Corona Virus InfectionPhase 3DisCoVeRyNCT04315948
Trial of Treatments for COVID-19 in Hospitalized Adults
A Phase 3 study testing Remdesivir, Lopinavir/ritonavir and Interferon Beta-1A in people with Corona Virus Infection, run by Institut National de la Santé Et de la Recherche Médicale, France at 62 sites in 7 countries.
Trial summary
DisCoVeRy is a randomized controlled trial among adults (≥18-year-old) hospitalized for COVID-19. This study is an adaptive, randomized, open or blinded, depending on the drug to be evaluated, clinical trial to evaluate the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corona Virus Infection
- What is being tested?
- Remdesivir, Lopinavir/ritonavir and Interferon Beta-1A
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,552 participants
- Where
- 62 sitesin 7 countries
- Study dates
- 22 Mar 2020to 25 Sep 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult ≥18 years of age at the time of enrolment
- Hospitalized patients with any of the following criteria:
- the presence of pulmonary rales/crackles on clinical exam OR
- SpO2 ≤ 94% on room air OR
- requirement of supplementary oxygen including high flow oxygen devices or non-invasive ventilation
- A time between onset of symptoms and randomization of less than 11 days
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- A positive SARS-CoV-2 PCR performed on a NP swab within the 5 days preceding randomization
- The result of a rapid antigen test performed on a NP swab within the 6 hours preceding randomization
- Contraceptive use by men or women.
- Male participants: Contraception for male participants is required; to avoid the transfer of any fluids, all male participants must use a condom from Day 1 and agree to continue for 90 days following administration of IMP.
- Female participants: Women of child-bearing potential must agree to use contraception for 365 days following administration of IMP
Who cannot join
- Refusal to participate expressed by patient or legally authorized representative
- Need for invasive mechanical ventilation and/or ECMO at the time of enrolment
- Spontaneous blood ALT/AST levels > 5 times the upper limit of normal
- Glomerular filtration rate (GFR) < 15 mL/min or requiring maintenance dialysis
- Pregnancy or breast-feeding
- Anticipated transfer to another hospital, which is not a study site within 72 hours following randomization
Show all 10Show fewer
- Known history of allergy or reaction to any component of the study drug formulation.
- Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of monoclonal or polyclonal antibodies.
- Any prior receipt of investigational or licensed other mAb/biologic indicated for the prevention of SARS-CoV-2 infection or COVID-19, and for those not vaccinated, expected receipt of vaccine in the 30 days following hospital discharge, according to current recommendation in each country.
- Any medical condition which, in the judgment of the investigator, could interfere with the interpretation of the trial results or that preludes to protocol adherence.
Trial locations and contacts
62 sites in 7 countries.
62 sites in 7 countries
France45 sites
Centre Hospitalier Universitaire Amiens-Picardie
Amiens, 80054
Centre Hospitalier Regional Metz-Thionville
Ars-Laquenexy, 57085
Centre Hospitalier Régional Universitaire de Besançon
Besançon, 25000
Centre Hospitalier Universitaire de Bordeaux
Bordeaux, 33000
CHU APHP Ambroise-Paré
Boulogne-Billancourt
Centre Hospitalier Andrée Rosemon
Cayenne, 97306
Hospices Civil
Colmar
APHP - hôpital Henri-Mondor
Créteil, 94010
Centre Hospitalier Universitaire Dijon-Bourgogne
Dijon, 21000
Centre Hospitalier Annecy Genevois
Épagny, 74370
Centre Hospitalier Universitaire de Martinique
Fort de France, 97261
Centre Hospitalo-Universitaire de Grenoble
La Tronche, 38700
AP-HP Hôpital Bicêtre
Le Kremlin-Bicêtre, 94270
Centre Hospitalier Régional Universitaire de Lille
Lille, 59000
Hospices Civils de Lyon
Lyon, 69000
Centre Hospitalier Universitaire de Montpellier
Montpellier, 34000
Groupe Hospitalier de la Région de Mulhouse Sud Alsace
Mulhouse, 68100
Centre Hospitalier Régional et Universitaire de Nancy
Nancy, 54000
Centre Hospitalier Universitaire de Nantes
Nantes, 44000
Centre Hospitalo-Universitaire de Nice
Nice, 06000
CHU Nîmes
Nîmes
APHP - Hôpital Lariboisière
Paris, 75010
APHP - Hôpital Saint Louis
Paris, 75010
APHP - Hôpital Saint Antoine
Paris, 75012
APHP - Hôpital Universitaire Pitié Salpêtrière
Paris, 75013
APHP - Hôpital Cochin
Paris, 75014
Hôpital Paris Saint-Joseph et Marie Lannelongue
Paris, 75014
APHP - Hôpital Necker
Paris, 75015
APHP- Hôpital Européen Georges-Pompidou
Paris, 75015
APHP - Hôpital Bichat Claude Bernard
Paris, 75018
APHP - Hôpital Tenon
Paris, 75020
CHU Poitiers
Poitiers
CH Cornouaille
Quimper
CHU de Reims
Reims, 51100
Centre Hospitalier Universitaire de Rennes
Rennes, 35033
Hopital DELAFONTAINE
Saint-Denis, 93200
Centre Hospitalier Universitaire de Saint Etienne
Saint-Etienne, 42055
Hôpital d'Instruction des Armées BEGIN
Saint-Mandé, 94160
Centre Hospitalier Régional Universitaire de Strasbourg
Strasbourg, 67000
Centre Hospitalier Universitaire de Toulouse
Toulouse, 31000
Centre Hospitalier Universitaire de Toulouse
Toulouse, 31300
Centre Hospitalier de Tourcoing
Tourcoing, 59208
Centre Hospitalier Universitaire de Tours
Tours, 37000
CH Bretagne Atlantique
Vannes, 56000
CH Bretagne Atlantique
Vannes
Belgium4 sites
Hôpital Erasme - Cliniques universitaires de Bruxelles
Brussels, 1070
Hôpital Saint Luc
Brussels, 1200
Hôpital La Citadelle
Liège, 4000
Pôle Hospitalier Jolimont / site de Mons-Warquignies
Mons
Austria3 sites
Medizinische Universität Innsbruck
Innsbruck, 6020
Kepler Universitätsklinikum Linz
Linz
Landeskrankenhaus Salzburg Universitätsklinikum der Paracelsus Medizinischen Privatuniversität
Salzburg, 5020
Norway3 sites
Akershus Unniversity Hospital
Oslo
Lovisenberg Diaconal Hospital
Oslo
Oslo University Hospital
Oslo
Portugal3 sites
Hospital de Cascais
Cascais
CHULN- Hospital de Santa Maria
Lisbon
Centro Hospitalar Universitário de São João, EPE
Porto
Greece2 sites
Evaggelismos General Hospital
Athens
General University Hospital of Patras
Pátrai
Luxembourg2 sites
Centre Hospitalier Luxembourg
Luxembourg, L-1210
Hôpitaux Robert Schuman
Luxembourg, L-2450
About this study
Official title: Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults
DisCoVeRy is a randomized controlled trial among adults (≥18-year-old) hospitalized for COVID-19. This study is an adaptive, randomized, open or blinded, depending on the drug to be evaluated, clinical trial to evaluate the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed with COVID-19. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. The study will compare different investigational therapeutic agents to a control group managed with the SoC including corticosteroids and anticoagulants. There will be interim monitoring to allow early stopping for safety and to introduce new therapies as they become available. If one therapy proves to be superior to others in the trial, this treatment may become part of the SoC for comparison(s) with new experimental treatment(s).
