Effect of aclidinium bromide on cough and sputum symptoms in moderate-to-severe COPD in three phase III trials

Background: Cough and sputum are troublesome symptoms in chronic obstructive pulmonary disease (COPD) and are associated with adverse outcomes. The efficacy of aclidinium bromide 400 mu g twice daily in patients with stable COPD has been established in two phase III studies (ACCORD COPD I and ATTAIN) and a phase IIIb active-comparator study. This analysis evaluated cough-related symptoms across these studies. Method: Patients were randomised to placebo, aclidinium 200 mu g or 400 mu g twice daily in ACCORD (12 weeks) and ATTAIN (24 weeks), or to placebo, aclidinium 400 mu g twice daily or tiotropium 18 mu g once daily (6-week active-comparator study). Analysed end points included changes from baseline in Evaluating Respiratory Symptoms (E-RS; formerly known as EXAcerbations of Chronic pulmonary disease Tool), total and cough/sputum scores and frequency/severity of morning and night-time cough and sputum symptoms. Results: Data for 1792 patients were evaluated. E-RS cough/sputum domain scores were significantly reduced with aclidinium 400 mu g versus placebo in ATTAIN (-0.7 vs -0.3, respectively; p<0.01) and the active-comparator study (-0.6 vs -0.2, respectively; p<0.01). In the active-comparator study, significantly greater improvements were observed with aclidinium versus placebo for severity of morning cough (-0.19 vs -0.02; p<0.01) and phlegm (-0.19 vs -0.02; p<0.05). In ACCORD, aclidinium reduced night-time cough frequency (-0.36 vs 0.1 for placebo; p<0.001) and severity (-0.24 vs -0.1 for placebo; p<0.05), and frequency of night-time sputum production (-0.37 vs 0.05 for placebo; p<0.001). Conclusions: Aclidinium 400 mu g twice daily improves cough and sputum expectoration versus placebo in stable COPD.