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

Abstract

BackgroundCough and sputum are troublesome symptoms in chronic obstructive pulmonary disease (COPD) and are associated with adverse outcomes. The efficacy of aclidinium bromide 400 µg 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.MethodPatients were randomised to placebo, aclidinium 200 µg or 400 µg twice daily in ACCORD (12 weeks) and ATTAIN (24 weeks), or to placebo, aclidinium 400 µg twice daily or tiotropium 18 µg 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.ResultsData for 1792 patients were evaluated. E-RS cough/sputum domain scores were significantly reduced with aclidinium 400 µg 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).ConclusionsAclidinium 400 µg twice daily improves cough and sputum expectoration versus placebo in stable COPD.Trial registration numbersNCT00891462; NCT01001494; NCT01462929.

<p>A Real-World Observational Study Examining the Impact of Aclidinium Bromide Therapy on the Quality of Life, Symptoms, and Activity Impairment of Patients with Chronic Obstructive Pulmonary Disease: The Greek ON-AIR Study</p>

“…Similar findings have been reported in other real-world studies after 12 weeks of aclidinium bromide treatment, [19][20][21] complementing the data from earlier Phase III studies. 18,26 As we expected, improvements in symptom severity were accompanied by a decrease in the number of nocturnal awakenings.…”

“…10 Moreover, aclidinium-induced improvements in cough and sputum symptoms are supported by its antitussive activity, which is mediated by acid-sensing ion channels and mechanoreceptors. 26 These characteristics of aclidinium may explain why in a phase IIIb study, aclidinium, but not tiotropium, compared to placebo yielded significant reductions in the severity of night-time and individual early-morning (cough, wheeze, shortness of breath, and phlegm) symptoms, as well as an improvement in activity limitation due to COPD symptoms. 18 Improvement in symptom severity should be a priority for patients with COPD, as symptoms have been associated with disease exacerbations, as well as with daily activity impairment, physical activity and sleep impairments, anxiety, and depression.…”

Palliative care and management of troublesome symptoms for people with chronic obstructive pulmonary disease

“…Optimal respiratory management includes mucolytics treating infection, and sputum clearance physiotherapy as appropriate. 74 Nonpharmacological treatments for refractory cough may include patient education on cough reflex hyper-sensitivity and the effect of repeated coughing, laryngeal hygiene and hydration, e.g. through use of nasal breathing, cough control techniques, and psychoeducation counselling.…”

Daytime symptoms of chronic obstructive pulmonary disease: a systematic review

“…23,28, These articles related to clinical studies of pharmacotherapy for COPD, and included evaluations of shortacting muscarinic antagonists (SAMA; ipratropium), long-acting muscarinic antagonists (LAMA; aclidinium, glycopyrronium, tiotropium), short-acting β 2 -agonists (SABA; albuterol, salbutamol), long-acting β 2 -agonists (LABA; indacaterol, formoterol, salmeterol), and inhaled corticosteroids (ICS; fluticasone, budesonide), either alone or in different combinations. Eighteen articles reported on placebo-controlled studies; 17 articles showed that the tested active therapies/combinations provided statistically significant improvements in daytime symptomatology compared with placebo 23,40,42,44,[46][47][48][49][50][51]54,[56][57][58][59]61,64 and one study reported significant improvement in 24-h lung function with twice-daily LAMA/LABA compared with placebo. 65 Combinations consisting of LAMA/LABA (±ICS) tended to improve daytime symptoms more effectively than either LABA or LAMA monotherapy.…”