QVA vs. Salmeterol/Fluticasone, 52-week Exacerbation Study, FLAME (EFfect of Indacaterol Glycopyronium Vs Fluticasone Salmeterol on COPD Exacerbations)

Summary

This study will assess the efficacy, safety and tolerability of QVA149 in patients with moderate to very severe COPD.

Timeline

Start

2013-07

Primary completion

2015-09

Completion

2015-09

Outcome

Met primary endpoint

registry QVA149 vs Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS); p = 0.003; Rate Ratio 0.89 (95% CI 0.83 to 0.96) NCT01782326 ↗

paper Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations PMID 27181606 ↗

Publications

• Mathioudakis AG, Bate S, Chatzimavridou-Grigoriadou V, Sivapalan P, Jensen JS, Bakerly ND, Vestbo J, Singh D. Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial. Thorax. 2026 May 14;81(6):533-540. doi: 10.1136/thorax-2025-223282.
• Mathioudakis AG, Bate S, Sivapalan P, Jensen JS, Singh D, Vestbo J. Rethinking Blood Eosinophils for Assessing Inhaled Corticosteroids Response in COPD: A Post Hoc Analysis From the FLAME Trial. Chest. 2024 Nov;166(5):987-997. doi: 10.1016/j.chest.2024.06.3790. Epub 2024 Jul 9.
• Mackay AJ, Kostikas K, Roche N, Frent SM, Olsson P, Pfister P, Gupta P, Patalano F, Banerji D, Wedzicha JA. Impact of baseline symptoms and health status on COPD exacerbations in the FLAME study. Respir Res. 2020 Apr 22;21(1):93. doi: 10.1186/s12931-020-01354-8.
• Wedzicha JA, Singh D, Tsiligianni I, Jenkins C, Fucile S, Fogel R, Shen S, Goyal P, Mezzi K, Kostikas K. Treatment response to indacaterol/glycopyrronium versus salmeterol/fluticasone in exacerbating COPD patients by gender: a post-hoc analysis in the FLAME study. Respir Res. 2019 Jan 8;20(1):4. doi: 10.1186/s12931-019-0972-7.
• Frent SM, Chapman KR, Larbig M, Mackay A, Fogel R, Gutzwiller FS, Shen S, Patalano F, Banerji D, Kostikas K, Wedzicha JA. 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.
• Anzueto AR, Kostikas K, Mezzi K, Shen S, Larbig M, Patalano F, Fogel R, Banerji D, Wedzicha JA. Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study. Respir Res. 2018 Jun 20;19(1):121. doi: 10.1186/s12931-018-0830-z.
• Roche N, Chapman KR, Vogelmeier CF, Herth FJF, Thach C, Fogel R, Olsson P, Patalano F, Banerji D, Wedzicha JA. Blood Eosinophils and Response to Maintenance Chronic Obstructive Pulmonary Disease Treatment. Data from the FLAME Trial. Am J Respir Crit Care Med. 2017 May 1;195(9):1189-1197. doi: 10.1164/rccm.201701-0193OC.
• Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, Thach C, Fogel R, Patalano F, Vogelmeier CF; FLAME Investigators. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med. 2016 Jun 9;374(23):2222-34. doi: 10.1056/NEJMoa1516385. Epub 2016 May 15.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Fluticasone	Other / unclassified	500 ug	Other
Subject	Glycopyrronium	Unknown	50 ug	Other
Subject	Indacaterol	Other / unclassified	110 ug	Other
Comparator	Salmeterol	Other / unclassified	50 ug	Other

Indications