In previous versions of the DisCoVeRy protocol, remdesivir, lopinavir/ritonavir with or without interferon ß-1a and hydroxychloroquine were evaluated as potential treatments for COVID-19. These treatments have been discontinued based on analyses review by both DSMC/DSMB, the Solidarity Executive Group and the DisCoVeRy steering committee.
Read more
This version of the protocol, therefore, describes a randomized blinded placebo-controlled trial among adults (≥18-year-old) hospitalized for COVID-19 that randomly allocates them (1:1 ratio) between 2 arms: SoC + placebo versus SoC + AZD7442.
Randomization will be stratified by region (according to the administrative definition in each country), antigenic status (positive or negative) obtained from the result of a rapid antigen test on nasopharyngeal swab performed at enrolment and vaccination initiation (yes or no).
The primary analyses will be conducted on patients with antigen-positive results. A positive antigenic test is evidence of high viral shedding consistent with a recently started or uncontrolled infection. Overall, the number of antigen-negative patients will be at most 30% of all included subjects. The number of patients with vaccination (partly or fully) will be limited to 20% of all participants, split evenly between antigen positive and antigen negative patients (i.e. vaccinated patients can make up at most 20% of antigene positive patients and 20% of antigene negative patients). Sensitivity analyses will be performed in all patients, stratified by antigenic status and vaccination initiation.
A global independent data and safety monitoring board (DSMB) monitors interim data to make recommendations about early study closure or changes to conduct, including adding or removing treatment arms. However, the current version of the protocol does not allow for efficacy or futility analysis, and the ability to add trial arms will be limited by the study being blinded and placebo-controlled during the investigation of AZD7442.
Read the detailed description
DisCoVeRy is a randomized controlled trial among adults (≥18-year-old) hospitalized for COVID-19. This study is an adaptive, randomized, open or blinded, depending on the drug to be evaluated, clinical trial to evaluate the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed with COVID-19. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. The study will compare different investigational therapeutic agents to a control group managed with the SoC including corticosteroids and anticoagulants. There will be interim monitoring to allow early stopping for safety and to introduce new therapies as they become available. If one therapy proves to be superior to others in the trial, this treatment may become part of the SoC for comparison(s) with new experimental treatment(s).
In previous versions of the DisCoVeRy protocol, remdesivir, lopinavir/ritonavir with or without interferon ß-1a and hydroxychloroquine were evaluated as potential treatments for COVID-19. These treatments have been discontinued based on analyses review by both DSMC/DSMB, the Solidarity Executive Group and the DisCoVeRy steering committee.
This version of the protocol, therefore, describes a randomized blinded placebo-controlled trial among adults (≥18-year-old) hospitalized for COVID-19 that randomly allocates them (1:1 ratio) between 2 arms: SoC + placebo versus SoC + AZD7442.
Randomization will be stratified by region (according to the administrative definition in each country), antigenic status (positive or negative) obtained from the result of a rapid antigen test on nasopharyngeal swab performed at enrolment and vaccination initiation (yes if at least one injection of any vaccine against SARS-CoV-2 was reveived prior to enrolment whatever the delay or no).
The primary analyses will be conducted on patients with antigen-positive results. A positive antigenic test is evidence of high viral shedding consistent with a recently started or uncontrolled infection. Overall, the number of antigen-negative patients will be at most 30% of all included subjects. The number of patients with vaccination (partly or fully) will be limited to 20% of all participants, split evenly between antigen positive and antigen negative patients (i.e. vaccinated patients can make up at most 20% of antigene positive patients and 20% of antigene negative patients). Sensitivity analyses will be performed in all patients, stratified by antigenic status and vaccination initiation.
A global independent data and safety monitoring board (DSMB) monitors interim data to make recommendations about early study closure or changes to conduct, including adding or removing treatment arms. However, the current version of the protocol does not allow for efficacy or futility analysis, and the ability to add trial arms will be limited by the study being blinded and placebo-controlled during the investigation of AZD7442.
All subjects will undergo a series of efficacy and safety assessments, including laboratory assays.
Subjects will be assessed at baseline, and at Days 3, 8 and 15 while hospitalized. Patients will be contacted by phone at Day 15 for evaluation of the Primary Endpoint if they have been discharged prior to Day 15-, and 14-days following hospital discharge for efficacy assessment.
Further follow-up assessments will be organized at Days 29, 90, 180, 365 and 456.
If discharged from the hospital, days 29 and 90 assessments will be organized as outpatients' consultations for all. For Days 180 and 365 assessments, a subset of 25% of patients enrolled in centers with available resources and selected at Day 90 will be evaluated during a medical consultation, while the other will be contacted by phone. For Day 456, all patients will be contacted by phone.
Nasopharyngeal swabs (NP) or lower respiratory tract samples will be obtained at baseline (Day 1 pre-treatment) and at Days 3, 8, 15 (while hospitalized) and 29 (while hospitalized or, if discharged from the hospital, in the outpatient setting).
Blood samples will be obtained at baseline (Day 1 pre-treatment) and at Days 3, 8, 15 (while hospitalized), at Days 29 and 90, and at Days 180 and 365 (for the subset of patients evaluated during a medical consultation at these times).
