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Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

39 Pages Posted: 14 Jun 2021

See all articles by Florence Ader

Florence Ader

Hospices Civils de Lyon - Département des Maladies Infectieuses et Tropicales; University of Claude Bernard Lyon 1 - ENS Lyon

Maude Bouscambert-Duchamp

University of Claude Bernard Lyon 1

Maya Hites

Université Libre de Bruxelles (ULB)

Nathan Peiffer-Smadja

National Institute for Health Research (NIHR) - Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance

Julien Poissy

Université de Lille

Drifa Belhadi

University of Paris

Alpha Diallo

ANRS

Christelle Delmas

University of Paris - INSERM

Juliette Saillard

Université de Rennes 1 - INSERM

Aline Dechanet

Hôpital Bichat, APHP

Claire Fougerou

University of Rennes 1 - CHU de Rennes

Minh-Patrick Lê

Hôpital Bichat, APHP

Gilles Peytavin

Hôpital Bichat, APHP

Noémie Mercier

ANRS-MIE

Priyanka Velou

Hôpital Bichat, APHP

Sarah Tubiana

Hôpital Bichat, APHP

Fraçois-Xavier Lescure

Hopital Bichat Claude Bernard

Emmanuel Faure

Université de Lille

Saad Nseir

Université de Lille

Jean-Christophe Richard

Hospices Civils de Lyon

Florent Wallet

Hospices Civils de Lyon - Medical Intensive Care Unit

François Goehringer

Université de Lorraine - CHRU de Nancy - Service des Maladies Infectieuses et Tropicales

Benjamin Lefèvre

Université de Lorraine - CHRU de Nancy - Service des Maladies Infectieuses et Tropicales

Antoine Kimmoun

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

François Raffi

CHU de Nantes

Bejamin Gaborit

CHU de Nantes

Jean Reignier

CHU de Nantes

Jean-Philippe Lanoix

University Picardie Jules Verne

Claire Andrejak

CHU Amiens-Picardie - Département de Pneumologie

Yoann Zerbib

Amiens Picardie University Hospital - Intensive Care Unit; CHU Amiens-Picardie - Département de Réanimation Médical

Firouzé Bani-Sadr

University of Reims Champagne-Ardenne

Bruno Mourvilliers

University of Reims Champagne-Ardenne

François Danion

University of Strasbourg - Department of Infectious and Tropical Diseases

Yvon Ruch

CHU Strasbourg

Raphaël Clere-Jehl

CHU Strasbourg

Vincent Le Moing

Department of Infectious Diseases, Hospital and University of Montpellier

Kada Klouche

University of Montpellier - Department of Intensive Care Medicine

Karine Lacombe

Sorbonne University - Infectious Disease Department

Guillaume Martin-Blondel

Université de Toulouse - Service des Maladies Infectieuses et Tropicales; Université Toulouse III - Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity)

Fanny Vardon-Bounes

Université de Toulouse - CHU de Toulouse

André Cabié

CHU Martinique

Jean-Marie Turmel

CHU Martinique

Lionel Piroth

Dijon University Hospital - Clinical Epidemiology Unit

Mathieu Blot

University of Burgundy Franche-Comté - LipSTIC LabEx

Elisabeth Botelho-Nevers

University of Saint Etienne - Centre Hospitalier Universitaire de Saint-Étienne

Amandine Gagneux-Brunon

University of Saint Etienne - Department of Hygiene and Infectious Diseases

Guillaume Thiery

University of Saint Etienne - Centre Hospitalier Universitaire de Saint-Étienne

François Bénézit

University of Rennes 1 - CHU de Rennes

Rostane Gaci

CHR Metz-Thionville

Joy Mootien

Groupe Hospitalier de la Région Mulhouse Sud-Alsace

Sébastien Gallien

University Hospital of Henri-Mondor, APHP

Denis Garot

CHRU Tours

Kevin Bouiller

Centre Hospitalier Régional et Universitaire de Besançon

Loïc Epelboin

Cayenne Hospital

Stéphane Jauréguiberry

Bicêtre University Hospital

Alexandre Gaymard

Laboratoire De Virologie, Institut Des Agents Infectieux, Laboratoire Associé Au Centre National De Référence Des Virus Des Infections Respiratoires, Hospices Civils De Lyon

