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Randomized Controlled Trial
. 2020 Jun 15;201(12):1508-1516.
doi: 10.1164/rccm.201911-2207OC.

Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

David A Lipson  1   2 , Courtney Crim  3 , Gerard J Criner  4 , Nicola C Day  5 , Mark T Dransfield  6 , David M G Halpin  7 , MeiLan K Han  8 , C Elaine Jones  9 , Sally Kilbride  10 , Peter Lange  11   12 , David A Lomas  13 , Sally Lettis  10 , Pamela Manchester  14 , Neil Martin  15   16 , Dawn Midwinter  10 , Andrea Morris  3 , Steven J Pascoe  1 , Dave Singh  17 , Robert A Wise  18 , Fernando J Martinez  19
Affiliations
Randomized Controlled Trial

Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

David A Lipson et al. Am J Respir Crit Care Med. .

Abstract

Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations. Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg following a run-in on their COPD therapies. Time to ACM was prespecified. Additional vital status data collection and subsequent analyses were performed post hoc.Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI. For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI. Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient's COPD.Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations.

Trial registration: ClinicalTrials.gov NCT02164513.

Keywords: COPD; mortality; survival; triple therapy.

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Figures

Figure 1.
Figure 1.
Kaplan-Meier plots of time to all-cause mortality for (A) on-treatment deaths and (B) on/off-treatment deaths. FF = fluticasone furoate; UMEC = umeclidinium; VI = vilanterol.
Figure 2.
Figure 2.
Forest plot of ACM analyses and hazard ratios FF/UMEC/VI versus UMEC/VI. ACM = all-cause mortality; CI = confidence interval; FF = fluticasone furoate; UMEC = umeclidinium; VI = vilanterol.
Figure 3.
Figure 3.
ACM by triple therapy or ICS use at screening*: (A) triple therapy at screening, (B) no triple therapy at screening, (C) ICS use at screening, (D) no ICS use at screening, and (E) forest plot of ACM analysis by therapy at screening. (A–D) Kaplan-Meier plots of ACM including off-treatment data (with additional vital status follow-up). ACM = all-cause mortality; CI = confidence interval; FF = fluticasone furoate; ICS = inhaled corticosteroid; UMEC = umeclidinium; VI = vilanterol. *Medication taken between date of screening −3 days and date of screening (inclusive).
Figure 3.
Figure 3.
ACM by triple therapy or ICS use at screening*: (A) triple therapy at screening, (B) no triple therapy at screening, (C) ICS use at screening, (D) no ICS use at screening, and (E) forest plot of ACM analysis by therapy at screening. (A–D) Kaplan-Meier plots of ACM including off-treatment data (with additional vital status follow-up). ACM = all-cause mortality; CI = confidence interval; FF = fluticasone furoate; ICS = inhaled corticosteroid; UMEC = umeclidinium; VI = vilanterol. *Medication taken between date of screening −3 days and date of screening (inclusive).
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