Thoracic computed tomography (CT)-scan will be obtained at baseline, depending on the centre's imagery capacities.
- Conditions
- Corona Virus Infection
- Being tested
- Remdesivir, Lopinavir/ritonavir, Interferon Beta-1A, Hydroxychloroquine, Standard of care
- Keywords
- COVID-19, SARS-CoV-2, Pneumonia
- Medical subject headings
- Coronavirus Infections, COVID-19, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemdesivirDrug
The lyophilized formulation of Remdesivir is a preservative-free, white to off-white or yellow, lyophilized solid containing 100 mg of Remdesivir to be reconstituted with 19 mL of sterile water for injection and diluted into IV infusion fluids prior to IV infusion. Following reconstitution, each vial contains a 5 mg/mL Remdesivir concentrated solution with sufficient volume to allow withdrawal of 20 mL (100 mg of remdesivir). It is supplied as a sterile product in a single-use, 30 mL, Type 1 clear glass vial.
Lopinavir/ritonavirDrug
The oral tablets of lopinavir/ritonavir contain 200 mg lopinavir, 50 mg ritonavir. They have a yellow colour, film-coated, ovaloid shape debossed with the "a" logo and the code KA. The oral solution for patients who cannot swallow is a light yellow to orange colored liquid containing 400 mg lopinavir and 100 mg ritonavir per 5 mL (80 mg lopinavir and 20 mg ritonavir per mL).
Interferon Beta-1ADrug
IFN-ß-1a is supplied as a sterile solution containing no preservative available in a prefilled syringe. It will be provided as a single-dose prefilled graduated syringe with 44 µg per 0.5 mL. The liquid should be clear to slightly yellow. Do not use if the liquid is cloudy, discolored or contains particles. Use a different syringe.
Hydroxychloroquine is supplied as film-coated 200 mg tablets. Hydroxychloroquine sulfate tablets are presented as white or whitish, peanut-shaped, oblong or round film-coated tablets containing 200 mg of hydroxychloroquine sulfate (equivalent to 155 mg base).
Standard of careOther
Standard of care
AZD7442Drug
AZD7442 will be supplied as separate vials of AZD8895 and AZD1061 containing 150 mg colorless to slightly yellow, clear to opalescent solutions for injection.
PlaceboOther
Since April, 2021, the placebo will be a 0.9% (w/v) NaCl solution for infusion also called saline. The placebo will be supplied as a single 10-mL, clear and colorless vial.
| Study group | Role | What they receive |
|---|---|---|
| Remdesivir | Experimental | Remdesivir will be administered as a 200 mg intravenous loading dose on Day 1, followed by a 100 mg once-daily intravenous maintenance dose for the duration of the hospitalization up to a 10 days total course.
n=475 Receives: Drug: Remdesivir; Other: Standard of care |
| Lopinavir/ritonavir (stopped on June 29, 2020) | Experimental | Lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered every 12 h for 14 days in tablet form. For patients who are unable to take medications by mouth, the lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered as a 5-ml suspension every 12 h for 14 days via a pre-existing or newly placed nasogastric tube.
n=620 Receives: Drug: Lopinavir/ritonavir; Other: Standard of care |
| Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29) | Experimental | Lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered every 12 h for 14 days in tablet form. For patients who are unable to take medications by mouth, the lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered as a 5-ml suspension every 12 h for 14 days via a pre-existing or newly placed nasogastric tube.
Interferon ß1a will be administered subcutaneously at the dose of 44 µg for a total of 3 doses in 6 days (day 1, day 3, day 6).
n=620 Receives: Drug: Lopinavir/ritonavir; Drug: Interferon Beta-1A; Other: Standard of care |
| Hydroxychloroquine (stopped on May 24, 2020) | Experimental | Hydroxychloroquine will be administered orally as a loading dose of 400 mg twice daily for one day followed by 400 mg once daily for 9 days. The loading dose of hydroxychloroquine through a nasogastric tube will be increased to 600 mg twice a day for one day, followed by a maintenance dose of 400 mg once a day for 9 days n=620 Receives: Drug: Hydroxychloroquine; Other: Standard of care |
| Standard of care alone | Active comparator | Standard of care alone before March, 2021. Receives: Other: Standard of care |
| AZD7442 | Experimental | Participants randomized to the AZD7442 group will receive a total dose of 600 mg AZD7442 via a co-administered (300 mg AZD8895 and 300 mg AZD1061) single IV infusion on Day 1.
n=620 Receives: Other: Standard of care; Drug: AZD7442 |
| Standard of care with placebo | Active comparator | Standard of care with placebo since April, 2021 n=620 Receives: Other: Standard of care; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects reporting each severity rating on a 7-point ordinal scale
- Not hospitalized, no limitations on activities
- Not hospitalized, limitation on activities;
- Hospitalized, not requiring supplemental oxygen;
- Hospitalized, requiring supplemental oxygen;
- Hospitalized, on non-invasive ventilation or high flow oxygen devices;
- Hospitalized, on invasive mechanical ventilation or ECMO;
- Death.
Measured: Day 15
Secondary outcomes (16)
Status on an ordinal scale
Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale
Measured: Days 29, 90, 180 and 365
National Early Warning Score 2 (NEWS-2 score)
Change from baseline in NEWS-2.
Measured: Days 3, 8, 15, and 29
Number of oxygenation free days in the first 28 days
Measured: 29 days
Incidence of new oxygen use, non-invasive ventilation or high flow oxygen devices during the trial.
Measured: 29 days
Ventilator free days in the first 28 days
Measured: 29 days
Incidence of new mechanical ventilation use during the trial.
Measured: 29 days
Need for mechanical ventilation or death by Day 15
Proportion of patients with mechanical ventilation or death at day 15
Measured: Day 15
Hospitalization
Time to hospital discharge (days).
