ACCLAIM II 2009.

Methods	Design: double‐blind, randomised, placebo‐controlled, parallel‐group study Duration: 52 weeks (+ 2 week run‐in) Location: 119 sites in 7 countries (primarily in North America)
Participants	Population: 804 participants were randomised to aclidinium (600) and placebo (204) Baseline characteristics Age (mean years): Acl 65.1, Pbo 65.2 % Male: Acl 63.8, Pbo 60.8 % FEV1 predicted (post BD): Acl 50.6, Pbo 49.4 Pack‐years (mean): Acl 57.8, Pbo 58.2 Inclusion criteria: Male and non‐pregnant, non‐lactating female patients aged ≥40 years were included if they had a diagnosis of COPD according to GOLD criteria, with a post‐bronchodilator FEV1/FVC ratio of ≤70% and FEV1 <80% of the predicted value. The pre‐dose FEV1 at randomisation had to be within 80‐120% of the pre‐bronchodilator FEV1 at screening. All patients were current or previous cigarette smokers with a smoking history of ≥10 pack‐years. A previous history of exacerbations was not required. Exclusion criteria: history or current diagnosis of asthma, allergic rhinitis or atopy; blood eosinophil count >600 cell/mm3; respiratory tract infection or COPD exacerbation within 6 weeks prior to screening or during the run‐in period; hospitalisation for an acute COPD exacerbation within 3 months prior to screening; use of long‐term oxygen therapy; clinically significant respiratory diseases other than COPD; unstable cardiac conditions.
Interventions	1. Aclidinium 200 qd (LAMA) 2. Placebo (PBO) Inhaler device: Genuair Allowed co‐medications: Inhaled salbutamol was permitted on an as‐needed basis, but had to be discontinued 6 hours prior to and during a study visit. Inhaled corticosteroids or oral sustained‐release theophyllines; oral or parenteral corticosteroids at maximal doses equivalent to 10 mg/day of prednisone or 20 mg every other day; oxygen therapy (<15 hours per day) were allowed, provided their administration had been stable for at least 4 weeks prior to screening:
Outcomes	Trough FEV1, St George's Respiratory Questionnaire (SGRQ), and time to first moderate or severe COPD exacerbation
Notes	Funding: Almirall, S. A., Barcelona, Spain, and Forest Laboratories, Inc, NY, USA Identifier(s): NCT00358436
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible patients were randomised in a 3:1 ratio to receive aclidinium 200 mcg or matching placebo. Industry funded.
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, matching placebo
Blinding of outcome assessment (detection bias) All outcomes	Low risk	A centralised quality‐assurance review of all spirometry data was conducted throughout the study. The spirometry data were electronically transmitted to a data‐management centre where an independent, blinded, spirometric expert reviewed the acceptability and repeatability of the data according to ATS/ERS acceptability criteria. SGRQ self‐rated
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropout much higher in placebo group and high in both (42.2% versus 25.7 in aclidinium group). ITT included 99% of those randomised but high dropout is likely to have introduced bias.
Selective reporting (reporting bias)	Low risk	Trial registration located. Outcomes well reported.