Martinez 2011.

Methods	Design: multi‐centre, randomised, double‐blind, parallel‐group, placebo‐controlled trial Sponsor: National Heart, Lung and Blood Institute, USA
Participants	Setting: 5 clinical centres in the USA Eligible: 843 Randomly assigned: 71 (combined group); 72 (daily beclomethasone); 71 (rescue beclomethasone); 74 (placebo) Gender (male): 159/288 (55.2%) Age, years, mean ± SD: combined 11.4 ± 3.1; daily beclomethasone 10.8 ± 3.5; rescue beclomethasone 10.4 ± 2.8; placebo: 10.4 ± 3.2 Inclusion criteria: children and adolescents between 6 and 18 years of age; history of mild persistent asthma during the previous 2 years; naive to controller treatment with a history of 1 to 2 exacerbations in the previous year; treated for the previous 8 weeks with a monotherapy other than inhaled corticosteroids; illness controlled for the previous 8 weeks on low‐dose corticosteroids as monotherapy (≤ 160 μg daily with a beclomethasone equivalent) Exclusion criteria: participants excluded from the study if they had a pre‐bronchodilator FEV1 less than 60% predicted at first visit; admitted to hospital for asthma in the previous year; any asthma exacerbation in the previous 3 months or more than 2 in the previous year; history of life‐threatening asthma exacerbations that required intubation or mechanical ventilation, or that resulted in a hypoxic seizure Previous regular use of ICS: ranged from 72%‐82% among treatment groups
Interventions	Test group: Combined group: twice‐daily HFA‐beclomethasone (100 μg/d) with HFA‐beclomethasone (100 μg) plus albuterol as rescue Daily beclomethasone: twice‐daily HFA‐beclomethasone (100 μg/d) with placebo plus albuterol as rescue Rescue beclomethasone: twice‐daily placebo with HFA‐beclomethasone (100 μg) plus albuterol as rescue Control group: placebo: twice‐daily placebo with placebo plus albuterol as rescue Daily treatment was given twice daily via HFA‐MDI. Rescue treatment was given via HFA‐MDI for symptom relief. Treatment duration was 44 weeks
Outcomes	Time to first exacerbation that required treatment with prednisone Spirometry FEV1 Fractional exhaled nitric oxide (FENO) Symptom diaries and control Quality of life questionnaires Change in height over time (cm/y) Method for height measure was not reported
Notes	Treatment compliance was not measured
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Data Coordinating Center (DCC; Penn State Hershey College, PA, USA) generated the random allocation sequence
Allocation concealment (selection bias)	Low risk	Central allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Use of matching placebo
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Use of matching placebo
Incomplete outcome data (attrition bias) All outcomes	High risk	Withdrawal rate was 30/214 (14.0%) in the active treatment groups and 24/74 (32.4%) in the placebo group
Selective reporting (reporting bias)	Low risk	Study protocol is not available, but published reports include all expected outcomes, including those that were prespecified
Other bias	Unclear risk	Method of height measure not reported