Lofdahl 1999.

Methods	DESIGN ‐parallel‐group ‐multicentre trial ALLOCATION ‐Random ‐computer‐generated allocation ‐opaque consecutive‐numbered envelopes containing assignment BLINDING ‐triple‐blind ‐placebo‐controlled ‐identical placebo WITHDRAWAL/DROPOUTS ‐ described JADAD's Quality Score = 5 Confirmation of methodology obtained
Participants	WELL‐CONTROLLED PARTICIPANTS RANDOMISED N = 226 Montelukast = 113 Placebo = 113 WITHDRAWALS Montelukast: 16% Control: 27% AGE: 16 to 70 years old Montelukast: 40 years (mean) Control: 41 years GENDER:(% male) Montelukast: 42% Control: 45% SEVERITY: not described BASELINE FEV1 (% predicted): Montelukast: 84.4 ± 11.1 % (SD) Control: 82.3 ± 12.9 % ALLERGEN TRIGGERS: not reported ASTHMA DURATION: Montelukast: 18 ± 13.3 (SD) years Control: 19 ± 14 years ELIGIBILITY CRITERIA ‐non‐smoking adults ‐clinical history of asthma for at least one year ‐treatment with stable, ICS bid for at least 3 weeks prior to pre‐study visit ‐>= 70% FEV1 % Pred ‐>= 15% reversibility after inhaled B2‐agonist ‐after two ICS dose reductions: ‐FEV1 >= 90% of baseline value, ‐levels < baseline level in asthma symptoms and B2‐agonist use, ‐>= 65% of maximum peak flow, and ‐a required prespecified minimum ICS dose was met EXCLUSION: ‐emergency treatment in past 1 month ‐hospitalised in past 3 months ‐upper respiratory tract infection within 3 weeks
Interventions	PROTOCOL: AL + ICS vs same dose ICS (TAPERING ICS dose) DURATION ‐Dose optimisation period: <=7 weeks (ICS dose reduced to minimum dose necessary to maintain stability before randomisation) ‐Intervention Period: 12 weeks TEST GROUP ‐Montelukast 10 mg die p.o. + ICS 300 to 3000 ug/day CONTROL GROUP ‐Placebo + ICS 300 to 3000 ug/day (Various ICS including fluticasone 7%, beclomethasone 16%, BUDesonide 22%, flunisolide 15%, triamcinolone 40%) DEVICE ‐variety used ‐CO‐TREATMENT: none reported CRITERIA FOR TAPERING every 2 weeks by 25% of their ICS dose ‐FEV1 >= 90% of value at randomisation ‐B2‐agonist use <= 135% of pre‐allocation ‐Daytime symptoms score <= 120% of pre‐allocation baseline MINIMAL DOSE OF ICS ALLOWED: None
Outcomes	INTENTION‐TO‐TREAT ANALYSES ‐outcomes used at last tolerated dose or 12 weeks PULMONARY FUNCTION TESTS ‐Change from baseline FEV1 at visit of lowest tolerated ICS dose SYMPTOM SCORES ‐Change from baseline daily symptom scores at visit of lowest tolerated ICS dose FUNCTIONAL STATUS ‐Change from baseline mean daily use of B2‐agonists at visit of lowest tolerated ICS dose ICS DOSE REDUCTION: ‐**Mean % change from baseline ICS dose reduction ‐**Change from baseline ICS dose (mcg) INFLAMMATORY MARKERS: not reported ADVERSE EFFECTS ‐elevated liver enzymes, headache, nausea, death WITHDRAWALS ‐reported (** denotes primary outcomes)
Notes	‐Full Text 1999 and unpublished data ‐Funded by Merck Frosst ‐Confirmation of methodology received June 1999 ‐Confirmation of data extraction graciously received from T.F Reiss and G.P. Noonan, June 2000. ‐User‐defined order: 98 (mean intervention ICS dose of 976 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)