Evidence map›Paper›PMID 29429593›Full record

Trial reportLancet (London, England)2018

Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial.

Alberto Papi, Jørgen Vestbo, Leonardo Fabbri, Massimo Corradi, Hélène Prunier, Géraldine Cohuet, Alessandro Guasconi, Isabella Montagna, Stefano Vezzoli, Stefano Petruzzelli and 3 more

Erratum issued 2 registry-linked trialsOpen access · greenAbstract readComparative StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Lancet (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 276 papers, 19 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
276citing papers in PubMed, 19 pooled it
62.9field-weighted citation impact, top 1% 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.

NCT02579850 phase3completednot on this map

52-week, Double Blind, Randomized, 2 Active Parallel Arms Study of Fixed Combination CHF 5993 Administered vs Ultibro® in COPD Patients

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2015 to 2017Enrolled1,532ConditionsChronic Obstructive Pulmonary Disease (COPD)ArmsCHF 5993 + Ultibro matched placebo, Ultibro + CHF 5993 matched placebo, Central spirometry, COPD assessment test, Local laboratory Assessments
NCT04320342 phase3completednot on this mapstarted 2022, after this paper: background citation

A Phase III, 52-week, Multinational, Multicenter, Randomized, Double-blind, 2-arm Parallel Group Study Comparing Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate Plus Glycopyrronium Bromide (CHF 5993) With the Fixed Dose Dual Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate (CHF 1535), Both Administered Via pMDI in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2022 to 2026Enrolled3,433ConditionsCOPD, COPD ExacerbationArmsBeclomethasone Dipropionate, Glycopyrronium Bromide, Formoterol Fumarate
3 · Its place in the literature

Who cites it

276 citing papers in PubMed, 19 syntheses or guidelines pooled it, 619 citations in OpenAlex.

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  4. Application of Discrete Event Simulation Models for COPD Management: A Systematic Review.International journal of chronic obstructive pulmonary disease · 2025
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  15. Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD.European respiratory review : an official journal of the European Respiratory Society · 2021
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  18. Romanian clinical guideline for diagnosis and treatment of COPD.The Journal of international medical research · 2020
    Guideline
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216 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 4 countries.

Alberto PapiResearch Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy. Electronic address: ppa@unife.it.
Jørgen VestboDivision of Infection, Immunity and Respiratory Medicine and Manchester University NHS Foundation Trust, University of Manchester, Manchester, UK.
Leonardo FabbriDepartment of Medicine, University of Ferrara, Ferrara, Italy; COPD Center, Sahlgrenska University Hospital, Gothenburg, Sweden.
Massimo CorradiDepartment of Medicine and Surgery, University of Parma, Italy.
Hélène PrunierGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Géraldine CohuetGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Alessandro GuasconiGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Isabella MontagnaGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Stefano VezzoliGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Stefano PetruzzelliGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Mario ScuriGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Nicolas RocheHôpital Cochin (APHP), Université Paris-Descartes (EA2511), Service de Pneumologie et Soins Intensifs Respiratoires, Paris, France.
Dave SinghDivision of Infection, Immunity and Respiratory Medicine and Manchester University NHS Foundation Trust, University of Manchester, Manchester, UK; Medicines Evaluation Unit, Manchester, UK.
Chiesi (Italy) · ITManchester University NHS Foundation Trust · GBSahlgrenska University Hospital · SEUniversité Paris Cité · FRUniversity of Ferrara · ITUniversity of Parma · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEvidence is scarce on the relative risk-benefit of inhaled triple therapy, consisting of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β

methodsThis randomised, parallel-group, double-blind, double-dummy study was done at 187 sites across 17 countries. Eligible patients had symptomatic COPD, severe or very severe airflow limitation, at least one moderate or severe exacerbation in the previous year, and were receiving inhaled maintenance medication. After a 2 week run-in period with one inhalation per day of IND/GLY (85 μg/43 μg), patients were randomly assigned (1:1), via an interactive response technology system, to receive 52 weeks of treatment with two inhalations of extrafine BDP/FF/G (87 μg/5 μg/9 μg) twice per day or one inhalation of IND/GLY (85 μg/43 μg) per day. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was the rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment in all randomised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02579850.

findingsBetween May, 29 2015, and July 10, 2017, 1532 patients received BDP/FF/G (n=764) or IND/GLY (n=768). Moderate-to-severe exacerbation rates were 0·50 per patient per year (95% CI 0·45-0·57) for BDP/FF/G and 0·59 per patient per year (0·53-0·67) for IND/GLY, giving a rate ratio of 0·848 (0·723-0·995, p=0·043) in favour of BDP/FF/G. Adverse events were reported by 490 (64%) of 764 patients receiving BDP/FF/G and 516 (67%) of 768 patients receiving IND/GLY. Pneumonia occurred in 28 (4%) patients receiving BDP/FF/G versus 27 (4%) patients receiving IND/GLY. One treatment-related serious adverse event occurred in each group: dysuria in a patient receiving BDP/FF/G and atrial fibrillation in a patient receiving IND/GLY.

interpretationIn patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation history despite maintenance therapy, extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY, without increasing the risk of pneumonia.

fundingChiesi Farmaceutici.

Indexed as

Administration, InhalationAdrenergic beta-2 Receptor AgonistsAgedBeclomethasoneBronchodilator AgentsDouble-Blind MethodDrug Therapy, CombinationFemaleFormoterol FumarateGlucocorticoidsGlycopyrrolateHumansIndansMaleMiddle AgedMuscarinic AntagonistsAdrenergic beta-2 Receptor AgonistsBeclomethasoneBronchodilator AgentsFormoterol FumarateGlucocorticoidsGlycopyrrolateindacaterolIndansMuscarinic AntagonistsQuinolones

Identifiers

PMID29429593
OpenAlexW2785999277

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.