Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial

D Singh, Alberto Papi, Massimo Corradi, Ilona Pavlišová, Isabella Montagna, Catherine Francisco, Géraldine Cohuet, Stefano Vezzoli, Mario Scuri, Jorgen Vestbo

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

Background: Few data are available for the efficacy of “triple therapy” with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We designed this study to assess efficacy of single-inhaler combination of an extra fine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) in COPD compared with beclometasone dipropionate and formoterol fumarate (BDP/FF) treatment. Methods: TRILOGY was a randomised, parallel group, double-blind, active-controlled study done in 159 sites across 14 countries. The sites were a mixture of primary, secondary, and tertiary care providers, and specialist investigation units. Eligible patients with COPD had post-bronchodilator forced expiratory volume in 1 s (FEV1) of lower than 50%, one or more moderate-to-severe COPD exacerbation in the previous 12 months, COPD Assessment Test total score of 10 or more, and a Baseline Dyspnea Index focal score of 10 or less. Patients who met the inclusion and exclusion criteria at screening entered a 2-week open-label run-in period where they received beclometasone dipropionate (100 μg) and formoterol fumarate (6 μg) in two actuations twice daily. Patients were then randomly assigned (1:1) with an interactive response technology system to either continue BDP (100 μg) and FF (6 μg) or step-up to BDP (100 μg), FF (6 μg), and GB (12·5 μg) in two actuations twice daily for 52 weeks via pressurised metered-dose inhaler. The three co-primary endpoints were pre-dose FEV1, 2-h post-dose FEV1, and Transition Dyspnea Index (TDI) focal score, all measured at week 26 in the intention-to-treat population (all patients who were randomly assigned and received at least one dose of study drug and had at least one post-baseline efficacy assessment). Safety outcomes were measured in the safety population (all patients who were randomly assigned and received at least one dose of study drug). Secondary endpoints included moderate-to-severe COPD exacerbation rate over 52 weeks. This study is registered with ClinicalTrials.gov, number NCT01917331. Findings: Between March 21, 2014, and Jan 14, 2016, 1368 patients received either BDP/FF/GB (n=687) or BDP/FF (n=681). At week 26, BDP/FF/GB improved pre-dose FEV1 by 0·081 L (95% CI 0·052–0·109; p<0·001) and 2-h post-dose FEV1 by 0·117 L (0·086–0·147; p<0·001) compared with BDP/FF. Mean TDI focal scores at week 26 were 1·71 for BDP/FF/GB and 1·50 for BDP/FF, with a difference of 0·21 (95% CI −0·08 to 0·51; p=0·160). Adjusted annual moderate-to-severe exacerbation frequencies were 0·41 for BDP/FF/GB and 0·53 for BDP/FF (rate ratio 0·77 [95% CI 0·65–0·92]; p=0·005), corresponding to a 23% reduction in exacerbations with BDP/FF/GB compared with BDP/FF. Adverse events were reported by 368 (54%) patients with BDP/FF/GB and 379 (56%) with BDP/FF. One serious treatment-related adverse event occurred (atrial fibrillation) in a patient in the BDP/FF/GB group. Interpretation: We provide evidence for the clinical benefits of stepping up patients with COPD from an inhaled corticosteroid/long-acting β2-agonist combination treatment to triple therapy using a single inhaler. Funding: Chiesi Farmaceutici SpA.
OriginalsprogEngelsk
TidsskriftThe Lancet
Vol/bind388
Udgave nummer10048
Sider (fra-til)963-973
Antal sider11
ISSN0140-6736
DOI
StatusUdgivet - 3. sep. 2016
Udgivet eksterntJa

Emneord

  • Administration, Inhalation
  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Aged
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Dyspnea
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists
  • Nebulizers and Vaporizers
  • Pulmonary Disease, Chronic Obstructive
  • Treatment Outcome
  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

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