Evidence map›Paper›PMID 33121501›Full record

Trial reportRespiratory research2020

Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER.

Dave Singh, Johann Christian Virchow, Giorgio Walter Canonica, Andrea Vele, Maxim Kots, George Georges, Alberto Papi

2 registry-linked trialsOpen access · goldAbstract readRandomized Controlled Trial
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 2 registered trials, which are not on this map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
1.8field-weighted citation impact, top 14% 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.

NCT02676076 phase3completednot on this map

A 52 WEEK, RANDOMIZED, DOUBLE BLIND, MULTINATIONAL, MULTICENTRE, ACTIVE CONTROLLED, 2-ARM PARALLEL GROUP TRIAL COMPARING CHF 5993 100/6/12.5 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE PLUS GLYCOPYRRONIUM BROMIDE) TO CHF 1535 100/6 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE) IN PATIENTS WITH ASTHMA UNCONTROLLED ON MEDIUM DOSES OF INHALED CORTICOSTEROIDS IN COMBINATION WITH LONG ACTING ß2 AGONISTS

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2016 to 2018Enrolled1,155ConditionsAsthmaArmsCHF 5993 100/6/12.5, CHF 1535 100/6 µg
NCT02676089 phase3completednot on this map

A 52 WEEK, RANDOMIZED, DOUBLE BLIND, MULTINATIONAL, MULTICENTRE, ACTIVE CONTROLLED, 3-ARM PARALLEL GROUP TRIAL COMPARING CHF 5993 200/6/12.5 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE PLUS GLYCOPYRRONIUM BROMIDE) TO CHF 1535 200/6 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE) ALONE OR ON TOP OF OPEN-LABEL TIOTROPIUM 2.5 µg RESPIMAT® IN PATIENTS WITH ASTHMA UNCONTROLLED ON HIGH DOSES OF INHALED CORTICOSTEROIDS IN COMBINATION WITH LONG-ACTING ß2-AGONISTS

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2016 to 2018Enrolled1,437ConditionsAsthmaArmsCHF 5993 200/6/12.5 µg, CHF 1535 200/6 µg, CHF 1535 200/6 µg + Tiotropium Respimat 2.5 µg
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Observational
  9. Article
  10. Review
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

7 authors at 5 institutions in 3 countries.

Dave SinghMedicines Evaluation Unit, The University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK. dsingh@meu.org.uk.ORCID http://orcid.org/0000-0001-8918-7075
Johann Christian VirchowZentrum Für Innere Medizin, Abteilung Für Pneumologie, Universitätsmedizin Rostock, Rostock, Germany.
Giorgio Walter CanonicaCenter of Personalized Medicine: Asthma and Allergy, Humanitas University and Research Hospital IRCCS, Milan, Italy.
Andrea VeleGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Maxim KotsGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
George GeorgesGlobal Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Alberto PapiRespiratory Medicine Unit, University of Ferrara, University Hospital S.Anna, Ferrara, Italy.
Chiesi (Italy) · ITHumanitas University · ITManchester University NHS Foundation Trust · GBUniversitätsmedizin Rostock · DEUniversity of Ferrara · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA number of single-inhaler triple therapies are being developed for asthma, including the extrafine formulation of beclometasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium (G). Given asthma is a heterogenous disease, we investigated whether the clinical response to the addition of the long-acting muscarinic antagonist component within inhaled triple therapy was impacted by a range of clinical characteristics.

methodsThese were pre-specified and post-hoc sub-group analyses of TRIMARAN and TRIGGER, which were double-blind, 52-week studies comparing medium-strength (100/6/10 µg; TRIMARAN) and high-strength (200/6/10 µg; TRIGGER) BDP/FF/G with the respective BDP/FF strengths in adults with uncontrolled asthma and a history of ≥ 1 exacerbation. Co-primary endpoints were pre-dose forced expiratory volume in 1 s (FEV

resultsBaseline clinical characteristics (pre-specified analyses) had no consistent effect on the lung function improvements with BDP/FF/G. For the exacerbation endpoints, sub-groups with higher reversibility gained greatest relative benefit from BDP/FF/G versus BDP/FF. In post-hoc analyses with patients sub-grouped by screening blood eosinophil values, in TRIMARAN the greatest relative effect of BDP/FF/G versus BDP/FF on the lung function endpoints was in the ≤ 300 cells/µL group; in TRIGGER, eosinophil levels did not markedly influence the relative efficacy of BDP/FF/G versus BDP/FF. Eosinophil levels did not influence relative efficacy on moderate-to-severe or severe exacerbations.

conclusionOverall, the relative efficacy of extrafine BDP/FF/G versus BDP/FF was not influenced by a range of clinical characteristics. However, some patient sub-groups gained additional benefit from BDP/FF/G for certain endpoints. In particular, for exacerbations the relative efficacy of BDP/FF/G was greater in more reversible patients. Trial registration ClinicalTrials.gov: TRIMARAN, NCT02676076 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676076?term=NCT02676076&draw=2&rank=1 ,); TRIGGER, NCT02676089 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676089?term=NCT02676089&draw=2&rank=1 ).

Indexed as

Administration, InhalationAdultAgedAsthmaBeclomethasoneBronchodilator AgentsDouble-Blind MethodDrug Therapy, CombinationFemaleFormoterol FumarateGlycopyrrolateHumansMaleMiddle AgedMuscarinic AntagonistsTreatment OutcomeBeclomethasoneBronchodilator AgentsFormoterol FumarateGlycopyrrolateMuscarinic AntagonistsAsthmaEosinophilsInhaled corticosteroidsLong-acting muscarinic antagonistsLong-acting β2-agonistsPharmacotherapySubgroup analyses

Identifiers

PMID33121501
PMCPMC7597025
OpenAlexW3095443276

What OpenQuestion 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 OpenQuestion graph.