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. |