Gil Verschelden

Université Libre de Bruxelles

Sandra Braz

Centro Hospitalar Universitário Lisboa Norte (CHLN)

Joao-Miguel Ferreira Ribeiro

Centro Hospitalar Universitário Lisboa Norte (CHLN)

Michael Joannidis

Medical University of Innsbruck - Division of Intensive Care and Emergency Medicine

Thérèse Staub

Centre Hospitalier Luxembourg

Antoine Altdorfer

CHR de la Citadelle

Richard Greil

Paracelsus Medical University Salzburg

Alexander Egle

Paracelsus Medical University Salzburg

Jérémie Guedj

Université de Paris

Marion Noret

RENARCI - Réseau national de recherche clinique en infectiologie

Roberto Roncon-Albuquerque Jr

São João Universitary Hospital Center - Department of Intensive Care

Jose-Artur Paiva

Universidade do Porto

Bruno Lina

University of Claude Bernard Lyon 1

Dominique Costagliola

Sorbonne University - Institut Pierre Louis d'Épidémiologie et de Santé Publique IPLESP

Yazdan Yazdanpanah

Infection, Antimicrobials, Modelisation, Evolution (IAME)

Charles Burdet

Hôpital Bichat, APHP

France Mentré

Hôpital Bichat, APHP

More...

Multiple version iconThere are 2 versions of this paper

Abstract

Background: The antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in patients with COVID-19 requiring oxygen and/or ventilator support. Methods: In this European multicentre, open-label, parallel-group, randomised, controlled trial in adults hospitalised with COVID-19 (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care alone or in combination with intravenous remdesivir (200 mg on day 1, then 100 mg once-daily for 9 days or until discharge). Treatment assignation was performed via web-based randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population.

Findings: Between March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 832 participants were included for the evaluation of remdesivir (control, n=418; remdesivir, n=414). There was no difference in the clinical status neither at day 15 between treatment groups (OR for remdesivir, 0.98, 95% CI, 0.77 to 1.25, P=0.85) nor at day 29. The proportion of deaths at day 28 was not significantly different between control (8.9%) and remdesivir (8.2%) treatment groups (OR for remdesivir, 0.93 95%CI 0.57 to 1.52, P=0.77). There was also no difference on SARS-CoV-2 viral kinetics (effect of remdesivir on viral load slope, -0.004 log10 cp/10,000 cells/day, 95% CI, -0.03 to 0.02, P=0.75). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups.

Interpretation: The use of remdesivir for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15 or day 29, nor with a reduction in mortality, nor with a reduction in SARS-CoV-2 RNA.

Clinical Trials: Trial Registration number: DisCoVeRy, NCT04315948; EudraCT2020-000936-

Funding: European Union Commission, French Ministry of Health, DIM One Health Île-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE).

Declaration of Interest: Dr. Costagliola reports grants and personal fees from Janssen, personal fees from Gilead, outside the submitted work. Dr. Mentré reports grants from INSERM Reacting (French Government), grants from Ministry of Health (French Government), grants from European Commission, during the conduct of the study; grants from Sanofi, grants from Roche, outside the submitted work. Dr. Hites reports grants from The Belgian Center for Knowledge (KCE), grants from Fonds Erasme-COVID-ULB, during the conduct of the study; personal fees from Gilead, outside the submitted work. Dr. Mootien reports non-financial support from GILEAD, outside the submitted work. Dr. Gaborit reports non-financial support from Gilead, non- financial support from MSD, outside the submitted work. Dr. Botelho-Nevers reports other from Pfizer, other from Janssen, outside the submitted work. Dr. Lacombe reports personal fees and non-financial support from Gilead, personal fees and non-financial support from Janssen, personal fees and non-financial support from MSD, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Abbvie, during the conduct of the study. Dr. Wallet reports personal fees and non-financial support from Jazz pharmaceuticals, personal fees and non-financial support from Novartis, personal fees and non financial support from Kite-Gilead, outside the submitted work. Dr. Kimmoun reports personal fees from Aguettan, personal fees from Aspen, outside the submitted work. Dr. Thiery reports personal fees from AMGEN, outside the submitted work. Dr. Burdet reports personal fees from Da Volterra, personal fees from Mylan Pharmaceuticals, outside the submitted work. Dr. Poissy reports personal fees from Gilead for lectures, outside the submitted work. Dr. Goehringer reports personal fees from Gilead Sciences, non-financial support from Gilead Sciences, grants from Biomerieux, non-financial support from Pfizer, outside the submitted work. Dr. Peytavin reports personal fees from Gilead Sciences, personal fees from Merck France, personal fees from ViiV Healthcare, personal fees from TheraTechnologies, outside the submitted work. Dr. Danion reports personal fees from Gilead, outside the submitted work. Dr. Raffi reports personal fees from Gilead, personal fees from Janssen, personal fees from MSD, personal fees from Abbvie, personal fees from ViiV Healthcare, personal fees from Theratechnologies, personal fees from Pfizer, outside the submitted work. Dr. Gallien reports personal fees from Gilead, personal fees from Pfizer, personal fees from ViiV, personal fees from MSD, outside the submitted work; and has received consulting fee from Gilead in August 2020 to check the registration file of remdesivir for the French administration. Dr. Nseir reports personal fees from MSD, personal fees from Pfizer, personal fees from Gilead, personal fees from Biomérieux, personal fees from BioRad, outside the submitted work. Dr. Lefèvre reports personal fees from Mylan, personal fees from Gilead, outside the submitted work. Dr. Guedj reports personal fees from Roche, outside the submitted work. Other authors have nothing to disclose.

