Evidence map›Paper›PMID 32503599›Full record

Trial reportRespiratory research2020

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial.

Nicola C Day, Subramanya Kumar, Gerard Criner, Mark Dransfield, David M G Halpin, MeiLan K Han, C Elaine Jones, Morrys C Kaisermann, Sally Kilbride, Peter Lange and 6 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIIComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Respiratory research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02164513 (A Phase III, 52 Week, Randomized, Double-blind, 3-arm Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI With the Fixed Dose Dual Combinations of FF/VI and UMEC/VI, All Administered Once-daily in the Morning Via a Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease), which is not on this map. Cited by 9 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 2 pooled it
1.3field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02164513 phase3completednot on this map

A Phase III, 52 Week, Randomized, Double-blind, 3-arm Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI With the Fixed Dose Dual Combinations of FF/VI and UMEC/VI, All Administered Once-daily in the Morning Via a Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease

TypeinterventionalSponsorGlaxoSmithKlineRan2014 to 2017Enrolled10,355ConditionsPulmonary Disease, Chronic ObstructiveArmsfluticasone furoate (FF), vilanterol (VI), umeclidinium bromide (UMEC)
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 12 institutions in 3 countries.

Nicola C DayGlaxoSmithKline, Stockley Park West, 1-3 Ironbridge Road, Uxbridge, Middlesex, UB11 1BT, UK. nicola.x.day@gsk.com.
Subramanya KumarGlaxoSmithKline, Stockley Park West, 1-3 Ironbridge Road, Uxbridge, Middlesex, UB11 1BT, UK.
Gerard CrinerLewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Mark DransfieldDivision of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA.
David M G HalpinUniversity of Exeter Medical School, College of Medicine and Health, Exeter, UK.
MeiLan K HanUniversity of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, USA.
C Elaine JonesGlaxoSmithKline, Research Triangle Park, NC, USA.
Morrys C KaisermannGlaxoSmithKline, Collegeville, PA, USA.
Sally KilbrideGlaxoSmithKline, Stockley Park West, 1-3 Ironbridge Road, Uxbridge, Middlesex, UB11 1BT, UK.
Peter LangeDepartment of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark.
David A LomasUCL Respiratory, University College London, London, UK.
Neil MartinGlaxoSmithKline, Brentford, UK.
Fernando J MartinezNew York-Presbyterian Weill Cornell Medical Center, New York, NY, USA.
Dave SinghUniversity of Manchester, Manchester University NHS Foundation Trust, Manchester, UK.
Robert WiseDivision of Pulmonary and Critical Care Medicine, Johns Hopkins Medicine, Baltimore, MD, USA.
David A LipsonGlaxoSmithKline, Collegeville, PA, USA.
GlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USCornell University · USJohns Hopkins Medicine · USManchester University NHS Foundation Trust · GBTemple University · USUniversity College London · GBUniversity of Alabama at Birmingham · USUniversity of Copenhagen · DKUniversity of Exeter · GBUniversity of Michigan–Ann Arbor · USUniversity of Pennsylvania · US

Funding

GlaxoSmithKline study number CTT116855
6 · The paper itself

Abstract

backgroundThis analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy.

methodsIMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death.

resultsBaseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments.

conclusionsIn a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10-11% and 1-3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI.

trial registrationNCT02164513 (GSK study number CTT116855).

Indexed as

AgedAndrostadienesBenzyl AlcoholsCardiovascular DiseasesChlorobenzenesDouble-Blind MethodDrug CombinationsFemaleHumansMaleMiddle AgedNebulizers and VaporizersPulmonary Disease, Chronic ObstructiveQuinuclidinesAndrostadienesBenzyl AlcoholsChlorobenzenesDrug Combinationsfluticasone furoateGSK573719QuinuclidinesvilanterolCardiovascular safetyCOPDICS/LABALAMA/LABATriple therapy

Identifiers

PMID32503599
PMCPMC7275457
OpenAlexW3033269533

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.