Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial

Abstract

Background: Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD). This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.

Methods: Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg. Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.

Results: Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001). UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL. Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George's Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks. The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.

Conclusions: Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.

Trial registration: NCT01822899 Registration date: March 28, 2013.

Fig. 1

Flow diagram for disposition of patients (CONSORT). Abbreviations: ITT, intent-to-treat; FP/SAL, fluticasone propionate/salmeterol; UMEC, umeclidinium; VI, vilanterol. ^aOne patient was randomised in error; this patient was a run-in failure

Fig. 2

Change from baseline in FEV₁ (L) over 0–24 h on Day 84 (ITT population). Data are least squares mean (95 % CI) change from baseline. Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; ITT, intent-to-treat; LS, least squares; FP/SAL, fluticasone propionate/salmeterol; UMEC, umeclidinium; VI, vilanterol

Fig. 3

Change from baseline in trough FEV₁ (L) (ITT population). Data are least squares mean (95 % CI) differences of change from baseline in trough FEV₁ (L) at Days 28, 56, 84 and 85. Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; ITT, intent-to-treat; LS, least squares; FP/SAL, fluticasone propionate/salmeterol; UMEC, umeclidinium; VI, vilanterol