Ethical Approval: The trial was approved by the Ethics Committee (CPP Ile-de-France-III, approval #20.03.06.51744), and is sponsored by the Institut national de la santé et de la recherche médicale (Inserm, France); it was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all included participants (or their legal representatives if unable to consent).

Suggested Citation

Ader, Florence and Bouscambert-Duchamp, Maude and Hites, Maya and Peiffer-Smadja, Nathan and Poissy, Julien and Belhadi, Drifa and Diallo, Alpha and Delmas, Christelle and Saillard, Juliette and Dechanet, Aline and Fougerou, Claire and Lê, Minh-Patrick and Peytavin, Gilles and Mercier, Noémie and Velou, Priyanka and Tubiana, Sarah and Lescure, Fraçois-Xavier and Faure, Emmanuel and Nseir, Saad and Richard, Jean-Christophe and Wallet, Florent and Goehringer, François and Lefèvre, Benjamin and Kimmoun, Antoine and Raffi, François and Gaborit, Bejamin and Reignier, Jean and Lanoix, Jean-Philippe and Andrejak, Claire and Zerbib, Yoann and Bani-Sadr, Firouzé and Mourvilliers, Bruno and Danion, François and Ruch, Yvon and Clere-Jehl, Raphaël and Le Moing, Vincent and Klouche, Kada and Lacombe, Karine and Martin-Blondel, Guillaume and Vardon-Bounes, Fanny and Cabié, André and Turmel, Jean-Marie and Piroth, Lionel and Blot, Mathieu and Botelho-Nevers, Elisabeth and Gagneux-Brunon, Amandine and Thiery, Guillaume and Bénézit, François and Gaci, Rostane and Mootien, Joy and Gallien, Sébastien and Garot, Denis and Bouiller, Kevin and Epelboin, Loïc and Jauréguiberry, Stéphane and Gaymard, Alexandre and Verschelden, Gil and Braz, Sandra and Ferreira Ribeiro, Joao-Miguel and Joannidis, Michael and Staub, Thérèse and Altdorfer, Antoine and Greil, Richard and Egle, Alexander and Guedj, Jérémie and Noret, Marion and Roncon-Albuquerque Jr, Roberto and Paiva, Jose-Artur and Lina, Bruno and Costagliola, Dominique and Yazdanpanah, Yazdan and Burdet, Charles and Mentré, France, Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial. Available at SSRN: https://ssrn.com/abstract=3866603 or http://dx.doi.org/10.2139/ssrn.3866603

Florence Ader

Hospices Civils de Lyon - Département des Maladies Infectieuses et Tropicales ( email )

103 Grande Rue de la Croix-Rousse
Lyon, F-69004
France
+33 (0)472 071 560 (Phone)
+33 (0)472 072 441 (Fax)

University of Claude Bernard Lyon 1 - ENS Lyon ( email )

