Methods	Parallel group design. Randomisation: computer generated. Numbers were generated off-site. Once a treatment number had been assigned to a participant it could not be assigned to any other participant. Blinding: Double blind. Participants received identically packaged and presented placebos. Excluded: Described. Withdrawals: Described. Trial duration: 2 week run-in period, 52 weeks treatment, 2-week follow-up Baseline characteristics: Comparable Intention to treat analysis: stated Jadad Score: 5
Participants	Setting: 196 centres in Europe, South Africa and Australia. Participants randomised: 719 (FPS: 358; PLA: 361) Additional treatment groups not covered in this review: SAL: 372; FP: 375. Baseline characteristics: Mean age 63 years, mean FEV1 = 1.26L (44% predicted). Inclusion criteria: Baseline FEV1 25 - 75% predicted; FEV1/FVC ratio </= 70%; Poor reversibility: < 10% increase of predicted FEV1 30 minutes after inhaling 400 mcg salbutamol; at least 10 pack years smoking history; history of exacerbations (at least 1 in the last year) requiring OCS and/or antibiotics. At least one episode of acute COPD per year in the previous 3 years. Exclusion criteria: respiratory disorders other than COPD. Oxygen treatment, systemic corti-costeroids, high doses of inhaled corticosteroids (>1000 mcg daily beclomethasone dipropionate, budesonide or flunisolide or > 500 mcg daily fluticasone) or antibiotics in the four weeks before the 2 week run-in period
Interventions	Run-in: 2 weeks. All maintenance treatment with ICS and LABA ceased FPS 50 mcg/500 mcg bid. Placebo Additional treatment groups not covered in this review: SAL 50 mcg bid. FP 500 mcg bid. Inhaler device: DPI
Outcomes	FEV1; PEF; exercise tolerance; quality of life: SGRQ; dyspnoea and symptoms (symptom score for shortness of breath, cough and sputum production); exacerbations (defined as requirement for antibiotics, oral steroids or both); rescue salbutamol use
Notes	FEV1 reversibility (% predicted normal) Mean Reversibility (% predicted) = 3.8
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Computer generated randomisation schedule.
Allocation concealment?	Yes	Numbers were generated off-site. Once a treatment number had been assigned to a participant it could not be assigned to any other participant
Blinding? All outcomes	Yes	Identical inhaler device

BD: bronchodilator; BDF: Budesonide/formoterol combination; bid: twice daily; BUD: Busesonide; CBSQ: Chronic bronchitis symptom questionnaire; CRDQ: Canadian respiratory disease questionnaire; F: Formoterol; FEV1: Forced expiratory volume in one second; FP: Fluticasone; FPS: Fluticasone/salmeterol combination; FVC: Forced vital capacity; ICS: inhaled corticosteroid; LABA: long acting beta agonist; LTOT: Long-term oxygen therapy; MMRC: Modified Medical Research Council; OCS: oral corticosteroids; PLA: Placebo; PRN: as needed; SABA: short acting beta agonist SAL: Salmeterol; SGRQ: St George respiratory questionnaire;