Lemanske 2001.
| Methods | Study Design: Parallel RCT Randomisation: Described Concealment of Allocation: Described. Double Blinding: triple blind Withdrawals / dropouts: Described Adverse events: described Statistical analysis: Intention to treat Jadad Score: 5 | |
| Participants | Study site: multicentre No eligible: 339 (164 controlled asthmatics entered SOCS trial) No randomised: 175 No completed: 160 ( Intervention 1:18; Intervention 2A: 71; Intervention 2B:71) at end of TAA reduction phase Sex: Males ‐intervention 1: 8(42%); Intervention 2B: 35(47.3%) Age(mean, SD): 1: 35.6 14.4); 2B: 34.2 (10.8) yrs Diagnostic criteria for asthma: ATS criteria Inclusion criteria: 12‐65 yrs, persistent asthma (FEV1<=80% and >=12% bronchodilator reversibility, if on ICS & FEV1 > 80% then needed to demonstrate a 20% reduction in FEV1 to provocative methacholine challenge. Exclusion criteria: Smoking history, >=10 pack years, use of other medicines except oral contraceptive and nasal beclomethasone, respiratory infection or asthma exacerbation in past 6 weeks, comorbid serious illness. Baseline severity of asthma: mean(SD) FEV1 pre bronchodilator: Intervention 1: 72.5% (12.5); Intervention 2B: 73.8% (11.2) | |
| Interventions | Run in phase: 6 weeks Triamcinolone 800mcg/day. If controlled entered in SOCS trial. If uncontrolled (FEV1 <=80% or PEF variability > 2‐%) randomised to:
Salmeterol introduction phase
1: TAA 400mcg bid(800mcg/day) + placebo
2: TAA 400mcg bid (800mcg/day) + salmeterol 42mcg bid(84mcg/day)
After 8 weeks enter:
TAA reduction phase
1: TAA 200mcg bid(400mcg/day) + placebo
2: Subjects randomised to
2A: TAA 400mcg bid (800mcg/day) + salmeterol 42mcg bid(84mcg/day)
or
2B: TAA 200mcg bid(400mcg/day) + salmeterol 42mcg bid (84mcg/day)
After 8 weeks enter:
TAA elimination phase
1: placebo + placebo
2A: TAA 400mcg bid (800mcg/day) + salmeterol 42mcg bid(84mcg/day)
2B: placebo + salmeterol 42mcg bid(84mcg/day)
Delivery device: pMDI
Duration of treatment: 24 weeks total, Outcomes used after TAA reduction phase (16 weeks treatment) Other: |
|
| Outcomes | Time to treatment failure, PEF, FEV1, AHR (methacholine), Asthma symptoms, QOL | |
| Notes | Comparison 2: Reduced dose ICS Interventions 1 vs intervention 2B outcomes at end TAA reduction phase eligible for review. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Adequate sequence generation? | Low risk | 'Patient randomization was performed online via an Internet connection to the computer system at the data coordinating centre (...) The first randomization at the end of the triamcinolone run‐in period was stratified according to clinical centre, and the second randomization before the triamcinolone reduction phase was stratified according to ethnic group, sex, and age.' |
| Allocation concealment? | Low risk | 'Staff members entered and verified the pertinent data and received a drug packet number to give each eligible patient at the 2 randomizations.' |
| Blinding? All outcomes | Low risk | Triple blind. 'Medication for each patient was packaged together, labelled with a unique number, and distributed to the clinical centres. The contents of the drug packages were known only to administrative personnel at the data coordinating centre.' |