Lyon, F-69372
France
+33 (0)472 071 560 (Phone)
+33 (0)472 072 441 (Fax)

Maude Bouscambert-Duchamp

University of Claude Bernard Lyon 1 ( email )

43 Bl du 11 novembre 1918
Lyon, Villeurbanne cedex 69622
France

Maya Hites

Université Libre de Bruxelles (ULB)

CP 132 Av FD Roosevelt 50
Brussels, Brussels 1050
Belgium

Nathan Peiffer-Smadja

National Institute for Health Research (NIHR) - Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance ( email )

London, Oxfordshire
United Kingdom

Julien Poissy

Université de Lille ( email )

Cité Scientifique
Villeneuve-d'Ascq, 59650
France

Drifa Belhadi

University of Paris ( email )

Paris
France

Alpha Diallo

ANRS

France

Christelle Delmas

University of Paris - INSERM ( email )

Paris
France

Juliette Saillard

Université de Rennes 1 - INSERM ( email )

Rennes
France

Aline Dechanet

Hôpital Bichat, APHP ( email )

Paris
France

Claire Fougerou

University of Rennes 1 - CHU de Rennes ( email )

Rennes
France

Minh-Patrick Lê

Hôpital Bichat, APHP ( email )

Paris
France

Gilles Peytavin

Hôpital Bichat, APHP ( email )

Paris
France

Noémie Mercier

ANRS-MIE ( email )

Paris, F-75013
France

Priyanka Velou

Hôpital Bichat, APHP ( email )

Paris
France

Sarah Tubiana

Hôpital Bichat, APHP ( email )

Paris
France

Fraçois-Xavier Lescure

Hopital Bichat Claude Bernard ( email )

Paris
France

Emmanuel Faure

Université de Lille ( email )

Cité Scientifique
Villeneuve-d'Ascq, 59650
France

Saad Nseir

Université de Lille ( email )

Cité Scientifique
Villeneuve-d'Ascq, 59650
France

Jean-Christophe Richard

Hospices Civils de Lyon ( email )

Florent Wallet

Hospices Civils de Lyon - Medical Intensive Care Unit ( email )

France

François Goehringer

Université de Lorraine - CHRU de Nancy - Service des Maladies Infectieuses et Tropicales ( email )

Nancy, 54000
France

Benjamin Lefèvre

Université de Lorraine - CHRU de Nancy - Service des Maladies Infectieuses et Tropicales ( email )

Nancy, 54000
France

Antoine Kimmoun

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

Nancy, F-54000
France

François Raffi

CHU de Nantes ( email )

27 Rue la Pérouse
Nantes Cedex 1, 44000
France

Bejamin Gaborit

CHU de Nantes ( email )

27 Rue la Pérouse
Nantes Cedex 1, 44000
France

Jean Reignier

CHU de Nantes ( email )

27 Rue la Pérouse
Nantes Cedex 1, 44000
France

Jean-Philippe Lanoix

University Picardie Jules Verne ( email )

Amiens
France

Claire Andrejak

CHU Amiens-Picardie - Département de Pneumologie ( email )

Amiens, F-80000
France

Yoann Zerbib

Amiens Picardie University Hospital - Intensive Care Unit ( email )

Amiens
France

CHU Amiens-Picardie - Département de Réanimation Médical ( email )

Amiens, F-80000
France

Firouzé Bani-Sadr

University of Reims Champagne-Ardenne ( email )

51096 Reims Cedex
France

Bruno Mourvilliers

University of Reims Champagne-Ardenne ( email )

51096 Reims Cedex
France

François Danion

University of Strasbourg - Department of Infectious and Tropical Diseases ( email )

Strasbourg
France
0369550545 (Phone)
0369551836 (Fax)

Yvon Ruch

CHU Strasbourg ( email )

Raphaël Clere-Jehl

CHU Strasbourg ( email )

1 place de l’hôpital
67000
France

Vincent Le Moing

Department of Infectious Diseases, Hospital and University of Montpellier ( email )

France

Kada Klouche

University of Montpellier - Department of Intensive Care Medicine ( email )

163 rue Auguste Broussonnet
France

Karine Lacombe

Sorbonne University - Infectious Disease Department ( email )

