Hagedorn 2013.

Study characteristics
Methods	Design: RCT (unblinded) Duration: 52 weeks Location: Germany Setting: multi‐centre
Participants	Population: 212 adults with COPD Baseline characteristics COPD severity: severe to very severe (GOLD stages III and IV) Age (mean): SFC 65.5 (SD 8.3) years; sal/FP 64.2 (SD 8.9) years % male: SFC 69.2%; sal/FP 72.4% Duration of COPD (mean): SFC 12.4 (SD 7.3) years; sal/FP 13.3 (SD 8.3) years Pack‐years: SFC 39.2 (SD 16.6); sal/FP 40.4 (SD 24.1) Exacerbations in last 12 months: SFC 2.2 (0.5); sal/FP 2.3 (0.6) COPD hospitalisations in last 12 months: SFC 84; sal/FP 87 Inclusion criteria: aged ≥ 40 years, COPD diagnosis (ATS, ERS) GOLD stage III or IV, postbronchodilator < 50% predicted, FEV1/FVC ratio < 70%, ≥ 2 moderate or severe exacerbations leading to medical consultation, stable COPD 4 weeks prior to study start, ≥ 10 pack‐years Exclusion criteria: other respiratory conditions, significant inflammatory condition other than COPD, chronic or prophylactic antibiotic use, moderate or severe COPD exacerbation, lower tract infection 4 weeks before randomisation Maintenance systemic steroids were not allowed at start of study
Interventions	Treatment arms Salmeterol xinafoate 50 µg and fluticasone propionate 500 µg inhalation powder; dosage of 1 inhalation twice daily via single Diskus inhaler (SFC) Salmeterol xinafoate 50 µg and fluticasone propionate 500 µg inhalation powder; dosage of 1 inhalation twice daily via 2 separate Diskus inhalers (sal/FP) Allowed co‐medications: individual existing therapy
Outcomes	Primary outcome: compliance to inhalers
Notes	Funding: GlaxoSmithKline Identifiers: NCT00527826
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Reported as randomised, but no further information.
Allocation concealment (selection bias)	Unclear risk	No further information.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Unblinded trial.
Blinding of outcome assessment (detection bias) all outcomes	High risk	Unblinded trial.
Incomplete outcome data (attrition bias) all outcomes	High risk	Higher rate of attrition in the treatment group (24%) vs control (19.4%).
Selective reporting (reporting bias)	High risk	Trial was registered on website; however, some outcomes were not reported in the publication, but were reported on the trial website. Mortality was not reported on the trial website but was reported in the publication.
Other bias	Low risk	None identified.