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Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study.
Respir Res 2018; 19(1):19RR

Abstract

BACKGROUND

Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg has been shown to improve lung function and health status, and reduce exacerbations, versus budesonide/formoterol in patients with chronic obstructive pulmonary disease (COPD). We evaluated the non-inferiority of single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers.

METHODS

Eligible patients with COPD (aged ≥40 years; ≥1 moderate/severe exacerbation in the 12 months before screening) were randomized (1:1; stratified by the number of long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week FF/UMEC/VI 100/62.5/25 μg and placebo or FF/VI 100/25 μg + UMEC 62.5 μg; all treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the morning. Primary endpoint: change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week 24. The non-inferiority margin for the lower 95% confidence limit was set at - 50 mL.

RESULTS

A total of 1055 patients (844 [80%] of whom were enrolled on combination maintenance therapy) were randomized to receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528). Mean change from baseline in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95% CI -13, 50) confirmed FF/UMEC/VI's was considered non-inferior to FF/VI + UMEC. At Week 24, the proportion of responders based on St George's Respiratory Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the proportion of responders based on the Transitional Dyspnea Index focal score was similar (56% both groups). A similar proportion of patients experienced a moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%) groups; the hazard ratio for time to first moderate/severe exacerbation with FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12). The incidence of adverse events was comparable in both groups (48%); the incidence of serious adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC).

CONCLUSIONS

Single-inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI + UMEC) on trough FEV1 change from baseline at 24 weeks. Results were similar on all other measures of efficacy, health-related quality of life, and safety.

TRIAL REGISTRATION

GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31 March 2016).

Authors+Show Affiliations

University of Notre Dame, Fremantle, WA, Australia.GSK, Stockley Park West, Uxbridge, Middlesex, UK.GSK, Stockley Park West, Uxbridge, Middlesex, UK.GSK, Collegeville, PA, USA. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.GSK, Stockley Park West, Uxbridge, Middlesex, UK.GSK, 709 Swedeland Road, UW2531, King of Prussia, PA, 19406, USA. david.a.lipson@gsk.com. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. david.a.lipson@gsk.com.

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29370819

Citation

Bremner, Peter R., et al. "Single-inhaler Fluticasone Furoate/umeclidinium/vilanterol Versus Fluticasone Furoate/vilanterol Plus Umeclidinium Using Two Inhalers for Chronic Obstructive Pulmonary Disease: a Randomized Non-inferiority Study." Respiratory Research, vol. 19, no. 1, 2018, p. 19.
Bremner PR, Birk R, Brealey N, et al. Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study. Respir Res. 2018;19(1):19.
Bremner, P. R., Birk, R., Brealey, N., Ismaila, A. S., Zhu, C. Q., & Lipson, D. A. (2018). Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study. Respiratory Research, 19(1), p. 19. doi:10.1186/s12931-018-0724-0.
Bremner PR, et al. Single-inhaler Fluticasone Furoate/umeclidinium/vilanterol Versus Fluticasone Furoate/vilanterol Plus Umeclidinium Using Two Inhalers for Chronic Obstructive Pulmonary Disease: a Randomized Non-inferiority Study. Respir Res. 2018 01 25;19(1):19. PubMed PMID: 29370819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study. AU - Bremner,Peter R, AU - Birk,Ruby, AU - Brealey,Noushin, AU - Ismaila,Afisi S, AU - Zhu,Chang-Qing, AU - Lipson,David A, Y1 - 2018/01/25/ PY - 2017/11/07/received PY - 2018/01/16/accepted PY - 2018/1/27/entrez PY - 2018/1/27/pubmed PY - 2018/11/6/medline KW - COPD KW - Exacerbations KW - FEV1 KW - Fluticasone furoate/umeclidinium/vilanterol KW - Lung function KW - Randomized controlled trial KW - Single-inhaler triple therapy SP - 19 EP - 19 JF - Respiratory research JO - Respir. Res. VL - 19 IS - 1 N2 - BACKGROUND: Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg has been shown to improve lung function and health status, and reduce exacerbations, versus budesonide/formoterol in patients with chronic obstructive pulmonary disease (COPD). We evaluated the non-inferiority of single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers. METHODS: Eligible patients with COPD (aged ≥40 years; ≥1 moderate/severe exacerbation in the 12 months before screening) were randomized (1:1; stratified by the number of long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week FF/UMEC/VI 100/62.5/25 μg and placebo or FF/VI 100/25 μg + UMEC 62.5 μg; all treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the morning. Primary endpoint: change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week 24. The non-inferiority margin for the lower 95% confidence limit was set at - 50 mL. RESULTS: A total of 1055 patients (844 [80%] of whom were enrolled on combination maintenance therapy) were randomized to receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528). Mean change from baseline in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95% CI -13, 50) confirmed FF/UMEC/VI's was considered non-inferior to FF/VI + UMEC. At Week 24, the proportion of responders based on St George's Respiratory Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the proportion of responders based on the Transitional Dyspnea Index focal score was similar (56% both groups). A similar proportion of patients experienced a moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%) groups; the hazard ratio for time to first moderate/severe exacerbation with FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12). The incidence of adverse events was comparable in both groups (48%); the incidence of serious adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC). CONCLUSIONS: Single-inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI + UMEC) on trough FEV1 change from baseline at 24 weeks. Results were similar on all other measures of efficacy, health-related quality of life, and safety. TRIAL REGISTRATION: GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31 March 2016). SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/29370819/Single_inhaler_fluticasone_furoate/umeclidinium/vilanterol_versus_fluticasone_furoate/vilanterol_plus_umeclidinium_using_two_inhalers_for_chronic_obstructive_pulmonary_disease:_a_randomized_non_inferiority_study_ L2 - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-018-0724-0 DB - PRIME DP - Unbound Medicine ER -