Pedersen 2010.

Methods	DESIGN: randomised, double‐blind, placebo‐controlled, parallel‐group clinical study
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 465 ANALYSED PARTICIPANTS: N = 465 INTERVENTION: ICS (ciclesonide 40 μg/d): 305 CONTROL: ICS (ciclesonide 80 μg/d): 312 WITHDRAWALS: reported AGE: median (years) (range): INTERVENTION: ICS (ciclesonide 40 μg/d): 8.0 (6‐11) CONTROL: ICS (ciclesonide 80 μg/d): 8.0 (6‐11) GENDER: N (male %): INTERVENTION: ICS (ciclesonide 40 μg/d): 210 (68.9%) CONTROL: ICS (ciclesonide 80 μg/d): 191 (61.2%) ASTHMA SEVERITY: persistent asthma but severity not reported ASTHMA DURATION: median (months) (range): INTERVENTION: ICS (ciclesonide 40 μg/d): 41.4 (6‐127) CONTROL: ICS (ciclesonide 80 μg/d): 41.9 (5‐128) MEAN (± SD) β2‐AGONIST USE (puffs/d): median (months) (range) INTERVENTION: ICS (ciclesonide 40 μg/d): 1.43 (0.00‐7.86) CONTROL: ICS (ciclesonide 80 μg/d): 1.43 (0.00‐7.14) DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: placebo ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Male and female outpatients aged 6 to 11 years with a history of persistent bronchial asthma for ≥ 6 months Ability to perform reproducible lung function tests and use an acceptable MDI inhalation technique In the 30 days before study entry, participants could be treated with rescue medication only; a constant dose of fluticasone propionate 200 mg/d or equivalent; or other controller medications Randomisation criteria at the end of the run‐in period included mean PEFR value (over last week) of 40% to 90% of predicted value, as well as FEV1 reversibility of 12% predicted after inhalation of 200 to 400 mg salbutamol In addition, participants had to present asthma symptoms on at least 6 of the last 10 days of the baseline period, or had to have used at least 8 puffs of rescue medication within the last 10 days of the baseline period EXCLUSION CRITERIA History of near fatal asthma; respiratory tract infection or asthma exacerbation within the last 30 days; 2 or more in‐patient hospitalisations for asthma in the previous year; use of systemic glucocorticosteroids within 30 days before study entry or for > 60 days in the previous 2 years
Interventions	PROTOCOL DURATION Run‐in = 2 to 4 weeks Intervention = 12 weeks DEVICE: metered‐dose inhaler with or without spacer DOSE OF ICS INTERVENTION: ciclesonide 40 μg/d CONTROL: ciclesonide 80 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: intent‐to‐treat analysis OUTCOMES: reported at 12 weeks; change in height reported as least squares mean growth rate GROWTH MEASUREMENT TECHNIQUE: At investigational sites where a stadiometer was available, height was also measured at the start and the end of the treatment period, as stadiometry is widely acknowledged as the most reliable means of measuring height and is recommended by the Food and Drug Administration (FDA) for studies assessing growth PULMONARY FUNCTION TESTS: mean change in FEV1 and PEFR reported FUNCTIONAL STATUS Percentage of days with asthma control Change in asthma symptom score Change in use of rescue medications Change in PAQLQ overall score BIOMARKERS Change in urinary cortisol ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (2010) FUNDING: funded by Nycomed CONFIRMATION OF METHODOLOGY: not received Data received from Takeda Global Research & Development Centre (Europe) Ltd
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using a computer random number generator: ”Patients were then randomised into one of four treatment groups in a 2:2:2:1 ratio (ciclesonide 40 mg: ciclesonide 80 mg: ciclesonide 160 mg: placebo) by means of a computer generated randomisation scheme”
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