Mansfield 2017

Methods	A 26‐week, open‐label, randomised, active drug‐controlled trial with a 14‐day run‐in period
Participants	Population: 758 participants with persistent asthma were enrolled Baseline characteristics: mean age ranged from 38.4 to 46.1 years; mean baseline FEV₁ ranged from 2.31 to 2.70 L Inclusion criteria: those with FEV₁ > 40% of relevant predicted value, those already on an established treatment regimen of SABA for use as needed and either a mid‐ or high‐dose ICS or ICS/LABA combination as preventive therapy for over 8 weeks, those with demonstrated reversibility of FEV₁ > 12% within 30 minutes after short‐acting beta‐agonist administration Exclusion criteria: treatment with low‐dose ICS without LABA, history of life‐threatening asthma exacerbation, asthma exacerbation within 30 days of screening, hospitalisation for asthma 2 months before screening, use of immunosuppressive medications 4 weeks before screening, documented or suspected bacterial or viral infection within 2 weeks of screening, any illness that in the judgement of investigators would put the patient at risk during the study, current smokers and those with a 10‐pack‐year smoking history, patients who used tobacco products within the past year
Interventions	• Fluticasone propionate and salmeterol given as a multi‐dose dry powder inhaler at doses of 100 μg/12.5 μg or 200 μg/12.5 μg twice daily, or via a dry powder inhaler at doses of 250 μg/50 μg or 500 μg/50 μg twice daily • Fluticasone propionate given as a multi‐dose dry powder inhaler at doses of 100 μg or 200 μg twice daily, or in a hydrofluoroalkane inhaler at doses of 220 μg or 440 μg twice daily
Outcomes	Primary outcome: change from baseline in morning trough FEV₁ over the 26‐week treatment period
Notes	Sponsored by Teva Pharmaceuticals
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Methods used for sequence generation were not clearly reported ‐ only that participants were randomised
Allocation concealment (selection bias)	Unclear risk	Methods used for allocation concealment were not clearly reported
Blinding (performance bias and detection bias) All outcomes	High risk	This was an open‐label study
Independent Assessment of causation (detection bias) Asthma‐related events	High risk	No report of independent assessment of SAEs
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition was below 80%, and all participants randomised were available for the safety study, even if they did not complete the full study
Selective reporting (reporting bias)	Low risk	Data were extracted for all outcomes of the review