Wasserman 2006.

Methods	DESIGN: randomised, double‐blind, placebo‐controlled, parallel‐group study; multi‐centre
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 219 ANALYSED: N = 218 INTERVENTION: ICS (fluticasone 88 μg/d): 111 CONTROL: ICS (fluticasone 176 μg/d): 108 WITHDRAWALS: reported AGE: mean (months) (range): INTERVENTION: ICS (fluticasone 88 μg/d): 35.6 (24‐47) CONTROL: ICS (fluticasone 176 μg/d): 35.5 (24‐47) GENDER: N male (%): INTERVENTION: ICS (fluticasone 88 μg/d): 70 (63) CONTROL: ICS (fluticasone 176 μg/d): 63 (58.3) ASTHMA SEVERITY: not reported ASTHMA DURATION: mean (months) (range): INTERVENTION: ICS (fluticasone 88 μg/d): 25.0 (6‐46) CONTROL: ICS (fluticasone 176 μg/d): 24.4 (4‐46) MEAN (± SD) β2‐AGONIST USE (puffs/d): not reported; LS mean (SE) change to end point was reported DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: not reported ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Children aged 24 to 47 months who had experienced at least 2 exacerbations in the year before screening Regular maintenance therapy for asthma during the 6 weeks before screening and/or short‐acting agonist therapy at least twice weekly during the 3 weeks before screening EXCLUSION CRITERIA History of life‐threatening asthma Upper or lower respiratory tract infection Use of systemic or moderate to high doses of ICS within 8 weeks Treatment with more than 2 courses of systemic corticosteroids during the previous 6 months Use of investigational drug within 30 days of screening
Interventions	PROTOCOL DURATION Run‐in = 2 to 4 weeks Intervention = 12 weeks DEVICE: metered‐dose inhaler. Treatments were administered via a valve holding (Aerochamber Plus [Trudell Medical International, London, Ontario] or OptiChamber [Respironics, Murrysville, PA], each used by approximately half of the children) with an attached face mask DOSE OF ICS INTERVENTION: fluticasone propionate 88 μg/d = 44 μg bid CONTROL: fluticasone propionate 176 μg/d = 88 μg bid CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: Safety analyses were based on data from the intent‐to‐treat population; analysis of co‐variance was used OUTCOMES GROWTH MEASUREMENT TECHNIQUE: Growth (standing height) was measured in triplicate and at approximately the same time of day using a calibrated stadiometer at screening and at weeks 1, 2, 4, 8 and 12 PULMONARY FUNCTION TESTS: morning PEFR measurements (in children capable of performing this manoeuvre) FUNCTIONAL STATUS Growth (standing height) at screening and at weeks 1,2, 4, 8 and 12 24 hour asthma symptom scores Time to treatment failure % of symptom‐free 24 hour days BIOMARKERS Urine cortisol values at screening and at week 12 ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (2006) FUNDING: grant from GlaxoSmithKline Inc CONFIRMATION OF METHODOLOGY: received Data received from GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information on sequence generation; randomly assigned in 1:1:1 ratio; stratified by age (< 36 months; > 36 months)
Allocation concealment (selection bias)	Unclear risk	Insufficient information
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	Blinding of participants and key study personnel ensured
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	Low risk	Study protocol not available but published reports include all expected outcomes, including those that were prespecified
Other bias	Low risk	Study apparently free of other sources of bias

ACQ = asthma control questionnaire; ACTH = adrenocorticotrophic hormone; ANCOVA = analysis of co‐variance; ANOVA = analysis of variance; BALP = bone alkaline phosphate; BD = bronchodilator; BMD = body mass index; eNO = exhaled nitric oxide; FEF_25%–75% = forced expiratory flow between 25% and 75% of FVC; FEV₁ = forced expired volume in 1 second; FVC = forced vital capacity; GCS = glucocorticosteroids; HPAA = hypothalamic‐pituitary‐adrenal axis; ICS = inhaled corticosteroids; ICTP = type I collagen telopeptide; ITT = intent‐to‐treat; MEF₅₀ = maximal expiratory flow at 50%; mITT = modified intent‐to‐treat; OC = serum osteocalcin; o.d. = once daily; PACT = Pediatric Asthma Controller Trial; PAQLQ = Paediatric Asthma Quality of Life Questionnaire; PD₂₀ = dose of methacholine causing a 20% fall in forced expiratory volume in 1 sec (FEV1) from baseline; PEFR = peak expiratory flow rate; PICP = procollagen type I carboxyterminal propeptide; SD = standard deviation; SE = standard error.