NCT00524095.

Methods	Prospective, randomised, controlled cross‐over trial. Open‐label. Planned 52 weeks treatment duration
Participants	Planned recruitment of 210 participants aged 45 to 85 years Smokers or former smokers of at least 10 pack‐years, COPD demonstrated by forced spirometry with FEV1 > 0.7 L, FEV1 post‐bronchodilator < 60% and FEV1/FVC < 70%, bronchodilator test performed at inclusion or no more than 6 months before inclusion should have been negative (increase in FEV1 < 200 mL and 12%, 10 minutes after administration of 2 puffs of salbutamol). Stable phase defined by clinical criteria of the attending investigator, but at least 6 weeks from the last exacerbation Exclusions: receiving OCS at any dose or another immunosuppressor, formal contraindication for sputum collection, or impossibility to obtain a sample of sputum valid for analysis, allergy to steroids or macrolides
Interventions	Prophylaxis: 1. Azithromycin 500 mg 3 times a week for 6 months and then inhaled steroids (fluticasone 500 μg twice a day) for 6 months 2. Inhaled steroids (fluticasone 500 μg twice a day) for 6 months and then azithromycin 500 mg 3 times a week for 6 months 3. Usual care
Outcomes	Primary 1. Effects of treatments on bronchial inflammation parameters Secondary: 2. Effects of treatments on exacerbations frequency (time frame: six months) 3. Effects of treatments on pulmonary function (time frame: six months)
Notes	NB: study terminated before treatment phase. Reason not given
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not assessed as study terminated before treatment phase
Allocation concealment (selection bias)	Unclear risk	Not assessed as study terminated before treatment phase
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not assessed as study terminated before treatment phase
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not assessed as study terminated before treatment phase
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not assessed as study terminated before treatment phase
Selective reporting (reporting bias)	Unclear risk	Not assessed as study terminated before treatment phase
Other bias	Unclear risk	Not assessed as study terminated before treatment phase