Measured: 29 days
Mortality
Rate of mortality
Measured: In hospital, Days 29, 90, 180, 365, 456
Occurrence of new hospitalization
Measured: Days 90, 180 and 365
Occurrence of confirmed re-infection with SARS-CoV-2
Measured: Days 90, 180 and 365
Cumulative incidence of serious adverse events (SAEs)
Measured: 29 days
Cumulative incidence of Grade 1- 2 hypersensitivity- related and infusion related AEs until D29 visit
Measured: 29 days
Cumulative incidence of Grade 3 and 4 adverse events (AEs)
Measured: 29 days
Number of participants with a discontinuation or temporary suspension of study drugs (for any reason)
Measured: 29 days
Cumulative incidence of AEs of Special Interest
Measured: 29 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start22 Mar 2020
- Primary completion9 Jul 2022
- Study completion25 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Corona Virus InfectionStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- From March 22, 2020 to May 24, 2020, the study randomized participants 1:1:1:1:1 to standard of care alone (control) or with investigational product added. From May 24, 2020 to June 29, 2020, the study randomized participants 1:1:1:1 to standard of care alone (control) or with investigational product added. From June 29, 2020 to January 19,2021, the study randomized participants 1:1 to standard of care alone (control) or with investigational product added. Since April, 2021, the study will randomize participants 1:1 to standard of care with placebo (control) or standard of care with investigational product added.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,552 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Florence Ader, MD, Study chair, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04315948
- Sponsor's protocol ID
- C20-15
- Other IDs
- 101015736, 2020-000936-23
- Acronym
- DisCoVeRy
- Status last verified
- Jul 2026
- First submitted
- 13 Mar 2020
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study protocol and statistical analysis plan will be available. Systematic individual patient data sharing is not intended, but all requests for the trial's data will be considered by the French DisCoVeRy Trial Management Team.
Publications
Ader F; Discovery French Trial Management Team. 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.
PubMed 32958495EU-Response investigators group; Diallo A, Troseid M, Simensen VC, Boston A, Demotes J, Olsen IC, Chung F, Paiva JA, Hites M, Ader F, Arribas JR, Baratt-Due A, Melien O, Tacconelli E, Staub T, Greil R, Tsiodras S, Briel M, Esperou H, Mentre F, Eustace J, Saillard J, Delmas C, LeMestre S, Dumousseaux M, Costagliola D, Rottingen JA, Yazdanpanah Y. Accelerating clinical trial implementation in the context of the COVID-19 pandemic: challenges, lessons learned and recommendations from DisCoVeRy and the EU-SolidAct EU response group. Clin Microbiol Infect. 2022 Jan;28(1):1-5. doi: 10.1016/j.cmi.2021.10.011. Epub 2021 Nov 8. No abstract available.
PubMed 34763056Troseid M, Hentzien M, Ader F, Cardoso SW, Arribas JR, Molina JM, Mueller N, Hites M, Bonnet F, Manuel O, Costagliola D, Grinsztejn B, Olsen IC, Yazdapanah Y, Calmy A; EU RESPONSE; COMBINE. Immunocompromised patients have been neglected in COVID-19 trials: a call for action. Clin Microbiol Infect. 2022 Sep;28(9):1182-1183. doi: 10.1016/j.cmi.2022.05.005. Epub 2022 May 25. No abstract available.
PubMed 35623577Terzic V, Levoyer L, Figarella M, Bigagli E, Mercier N, De Gastines L, Gibowski S, Troseid M, Demotes J, Olsen IC, Hites M, Ader F, Lopez JRA, Mentre F, Esperou H, Costagliola D, Rottingen JA, Poissy J, Roze JC, Warris A, O'Leary J, Fernandes RM, Assoumou L, Hankard R, Turner MA, Yazdanpanah Y, Diallo A; EU-Response safety group; c4c safety group. Implementation of a centralized pharmacovigilance system in academic pan-European clinical trials: Experience from EU-Response and conect4children consortia. Br J Clin Pharmacol. 2023 Apr;89(4):1318-1328. doi: 10.1111/bcp.15669. Epub 2023 Feb 8.
PubMed 36680782Amstutz A, Speich B, Mentre F, Rueegg CS, Belhadi D, Assoumou L, Burdet C, Murthy S, Dodd LE, Wang Y, Tikkinen KAO, Ader F, Hites M, Bouscambert M, Trabaud MA, Fralick M, Lee TC, Pinto R, Barratt-Due A, Lund-Johansen F, Muller F, Nevalainen OPO, Cao B, Bonnett T, Griessbach A, Taji Heravi A, Schonenberger C, Janiaud P, Werlen L, Aghlmandi S, Schandelmaier S, Yazdanpanah Y, Costagliola D, Olsen IC, Briel M. Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials. Lancet Respir Med. 2023 May;11(5):453-464. doi: 10.1016/S2213-2600(22)00528-8. Epub 2023 Feb 21.
PubMed 36828006Le MP, Peiffer-Smadja N, Guedj J, Neant N, Mentre F, Ader F, Yazdanpanah Y, Peytavin G. Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial. J Antimicrob Chemother. 2020 Sep 1;75(9):2376-2380. doi: 10.1093/jac/dkaa191.
PubMed 32473020Le MP, Peiffer-Smadja N, Guedj J, Neant N, Mentre F, Ader F, Yazdanpanah Y, Peytavin G; C-20-15 DisCoVeRy French Steering Committee. Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial-authors' response. J Antimicrob Chemother. 2021 Jan 1;76(1):277-279. doi: 10.1093/jac/dkaa415. No abstract available.
PubMed 33089306Mercier N, Belhadi D, DeChanet A, Delmas C, Saillard J, Dumousseaux M, Le Mestre S, Fougerou-Leurent C, Ferrane A, Burdet C, Esperou H, Ader F, Hites M, Peiffer-Smadja N, Poissy J, Andrejak C, Paiva JA, Tacconelli E, Staub T, Greil R, Costagliola D, Mentre F, Yazdanpanah Y, Diallo A; DisCoVeRy Safety Working group. Management of pharmacovigilance during the COVID-19 pandemic crisis by the safety department of an academic sponsor: Lessons learnt and challenges from the EU DisCoVeRy clinical trial. Pharmacol Res Perspect. 2023 Jun;11(3):e01072. doi: 10.1002/prp2.1072.
PubMed 37269068Fougerou-Leurent C, Delmas C, Saillard J, Dumousseaux M, Ferrane A, Mercier N, Terzic V, Le Mestre S, Dechanet A, Belhadi D, Metois A, Burdet C, Mentre F, Noret M, Diallo A, Petrov-Sanchez V, Couffin-Cadiergues S, Hites M, Ader F, Esperou H. Ensuring quality control in a COVID-19 clinical trial during the pandemic: The experience of the Inserm C20-15 DisCoVeRy study. Contemp Clin Trials. 2023 Aug;131:107267. doi: 10.1016/j.cct.2023.107267. Epub 2023 Jun 9.
