Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial - Université de Rennes Access content directly
Journal Articles The Lancet Infectious Diseases Year : 2022

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

Florence Ader (1, 2) , Maude Bouscambert-Duchamp (1) , Maya Hites (3) , Nathan Peiffer-Smadja (4, 5) , Julien Poissy (6) , Drifa Belhadi (4) , Alpha Diallo (7) , Minh-Patrick Lê (8) , Gilles Peytavin (4) , Thérèse Staub (9) , Richard Greil (10) , Jérémie Guedj (4) , Jose-Artur Paiva (11) , Dominique Costagliola (12) , Yazdan Yazdanpanah (4) , Charles Burdet (4) , France Mentré (4) , Alexander Egle , Richard Greil , Michael Joannidis , Bernd Lamprecht , Antoine Altdorfer , Leila Belkhir , Vincent Fraipont , Maya Hites , Gil Verschelden , Jérôme Aboab , Florence Ader , Hafid Ait-Oufella , Claire Andrejak , Pascal Andreu , Laurent Argaud , Firouzé Bani-Sadr , François Benezit , Mathieu Blot , Elisabeth Botelho-Nevers , Lila Bouadma , Olivier Bouchaud , David Bougon , Kevin Bouiller , Fanny Bounes-Vardon , David Boutoille , Alexandre Boyer , Cédric Bruel , André Cabié , Emmanuel Canet , Charles Cazanave , Cyrille Chabartier , Catherine Chirouze , Raphaël Clere-Jehl , Johan Courjon , Flora Crockett , François Danion , Agathe Delbove , Jean Dellamonica , Félix Djossou , Clément Dubost , Alexandre Duvignaud , Olivier Epaulard , Loïc Epelboin , Murielle Fartoukh , Karine Faure , Emmanuel Faure , Tristan Ferry , Cécile Ficko , Samy Figueiredo , Benjamin Gaborit , Rostane Gaci , Amandine Gagneux-Brunon , Sébastien Gallien , Denis Garot , Guillaume Geri , Sébastien Gibot , François Goehringer , Marie Gousseff , Didier Gruson , Yves Hansmann , Olivier Hinschberger , Stéphane Jaureguiberry , Vanessa Jeanmichel , Solen Kerneis , Antoine Kimmoun , Kada Klouche (13, 14) , Marie Lachâtre , Karine Lacombe , Fabrice Laine , Jean-Philippe Lanoix , Odile Launay , Bruno Laviolle (15, 16) , Vincent Le Moing , Jérôme Le Pavec , Yves Le Tulzo (15) , Paul Le Turnier , David Lebeaux , Benjamin Lefevre , Sylvie Leroy , François-Xavier Lescure , Henry Lessire , Benjamin Leveau , Paul Loubet , Alain Makinson , Denis Malvy , Charles-Hugo Marquette , Guillaume Martin-Blondel , Martin Martinot , Julien Mayaux , Armand Mekontso-Dessap , Ferhat Meziani , Jean-Paul Mira , Jean-Michel Molina , Xavier Monnet , Joy Mootien , Bruno Mourvillier , Marlène Murris-Espin , Jean-Christophe Navellou , Saad Nseir , Walid Oulehri , Nathan Peiffer-Smadja , Thomas Perpoint , Gilles Pialoux , Benoît Pilmis , Vincent Piriou , Lionel Piroth , Julien Poissy , Valérie Pourcher , Jean-Pierre Quenot , François Raffi , Jean Reignier , Matthieu Revest (15, 17) , Jean-Christophe Richard (18, 19) , Béatrice Riu-Poulenc , Céline Robert , Pierre-Alexandre Roger , Claire Roger , Elisabeth Rouveix-Nordon , Yvon Ruch , Nadia Saidani , Naomi Sayre , Eric Senneville , Albert Sotto , Francois Stefan , Charles Tacquard , Nicolas Terzi , Julien Textoris , Guillaume Thiery , Jean-François Timsit , Violaine Tolsma , Jean-Marie Turmel , Florent Valour , Florent Wallet , Guilhem Wattecamps , Yazdan Yazdanpanah , Yoann Zerbib , Marc Berna , Jean Reuter , Thérèse Staub , Sandra Braz , Joao-Miguel Ferreira Ribeiro , José-Artur Paiva , Roberto Roncon-Albuquerque , Maude Bouscambert-Duchamp , Alexandre Gaymard , Minh-Patrick Lê , Bruno Lina , Gilles Peytavin , Sarah Tubiana , Sandrine Couffin-Cadièrgues , Hélène Esperou , Drifa Belhadi , Charles Burdet , Dominique Costagliola , Aline Dechanet , Christelle Delmas , Alpha Diallo , Claire Fougerou , Jérémie Guedj , France Mentré , Noémie Mercier , Marion Noret , Juliette Saillard , Priyanka Velou