UFR 927, 4 Place Jussieu
Paris, F-75252
France

Guillaume Martin-Blondel

Université de Toulouse - Service des Maladies Infectieuses et Tropicales ( email )

Toulouse
France

Université Toulouse III - Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity)

Toulouse
France

Fanny Vardon-Bounes

Université de Toulouse - CHU de Toulouse ( email )

Toulouse
France

André Cabié

CHU Martinique ( email )

France

Jean-Marie Turmel

CHU Martinique ( email )

France

Lionel Piroth

Dijon University Hospital - Clinical Epidemiology Unit ( email )

Dijon
France

Mathieu Blot

University of Burgundy Franche-Comté - LipSTIC LabEx ( email )

45 D, Av. de l’Observatoire
Besancon, Besancon F-25000
France

Elisabeth Botelho-Nevers

University of Saint Etienne - Centre Hospitalier Universitaire de Saint-Étienne ( email )

Saint-Etienne
Saint-Priest en Jarez, 42270
France

Amandine Gagneux-Brunon

University of Saint Etienne - Department of Hygiene and Infectious Diseases ( email )

France

Guillaume Thiery

University of Saint Etienne - Centre Hospitalier Universitaire de Saint-Étienne ( email )

Saint-Etienne
Saint-Priest en Jarez, 42270
France

François Bénézit

University of Rennes 1 - CHU de Rennes ( email )

Rennes
France

Rostane Gaci

CHR Metz-Thionville ( email )

France

Joy Mootien

Groupe Hospitalier de la Région Mulhouse Sud-Alsace

Mulhouse
France

Sébastien Gallien

University Hospital of Henri-Mondor, APHP ( email )

51 Avenue du Maréchal de Lattre de Tassigny
Créteil, 94010
France

Denis Garot

CHRU Tours ( email )

Tours
France

Kevin Bouiller

Centre Hospitalier Régional et Universitaire de Besançon ( email )

Besançon
France

Loïc Epelboin

Cayenne Hospital ( email )

Inserm 1424
Cayenne
French Guiana

Stéphane Jauréguiberry

Bicêtre University Hospital ( email )

Le Kremlin Bicêtre
France

Alexandre Gaymard

Laboratoire De Virologie, Institut Des Agents Infectieux, Laboratoire Associé Au Centre National De Référence Des Virus Des Infections Respiratoires, Hospices Civils De Lyon ( email )

Gil Verschelden

Université Libre de Bruxelles ( email )

Brussels
Belgium

Sandra Braz

Centro Hospitalar Universitário Lisboa Norte (CHLN) ( email )

Portugal

Joao-Miguel Ferreira Ribeiro

Centro Hospitalar Universitário Lisboa Norte (CHLN) ( email )

Portugal

Michael Joannidis

Medical University of Innsbruck - Division of Intensive Care and Emergency Medicine ( email )

Innrain 52
Christoph-Probst-Platz
Innsbruck, 6020
Austria

Thérèse Staub

Centre Hospitalier Luxembourg ( email )

Luxembourg
Luxembourg

Antoine Altdorfer

CHR de la Citadelle ( email )

Liège
Belgium

Richard Greil

Paracelsus Medical University Salzburg

Salzburg
Austria

Alexander Egle

Paracelsus Medical University Salzburg ( email )

Salzburg
Austria

Jérémie Guedj

Université de Paris ( email )

Paris
France

Marion Noret

RENARCI - Réseau national de recherche clinique en infectiologie ( email )

France

Roberto Roncon-Albuquerque Jr

São João Universitary Hospital Center - Department of Intensive Care ( email )

Jose-Artur Paiva

Universidade do Porto ( email )

Rua Dr. Roberto Frias
4200-464 Porto
Portugal

Bruno Lina

University of Claude Bernard Lyon 1

43 Bl du 11 novembre 1918
Lyon, Villeurbanne cedex 69622
France

Dominique Costagliola

Sorbonne University - Institut Pierre Louis d'Épidémiologie et de Santé Publique IPLESP ( email )

Paris
France

Yazdan Yazdanpanah

Infection, Antimicrobials, Modelisation, Evolution (IAME)

Paris, F-75018
France

Charles Burdet (Contact Author)

Hôpital Bichat, APHP ( email )

France

France Mentré

Hôpital Bichat, APHP ( email )

France

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