Protocol for the DisCoVeRy trial: multicentre, adaptive, randomised trial of the safety and efficacy of treatments for COVID-19 in hospitalised adults

BMJ Open. 2020 Sep 21;10(9):e041437. doi: 10.1136/bmjopen-2020-041437.


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 ( 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.

Keywords: clinical trials; infectious diseases; intensive & critical care; public health; respiratory infections.

Publication types

  • Adaptive Clinical Trial
  • Clinical Trial Protocol
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Adult
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Betacoronavirus
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / therapy
  • Drug Combinations
  • Drug Therapy, Combination
  • Early Warning Score
  • Extracorporeal Membrane Oxygenation
  • Hospital Mortality
  • Hospitalization
  • Humans
  • Hydroxychloroquine / therapeutic use*
  • Interferon beta-1a / therapeutic use*
  • Length of Stay
  • Lopinavir / therapeutic use*
  • Oxygen Inhalation Therapy
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / therapy
  • Respiration, Artificial
  • Ritonavir / therapeutic use*
  • SARS-CoV-2
  • Standard of Care
  • Treatment Outcome


  • Antiviral Agents
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • remdesivir
  • Adenosine Monophosphate
  • Hydroxychloroquine
  • Ritonavir
  • Alanine
  • Interferon beta-1a

Associated data

  • EudraCT/Eudra-CT 2020-000936-23