PubMed 37302469Beaulieu M, Gaymard A, Massonnaud C, Peiffer-Smadja N, Bouscambert-Duchamp M, Carcelain G, Lingas G, Mentre F, Ader F, Hites M, Poignard P, Guedj J. Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial. J Antimicrob Chemother. 2024 Nov 4;79(11):2887-2895. doi: 10.1093/jac/dkae301.
PubMed 39236218Siempos II, Kalil AC, Belhadi D, Veiga VC, Cavalcanti AB, Branch-Elliman W, Papoutsi E, Gkirgkiris K, Xixi NA, Kotanidou A, Hermine O, Porcher R, Mariette X; CORIMUNO-19 Collaborative Group; DisCoVeRy Study Group; ACTT-2 Study Group; ACTT-3 Study Group. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials. EClinicalMedicine. 2024 Feb 9;69:102472. doi: 10.1016/j.eclinm.2024.102472. eCollection 2024 Mar.
PubMed 38361992Smadja DM, Massonnaud CR, Philippe A, Rosa M, Luneau S, Rauch A, Peiffer-Smadja N, Gagneux-Brunon A, Poissy J, Gruest M, Ung A, Pourcher V, Raffi F, Piroth L, Bouiller K, Esperou H, Delmas C, Belhadi D, Diallo A, Saillard J, Dechanet A, Mercier N, Dupont A, Lescure FX, Goehringer F, Jaureguiberry S, Danion F, Tolsma V, Cabie A, Courjon J, Leroy S, Mootien J, Mourvillier B, Gallien S, Lanoix JP, Botelho-Nevers E, Wallet F, Richard JC, Reuter J, Gaymard A, Greil R, Martin-Blondel G, Andrejak C, Yazdanpanah Y, Burdet C, Diehl JL, Hites M, Ader F, Susen S, Mentre F, Dupont A; Discovery Study Group. sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial. Sci Rep. 2025 Apr 24;15(1):14348. doi: 10.1038/s41598-025-95122-7.
PubMed 40274842Massonnaud CR, Hites M, Peiffer-Smadja N, Rancic J, Yazdanpanah Y, Luneau S, Dupont A, Delmas C, Diehl JL, Philippe A, Susen S, Mentre F, Ader F, Smadja DM; DisCoVeRy Study group. Hydroxychloroquine does not affect endotheliopathy or coagulopathy biomarkers in COVID-19: longitudinal results from the DisCoVeRy randomized trial. Angiogenesis. 2025 Dec 7;29(1):8. doi: 10.1007/s10456-025-10023-7.
PubMed 41353681Gendron N, Rial C, Massonnaud CR, Nguyen A, Philippe A, Rus K, Nunes H, Sanchez O, Diehl JL, Peiffer-Smadja N, Hites M, Rancic J, Yazdanpanah Y; DisCoVeRy Study Group; Mentre F, Ader F, Israel-Biet D, Espitia O, Smadja DM. Plasma CXCL13 and fibrosis biomarkers in COVID-19 compared with idiopathic pulmonary fibrosis. Sci Rep. 2026 Jun 25. doi: 10.1038/s41598-026-55451-7. Online ahead of print.
PubMed 42350449Marchal A, Kerdiles T, Perrin A, Gervais A, Bastard P, Bizien L, Lingas G, Massonnaud CR, Bouscambert-Duchamp M, Gaymard A, Peiffer-Smadja N, Mentre F, Guedj J, Abel L, Casanova JL, Puel A, Hites M, Ader F, Bertrand J, Cobat A; DisCoVeRy Study Group. High Nasopharyngeal SARS-CoV-2 Load and Delayed Clearance in Hospitalized Patients With Blood Autoantibodies Neutralizing Type I Interferons. J Infect Dis. 2026 Apr 29:jiag172. doi: 10.1093/infdis/jiag172. Online ahead of print.
PubMed 42053985
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults
- ClinicalTrials.gov ID
- NCT04315948
- Acronym / sponsor ID
- DisCoVeRy / C20-15
- Conditions
- Corona Virus Infection
- Keywords
- COVID-19, SARS-CoV-2, Pneumonia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,552 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- 22 Mar 2020 (actual)
- Primary completion
- 9 Jul 2022 (actual)
- Study completion
- 25 Sep 2023 (actual)
- First posted
- 20 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
DisCoVeRy is a randomized controlled trial among adults (≥18-year-old) hospitalized for COVID-19. This study is an adaptive, randomized, open or blinded, depending on the drug to be evaluated, clinical trial to evaluate the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed with COVID-19. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. The study will compare different investigational therapeutic agents to a control group managed with the SoC including corticosteroids and anticoagulants. There will be interim monitoring to allow early stopping for safety and to introduce new therapies as they become available. If one therapy proves to be superior to others in the trial, this treatment may become part of the SoC for comparison(s) with new experimental treatment(s).
In previous versions of the DisCoVeRy protocol, remdesivir, lopinavir/ritonavir with or without interferon ß-1a and hydroxychloroquine were evaluated as potential treatments for COVID-19. These treatments have been discontinued based on analyses review by both DSMC/DSMB, the Solidarity Executive Group and the DisCoVeRy steering committee.
This version of the protocol, therefore, describes a randomized blinded placebo-controlled trial among adults (≥18-year-old) hospitalized for COVID-19 that randomly allocates them (1:1 ratio) between 2 arms: SoC + placebo versus SoC + AZD7442.
Randomization will be stratified by region (according to the administrative definition in each country), antigenic status (positive or negative) obtained from the result of a rapid antigen test on nasopharyngeal swab performed at enrolment and vaccination initiation (yes or no).
The primary analyses will be conducted on patients with antigen-positive results. A positive antigenic test is evidence of high viral shedding consistent with a recently started or uncontrolled infection. Overall, the number of antigen-negative patients will be at most 30% of all included subjects. The number of patients with vaccination (partly or fully) will be limited to 20% of all participants, split evenly between antigen positive and antigen negative patients (i.e. vaccinated patients can make up at most 20% of antigene positive patients and 20% of antigene negative patients). Sensitivity analyses will be performed in all patients, stratified by antigenic status and vaccination initiation.
