Capturing Exacerbations of Chronic Obstructive Pulmonary Disease with EXACT. A Subanalysis of FLAME

Am J Respir Crit Care Med. 2019 Jan 1;199(1):43-51. doi: 10.1164/rccm.201801-0038OC.

Abstract

Rationale: Chronic obstructive pulmonary disease exacerbations accelerate lung function decline, reduce quality of life, and increase mortality. A subset of patients (n = 457) from the FLAME (Effect of Indacaterol Glycopyrronium vs. Fluticasone Salmeterol on COPD Exacerbations) study used the Exacerbations of COPD Tool (EXACT) to capture symptom-defined exacerbations.

Objectives: To evaluate the effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on symptom-defined exacerbations measured using EXACT, and to assess differences between these events and exacerbations requiring healthcare resource use (HCRU).

Methods: All patients in FLAME used an electronic diary to record and detect symptom deteriorations; HCRU-related exacerbations were confirmed by investigators. In patients using the EXACT questionnaire, the onset, recovery, and magnitude of symptom-defined exacerbations were identified by changes in total scores relative to baseline. We analyzed the annualized rate and time to first symptom-defined (EXACT) exacerbation and assessed differences between symptom-defined and HCRU events in terms of number, severity, and concordance.

Measurements and main results: A nonsignificant 17% reduction in the annualized rate of symptom-defined (EXACT) exacerbations (rate ratio, 0.83; 95% confidence interval [CI], 0.60-1.14; P = 0.242) and a numerically longer time to first symptom-defined exacerbation were observed with indacaterol/glycopyrronium versus salmeterol/fluticasone (hazard ratio, 0.76; 95% CI, 0.56-1.03; P = 0.075). These results were consistent with data from the overall FLAME population. Of the symptom-defined (EXACT) events, 23.5% corresponded to HCRU events, and 22.2% of HRCU events were captured by EXACT (κ index, 0.24; 95% CI, 0.15-0.33).

Conclusions: Regardless of the exacerbation definition used, our findings support the use of long-acting β2 agonists/long-acting muscarinic receptor antagonists as the preferred treatment option for patients at risk of future exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).

Keywords: concordance; defined symptom; exacerbation; treatment.

Publication types

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

MeSH terms

  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Fluticasone / administration & dosage
  • Fluticasone / therapeutic use*
  • Glycopyrrolate / administration & dosage
  • Glycopyrrolate / therapeutic use*
  • Humans
  • Indans / administration & dosage
  • Indans / therapeutic use*
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / prevention & control*
  • Quinolones / administration & dosage
  • Quinolones / therapeutic use*
  • Risk Factors
  • Salmeterol Xinafoate / administration & dosage
  • Salmeterol Xinafoate / therapeutic use*
  • Surveys and Questionnaires

Substances

  • Bronchodilator Agents
  • Indans
  • Quinolones
  • Salmeterol Xinafoate
  • indacaterol
  • Fluticasone
  • Glycopyrrolate

Associated data

  • ClinicalTrials.gov/NCT01782326