Albert 2011.

Study characteristics
Methods	Design: randomised, double‐blind, placebo‐controlled, parallel‐group design Duration: 52 weeks Location: 17 sites associated with 12 academic health centres across the USA
Participants	Population: 1142 adults with moderate to severe COPD were randomly assigned to azithromycin (n = 570) or placebo (n = 572) Baseline characteristics: age (mean years): 65.5 (SD 8.5); % male (mean): 59; % FEV₁ predicted (mean): 39.5 (SD 16); pack‐years (mean): 58.5 (SD 32); exacerbation history. Approximately 50% of participants in each treatment arm had required hospitalisation or an ED visit in the previous 12 months Inclusion criteria: severity of COPD moderate or worse as defined by GOLD criteria; mean FEV₁ (L): 1.10 (SD 0.50) (azithromycin) and 1.12 (SD 0.52) (placebo); presence of either (a) using continuous supplemental oxygen or (b) received systemic glucocorticoids within the previous year/had gone to an emergency room/hospitalisation for an acute exacerbation; no acute exacerbation of COPD for at least 4 weeks Exclusion criteria: asthma; resting heart rate > 100/min; prolonged QT interval > 450 ms; using medications that prolong QTc; hearing impairment documented by audiometry
Interventions	Azithromycin (250 mg daily) Placebo Allowed co‐medications: supplemental oxygen or systemic glucocorticoids received in the last year
Outcomes	Number of people with ≥1 exacerbations, time to first acute exacerbation of COPD, quality of life (SGRQ, SF‐36), nasopharyngeal colonisation with selected respiratory pathogens, adherence to taking study medication as prescribed, serious adverse events.
Notes	Funding: National Institutes of Health Identifier: NCT00325897
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The stratified random sequence generation was well described in the journal article under "protocol"
Allocation concealment (selection bias)	Low risk	Well explained. Central allocation was pharmacy controlled
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Active drug and placebo will be identical in appearance. Both patients and treating medical staff were blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Trial staff were unaware of the randomisation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All outcome data were accounted for in a CONSORT diagram for the entire study However data on the secondary outcome: HRQoL ‐ reported loss to follow‐up of 20% in the prophylactic antibiotic arm and 18% in the placebo arm. Reasons for missing data pertaining to HRQoL were not given
Selective reporting (reporting bias)	Low risk	All pre‐specified outcomes were reported
Other bias	Low risk	No other bias was identified