A global independent data and safety monitoring board (DSMB) monitors interim data to make recommendations about early study closure or changes to conduct, including adding or removing treatment arms. However, the current version of the protocol does not allow for efficacy or futility analysis, and the ability to add trial arms will be limited by the study being blinded and placebo-controlled during the investigation of AZD7442.
Detailed description
DisCoVeRy is a randomized controlled trial among adults (≥18-year-old) hospitalized for COVID-19. This study is an adaptive, randomized, open or blinded, depending on the drug to be evaluated, clinical trial to evaluate the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed with COVID-19. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. The study will compare different investigational therapeutic agents to a control group managed with the SoC including corticosteroids and anticoagulants. There will be interim monitoring to allow early stopping for safety and to introduce new therapies as they become available. If one therapy proves to be superior to others in the trial, this treatment may become part of the SoC for comparison(s) with new experimental treatment(s).
In previous versions of the DisCoVeRy protocol, remdesivir, lopinavir/ritonavir with or without interferon ß-1a and hydroxychloroquine were evaluated as potential treatments for COVID-19. These treatments have been discontinued based on analyses review by both DSMC/DSMB, the Solidarity Executive Group and the DisCoVeRy steering committee.
This version of the protocol, therefore, describes a randomized blinded placebo-controlled trial among adults (≥18-year-old) hospitalized for COVID-19 that randomly allocates them (1:1 ratio) between 2 arms: SoC + placebo versus SoC + AZD7442.
Randomization will be stratified by region (according to the administrative definition in each country), antigenic status (positive or negative) obtained from the result of a rapid antigen test on nasopharyngeal swab performed at enrolment and vaccination initiation (yes if at least one injection of any vaccine against SARS-CoV-2 was reveived prior to enrolment whatever the delay or no).
The primary analyses will be conducted on patients with antigen-positive results. A positive antigenic test is evidence of high viral shedding consistent with a recently started or uncontrolled infection. Overall, the number of antigen-negative patients will be at most 30% of all included subjects. The number of patients with vaccination (partly or fully) will be limited to 20% of all participants, split evenly between antigen positive and antigen negative patients (i.e. vaccinated patients can make up at most 20% of antigene positive patients and 20% of antigene negative patients). Sensitivity analyses will be performed in all patients, stratified by antigenic status and vaccination initiation.
A global independent data and safety monitoring board (DSMB) monitors interim data to make recommendations about early study closure or changes to conduct, including adding or removing treatment arms. However, the current version of the protocol does not allow for efficacy or futility analysis, and the ability to add trial arms will be limited by the study being blinded and placebo-controlled during the investigation of AZD7442.
All subjects will undergo a series of efficacy and safety assessments, including laboratory assays.
Subjects will be assessed at baseline, and at Days 3, 8 and 15 while hospitalized. Patients will be contacted by phone at Day 15 for evaluation of the Primary Endpoint if they have been discharged prior to Day 15-, and 14-days following hospital discharge for efficacy assessment.
Further follow-up assessments will be organized at Days 29, 90, 180, 365 and 456.
If discharged from the hospital, days 29 and 90 assessments will be organized as outpatients' consultations for all. For Days 180 and 365 assessments, a subset of 25% of patients enrolled in centers with available resources and selected at Day 90 will be evaluated during a medical consultation, while the other will be contacted by phone. For Day 456, all patients will be contacted by phone.
Nasopharyngeal swabs (NP) or lower respiratory tract samples will be obtained at baseline (Day 1 pre-treatment) and at Days 3, 8, 15 (while hospitalized) and 29 (while hospitalized or, if discharged from the hospital, in the outpatient setting).
Blood samples will be obtained at baseline (Day 1 pre-treatment) and at Days 3, 8, 15 (while hospitalized), at Days 29 and 90, and at Days 180 and 365 (for the subset of patients evaluated during a medical consultation at these times).
Thoracic computed tomography (CT)-scan will be obtained at baseline, depending on the centre's imagery capacities.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 7
- Model description
- From March 22, 2020 to May 24, 2020, the study randomized participants 1:1:1:1:1 to standard of care alone (control) or with investigational product added. From May 24, 2020 to June 29, 2020, the study randomized participants 1:1:1:1 to standard of care alone (control) or with investigational product added. From June 29, 2020 to January 19,2021, the study randomized participants 1:1 to standard of care alone (control) or with investigational product added. Since April, 2021, the study will randomize participants 1:1 to standard of care with placebo (control) or standard of care with investigational product added.
| Arm | Type | Receives |
|---|---|---|
| Remdesivir | Experimental | Drug: Remdesivir, Other: Standard of careRemdesivir will be administered as a 200 mg intravenous loading dose on Day 1, followed by a 100 mg once-daily intravenous maintenance dose for the duration of the hospitalization up to a 10 days total course. n=475 |
| Lopinavir/ritonavir (stopped on June 29, 2020) | Experimental | Drug: Lopinavir/ritonavir, Other: Standard of careLopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered every 12 h for 14 days in tablet form. For patients who are unable to take medications by mouth, the lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered as a 5-ml suspension every 12 h for 14 days via a pre-existing or newly placed nasogastric tube. n=620 |
| Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29) | Experimental | Drug: Lopinavir/ritonavir, Drug: Interferon Beta-1A, Other: Standard of careLopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered every 12 h for 14 days in tablet form. For patients who are unable to take medications by mouth, the lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered as a 5-ml suspension every 12 h for 14 days via a pre-existing or newly placed nasogastric tube. Interferon ß1a will be administered subcutaneously at the dose of 44 µg for a total of 3 doses in 6 days (day 1, day 3, day 6). n=620 |
