SAM40004

Methods	A multi‐centre, randomised, double‐blind, placebo‐controlled, parallel‐group study to compare effects on airway inflammation and remodelling of treatment with salmeterol/fluticasone propionate combination product (50/100 μg strength) twice daily via the Accuhaler inhaler, or fluticasone propionate 100 μg twice daily via the Accuhaler inhaler, or placebo via the Accuhaler inhaler for 16 weeks, followed by double‐blind treatment for 52 weeks with the salmeterol/fluticasone propionate combination product (50/100 μg strength) twice daily via the Accuhaler inhaler, or fluticasone propionate 100 μg twice daily via the Accuhaler inhaler, in adults with reversible airways obstruction (SIRIAS ‐ Seretide in Inflammation and Remodelling In Asthma Study)
Participants	Population: 63 adults (18 to 50 years) with mild asthma.  Baseline characteristics: mean age 32 years; FEV₁ unknown % predicted; concomitant ICS used by unknown % of participants, but all withdrawn during the run‐in period   Inclusion criteria: aged 18 to 50 years with a history of reversible airways obstruction; received short‐acting beta₂‐agonist alone or beclomethasone dipropionate or budesonide at a constant daily dose of up to 400 μg per day (excluding any CFC‐free formulation), or fluticasone propionate at a constant daily dose of up to 200 μg per day via any device for at least 4 weeks before the first visit. In addition, patients had to have had a fall in FEV₁ ≥ 20% with a histamine challenge test at the first visit and a post‐bronchodilator FEV₁ > 60% of predicted normal. To be randomised, participants had to have a fall in FEV₁ ≥ 20% with a standardised histamine challenge test, and at least 1 of the following criteria: recorded symptoms on at least 4 of the last 7 days of the preventer‐free run‐in period; recorded using their inhaled short‐acting beta₂ ‐agonist on at least 2 occasions on at least 4 of the last 7 days of the preventer‐free run‐in period; have a period variation ≥ 10% over the last 7 days of the preventer‐free run‐in period  Exclusion criteria: not reported
Interventions	• Fluticasone propionate and salmeterol 100/50 μg twice daily throughout • Placebo initially, and then fluticasone propionate/salmeterol 100/50 μg twice daily • Fluticasone propionate 100 μg twice daily throughout Delivery as DPI
Outcomes	Primary efficacy endpoint: level of airway hyperreactivity (as measured by histamine PC20); response of induced airway spasm to bronchodilator (post‐bronchodilator FEV₁) SAE data were used for the 52‐week extension period, as reported. No SAEs were reported in the 16‐week initial period
Notes	Sponsored by GSK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind
Independent Assessment of causation (detection bias) Asthma‐related events	High risk	Causation of SAEs not independently assessed
Incomplete outcome data (attrition bias) All outcomes	High risk	37/63 (59%) completed the study
Selective reporting (reporting bias)	Low risk	Data on GSK website