Skoner 2008.

Methods	DESIGN: randomised, double‐blind, multi‐centre, placebo‐controlled, parallel‐group study
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 440 ANALYSED: N = 408 INTERVENTION: ICS (ciclesonide 40 μg/d): 221 CONTROL: ICS (ciclesonide 160 μg/d): 219 WITHDRAWALS: reported AGE: mean (range) years INTERVENTION: ICS (ciclesonide 40 μg/d): 7.1 (5.5‐9.1) CONTROL: ICS (ciclesonide 160 μg/d): 7.2 (5.5‐9.0) GENDER: male N (%) INTERVENTION: ICS (ciclesonide 40 μg/d): 150 (67.9) CONTROL: ICS (ciclesonide 160 μg/d): 147 (67.1) ASTHMA SEVERITY: mild persistent asthma ASTHMA DURATION: at screening (6 months before randomisation) mean (SD) years INTERVENTION: ICS (ciclesonide 40 μg/d): 3.79 (1.95) CONTROL: ICS (ciclesonide 160 μg/d): 3.96 (1.98) MEAN (± SD) β2‐AGONIST USE (puffs/d): not reported DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: placebo. ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Diagnosis of mild, persistent asthma for 3 months before screening Forced expiratory volume in 1 second (FEV1) of 80% predicted (after 4‐hour albuterol withhold) Effective use of metered‐dose inhaler (MDI) devices Tanner stage 1 Normal height (5th–95th percentiles inclusive) at screening Growth velocity at the third or higher percentile during the 6‐month run‐in period Use of noncorticosteroid asthma medication on an as‐needed or daily basis or low ICS dosages EXCLUSION CRITERIA Inability or refusal to use study devices Any ICS within 30 days before screening, at a dosage exceeding fluticasone propionate 100 g/d or equivalent Previous daily or alternate‐day oral corticosteroid treatment for a total of 60 days within 2 years before visit 3 or within 30 days before screening Receipt of 2 14‐day courses of intranasal corticosteroids (which had to be separated by 3 months) or ICS treatment for 14 days during the run‐in period
Interventions	PROTOCOL DURATION Run‐in = 24 weeks Intervention = 48 weeks DEVICE: metered‐dose inhaler without a spacer DOSE OF ICS INTERVENTION: ciclesonide 40 μg/d CONTROL: ciclesonide 160 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: Using an analysis of co‐variance (ANCOVA) model, all growth analyses were conducted by using the modified intention‐to‐treat (mITT) population, which included all randomly assigned participants who completed 4 months of study treatment and who had stadiometry measurements at baseline and >= 4 months OUTCOMES GROWTH MEASUREMENT TECHNIQUE: All investigators were provided with detailed written and visual instructions, took part in onsite training and attended workshops before study initiation to standardise stadiometer measurements. In addition, most investigators had previous experience with Harpenden stadiometers. Study centres were supplied with identical Harpenden stadiometers, which were calibrated within 4 hours of each measurement, and height was measured at all visits using standard techniques. Measurements were taken by a trained technician, and an effort was made to use the same technician at each visit. A median of 4 acceptable serial measurements was used in the analysis PULMONARY FUNCTION TESTS Mean (SE) changes in FEV1 (L) from baseline to study end FUNCTIONAL STATUS Linear growth velocity during double‐blind treatment period (before randomisation every 3 months, after randomisation every month and 4 months and every 2 months and completion of double‐blind treatment and 2 months after the end of study) Mean change in stadiometer height (cm) from baseline (using mean range of the 4 stadiometer height measurements recorded at each visit) BIOMARKERS Urine samples (24 hours or 10 hours overnight) for cortisol measurements before randomisation and after completion of double‐blind treatment Wrist radiographs for assessment of bone age before randomisation and after completion of double‐blind treatment ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (2008) FUNDING: Financial support for this study was provided by Sanofi‐aventis US and Altana Pharma US, Inc, a Nycomed company CONFIRMATION OF METHODOLOGY: not received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using a computer random number generator: ”The randomisation schedule was generated by the Biostatistics Department of Quintiles, Inc (Kansas City, MO) and was stratified according to age‐gender classification”
Allocation concealment (selection bias)	Low risk	Central allocation (including telephone, web‐based and pharmacy‐controlled randomisation): “Randomization was conducted at a central location (Q‐Tone, Durham, NC) and was determined by an interactive voice response system, based on information entered by personnel at each investigative center”
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