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

Resumé

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

Fingeraftryk

Nebulizers and Vaporizers
Chronic Obstructive Pulmonary Disease
Adrenal Cortex Hormones
Randomized Controlled Trials
Glycopyrrolate
Forced Expiratory Volume
Formoterol Fumarate
Safety
Pharmaceutical Preparations
Population

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

Citer dette

Singh, D ; Papi, Alberto ; Corradi, Massimo ; Pavlišová, Ilona ; Montagna, Isabella ; Francisco, Catherine ; Cohuet, Géraldine ; Vezzoli, Stefano ; Scuri, Mario ; Vestbo, Jorgen. / 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. I: The Lancet. 2016 ; Bind 388, Nr. 10048. s. 963-973.
@article{fa7307204e0f41198ae38906343c410e,
title = "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",
abstract = "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.",
keywords = "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",
author = "D Singh and Alberto Papi and Massimo Corradi and Ilona Pavlišov{\'a} and Isabella Montagna and Catherine Francisco and G{\'e}raldine Cohuet and Stefano Vezzoli and Mario Scuri and Jorgen Vestbo",
year = "2016",
month = "9",
day = "3",
doi = "10.1016/S0140-6736(16)31354-X",
language = "English",
volume = "388",
pages = "963--973",
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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. / Singh, D; Papi, Alberto; Corradi, Massimo; Pavlišová, Ilona; Montagna, Isabella; Francisco, Catherine; Cohuet, Géraldine; Vezzoli, Stefano; Scuri, Mario; Vestbo, Jorgen.

I: The Lancet, Bind 388, Nr. 10048, 03.09.2016, s. 963-973.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY)

T2 - a double-blind, parallel group, randomised controlled trial

AU - Singh, D

AU - Papi, Alberto

AU - Corradi, Massimo

AU - Pavlišová, Ilona

AU - Montagna, Isabella

AU - Francisco, Catherine

AU - Cohuet, Géraldine

AU - Vezzoli, Stefano

AU - Scuri, Mario

AU - Vestbo, Jorgen

PY - 2016/9/3

Y1 - 2016/9/3

N2 - 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.

AB - 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.

KW - Administration, Inhalation

KW - Adrenal Cortex Hormones

KW - Adrenergic beta-2 Receptor Agonists

KW - Aged

KW - Delayed-Action Preparations

KW - Double-Blind Method

KW - Drug Combinations

KW - Drug Therapy, Combination

KW - Dyspnea

KW - Female

KW - Forced Expiratory Volume

KW - Humans

KW - Male

KW - Middle Aged

KW - Muscarinic Antagonists

KW - Nebulizers and Vaporizers

KW - Pulmonary Disease, Chronic Obstructive

KW - Treatment Outcome

KW - Comparative Study

KW - Journal Article

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/S0140-6736(16)31354-X

DO - 10.1016/S0140-6736(16)31354-X

M3 - Journal article

VL - 388

SP - 963

EP - 973

JO - Lancet

JF - Lancet

SN - 0140-6736

IS - 10048

ER -