Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial

Alberto Papi, Jorgen Vestbo, L Fabbri, Massimo Corradi, Hélène Prunier, Géraldine Cohuet, Alessandro Guasconi, Isabella Montagna, S. Vezzoli, Stefano Petruzzelli, Mario Scuri, Nicolas Roche, Dave Singh

Research output: Contribution to journalArticlepeer-review

144 Downloads (Pure)

Abstract

Background
Evidence is scarce on the relative risk-benefit of inhaled triple therapy, consisting of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist, versus dual bronchodilation for chronic obstructive pulmonary disease (COPD). We aimed to compare a single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium (IND/GLY) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment.

Methods
This randomised, parallel-group, double-blind, double-dummy study was done at 187 sites across 17 countries. Eligible patients had symptomatic COPD, severe or very severe airflow limitation, at least one moderate or severe exacerbation in the previous year, and were receiving inhaled maintenance medication. After a 2 week run-in period with one inhalation per day of IND/GLY (85 μg/43 μg), patients were randomly assigned (1:1), via an interactive response technology system, to receive 52 weeks of treatment with two inhalations of extrafine BDP/FF/G (87 μg/5 μg/9 μg) twice per day or one inhalation of IND/GLY (85 μg/43 μg) per day. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was the rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment in all randomised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02579850.

Findings
Between May, 29 2015, and July 10, 2017, 1532 patients received BDP/FF/G (n=764) or IND/GLY (n=768). Moderate-to-severe exacerbation rates were 0·50 per patient per year (95% CI 0·45–0·57) for BDP/FF/G and 0·59 per patient per year (0·53–0·67) for IND/GLY, giving a rate ratio of 0·848 (0·723–0·995, p=0·043) in favour of BDP/FF/G. Adverse events were reported by 490 (64%) of 764 patients receiving BDP/FF/G and 516 (67%) of 768 patients receiving IND/GLY. Pneumonia occurred in 28 (4%) patients receiving BDP/FF/G versus 27 (4%) patients receiving IND/GLY. One treatment-related serious adverse event occurred in each group: dysuria in a patient receiving BDP/FF/G and atrial fibrillation in a patient receiving IND/GLY.

Interpretation
In patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation history despite maintenance therapy, extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY, without increasing the risk of pneumonia.
Original languageEnglish
Pages (from-to)1076-1084
Number of pages9
JournalThe Lancet
Volume391
Issue number10125
Early online date8 Feb 2018
DOIs
Publication statusPublished - 17 Mar 2018

Keywords

  • Combination drug therapy
  • Pulmonary disease
  • Chronic obstructive
  • bronchitis
  • chronic
  • Pulmonary emphysema
  • Lung
  • Airway obstruction

Fingerprint

Dive into the research topics of 'Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial'. Together they form a unique fingerprint.

Cite this