Knox 2007.

Methods	Study design: randomised controlled, double‐blind, double‐dummy, parallel group Total duration of study: 14 weeks 'Run‐in' period: 2 weeks Number of study centres and locations: 16 centres (8 each in UK and Belgium) Study setting: not stated Withdrawals: 5 participants (CIC 160 μg, n = 4; FP 250 μg, n = 1) Date of study: October 2004 to July 2005
Participants	N: 111 randomised Mean age, years: CIC 160 μg OD: 43; FP 250 μg BID: 46 Age range, years: 18‐75 Gender M/F, n: CIC 160 μg OD: 28/30; FP 250 μg BID: 30/23 Severity of condition: controlled on step 2 Baseline lung function ‐ mean (SD) FEV1, L: CIC 160 μg OD: 3.272 (0.869); FP 250 μg BID: 3.146 (0.823) Smoking history ‐ non‐smoker/ex‐smoker/current smoker, n: CIC 160 μg OD: 38/18/2; FP 250 μg BID: 34/18/1 Inclusion criteria: male and female patients aged 17–75 years; diagnosis of asthma as defined by American Thoracic Society guidelines for at least 6 months, but otherwise in good health; FEV1 ≥ 90% of predicted; maintained asthma control over previous 3 months using fluticasone propionate 250 μg twice daily, or equivalent, with short‐acting bronchodilator use as rescue medication only Exclusion criteria: concomitant severe disease, such as a lower respiratory tract infection; chronic obstructive pulmonary disease or other relevant lung diseases; more than 1 emergency care visit or hospitalisation due to asthma exacerbations in the previous year; or clinically relevant abnormal laboratory values suggesting an unknown disease. Other exclusion criteria were use of systemic glucocorticoids, long‐acting β2‐agonists, oral β2‐agonists and sustained‐release xanthines within 3 months before study entry; pregnancy and breast‐feeding among female patients; and ex‐smokers or current smokers with ≥ 10 pack‐years. Details of criteria for step‐down treatment: Participants were randomised to step‐down (for eligibility, see inclusion and exclusion criteria).
Interventions	Intervention: ciclesonide 160 μg OD (i.e. ˜ 50% reduction according to GINA 2016) Comparison: fluticasone propionate 250 μg BID (i.e. no change) Concomitant medications: short‐acting bronchodilator used as rescue medication only Excluded medications: See exclusion criteria.
Outcomes	Primary outcomes: efficacy ‐ percentage of days with asthma control (defined as days without asthma symptoms and without rescue medication use); asthma symptom‐free days; rescue medication‐free days; and nocturnal awakening‐free days. Safety ‐ adverse events Secondary outcomes: efficacy ‐ FEV1; forced vital capacity (FVC); PEF from spirometry; PEF from participant diaries measured on a Mini‐Wright PEF meter; asthma symptom scores from participant diaries (sum scores based on a 9‐point scale, with 0 indicating no symptoms); use of rescue medication; number of participants with an asthma exacerbation; and time to onset of the first asthma exacerbation. Safety ‐ vital signs (blood pressure and pulse rate); standard laboratory tests (including haematology, blood chemistry and urinalysis); and number of participants with oral candidiasis
Notes	Funding for trial: This study was funded and sponsored by ALTANA Pharma AG, a member of the Nycomed Group. Notable conflicts of interest of trial authors: Editorial assistance for preparation of the manuscript was provided by Nathan Price‐Lloyd, PhD, Medicus International, which was funded by ALTANA Pharma AG, a member of the Nycomed Group. Study authors reported no conflicts of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information provided
Allocation concealment (selection bias)	Unclear risk	Insufficient information provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The study was reported as double‐blind, double‐dummy.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The study was reported as double‐blind, double‐dummy.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analyses were performed for safety analyses and comprised all randomised participants. Some data for lung function analyses were missing, but only from 3 participants in the step‐down group.
Selective reporting (reporting bias)	Unclear risk	Protocol was not available; however, the range of outcomes seems fairly comprehensive.
Other bias	Low risk	None identified