Long-Term Evaluation of the Effects of Aclidinium Bromide on Major Adverse Cardiovascular Events and COPD Exacerbations in Patients with Moderate to Very Severe COPD: Rationale and Design of the ASCENT COPD Study.

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness characterized by persistent airflow obstruction and exacerbations. Patients typically experience a decline in lung function, increasingly impaired health-related quality of life, and high mortality. Poor lung function and exacerbations are associated with an increased risk of cardiovascular (CV) and cerebrovascular events, and approximately 30% of patients with COPD die from CV‑related disease. Treatment with inhaled long-acting bronchodilators, such as long-acting muscarinic antagonists (LAMAs), is recommended; however, some studies have suggested that LAMAs may increase the risk of CV events. As patients with CV and cerebrovascular conditions are often excluded from clinical trials, an evaluation of the safety of COPD treatments in an at-risk population is vital. Aclidinium bromide is a LAMA approved for the long-term maintenance treatment of COPD. Methods and Objectives: The Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group Aclidinium Bromide on Long-Term Cardiovascular Safety and COPD Exacerbations in PatieNTs with Moderate to Very Severe COPD (ASCENT COPD) study (NCT01966107) is being conducted at 500 sites in the United States and Canada. The primary objectives are to evaluate the long-term effects of twice-daily aclidinium bromide 400 µg on CV safety and exacerbations in patients with moderate to very severe COPD with a history of cerebrovascular, coronary, or peripheral artery disease, or the presence of ≥2 atherothrombotic risk factors. The primary safety and efficacy variables are time to first major adverse CV event (MACE) (on-study analysis) and rate of moderate to severe COPD exacerbations during the first year of treatment (on-treatment analysis), respectively. The study will be terminated after approximately 122 MACE have occurred.