1. Reduction in clinically important deterioration in chronic obstructive pulmonary disease with aclidinium/formoterol.
- Author
-
Singh D, D'Urzo AD, Chuecos F, Muñoz A, and Garcia Gil E
- Subjects
- Adrenergic beta-2 Receptor Agonists adverse effects, Bronchodilator Agents adverse effects, Double-Blind Method, Drug Combinations, Female, Forced Expiratory Volume, Formoterol Fumarate adverse effects, Humans, Lung physiopathology, Male, Middle Aged, Muscarinic Antagonists adverse effects, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive physiopathology, Severity of Illness Index, Surveys and Questionnaires, Time Factors, Treatment Outcome, Tropanes adverse effects, Adrenergic beta-2 Receptor Agonists therapeutic use, Bronchodilator Agents therapeutic use, Clinical Deterioration, Formoterol Fumarate therapeutic use, Lung drug effects, Muscarinic Antagonists therapeutic use, Pulmonary Disease, Chronic Obstructive drug therapy, Tropanes therapeutic use
- Abstract
Background: 'Clinically important deterioration' (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations. ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg. This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD., Methods: A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV
1 ; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George's Respiratory Questionnaire (SGRQ) total score (≥4 units). A 'sustained' CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time. CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18., Results: AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05). Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01). AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05)., Conclusions: AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies., Trial Registration: Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011. Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.- Published
- 2017
- Full Text
- View/download PDF