Hultquist 2000.

Methods	DESIGN ‐parallel‐group study ‐multicentre trial (49 centres in 6 countries) ALLOCATION ‐Random ‐Methods of randomisation: computer generated ‐means of assignment by opaque consecutive numbered envelopes containing assignment BLINDING ‐double‐blind ‐double‐dummy WITHDRAWAL/DROPOUT ‐ described by treatment groups JADAD's Quality Score = 5 Confirmation of methodology: received
Participants	INADEQUATELY controlled participants on inhaled glucocorticoids at baseline BASELINE INHALED STEROID DOSAGE: 400‐1000 ug of ICS (not specified)/day RANDOMISED ‐Anti‐leukotriene= 118 ‐Long‐acting beta2‐agonist = 118 ‐Bud=116 WITHDRAWALS: ‐Anti‐leukotriene= 19/118 (16%) ‐Long‐acting beta2‐agonist = 12/118 (10%) ‐BUD= 9/116 (8%) AGE in years: mean ± SD ‐Anti‐leukotriene= 38.3 ± NS ‐Long‐acting beta2‐agonist = 38.1 ± NS ‐BUD=38.1 ± NS GENDER (% male) ‐Anti‐leukotriene= 47 % ‐Long‐acting beta2‐agonist = 49% ‐BUD=53% SEVERITY: Not described BASELINE FEV1 (% pred) ‐Anti‐leukotriene= 72.03 ± SD ‐Long‐acting beta2‐agonist = 69.71 ± SD ‐BUD=72.12 ± SD ALLERGEN TRIGGERS: ‐Not reported ALLERGIC RHINITIS: ‐Not reported ASTHMA DURATION in years ‐Anti‐leukotriene= 10.1 ± SD ‐Long‐acting beta2‐agonist = 12.1 ± SD ‐BUD=10.6 ± SD ELIGIBILITY CRITERIA ‐male or female outpatient ‐age 12‐70 years ‐treated for at least 3 mo with 400‐1000 mcg of inhaled glucocorticoids ‐asthma diagnosis ‐FEV1 50‐80% predicted ‐>=12 % reversibility in FEV1 and at least 200 mL after inhalation of 1 mg of terbutaline ‐smoking history of <=10 pack years In the 7 days prior to randomisation one or more of the following: ‐ an symptom score of >=1 on 4 days ‐awakening on >= 1 night due to asthma symptoms ‐use of B2‐agonists >=10 puffs as weekly mean EXCLUSION CRITERIA: ‐Respiratory infection ‐clinical obstructive pulmonary disease, or pulmonary dysfunction other than asthma ‐pregnant or lactating women ‐use of long‐acting beta2‐agonist within 1 month prior to visit 1 ‐previous use ever of a leukotriene antagonist ‐known intolerance to study drugs or inhaled lactose SETTING: not described
Interventions	PROTOCOL: AL + ICS vs SAME dose ICS (Stable dose of ICS) DURATION: ‐Run‐in Period: not reported ‐Intervention Period: 8 weeks INTERVENTION GROUP 1 ‐AL = Zafirlukast 20 mg bid + Budesonide 200 mcg bid via Turbuhaler INTERVENTION GROUP 2 (not used) ‐LAB2 = Formoterol 9 ug bid, via Turbuhalor + Budesonide 200 mcg bid via Turbuhaler CONTROL: Budesonide 200 mcg bid via Turbuhaler ‐CO‐TREATMENT: None allow other than rescue LAB2
Outcomes	Modified INTENTION‐TO‐TREAT ANALYSES (on all patients who receive at least 1 dose of study medication) ‐outcomes used at endpoint or 8 weeks PULMONARY FUNCTION TESTS ‐**Change from baseline in AM PEFR ‐Change from baseline in PM PEFR ? SYMPTOM SCORES ‐Change from baseline OVERALL symptom scores? ‐Change from baseline DAYTIME symptom scores? ‐Change in symptom‐free days? ‐ Patient satisfaction? EXACERBATIONS Definition: Any worsening of asthma symptoms requiring treatment beyond the use of blinded study drug &/or supplemental albuterol. Patients who experienced an asthma exacerbation were withdrawn from the study ?? FUNCTIONAL STATUS ‐Change from baseline in mean OVERALL use of B2‐agonists (puffs/DAY)? ‐Change from baseline in mean DAYTIME use of B2‐agonists (puffs/DAY)? ‐Change from baseline in mean NIGHT‐TIME use of B2‐agonists (puffs/DAY)? ‐Change in rescue‐free days? ‐Change in night‐time awakenings ? INFLAMMATORY MARKERS: Not reported ADVERSE EFFECTS ‐drug related & non‐drug related ? WITHDRAWALS ‐due to adverse effects reported ? (** denotes primary outcome)
Notes	‐ Unpublished data ‐Received full disclosure of unpublished data provided by Ian Naya and Roger Metcalf, AstraZeneca, Sept 2003 ‐Funded by Astra Zeneca Report #SD‐004CR‐0216 Confirmation with supportive documents received for methodology and data extraction (Sept 2003) User‐defined order: 40 (mean intervention BUD dose in 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)