| Hydroxychloroquine (stopped on May 24, 2020) | Experimental | Drug: Hydroxychloroquine, Other: Standard of careHydroxychloroquine will be administered orally as a loading dose of 400 mg twice daily for one day followed by 400 mg once daily for 9 days. The loading dose of hydroxychloroquine through a nasogastric tube will be increased to 600 mg twice a day for one day, followed by a maintenance dose of 400 mg once a day for 9 days n=620 |
| Standard of care alone | Active comparator | Other: Standard of careStandard of care alone before March, 2021. |
| AZD7442 | Experimental | Other: Standard of care, Drug: AZD7442Participants randomized to the AZD7442 group will receive a total dose of 600 mg AZD7442 via a co-administered (300 mg AZD8895 and 300 mg AZD1061) single IV infusion on Day 1. n=620 |
| Standard of care with placebo | Active comparator | Other: Standard of care, Other: PlaceboStandard of care with placebo since April, 2021 n=620 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Adult ≥18 years of age at the time of enrolment
- Hospitalized patients with any of the following criteria:
- A time between onset of symptoms and randomization of less than 11 days
- A positive SARS-CoV-2 PCR performed on a NP swab within the 5 days preceding randomization
- The result of a rapid antigen test performed on a NP swab within the 6 hours preceding randomization
Key exclusion criteria (10 listed)
- Refusal to participate expressed by patient or legally authorized representative
- Need for invasive mechanical ventilation and/or ECMO at the time of enrolment
- Spontaneous blood ALT/AST levels > 5 times the upper limit of normal
- Glomerular filtration rate (GFR) < 15 mL/min or requiring maintenance dialysis
- Pregnancy or breast-feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemdesivirThe lyophilized formulation of Remdesivir is a preservative-free, white to off-white or yellow, lyophilized solid containing 100 mg of Remdesivir to be reconstituted with 19 mL of sterile water for injection and diluted into IV infusion fluids prior to IV infusion. Following reconstitution, each vial contains a 5 mg/mL Remdesivir concentrated solution with sufficient volume to allow withdrawal of 20 mL (100 mg of remdesivir). It is supplied as a sterile product in a single-use, 30 mL, Type 1 clear glass vial. | Drug | Remdesivir |
| Lopinavir/ritonavirThe oral tablets of lopinavir/ritonavir contain 200 mg lopinavir, 50 mg ritonavir. They have a yellow colour, film-coated, ovaloid shape debossed with the "a" logo and the code KA. The oral solution for patients who cannot swallow is a light yellow to orange colored liquid containing 400 mg lopinavir and 100 mg ritonavir per 5 mL (80 mg lopinavir and 20 mg ritonavir per mL). | Drug | Lopinavir/ritonavir (stopped on June 29, 2020), Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29) |
| Interferon Beta-1AIFN-ß-1a is supplied as a sterile solution containing no preservative available in a prefilled syringe. It will be provided as a single-dose prefilled graduated syringe with 44 µg per 0.5 mL. The liquid should be clear to slightly yellow. Do not use if the liquid is cloudy, discolored or contains particles. Use a different syringe. | Drug | Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29) |
| HydroxychloroquineHydroxychloroquine is supplied as film-coated 200 mg tablets. Hydroxychloroquine sulfate tablets are presented as white or whitish, peanut-shaped, oblong or round film-coated tablets containing 200 mg of hydroxychloroquine sulfate (equivalent to 155 mg base). | Drug | Hydroxychloroquine (stopped on May 24, 2020) |
| Standard of careStandard of care | Other | AZD7442, Hydroxychloroquine (stopped on May 24, 2020), Lopinavir/ritonavir (stopped on June 29, 2020), Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29), Remdesivir, Standard of care alone, Standard of care with placebo |
| AZD7442AZD7442 will be supplied as separate vials of AZD8895 and AZD1061 containing 150 mg colorless to slightly yellow, clear to opalescent solutions for injection. | Drug | AZD7442 |
| PlaceboSince April, 2021, the placebo will be a 0.9% (w/v) NaCl solution for infusion also called saline. The placebo will be supplied as a single 10-mL, clear and colorless vial. | Other | Standard of care with placebo |
Primary outcome
Percentage of subjects reporting each severity rating on a 7-point ordinal scale
Time frame: Day 15
1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.
16 secondary outcomes
Status on an ordinal scale
Time frame: Days 29, 90, 180 and 365
National Early Warning Score 2 (NEWS-2 score)
Time frame: Days 3, 8, 15, and 29
Number of oxygenation free days in the first 28 days
Time frame: 29 days
Incidence of new oxygen use, non-invasive ventilation or high flow oxygen devices during the trial.
Time frame: 29 days
Ventilator free days in the first 28 days
Time frame: 29 days
Incidence of new mechanical ventilation use during the trial.
Time frame: 29 days
Need for mechanical ventilation or death by Day 15
Time frame: Day 15
Hospitalization
Time frame: 29 days
Mortality
Time frame: In hospital, Days 29, 90, 180, 365, 456
Occurrence of new hospitalization
Time frame: Days 90, 180 and 365
Occurrence of confirmed re-infection with SARS-CoV-2
Time frame: Days 90, 180 and 365
Cumulative incidence of serious adverse events (SAEs)
Time frame: 29 days
Cumulative incidence of Grade 1- 2 hypersensitivity- related and infusion related AEs until D29 visit
Time frame: 29 days
Cumulative incidence of Grade 3 and 4 adverse events (AEs)
Time frame: 29 days
Number of participants with a discontinuation or temporary suspension of study drugs (for any reason)
Time frame: 29 days
Cumulative incidence of AEs of Special Interest
Time frame: 29 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Background: PubMed 32958495Ader F; Discovery French Trial Management Team. 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.
- Background: PubMed 34763056EU-Response investigators group; Diallo A, Troseid M, Simensen VC, Boston A, Demotes J, Olsen IC, Chung F, Paiva JA, Hites M, Ader F, Arribas JR, Baratt-Due A, Melien O, Tacconelli E, Staub T, Greil R, Tsiodras S, Briel M, Esperou H, Mentre F, Eustace J, Saillard J, Delmas C, LeMestre S, Dumousseaux M, Costagliola D, Rottingen JA, Yazdanpanah Y. Accelerating clinical trial implementation in the context of the COVID-19 pandemic: challenges, lessons learned and recommendations from DisCoVeRy and the EU-SolidAct EU response group. Clin Microbiol Infect. 2022 Jan;28(1):1-5. doi: 10.1016/j.cmi.2021.10.011. Epub 2021 Nov 8. No abstract available.
- Background: PubMed 35623577Troseid M, Hentzien M, Ader F, Cardoso SW, Arribas JR, Molina JM, Mueller N, Hites M, Bonnet F, Manuel O, Costagliola D, Grinsztejn B, Olsen IC, Yazdapanah Y, Calmy A; EU RESPONSE; COMBINE. Immunocompromised patients have been neglected in COVID-19 trials: a call for action. Clin Microbiol Infect. 2022 Sep;28(9):1182-1183. doi: 10.1016/j.cmi.2022.05.005. Epub 2022 May 25. No abstract available.
