Evidence map›Paper›PMID 27181606›Full record

Trial reportThe New England journal of medicine2016

Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD.

Jadwiga A Wedzicha, Donald Banerji, Kenneth R Chapman, Jørgen Vestbo, Nicolas Roche, R Timothy Ayers, Chau Thach, Robert Fogel, Francesco Patalano, Claus F Vogelmeier and 1 more

5 registry-linked trialsOpen access · bronzeAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 342 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
342citing papers in PubMed, 18 pooled it
121.2field-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.

NCT01782326 phase3completednot on this map

A 52-week Treatment, Multi-center, Randomized, Double-blind, Double Dummy, Parallel-group, Active Controlled Study to Compare the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) With Salmeterol/Fluticasone on the Rate of Exacerbations in Subjects With Moderate to Very Severe COPD. (FLAME).

TypeinterventionalSponsorNovartis PharmaceuticalsRan2013 to 2015Enrolled3,362ConditionsChronic Obstructive Pulmonary Disease (COPD)ArmsQVA149, Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)
NCT03084718 phase2completednot on this mapstarted 2017, after this paper: background citation

An 8-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 3 Doses of CHF 718 pMDI (HFA Beclomethasone Dipropionate Via Pressured Metered Dose Inhaler) in Asthmatic Subjects.

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2017 to 2018Enrolled610ConditionsAsthmaArmsCHF 718 pMDI, Placebo pMDI, Beclomethasone Dipropionate (BDP)
NCT03084796 phase2completednot on this mapstarted 2017, after this paper: background citation

A 6-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF 5259 pMDI (HFA Glycopyrronium Bromide Via Pressurized Metered Dose Inhaler) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2017 to 2018Enrolled733ConditionsCOPD, Chronic Obstructive Pulmonary DiseaseArmsCHF 5259, Placebo, Tiotropium Bromide 18 µg Inhalation Capsule
NCT03086460 phase2completednot on this mapstarted 2017, after this paper: background citation

A Randomized, Double-blind, Placebo and Active-controlled, Incomplete Block Cross-over, Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF 1531 pMDI (Formoterol Fumarate) in Asthmatic Subjects

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2017 to 2018Enrolled67ConditionsAsthmaArmsCHF 1531 pMDI, Formoterol Inhalation Solution, Placebo pMDI
NCT05342558 phase4completednot on this mapstarted 2017, after this paper: background citation

Efficacy and Safety of Fluticasone Furoate/Vilanterol vs. Umeclidinium/Vilanterol in Patients With COPD-asthma Phenotype vs. Emphysema Phenotype. A Controled Clinical Trial.

TypeinterventionalSponsorNational Institute of Respiratory Diseases, MexicoRan2017 to 2021Enrolled133ConditionsCOPDArmsFluticasone Furoate/Vilanterol 100/25 mcgs, Umeclidinium/Vilanterol 62.5/25 mcgs
3 · Its place in the literature

Who cites it

342 citing papers in PubMed, 18 syntheses or guidelines pooled it, 861 citations in OpenAlex.

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  10. 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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  12. Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO.International journal of chronic obstructive pulmonary disease · 2021
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  14. Romanian clinical guideline for diagnosis and treatment of COPD.The Journal of international medical research · 2020
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282 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 2 countries.

Jadwiga A WedzichaFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Donald BanerjiFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Kenneth R ChapmanFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Jørgen VestboFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Nicolas RocheFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
R Timothy AyersFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Chau ThachFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Robert FogelFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Francesco PatalanoFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
Claus F VogelmeierFrom the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique-Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).
FLAME Investigators
Université Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMost guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.

methodsWe conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.

resultsA total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).

conclusionsIndacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.).

Indexed as

Administration, InhalationAdrenergic beta-2 Receptor AgonistsAgedDouble-Blind MethodDrug CombinationsFemaleFluticasone-Salmeterol Drug CombinationGlucocorticoidsGlycopyrrolateHumansIndansMaleMiddle AgedMuscarinic AntagonistsPulmonary Disease, Chronic ObstructiveQuinolonesAdrenergic beta-2 Receptor AgonistsDrug CombinationsFluticasone-Salmeterol Drug CombinationGlucocorticoidsGlycopyrrolateindacaterolIndansMuscarinic AntagonistsQuinolones

Identifiers

PMID27181606
OpenAlexW2365138737

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.