PURPOSE: ATTAIN investigated the efficacy and safety of twice-daily aclidinium bromide (200 or 400 µg), a long-acting muscarinic antagonist, on exacerbation rate in patients with moderate-to-severe COPD.
METHODS: In this 24-week, double-blind trial, patients (mean forced expiratory volume in 1 second [FEV1] 56.8±12.8% predicted) were randomized (1:1:1) to aclidinium (200 or 400 µg) or placebo, twice daily. Prior history of exacerbations was not an inclusion criterion. Exacerbations were a secondary endpoint and were assessed by healthcare resource utilization (HCRU; increased symptoms on ≥2 consecutive days that required a change in treatment) and the EXACT (EXAcerbations of Chronic pulmonary disease Tool) daily diary card (using the developer’s criteria for an exacerbation). Endpoints included exacerbation rate, number of patients with ≥1 exacerbation, and exacerbation duration.
RESULTS: A total of 828 patients were randomized; the intention-to-treat population was 819 patients. EXACT captured more exacerbations than HCRU (EXACT: 1.0, 0.98, and 1.39 exacerbations per patient per year for aclidinium 200 µg, 400 µg, and placebo, respectively; HCRU: 0.43, 0.40, and 0.60 exacerbations per patient per year, respectively). Exacerbation frequency was significantly lower for both aclidinium doses compared with placebo (rate ratio difference - EXACT: 200 µg, 0.72 [p=0.017] and 400 µg, 0.71 [p=0.012]; HCRU: 200 µg, 0.72 [p=0.043] and 400 µg, 0.67 [p=0.020]). The percentage of patients with ≥1 exacerbation was lower with aclidinium compared with placebo, but did not reach statistical significance (either dose or definition).
CONCLUSIONS: Despite the low rate of exacerbations reported, both doses of aclidinium (200 and 400 µg) reduced the number of exacerbations compared with placebo as assessed by HCRU and EXACT.
CLINICAL IMPLICATIONS: These results indicate that aclidinium could be a valuable new option for the treatment of COPD and related exacerbations. EXACT captured more exacerbations than HCRU. This study was supported by Almirall S.A., Barcelona, Spain, and Forest Laboratories, Inc, New York, USA.
DISCLOSURE: Paul Jones: Consultant fee, speaker bureau, advisory committee, etc.: Consultancy fees charged through my University
David Singh: Other: Lecture fees, research grants, consultancy fees and support for conference attendance from companies including AstraZeneca, GlaxoSmithKline, Boehringer Inghelheim, Chiesi and Roche
Alvar Agusti: Other: Member of advisory boards, grant money and funding for accommodation and travel from Almirall
Eric Bateman: Grant monies (from industry related sources): Institution for clinical trial participation (not to self), Consultant fee, speaker bureau, advisory committee, etc.: Advisory board and consultancy payments from Almirall and Forest
Rosa Lamarca: Employee: Almirall
Gonzalo de Miquel: Employee: Almirall
Cynthia Caracta: Employee: Forest
Esther Garcia Gil: Employee: Almirall
Aclidinium bromide is a long-acting anti-muscarinic agent, property of Almirall S.A., which is being developed for the treatment of COPD. Aclidinium is not yet approved and the current presentation is about clinical trial results with this compound under research.