Alexander Egle
  • Function : Author
Richard Greil
  • Function : Author
Michael Joannidis
  • Function : Author
Bernd Lamprecht
  • Function : Author
Antoine Altdorfer
  • Function : Author
Leila Belkhir
  • Function : Author
Vincent Fraipont
  • Function : Author
Maya Hites
  • Function : Author
Gil Verschelden
  • Function : Author
Jérôme Aboab
  • Function : Author
Florence Ader
  • Function : Author
Hafid Ait-Oufella
  • Function : Author
Claire Andrejak
Pascal Andreu
  • Function : Author
Laurent Argaud
  • Function : Author
Firouzé Bani-Sadr
  • Function : Author
François Benezit
  • Function : Author
Mathieu Blot
  • Function : Author
Elisabeth Botelho-Nevers
  • Function : Author
Lila Bouadma
  • Function : Author
Olivier Bouchaud
  • Function : Author
David Bougon
  • Function : Author
Kevin Bouiller
  • Function : Author
Fanny Bounes-Vardon
  • Function : Author
David Boutoille
  • Function : Author
Alexandre Boyer
  • Function : Author
Cédric Bruel
André Cabié
  • Function : Author
Emmanuel Canet
  • Function : Author
Charles Cazanave
  • Function : Author
Cyrille Chabartier
  • Function : Author
Catherine Chirouze
Raphaël Clere-Jehl
  • Function : Author
Johan Courjon
  • Function : Author
Flora Crockett
  • Function : Author
François Danion
  • Function : Author
Agathe Delbove
  • Function : Author
Jean Dellamonica
Félix Djossou
  • Function : Author
Clément Dubost
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Alexandre Duvignaud
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Olivier Epaulard
  • Function : Author
Loïc Epelboin
  • Function : Author
Murielle Fartoukh
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Karine Faure
  • Function : Author
Emmanuel Faure
  • Function : Author
Tristan Ferry
  • Function : Author
Cécile Ficko
  • Function : Author
Samy Figueiredo
  • Function : Author
Benjamin Gaborit
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Rostane Gaci
  • Function : Author
Amandine Gagneux-Brunon
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Sébastien Gallien
  • Function : Author
Denis Garot
  • Function : Author
Guillaume Geri
  • Function : Author
Sébastien Gibot
François Goehringer
  • Function : Author
Marie Gousseff
  • Function : Author
Didier Gruson
  • Function : Author
Yves Hansmann
  • Function : Author
Olivier Hinschberger
  • Function : Author
Stéphane Jaureguiberry
  • Function : Author
Vanessa Jeanmichel
  • Function : Author
Solen Kerneis
  • Function : Author
Antoine Kimmoun
  • Function : Author
Marie Lachâtre
  • Function : Author
Karine Lacombe
  • Function : Author
Fabrice Laine
  • Function : Author
Jean-Philippe Lanoix
Odile Launay
  • Function : Author
Vincent Le Moing
  • Function : Author
Jérôme Le Pavec
  • Function : Author
Paul Le Turnier
  • Function : Author
David Lebeaux
  • Function : Author
Benjamin Lefevre
  • Function : Author
Sylvie Leroy
  • Function : Author
François-Xavier Lescure
  • Function : Author
Henry Lessire
  • Function : Author
Benjamin Leveau
  • Function : Author
Paul Loubet
  • Function : Author
Alain Makinson
  • Function : Author
Denis Malvy
  • Function : Author
Charles-Hugo Marquette
  • Function : Author
Guillaume Martin-Blondel
  • Function : Author
Martin Martinot
  • Function : Author
Julien Mayaux
  • Function : Author
Armand Mekontso-Dessap
