Albert 2011.

Methods	Prospective, randomised, double‐blind, placebo‐controlled clinical trial with 12‐month treatment duration Intention‐to‐treat analysis
Participants	N = 1142. Aged 40 years or over. Mean age (years): 65 (azithromycin) and 66 (placebo) 41% female 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 Exclusions: asthma, resting heart rate > 100/min, prolonged QT interval > 450 ms, using medications that prolong QTc, hearing impairment documented by audiometry
Interventions	Prophylaxis: 1. Azithromycin 250 mg daily 2. Placebo
Outcomes	Primary: 1. Time to the first acute exacerbation of COPD Secondary: 1. Quality of life 2. Nasopharyngeal colonisation of selected respiratory pathogens 3. Compliance to the treatment 4. Adverse events
Notes	Funding: Grants listed from National Institutes of Health
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": "Randomization will be carried out by linking to the Data Coordinating Center through a website, (http://www.copdcrn.org)".
Allocation concealment (selection bias)	Low risk	Well explained. Central allocation was pharmacy controlled: "Only the pharmacist and the staff of the Data Coordinating Center knew this schedule and the pharmacists could not know the actual assignment until after the DCC specified an accession number. Treatment assignment was only disclosed in cases of emergency."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Active drug and placebo will be identical in appearance. Both participants and treating medical staff were blinded: "The actual assignment will only be revealed in cases of emergencies where caregivers need to know what drugs the person was taking to provide treatment, or to avoid prescribing other medications that might adversely interact with the study drug. Active‐drug and placebo capsules will be identical in appearance."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Trial staff were unaware of the randomisation: "Clinic staff (who undertook outcome assessment) will make no attempt to determine the content of any capsules except in cases of emergency".
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All outcome data accounted for in a consort diagram for the entire study. However, data on the secondary outcome (HRQoL) had reported loss to follow‐up of 20% in the prophylactic antibiotic arm and 18% on the placebo arm. The reasons for the missing data pertaining to HRQoL were not given.
Selective reporting (reporting bias)	Low risk	All prespecified outcomes have been reported
Other bias	Low risk	No other bias identified