wk; AUC
Secondary: change max % fall FEV1; FEV1 L change from baseline; % protection
FEV1 measured at 5, 10, 15, 30, 45, 60 min post ECT
Salm vs. M: bronchoconstriction 32% vs. 24%; headache 8% vs. 10%; pharyngitis 7% vs. 8%; URTI 8% vs. 3%

Ach = anticholinergic; AE = adverse events; AUC = area under curve; bid = twice/day; C = Celsius; d = day(s); ECT = exercise challenge test; EIB/EIA = exercise-induced bronchoconstriction/asthma; F=formoterol; FEV1 = forced expiratory volume in 1 second; hr = hour(s); HR = heart rate; ICS = inhaled corticosteroid; L = liter; LABA = long-acting beta-agonist; LTRA = leukotriene receptor antagonist; μg = microgram; max = maximum; m = meters; M=montelukast; MDI = metered dose inhaler; min = minute(s); mg = milligram; mo = month(s); NR = not reported; NS=nedocromil sodium; P = placebo; PEF = peak expiratory flow; RH = relative humidity; SABA = short-acting beta-agonist; SALM=salmeterol; SCG = sodium cromoglycate; temp = temperature; Tx = treatment; URTI = upper respiratory tract infection; wk = week(s)

From: 3, Results

Cover of Exercise-Induced Bronchoconstriction and Asthma
Exercise-Induced Bronchoconstriction and Asthma.
Evidence Reports/Technology Assessments, No. 189.
Dryden DM, Spooner CH, Stickland MK, et al.

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