Ferhat Meziani
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Jean-Paul Mira
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  • PersonId : 928244
Jean-Michel Molina
  • Function : Author
Xavier Monnet
  • Function : Author
Joy Mootien
  • Function : Author
Bruno Mourvillier
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Marlène Murris-Espin
  • Function : Author
Jean-Christophe Navellou
  • Function : Author
Saad Nseir
Walid Oulehri
  • Function : Author
Nathan Peiffer-Smadja
  • Function : Author
Thomas Perpoint
  • Function : Author
Gilles Pialoux
  • Function : Author
Benoît Pilmis
  • Function : Author
Vincent Piriou
  • Function : Author
Lionel Piroth
  • Function : Author
Julien Poissy
  • Function : Author
Valérie Pourcher
  • Function : Author
Jean-Pierre Quenot
François Raffi
  • Function : Author
Jean Reignier
  • Function : Author
Béatrice Riu-Poulenc
  • Function : Author
Céline Robert
  • Function : Author
Pierre-Alexandre Roger
  • Function : Author
Claire Roger
  • Function : Author
Elisabeth Rouveix-Nordon
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Yvon Ruch
  • Function : Author
Nadia Saidani
  • Function : Author
Naomi Sayre
  • Function : Author
Eric Senneville
  • Function : Author
Albert Sotto
  • Function : Author
Francois Stefan
  • Function : Author
Charles Tacquard
  • Function : Author
Nicolas Terzi
Julien Textoris
Guillaume Thiery
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Jean-François Timsit
Violaine Tolsma
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Jean-Marie Turmel
  • Function : Author
Florent Valour
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Florent Wallet
  • Function : Author
Guilhem Wattecamps
  • Function : Author
Yazdan Yazdanpanah
  • Function : Author
Yoann Zerbib
  • Function : Author
Marc Berna
  • Function : Author
Jean Reuter
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Thérèse Staub
  • Function : Author
Sandra Braz
  • Function : Author
Joao-Miguel Ferreira Ribeiro
  • Function : Author
José-Artur Paiva
  • Function : Author
Roberto Roncon-Albuquerque
  • Function : Author
Maude Bouscambert-Duchamp
  • Function : Author
Alexandre Gaymard
  • Function : Author
Minh-Patrick Lê
  • Function : Author
Bruno Lina
  • Function : Author
Gilles Peytavin
  • Function : Author
Sarah Tubiana
  • Function : Author
Sandrine Couffin-Cadièrgues
  • Function : Author
Hélène Esperou
  • Function : Author
Drifa Belhadi
  • Function : Author
Charles Burdet
  • Function : Author
Dominique Costagliola
  • Function : Author
Aline Dechanet
  • Function : Author
Christelle Delmas
  • Function : Author
Alpha Diallo
  • Function : Author
Claire Fougerou
  • Function : Author
Jérémie Guedj
  • Function : Author
France Mentré
  • Function : Author
Noémie Mercier
  • Function : Author
Marion Noret
  • Function : Author
Juliette Saillard
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Priyanka Velou
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Abstract

Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support.
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hal-03812289 , version 1 (12-10-2022)

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Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, et al.. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. The Lancet Infectious Diseases, 2022, 22 (2), pp.209-221. ⟨10.1016/S1473-3099(21)00485-0⟩. ⟨hal-03812289⟩
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