Uzun 2014.

Study characteristics
Methods	Design: randomised, double‐blind, placebo‐controlled, single‐centre design. Duration: 52 weeks Location: a hospital in the Netherlands
Participants	Population: 92 adults with mild to very severe COPD were randomly assigned to azithromycin (n = 47) or placebo (n = 45) Baseline characteristics: age (mean); 64.8 (SD 10.2); FEV₁ (L): 1.1 (SD 0.45); % FEV₁ predicted: 44.6 (SD 19,4); FEV₁‐to‐FVC (mean %, SD): 39.2 (SD 12), exacerbation history: participants had a mean of 4 (SD 1.1) acute exacerbations in the previous 12 months Inclusion criteria: mean % FEV₁ predicted: 44.2 (SD 19.3) (azithromycin) and 45.0 (SD 19.5) (placebo). Diagnosis of COPD according to GOLD guidelines; had received treatment for ≥ 3 exacerbations of COPD in the previous year for which they received steroids or antibiotic treatment; clinically stable; could not have had a COPD exacerbation or respiratory tract infection in the month before involvement in the study Exclusion criteria: history of other clinically significant respiratory disease (e.g. asthma, cystic fibrosis); presence of bronchiectasis, as assessed by CT scan; maintenance antibiotic treatment; use of > 10 mg prednisolone a day; allergy to macrolides; pregnancy or lactation in women; liver disease (alanine transaminase or aspartate transaminase concentrations that were ≥ 2 times the upper limit of normal); malignant disease of any kind for which the patient received treatment or was being monitored as part of follow‐up after treatment; heart failure; use of drugs that could adversely interact with macrolides and for which therapeutic monitoring could not be undertaken
Interventions	Azithromycin (500 mg 3 times a week) Placebo Allowed co‐medications: no more than 10 mg prednisolone per day. No maintenance antibiotic treatment was allowed
Outcomes	Rate of COPD exacerbations, time to first exacerbation, hospital admission for acute exacerbations, change in proportion of exacerbations needing admission to hospital vs treatment in an outpatient department compared with the previous year, treatment for an acute COPD exacerbation, FEV₁ after bronchodilation, FVC after bronchodilation, 6MWT, quality of life (SF36 and SGRQ), colonisation of macrolide‐resistant micro‐organisms in sputum, adverse events
Notes	Funding: SoLong (Department of Respiratory Medicine, Amphia Hospital, Breda, The Netherlands) Identifier: NCT00985244
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	An independent pharmacy randomly assigned patients (1:1) via a computer‐generated randomisation sequence with permutated blocks of 10
Allocation concealment (selection bias)	Low risk	Patients were automatically given the next allocated treatment by clinical trials staff at the hospital pharmacy. Participants and investigators were masked to treatment allocation throughout the study
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and investigators were masked to treatment allocation throughout the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	After data collection and data cleaning were completed, and after final database lock, investigators were unmasked and could assess outcomes and complete the data analysis
Incomplete outcome data (attrition bias) All outcomes	Low risk	Higher dropout was reported in the placebo arm, but results from unadjusted and adjusted per‐protocol analyses were almost identical to those from the intention‐to‐treat analysis, and all participants were included in the safety analysis
Selective reporting (reporting bias)	Low risk	Planned outcomes according to trial registration relevant to this review were reported
Other bias	Low risk	No other bias was identified