Vaessen‐Verberne 2010.

Methods	DESIGN: randomised, multi‐centre, parallel‐group, double‐blind study
Participants	SYMPTOMATIC ON CONVENTIONAL DOSES OF INHALED CORTICOSTEROIDS RANDOMLY ASSIGNED: N = 158 ANALYSED: N = 151 INTERVENTION: ICS (fluticasone 200 μg/d): 78 CONTROL: ICS (fluticasone 400 μg/d): 80 WITHDRAWALS: reported AGE: years ± SD: INTERVENTION: ICS (fluticasone 200 μg/d): 9.4 ± 1.8 CONTROL: ICS (fluticasone 400 μg/d): 9.3 ± 1.9 GENDER: N (male %): INTERVENTION: ICS (fluticasone 200 μg/d): 42 (54%) CONTROL: ICS (fluticasone 400 μg/d): 49 (61%) ASTHMA SEVERITY: not reported ASTHMA DURATION (mean years ± SD): reported INTERVENTION: ICS (fluticasone 200 μg/d): 5.7 ± 3.1 CONTROL: ICS (fluticasone 400 μg/d): 5.5 ± 3.0 MEAN (± SD) β2‐AGONIST USE (puffs/d): not reported DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: not reported ATOPY: N (% of participants): reported INTERVENTION: ICS (fluticasone 200 μg/d): 60 (77%) CONTROL: ICS (fluticasone 400 μg/d): 58 (73%) ELIGIBILITY CRITERIA Male or female subjects aged 6 to 16 years (inclusive) Subjects with a documented history of asthma for at least 6 months Subjects with a documented history of BHR within 12 months before inclusion or BHR on visit 1 and/or visit 2/2A (PD20 methacholine < 150 μg or an equivalence for histamine) Subjects who had received BDP, budesonide up to 100 to 200 μg bd or fluticasone propionate at a dose of up to 125 μg bd for at least 4 weeks before the start of the run‐in period Subjects who had a normal length SD score between –2 SD and +2 SD as inclusion criteria for entry into the treatment period (end of run‐in period) Subjects who had recorded a cumulative symptom score (daytime plus nighttime) totaling > 14 the last 14 days of the run‐in period Compliance for use of FP during run‐in period of at least 50% Recorded data on > 70% of daily entries into their DRC throughout run‐in period EXCLUSION CRITERIA Children with history of severe respiratory infection, cystic fibrosis, aspirative pathology, pulmonary or airways anomalies, bronchopulmonary dysplasia and congenital heart disease, or who previously received ICS or sodium cromoglycate
Interventions	PROTOCOL DURATION Run‐in = 4 weeks Intervention = 26 weeks DEVICE: Diskus DOSE OF ICS INTERVENTION: fluticasone 100 μg with salmeterol 50 μg twice day CONTROL: fluticasone 200 μg twice daily CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: intention‐to‐treat analysis OUTCOMES: Many outcomes were reported at 26 weeks; participants were evaluated at 1, 6, 16 and 26 weeks GROWTH MEASUREMENT TECHNIQUE: Height was recorded using a stadiometer at the start of the run‐in period, and at the start and at the end of the treatment period PULMONARY FUNCTION TESTS FEV1 FVC FEV1/FVC MEF50 PEFR PD20 methacholine FUNCTIONAL STATUS Percentage of symptom‐free days BIOMARKERS Exhaled nitric oxide ADVERSE EVENTS Statural growth Exacerbations Adverse events WITHDRAWALS: reported
Notes	PUBLICATION: full paper (2010) FUNDING: funded by GlaxoSmithKline CONFIRMATION OF METHODOLOGY: received Data received from the study author
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using a computer random number generator
Allocation concealment (selection bias)	Low risk	Central allocation (including telephone, web‐based and pharmacy‐controlled randomisation)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Reasons for missing outcome data unlikely to be related to true outcomes
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	Low risk	Study protocol available and all of the study’s prespecified (primary and secondary) outcomes that are of interest in the review have been reported in the prespecified way
Other bias	Low risk	Study apparently free of other sources of bias