Berkhof 2013.

Study characteristics
Methods	Design: randomised, double‐blind, placebo‐controlled, parallel‐group design Duration: 12 weeks Location: 1 large teaching hospital in Zwolle, Netherlands
Participants	Population: 84 adults with COPD (GOLD stage ≥ 2) were randomly assigned to azithromycin (n = 42) or placebo (n = 42) Baseline characteristics: age (mean years): 67.5 (SD 9.5); % male (mean): 75; % FEV₁ predicted (mean): 48.6 (SD 14.6); pack‐years (median): azithromycin 30.5 (range 0 to 46), placebo 30 (range 1 to 69); exacerbation history: participants had a median of 1 exacerbation (range 0 to 13) in the previous 12 months Inclusion criteria: mean % FEV₁ predicted 49.8 (SD 16.4) (azithromycin) and 47.4 (SD 12.9) (placebo); clinical diagnosis of COPD GOLD stage ≥ 2 (defined as post‐bronchodilator FEV₁ < 80% and ratio of FEV₁‐to‐FVC < 70%); chronic productive cough, defined as cough for at least the last 12 weeks, in 2 subsequent years Exclusion criteria: prior history of asthma; use of intravenous or OCS and/or antibiotics for an exacerbation 3 weeks before inclusion; other relevant lung or liver disease at the discretion of the treating physician; pregnancy or lactation; use of macrolides in the last 6 weeks before inclusion; allergy or intolerance to macrolides; use of other investigational medication started 2 months before inclusion
Interventions	Azithromycin (250 mg 3 times a week) Placebo Allowed co‐medications: long‐term treatment with aerosolised antibiotics, inhaled corticosteroids, and/or bronchodilators was permitted during the trial provided that it was kept constant
Outcomes	LCQ, quality of life (SGRQ, SF‐36), spirometry (FEV₁, % FEV₁ predicted), blood values, microbiology. Other endpoints included number of people with ≥ 1 exacerbations, time to first exacerbation of COPD, exacerbation rates and hospitalisation rates for COPD, adverse events
Notes	Funding: Stichting Astma Bestrijding (SAB) Identifier: NCT01071161
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation codes were generated using a computer allocation programme at a 1:1 ratio and a permutated block size of 4
Allocation concealment (selection bias)	Unclear risk	This was not specifically described but was probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Investigators, research nurses, and participants were masked to treatment allocation until final analyses of data were performed
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigators, research nurses, and participants were masked to treatment allocation until final analyses of data were performed
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropout was low and balanced. All participants were accounted for in a flow diagram
Selective reporting (reporting bias)	Low risk	Outcomes were measured but were not reported in a way that allowed inclusion in meta‐analysis in the published paper, but study authors supplied additional data on request
Other bias	Low risk	No other bias was identified