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

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2018 Jan 27

PMID 29370819

Citations 23

Authors

Peter R Bremner

Ruby Birk

Noushin Brealey

Afisi S Ismaila

Chang-Qing Zhu

David A Lipson

Affiliations

Soon will be listed here.

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 (FEV) 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 FEV 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 FEV 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).

Citing Articles

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Zhu H, Lei J, Gao F, Guo Y, Zhao L BMC Pulm Med. 2024; 24(1):609.

PMID: 39696097 PMC: 11654331. DOI: 10.1186/s12890-024-03445-4.

Triple Therapy in COPD in Real Life: Is It Better to Use Single or Multiple Inhalers?.

Sposato B, Ricci A, Lacerenza L, Petrucci E, Cresti A, Baratta P J Clin Med. 2024; 13(20).

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Adherence to single inhaler triple therapy and digital inhalers in Chronic Obstructive Pulmonary Disease: a literature review and protocol for a randomized controlled trial (TRICOLON study).

Cuperus L, van der Palen J, Aldenkamp A, van Huisstede A, Bischoff E, van Boven J BMC Pulm Med. 2024; 24(1):317.

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Whittaker H, Torkpour A, Quint J Respir Res. 2024; 25(1):43.

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Wang J, Wang P, Shao Y, He D Pharmaceutics. 2023; 15(8).

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