Reduction in clinically important deterioration in chronic obstructive pulmonary disease with aclidinium/formoterol

Respir Res. 2017 May 30;18(1):106. doi: 10.1186/s12931-017-0583-0.

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 (FEV1; ≥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.

Keywords: Bronchodilation; COPD; Chronic respiratory disease; LABA; LAMA.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Clinical Deterioration*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Forced Expiratory Volume
  • Formoterol Fumarate / adverse effects
  • Formoterol Fumarate / therapeutic use*
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Muscarinic Antagonists / adverse effects
  • Muscarinic Antagonists / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • Tropanes / adverse effects
  • Tropanes / therapeutic use*

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Drug Combinations
  • Muscarinic Antagonists
  • Tropanes
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT01462942
  • ClinicalTrials.gov/NCT01437397