Tohda 2002.

Methods	DESIGN ‐parallel‐group ‐multicentre (16 study sites) ALLOCATION ‐Computer generated random allocation ‐Mode of allocation (not described) BLINDING ‐double‐blind ‐placebo‐controlled ‐identical placebo WITHDRAWL/DROPOUTS ‐described JADAD's Quality score = 5 Confirmation of methodology confirmed
Participants	WELL‐CONTROLLED PARTICIPANTS RANDOMISED N = 191 ‐Montelukast = 93 ‐Control = 98 WITHDRAWALS: ‐Montelukast = 14 (15%) ‐Control = 20 (20%) AGE (years): ‐Montelukast: 50.1 ± 14.5 (SD) ‐Control: 53.0 ± 13.2 (SD) GENDER (% male): ‐Montelukast: 58.3% ‐Control: 58.3% SEVERITY: ‐moderate‐to‐severe bronchial asthma BASELINE PREDICTED FEV1 (%): ‐Montelukast: 87.4 ± 18.4 (SD) ‐Control: 85.6 ± 24.8 (SD) ALLERGEN TRIGGERS ‐not reported ASTHMA DURATION ‐montelukast: < 10 years = 57 (67.9); >10 years = 27 (32.1) ‐ control: < 10 years = 56 (66.7); > 10 years = 28 (33.3) ELIGIBILITY CRITERIA ‐taking a dose of ICS 800‐1600 ug/day ‐PEFR >= 80% of patients best or predicted ‐diurnal variation PEFR of no more than 20% ‐asthma symptom score of no more than 5 points/week EXCLUSION CRITERIA ‐ use of following medication one month prior to run‐in period ‐ anti‐allergic drugs (disodium cromoglycate, ketotifen or pranlukast) ‐ oral corticosteroids at the start of the run‐in period ‐long‐acting corticosteroids (methylprednisolone acetate or triamcinolone acetonide)
Interventions	PROTOCOL: AL + ICS vs same dose ICS (TAPERING ICS dose) DURATION ‐4 week run‐in period ‐24 week treatment period with ICS titrated at weeks 8 and 16 TEST GROUP ‐Montelukast 10 mg film‐coated tablet once daily + BDP 800‐1600 mcg daily CONTROL GROUP ‐Placebo + + BDP 800‐1600 mcg daily DEVICE ‐ not reported CO‐TREATMENT: ‐ bronchodilators : xanthine derivatives, anticholinergics ‐antibiotics, antitussive and expectorants, chinese medicine, desensitization therapy CRITERIA FOR TAPERING ‐ mean PEFR observed during previous 2 weeks in not less than 90% of value in run‐in ‐ weekly mean symptom score during the previous 2 weeks is not 3 points or more higher than score at run‐in period ‐ mean inhaled B‐agonist use during the previous 2 weeks is less than twice use at run‐in period CRITERIA FOR MAINTAINING ICS DOSE ‐ 2 out of the 3 criteria for dose tapering mentioned above CRITERIA FOR INCREASING ICS DOSE ‐ 1 or none of the criteria for dose tapering mentioned above MINIMAL DOSE OF ICS ALLOWED: ‐ no minimal dose required
Outcomes	EFFICACY ANALYSIS ‐ NO INTENTION TO TREAT ANALYSIS ‐outcomes available at 4, 8, 16 and 24 weeks PULMONARY FUNCTION TESTS ‐% change in PEFR ‐% change in FVC ‐% change in FEV1 SYMPTOM SCORES ‐% change in breathlessness and wheezing (range 0‐9) ‐ % change in therapy score (range not reported, based on Japanese Society of Allergology) ‐ % change in asthmatic score (combining symptom score with therapy score) FUNCTIONAL STATUS ‐ not reported ICS DOSE REDUCTION ‐ INFLAMATORY MARKERS ‐ not reported ADVERSE EFFECTS ‐ alopecia areata, headache, bitter taste, stomach ache, heartburn and asthma in the montelukast group, and toxicoderma, papules, headache, diarrhoea, constipation, retching, palpitations and nocturia in the placebo group ****data not reported**** WITHDRAWLS ‐ reported
Notes	‐Full text (2002) and unpublished data ‐Funded by Banyu Pharmaceutical Limited (makers of montelukast) ‐Confirmation of methodology and data extraction graciously obtained from Takaaki Ishine, PhD, Banyu Pharmaceutical Co, LTD, August 2003 ‐user‐defined order: 92.mcg/day (mean ICS dose of 925 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)