Evidence map›Paper›PMID 33910578›Full record

Trial reportRespiratory research2021

InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations.

Dave Singh, Gerard J Criner, Mark T Dransfield, David M G Halpin, MeiLan K Han, Peter Lange, Sally Lettis, David A Lipson, David Mannino, Neil Martin and 5 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Respiratory research, 2021. 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 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Predictors of Acute Exacerbations in COPD: A Systematic Review.International journal of chronic obstructive pulmonary disease · 2026
    Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Is Disease Stability an Attainable Chronic Obstructive Pulmonary Disease Treatment Goal?American journal of respiratory and critical care medicine · 2025
    Review
  8. Biomarkers in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Observational
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

15 authors at 13 institutions in 3 countries.

Dave SinghCentre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK.
Gerard J CrinerPulmonary and Critical Care Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Mark T 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, University of Exeter, Exeter, UK.
MeiLan K HanUniversity of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, USA.
Peter LangeDepartment of Public Health, University of Copenhagen, Copenhagen, Denmark.
Sally LettisBiostatistics, GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, UK.
David A LipsonClinical Sciences, GlaxoSmithKline, Collegeville, PA, USA.
David ManninoUniversity of Kentucky College of Public Health, Lexington, KY, USA.
Neil MartinGlobal Medical Affairs, GlaxoSmithKline, Brentford, Middlesex, UK.
Fernando J MartinezWeill Cornell Medicine, New York, NY, USA.
Bruce E MillerClinical Sciences, GlaxoSmithKline, Collegeville, PA, USA.
Robert WiseDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chang-Qing ZhuBiostatistics, GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, UK.
David LomasDivision of Medicine, UCL Respiratory, Rayne Building, University College London, London, WC1E 6BN, UK. d.lomas@ucl.ac.uk.
GlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USJohns Hopkins University · USManchester University NHS Foundation Trust · GBTemple University · USUniversity College London · GBUniversity of Alabama at Birmingham · USUniversity of Copenhagen · DKUniversity of Exeter · GBUniversity of Kentucky · USUniversity of Michigan–Ann Arbor · USUniversity of Pennsylvania · USWeill Cornell Medicine · US

Funding

GlaxoSmithKline Study number: CTT116855
6 · The paper itself

Abstract

backgroundFibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD.

methods8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs).

resultsRates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile.

conclusionsRate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes.

trial registrationNCT02164513.

Indexed as

AgedBiomarkersBronchodilator AgentsDisease ProgressionDouble-Blind MethodDrug CombinationsFemaleFibrinogenHumansLungMaleMiddle AgedPredictive Value of TestsPulmonary Disease, Chronic ObstructiveSeverity of Illness IndexTime FactorsBiomarkersBronchodilator AgentsDrug CombinationsFibrinogenCOPDCOPD exacerbationsFibrinogenPharmacotherapy

Identifiers

PMID33910578
PMCPMC8080358
OpenAlexW3158385683

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.