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Protocol
Protocol for the DisCoVeRy trial: multicentre, adaptive, randomised trial of the safety and efficacy of treatments for COVID-19 in hospitalised adults
  1. Florence Ader
  2. Discovery French Trial Management Team
    1. Infectious and tropical diseases department, Centre Hospitalier Universitaire de Lyon, F-69004 Lyon, and 1Inserm 1111-Centre International de Recherche en Infectiologie (CIRI), Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France
    1. Correspondence to Dr Florence Ader, Infectious and tropical diseases department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, FRANCE; florence.ader{at}chu-lyon.fr

    Abstract

    Introduction To find effective and safe treatments for COVID-19, the WHO recommended to systemically evaluate experimental therapeutics in collaborative randomised clinical trials. As COVID-19 was spreading in Europe, the French national institute for Health and Medical Research (Inserm) established a transdisciplinary team to develop a multi-arm randomised controlled trial named DisCoVeRy. The objective of the trial is to evaluate the clinical efficacy and safety of different investigational re-purposed therapeutics relative to Standard of Care (SoC) in patients hospitalised with COVID-19.

    Methods and analysis DisCoVeRy is a phase III, open-label, adaptive, controlled, multicentre clinical trial in which hospitalised patients with COVID-19 in need of oxygen therapy are randomised between five arms: (1) a control group managed with SoC and four therapeutic arms with re-purposed antiviral agents: (2) remdesivir + SoC, (3) lopinavir/ritonavir + SoC, (4) lopinavir/ritonavir associated with interferon (IFN)-β−1a + SoC and (5) hydroxychloroquine + SoC. The primary endpoint is the clinical status at Day 15 on the 7-point ordinal scale of the WHO Master Protocol (V.3.0, 3 March 2020). This trial involves patients hospitalised in conventional departments or intensive care units both from academic or non-academic hospitals throughout Europe. A sample size of 3100 patients (620 patients per arm) is targeted. This trial has begun on 22 March 2020. Since 5 April 2020, DisCoVeRy has been an add-on trial of the Solidarity consortium of trials conducted by the WHO in Europe and worldwide. On 8 June 2020, 754 patients have been included.

    Ethics and dissemination Inserm is the sponsor of DisCoVeRy. Ethical approval has been obtained from the institutional review board on 13 March 2020 (20.03.06.51744) and from the French National Agency for Medicines and Health Products (ANSM) on 9 March 2020. Results will be submitted for publication in peer-reviewed journals.

    Trial registration number NCT04315948 Eudra-CT 2020-000936-23.

    • clinical trials
    • infectious diseases
    • respiratory infections
    • public health
    • intensive & critical care
    http://creativecommons.org/licenses/by-nc/4.0/

    This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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    Footnotes

    • Collaborators Discovery French Trial Management Team: Yazdan Yazdanpanah; France Mentre; Nathan Peiffer-Smadja; François-Xavier Lescure; Julien Poissy; Lila Bouadma; Jean-FrançOis Timsit; Bruno Lina; Florence Morfin-Sherpa; Maude Bouscambert; Alexandre Gaymard; Gilles Peytavin; Laurent Abel; Jeremie Guedj; Claire Andrejak; Charles Burdet; Cedric Laouenan; Drifa Belhadi; Axelle Dupont; Toni Alfaiate; Basma Basli; Anissa Chair; Samira Laribi; Julie Level; Marion Schneider; Marie-Capucine Tellier; Aline Dechanet; Dominique Costagliola; Sandrine Couffin-Cadiergues; HéLèNe Esperou; Christelle Delmas; Juliette Saillard; Claire Fougerou; LaëTitia Moinot; Linda Wittkop; Carole Cagnot; Soizic Le Mestre; Delphine Lebrasseur-Longuet; Ventzislava Petrov-Sanchez; Alpha Diallo; NoéMie Mercier; Vinca Icard; Benjamin Leveau; Sarah Tubiana; Benjamin Hamze; Ambre Gelley; Marion Noret; Eric D’Ortenzio; Oriane Puechal; Caroline Semaille.

    • Contributors Conceptualisation, investigation, supervision, writing - original draft: FA.

    • Funding The trial is funded by a grant from Programme Hospitalier de Recherche Clinique - PHRC 2020 (PHRC-20–0351) (Ministry of Health). This study also received a financial support from REACTing, a French multidisciplinary collaborative network working on emerging infectious diseases. The trial is sponsored by Institut national de la santé et de la recherche médicale (INSERM, France).

    • Disclaimer The funder nor the sponsor did not have any role in the design of the trial.

    • Competing interests François-Xavier Lescure reports fees for development of educational presentations from Gilead, outside the submitted work. Dominique Costagliola reports personal fees from Merck Switzerland, grants and personal fees from MSD France, personal fees from Gilead France, grants and personal fees from Janssen, outside the submitted work. Jean-François Timsit reports grants and personal fees from Merck, grants and personal fees from Pfizer, grants from biomerieux, personal fees from medimune, personal fees from Paratek, personal fees from Gilead, outside the submitted work. Benjamin Hamze reports personal fees from Sanofi, outside the submitted work. Gilles Peytavin has received travel grants, consultancy fees, honoraria, or study grants from various pharmaceutical companies, including Gilead Sciences, Merck, TheraTechnologies and ViiV Healthcare. France Mentre reports grants and personal fees from Sanofi, outside the submitted work.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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