- Background: PubMed 36680782Terzic V, Levoyer L, Figarella M, Bigagli E, Mercier N, De Gastines L, Gibowski S, Troseid M, Demotes J, Olsen IC, Hites M, Ader F, Lopez JRA, Mentre F, Esperou H, Costagliola D, Rottingen JA, Poissy J, Roze JC, Warris A, O'Leary J, Fernandes RM, Assoumou L, Hankard R, Turner MA, Yazdanpanah Y, Diallo A; EU-Response safety group; c4c safety group. Implementation of a centralized pharmacovigilance system in academic pan-European clinical trials: Experience from EU-Response and conect4children consortia. Br J Clin Pharmacol. 2023 Apr;89(4):1318-1328. doi: 10.1111/bcp.15669. Epub 2023 Feb 8.
- Background: PubMed 36828006Amstutz A, Speich B, Mentre F, Rueegg CS, Belhadi D, Assoumou L, Burdet C, Murthy S, Dodd LE, Wang Y, Tikkinen KAO, Ader F, Hites M, Bouscambert M, Trabaud MA, Fralick M, Lee TC, Pinto R, Barratt-Due A, Lund-Johansen F, Muller F, Nevalainen OPO, Cao B, Bonnett T, Griessbach A, Taji Heravi A, Schonenberger C, Janiaud P, Werlen L, Aghlmandi S, Schandelmaier S, Yazdanpanah Y, Costagliola D, Olsen IC, Briel M. Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials. Lancet Respir Med. 2023 May;11(5):453-464. doi: 10.1016/S2213-2600(22)00528-8. Epub 2023 Feb 21.
- Background: PubMed 32473020Le MP, Peiffer-Smadja N, Guedj J, Neant N, Mentre F, Ader F, Yazdanpanah Y, Peytavin G. Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial. J Antimicrob Chemother. 2020 Sep 1;75(9):2376-2380. doi: 10.1093/jac/dkaa191.
- Background: PubMed 33089306Le MP, Peiffer-Smadja N, Guedj J, Neant N, Mentre F, Ader F, Yazdanpanah Y, Peytavin G; C-20-15 DisCoVeRy French Steering Committee. Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial-authors' response. J Antimicrob Chemother. 2021 Jan 1;76(1):277-279. doi: 10.1093/jac/dkaa415. No abstract available.
- Background: PubMed 37269068Mercier N, Belhadi D, DeChanet A, Delmas C, Saillard J, Dumousseaux M, Le Mestre S, Fougerou-Leurent C, Ferrane A, Burdet C, Esperou H, Ader F, Hites M, Peiffer-Smadja N, Poissy J, Andrejak C, Paiva JA, Tacconelli E, Staub T, Greil R, Costagliola D, Mentre F, Yazdanpanah Y, Diallo A; DisCoVeRy Safety Working group. Management of pharmacovigilance during the COVID-19 pandemic crisis by the safety department of an academic sponsor: Lessons learnt and challenges from the EU DisCoVeRy clinical trial. Pharmacol Res Perspect. 2023 Jun;11(3):e01072. doi: 10.1002/prp2.1072.
- Background: PubMed 37302469Fougerou-Leurent C, Delmas C, Saillard J, Dumousseaux M, Ferrane A, Mercier N, Terzic V, Le Mestre S, Dechanet A, Belhadi D, Metois A, Burdet C, Mentre F, Noret M, Diallo A, Petrov-Sanchez V, Couffin-Cadiergues S, Hites M, Ader F, Esperou H. Ensuring quality control in a COVID-19 clinical trial during the pandemic: The experience of the Inserm C20-15 DisCoVeRy study. Contemp Clin Trials. 2023 Aug;131:107267. doi: 10.1016/j.cct.2023.107267. Epub 2023 Jun 9.
- Background: PubMed 39236218Beaulieu M, Gaymard A, Massonnaud C, Peiffer-Smadja N, Bouscambert-Duchamp M, Carcelain G, Lingas G, Mentre F, Ader F, Hites M, Poignard P, Guedj J. Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial. J Antimicrob Chemother. 2024 Nov 4;79(11):2887-2895. doi: 10.1093/jac/dkae301.
- Background: PubMed 38361992Siempos II, Kalil AC, Belhadi D, Veiga VC, Cavalcanti AB, Branch-Elliman W, Papoutsi E, Gkirgkiris K, Xixi NA, Kotanidou A, Hermine O, Porcher R, Mariette X; CORIMUNO-19 Collaborative Group; DisCoVeRy Study Group; ACTT-2 Study Group; ACTT-3 Study Group. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials. EClinicalMedicine. 2024 Feb 9;69:102472. doi: 10.1016/j.eclinm.2024.102472. eCollection 2024 Mar.
- Background: PubMed 40274842Smadja DM, Massonnaud CR, Philippe A, Rosa M, Luneau S, Rauch A, Peiffer-Smadja N, Gagneux-Brunon A, Poissy J, Gruest M, Ung A, Pourcher V, Raffi F, Piroth L, Bouiller K, Esperou H, Delmas C, Belhadi D, Diallo A, Saillard J, Dechanet A, Mercier N, Dupont A, Lescure FX, Goehringer F, Jaureguiberry S, Danion F, Tolsma V, Cabie A, Courjon J, Leroy S, Mootien J, Mourvillier B, Gallien S, Lanoix JP, Botelho-Nevers E, Wallet F, Richard JC, Reuter J, Gaymard A, Greil R, Martin-Blondel G, Andrejak C, Yazdanpanah Y, Burdet C, Diehl JL, Hites M, Ader F, Susen S, Mentre F, Dupont A; Discovery Study Group. sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial. Sci Rep. 2025 Apr 24;15(1):14348. doi: 10.1038/s41598-025-95122-7.
- Individual participant dataSharing planned: Yes. Study protocol and statistical analysis plan will be available. Systematic individual patient data sharing is not intended, but all requests for the trial's data will be considered by the French DisCoVeRy Trial Management Team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florence Ader, MD study chair
Hospices Civils de Lyon
62 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Remdesivir, Lopinavir/ritonavir and Interferon Beta-1A in people with Corona Virus Infection, run by Institut National de la Santé Et de la Recherche Médicale, France at 62 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in France, Belgium, Austria, Norway, Portugal and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of subjects reporting each severity rating on a 7-point ordinal scale (time frame: Day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04315948, which also lists 30 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.