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

Lorcan McGarvey, Alyn H Morice, Jaclyn A Smith, Surinder S Birring, Ferran Chuecos, Beatriz Seoane, Diana Jarreta, Lorcan McGarvey, Alyn H Morice, Jaclyn A Smith, Surinder S Birring, Ferran Chuecos, Beatriz Seoane, Diana Jarreta

Abstract

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 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.

Method: Patients 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.

Results: Data 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).

Conclusions: Aclidinium 400 µg twice daily improves cough and sputum expectoration versus placebo in stable COPD.

Trial registration numbers: NCT00891462; NCT01001494; NCT01462929.

Keywords: COPD Pharmacology; Cough/Mechanisms/Pharmacology.

Conflict of interest statement

LMG has received honoraria and travel support from AstraZeneca. AHM has received honoraria, travel support and unrestricted grant aid from AstraZeneca. JAS is an inventor on a patent owned by the University Hospital South Manchester covering automated detection of cough from sound signals, and the patent is the subject of a license agreement with Vitalograph Ltd. (Buckinghamshire, UK); has received honoraria from Almirall and holds an MRC project grant part-funded by AstraZeneca. SSB received an honorarium for a scientific advisory board from Almirall. FC, BS and DJ are employees of AstraZeneca PLC and former employees of Almirall, Barcelona, Spain.

Figures

Figure 1
Figure 1
Change from baseline in (A) E-RS total score and (B) E-RS cough and sputum domain score over the study period in ATTAIN and the active-comparator study. Data are reported as LS mean+SE. E-RS total score ranged from 0 to 40; E-RS cough and sputum domain score ranged from 0 to 11. Higher scores indicate more severe symptoms. *p

Figure 2

Percentage of days with (A)…

Figure 2

Percentage of days with (A) morning symptoms and (B) night-time symptoms over the…

Figure 2
Percentage of days with (A) morning symptoms and (B) night-time symptoms over the study period in ATTAIN. Data are reported as least squares mean. **p

Figure 3

Change from baseline in the…

Figure 3

Change from baseline in the severity of morning cough and severity of difficulty…

Figure 3
Change from baseline in the severity of morning cough and severity of difficulty bringing up phlegm in the morning over the study period in the active-comparator study. Data are reported as LS mean+SE. Assessed on a 5-point scale: 0=‘no symptoms’ to 4=‘very severe symptoms’. *p

Figure 4

Change from baseline in the…

Figure 4

Change from baseline in the severity of night-time cough and the frequency of…

Figure 4
Change from baseline in the severity of night-time cough and the frequency of night-time sputum production at week 12 in ACCORD COPD I. Data are reported as mean+SE. Symptom frequency assessed on a 5-point scale: 0=‘never’ to 4=‘7 or more times’. Symptom severity assessed on a 5-point scale: 0=‘no symptoms’ to 4=‘severe symptoms that interfered with normal daily activities’. *p
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References
    1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2015. http://www.goldcopd.org (accessed 20 Feb 2016). - PMC - PubMed
    1. Vestbo J, Prescott E, Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med 1996;153:1530–5. doi:10.1164/ajrccm.153.5.8630597 - DOI - PubMed
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Figure 2
Figure 2
Percentage of days with (A) morning symptoms and (B) night-time symptoms over the study period in ATTAIN. Data are reported as least squares mean. **p

Figure 3

Change from baseline in the…

Figure 3

Change from baseline in the severity of morning cough and severity of difficulty…

Figure 3
Change from baseline in the severity of morning cough and severity of difficulty bringing up phlegm in the morning over the study period in the active-comparator study. Data are reported as LS mean+SE. Assessed on a 5-point scale: 0=‘no symptoms’ to 4=‘very severe symptoms’. *p

Figure 4

Change from baseline in the…

Figure 4

Change from baseline in the severity of night-time cough and the frequency of…

Figure 4
Change from baseline in the severity of night-time cough and the frequency of night-time sputum production at week 12 in ACCORD COPD I. Data are reported as mean+SE. Symptom frequency assessed on a 5-point scale: 0=‘never’ to 4=‘7 or more times’. Symptom severity assessed on a 5-point scale: 0=‘no symptoms’ to 4=‘severe symptoms that interfered with normal daily activities’. *p
Similar articles
Cited by
References
    1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2015. http://www.goldcopd.org (accessed 20 Feb 2016). - PMC - PubMed
    1. Vestbo J, Prescott E, Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med 1996;153:1530–5. doi:10.1164/ajrccm.153.5.8630597 - DOI - PubMed
    1. Burgel PR, Nesme-Meyer P, Chanez P et al. . Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009;135:975–82. doi:10.1378/chest.08-2062 - DOI - PubMed
    1. Lindberg A, Sawalha S, Hedman L et al. . Subjects with COPD and productive cough have an increased risk for exacerbations and death. Respir Med 2015;109:88–95. doi:10.1016/j.rmed.2014.12.001 - DOI - PubMed
    1. Hogg JC, Chu F, Utokaparch S et al. . The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645–53. doi:10.1056/NEJMoa032158 - DOI - PubMed
Show all 47 references
Associated data
Related information
LinkOut - more resources
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

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The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

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Figure 3
Figure 3
Change from baseline in the severity of morning cough and severity of difficulty bringing up phlegm in the morning over the study period in the active-comparator study. Data are reported as LS mean+SE. Assessed on a 5-point scale: 0=‘no symptoms’ to 4=‘very severe symptoms’. *p

Figure 4

Change from baseline in the…

Figure 4

Change from baseline in the severity of night-time cough and the frequency of…

Figure 4
Change from baseline in the severity of night-time cough and the frequency of night-time sputum production at week 12 in ACCORD COPD I. Data are reported as mean+SE. Symptom frequency assessed on a 5-point scale: 0=‘never’ to 4=‘7 or more times’. Symptom severity assessed on a 5-point scale: 0=‘no symptoms’ to 4=‘severe symptoms that interfered with normal daily activities’. *p
Similar articles
Cited by
References
    1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2015. http://www.goldcopd.org (accessed 20 Feb 2016). - PMC - PubMed
    1. Vestbo J, Prescott E, Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med 1996;153:1530–5. doi:10.1164/ajrccm.153.5.8630597 - DOI - PubMed
    1. Burgel PR, Nesme-Meyer P, Chanez P et al. . Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009;135:975–82. doi:10.1378/chest.08-2062 - DOI - PubMed
    1. Lindberg A, Sawalha S, Hedman L et al. . Subjects with COPD and productive cough have an increased risk for exacerbations and death. Respir Med 2015;109:88–95. doi:10.1016/j.rmed.2014.12.001 - DOI - PubMed
    1. Hogg JC, Chu F, Utokaparch S et al. . The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645–53. doi:10.1056/NEJMoa032158 - DOI - PubMed
Show all 47 references
Associated data
Related information
LinkOut - more resources
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 4
Figure 4
Change from baseline in the severity of night-time cough and the frequency of night-time sputum production at week 12 in ACCORD COPD I. Data are reported as mean+SE. Symptom frequency assessed on a 5-point scale: 0=‘never’ to 4=‘7 or more times’. Symptom severity assessed on a 5-point scale: 0=‘no symptoms’ to 4=‘severe symptoms that interfered with normal daily activities’. *p

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