Gelfand 2006.

Methods	DESIGN: randomised, double‐blind, multi‐centre, placebo‐controlled, parallel‐group clinical study. This comprises 2 identical trials
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 511 INTERVENTION: ICS (ciclesonide 40 μg/d): 252 CONTROL: ICS (ciclesonide 80 μg/d): 259 WITHDRAWALS: reported AGE: mean (years) (range): INTERVENTION: ICS (ciclesonide 40 μg/d): 8.14 ± 0.14 (4‐11) CONTROL: ICS (ciclesonide 80 μg/d): 8.20 ± 0.13 (4‐11) GENDER: N (male %): INTERVENTION: ICS (ciclesonide 40 μg/d): 160 (63.5) CONTROL: ICS (ciclesonide 80 μg/d): 169 (65.3) ASTHMA SEVERITY: persistent asthma with all severity ASTHMA DURATION: mean (months) (range): INTERVENTION: ICS (ciclesonide 40 μg/d): 4.32 ± 0.18 (0.26‐11.26) CONTROL: ICS (ciclesonide 80 μg/d): 4.35 ± 0.17 (0.25‐11.10) MEAN (± SD) β2‐AGONIST USE (puffs/d): INTERVENTION: ICS (ciclesonide 40 μg/d): 1.60 CONTROL: ICS (ciclesonide 80 μg/d): 1.64 DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: placebo ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Children aged 4 to 11 years with persistent asthma of all severity diagnosed ≥ 6 months as defined in National Institute of Health Guidelines Patients on controller medications Had FEV1 predicted value ≥ 40% and ≤ 100% at the screening visit after β2‐agonists were withheld for ≥ 6 hours EXCLUSION CRITERIA Patients with a history of life‐threatening asthma or 2 or more hospitalisations for asthma exacerbations 1 year or less before the study, receiving treatment with injectable or oral corticosteroids within 30 days before screening or with a urine cortisol level < 10 μg/dL at screening
Interventions	PROTOCOL DURATION Run‐in = 5 to 21 days Intervention = 12 weeks DEVICE: HFA‐metered dose inhaler DOSE OF ICS INTERVENTION: ciclesonide 40 μg/d CONTROL: ciclesonide 80 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: intention‐to‐treat analysis. All participants receiving 1 or more doses of study medication with 1 or more post‐baseline measurements of FEV1 and height were included in the analysis. Missing values for withdrawals were handled by the last value extended principle OUTCOMES: reported at 12 weeks. Outcomes were measured every 1, 2, 4, 8 and 12 weeks GROWTH MEASUREMENT TECHNIQUE: not reported PULMONARY FUNCTION TESTS Change in FEV1 percentage predicted between baseline and week 12 Change in FEV1 percentage predicted at all visits Absolute change in FEV1 Change in AM PEFR and PM PEFR from baseline FUNCTIONAL STATUS 24‐Hour asthma symptom score Albuterol use Nighttime awakenings Percentage of asthma symptom‐free days Quality of life assessments BIOMARKERS Blood samples for cortisol measurements Cosyntropin stimulation test ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (2006) FUNDING: funded by Aventis Pharmaceuticals CONFIRMATION OF METHODOLOGY: not received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information on sequence generation
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: ”We report the results of a prespecified integrated analysis of the efficacy and safety data from 2 identical, double‐blinded, randomised, placebo‐controlled studies of ciclesonide (at doses of 40, 80, and 160 μg) administered once daily to children with persistent asthma”
Other bias	Low risk	Study apparently free of other sources of bias