Laitinen 1995.

Methods	DESIGN ‐parallel‐group ‐multicentre trial (83 centres) ALLOCATION ‐Random: 2:1 ratio intervention:control ‐Computer‐generated BLINDING ‐double‐blind ‐placebo‐controlled ‐identical placebo WITHDRAWAL/DROPOUT ‐described JADAD's Quality Score = 5 Confirmation of methodology obtained
Participants	WELL‐CONTROLLED PARTICIPANTS ‐RANDOMISED N = 262 Zafirlukast:175 Control:87 WITHDRAWALS Zafirlukast:15% Control:14% AGE: Zafirlukast: 45.5 ±13.6 (SD) years Control: 43.5 ± 13.4 years GENDER (% male) Zafirlukast:46% Control:34% SEVERITY: moderate asthma BASELINE FEV1 (L) Zafirlukast: 2.58 ± 0.89 (SD) Control: 2.42 ± 0.78 ALLERGEN TRIGGERS: Zafirlukast: 45% Control:40% ASTHMA DURATION: Zafirlukast: 14.1 ± 13.1 (SD) years Control: 14.3 ± 12.5years ELIGIBILITY CRITERIA ‐taking a dose of ICS (BUD or BDP) between 800 and 2000 ug/day ‐stable in the preceding month
Interventions	PROTOCOL: AL + ICS vs same dose ICS (TAPERING ICS dose) DURATION: ‐Run‐in Period: 1 week to confirm asthma control ‐Dose optimisation period: 2 weeks to 3 months Zafirlukast: 7.7 ± 4.0 weeks (SD) Control: 7.9 ± 4.0 weeks ‐Intervention Period: 12 weeks TEST GROUP ‐ICI 204219 = Zafirlukast 20 mg bid p.o. + ICS (BUD or BDP) 800 to 2000 ug/day CONTROL GROUP Placebo + ICS (BUD or BDP) 800 to 2000 ug/day DEVICE ‐various devices used ‐CO‐TREATMENT: none reported CRITERIA FOR TAPERING every 2 weeks by 200 to 250 mcg/day ‐FEV1>= 80% predicted ‐B2‐agonist use <= 800 ug/day of salbutamol MINIMAL DOSE OF ICS ALLOWED: 400 mcg/day CRITERIA TO INCREASE CORTICOSTEROIDS: ‐FEV1< 60% of predicted
Outcomes	PER‐PROTOCOL (PP) ANALYSES ‐ some intention‐to‐treat (ITT) analysis ‐outcomes used at 6 and 12 weeks PULMONARY FUNCTION TESTS (reported as cross‐sectional values not as change from baseline) ‐FEV1 (L)‐ ITT ‐Mean Am PEFR (L/min) ‐PP SYMPTOM SCORES ‐ PP ‐Mean daytime symptom scores FUNCTIONAL STATUS ‐ PP ‐Mean daily use of beta2‐agonist (puffs/day) averaged over a week ICS DOSE REDUCTION: (PP) ‐**ICS dose reduction (% change from baseline) INFLAMMATORY MARKERS ‐not reported ADVERSE EFFECTS ‐elevated liver enzymes, headache, nausea, death, etc. WITHDRAWALS ‐reported (** denotes primary outcomes)
Notes	‐Abs (1995) and unpublished data graciously provided by Christopher Miller and Susan Shaffer from Astra‐Zeneca, USA (Oct 2000) ‐funded by Zeneca ‐Confirmation of methodology and data extraction received from M. Christopher Miller and Ms. Susan Shaffer, Astra‐Zeneca, Oct 2000 ‐User‐defined order: 114 (mean intervention ICS dose of 1137 mcg/ day X 0.1)
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	Study investigators unaware as to order of treatment group assignment (Cochrane Grade A)