Long-term triple therapy de-escalation to indacaterol/glycopyrronium in COPD patients (SUNSET): a randomized, double-blind, triple-dummy clinical trial

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Title: Long-term triple therapy de-escalation to indacaterol/glycopyrronium in COPD patients (SUNSET): a randomized, double-blind, triple-dummy clinical trial
Authors: Chapman, KR
Hurst, JR
Frent, S
Larbig, M
Fogel, R
Guerin, T
Banerji, D
Patalano, F
Goyal, P
Pfister, P
Kostikas, K
Wedzicha, JA
Item Type: Journal Article
Abstract: Rationale: There are no studies on ICS withdrawal in patients on long-term triple therapy in the absence of frequent exacerbations. Objective: To evaluate the efficacy and safety of the direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in non-frequently exacerbating COPD patients. Methods: This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50μg once daily) or continuation of triple therapy (tiotropium 18μg once daily plus combination of salmeterol/fluticasone propionate [50/500μg] twice daily) in non-frequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was non-inferiority on change from baseline in trough forced expiratory volume in 1 second (FEV1). Moderate or severe exacerbations were predefined secondary endpoints. Measurements and Main Results: 527 patients were randomized to indacaterol/glycopyrronium and 526 to triple therapy. ICS withdrawal led to a reduction in trough FEV1 of −26mL (95% confidence interval [CI], −53 to 1 mL) with confidence limits exceeding the non-inferiority margin of −50 mL. The annualized rate of moderate or severe COPD exacerbations did not differ between treatments (rate ratio 1.08; 95%CI, 0.83 to 1.40). Patients with ≥300 blood eosinophils/μL at baseline presented greater lung function loss and higher exacerbation risk. Adverse events were similar in the two groups. Conclusions: In COPD patients without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with ≥300 blood eosinophils/µL suggests that these patients are likely to benefit from triple therapy. Clinical trial registration available at, ID NCT02603393.
Issue Date: 1-Aug-2018
Date of Acceptance: 20-May-2018
ISSN: 1073-449X
Publisher: American Thoracic Society
Start Page: 329
End Page: 339
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 198
Issue: 3
Copyright Statement: © 2018 American Thoracic Society, All Rights Reserved.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: G1001372
Keywords: Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
triple therapy
lung function
lung function
triple therapy
11 Medical and Health Sciences
Respiratory System
Publication Status: Published
Online Publication Date: 2018-05-20
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine

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