Trial of Treatments for COVID-19 in Hospitalized Adults

NCT04315948 | Completed Phase 3 DMC

• 2 other identifiers: C20-15101015736
• Study Type: interventional
• Target: 1,552
• Locations: 7 countries
• Sites: 62

Brief 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 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.

Conditions

Corona Virus Infection

Keywords

COVID-19; SARS-CoV-2; Pneumonia

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects reporting each severity rating on a 7-point ordinal scale

  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.

  Day 15

Secondary Outcomes (16)

• Status on an ordinal scale

  Days 29, 90, 180 and 365

• National Early Warning Score 2 (NEWS-2 score)

  Days 3, 8, 15, and 29

• Number of oxygenation free days in the first 28 days

  29 days

• Incidence of new oxygen use, non-invasive ventilation or high flow oxygen devices during the trial.

  29 days

• Ventilator free days in the first 28 days

  29 days

Other Outcomes (3)

• Percent of subjects with SARS-CoV-2 detectable in nasopharyngeal sample

  Days 3, 5, 8, 11, 15, 29

• Quantitative SARS-CoV-2 virus in nasopharyngeal sample

  Days 3, 5, 8, 11, 15, 29

• Quantitative SARS-CoV-2 virus in blood

  Days 3, 8

Study Arms (7)

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

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

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

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

Drug: Hydroxychloroquine; Other: Standard of care

Standard of care alone

ACTIVE COMPARATOR

Standard of care alone before March, 2021.

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

Other: Standard of care; Drug: AZD7442

Standard of care with placebo

ACTIVE COMPARATOR

Standard of care with placebo since April, 2021 n=620

Other: Standard of care; Other: Placebo

Interventions

Remdesivir DRUG

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.

Remdesivir

Lopinavir/ritonavir DRUG

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).

Lopinavir/ritonavir (stopped on June 29, 2020); Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29)

Interferon Beta-1A DRUG

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.

Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29)

Hydroxychloroquine DRUG

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).

Hydroxychloroquine (stopped on May 24, 2020)

Standard of care OTHER

Standard of care

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

AZD7442 DRUG

AZD7442 will be supplied as separate vials of AZD8895 and AZD1061 containing 150 mg colorless to slightly yellow, clear to opalescent solutions for injection.

AZD7442

Placebo OTHER

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.

Standard of care with placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (62)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Kepler Universitätsklinikum Linz

Linz, Austria

Location

Landeskrankenhaus Salzburg Universitätsklinikum der Paracelsus Medizinischen Privatuniversität

Salzburg, 5020, Austria

Location

Hôpital Erasme - Cliniques universitaires de Bruxelles

Brussels, 1070, Belgium

Location

Hôpital Saint Luc

Brussels, 1200, Belgium

Location

Hôpital La Citadelle

Liège, 4000, Belgium

Location

Pôle Hospitalier Jolimont / site de Mons-Warquignies

Mons, Belgium

Location

Centre Hospitalier Universitaire Amiens-Picardie

Amiens, 80054, France

Location

Centre Hospitalier Regional Metz-Thionville

Ars-Laquenexy, 57085, France

Location

Centre Hospitalier Régional Universitaire de Besançon

Besançon, 25000, France

Location

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, 33000, France

Location

CHU APHP Ambroise-Paré

Boulogne-Billancourt, France

Location

Centre Hospitalier Andrée Rosemon

Cayenne, 97306, France

Location

Hospices Civil

Colmar, France

Location

APHP - hôpital Henri-Mondor

Créteil, 94010, France

Location

Centre Hospitalier Universitaire Dijon-Bourgogne

Dijon, 21000, France

Location

Centre Hospitalier Annecy Genevois

Épagny, 74370, France

Location

Centre Hospitalier Universitaire de Martinique

Fort de France, 97261, France

Location

Centre Hospitalo-Universitaire de Grenoble

La Tronche, 38700, France

Location

AP-HP Hôpital Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

Centre Hospitalier Régional Universitaire de Lille

Lille, 59000, France

Location

Hospices Civils de Lyon

Lyon, 69000, France

Location

Centre Hospitalier Universitaire de Montpellier

Montpellier, 34000, France

Location

Groupe Hospitalier de la Région de Mulhouse Sud Alsace

Mulhouse, 68100, France

Location

Centre Hospitalier Régional et Universitaire de Nancy

Nancy, 54000, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, 44000, France

Location

Centre Hospitalo-Universitaire de Nice

Nice, 06000, France

Location

CHU Nîmes

Nîmes, France

Location

APHP - Hôpital Lariboisière

Paris, 75010, France

Location

APHP - Hôpital Saint Louis

Paris, 75010, France

Location

APHP - Hôpital Saint Antoine

Paris, 75012, France

Location

APHP - Hôpital Universitaire Pitié Salpêtrière

Paris, 75013, France

Location

APHP - Hôpital Cochin

Paris, 75014, France

Location

Hôpital Paris Saint-Joseph et Marie Lannelongue

Paris, 75014, France

Location

APHP - Hôpital Necker

Paris, 75015, France

Location

APHP- Hôpital Européen Georges-Pompidou

Paris, 75015, France

Location

APHP - Hôpital Bichat Claude Bernard

Paris, 75018, France

Location

APHP - Hôpital Tenon

Paris, 75020, France

Location

CHU Poitiers

Poitiers, France

Location

CH Cornouaille

Quimper, France

Location

CHU de Reims

Reims, 51100, France

Location

Centre Hospitalier Universitaire de Rennes

Rennes, 35033, France

Location

Hopital DELAFONTAINE

Saint-Denis, 93200, France

Location

Centre Hospitalier Universitaire de Saint Etienne

Saint-Etienne, 42055, France

Location

Hôpital d'Instruction des Armées BEGIN

Saint-Mandé, 94160, France

Location

Centre Hospitalier Régional Universitaire de Strasbourg

Strasbourg, 67000, France

Location

Centre Hospitalier Universitaire de Toulouse

Toulouse, 31000, France

Location

Centre Hospitalier Universitaire de Toulouse

Toulouse, 31300, France

Location

Centre Hospitalier de Tourcoing

Tourcoing, 59208, France

Location

Centre Hospitalier Universitaire de Tours

Tours, 37000, France

Location

CH Bretagne Atlantique

Vannes, 56000, France

Location

CH Bretagne Atlantique

Vannes, France

Location

Evaggelismos General Hospital

Athens, Greece

Location

General University Hospital of Patras

Pátrai, Greece

Location

Centre Hospitalier Luxembourg

Luxembourg, L-1210, Luxembourg

Location

Hôpitaux Robert Schuman

Luxembourg, L-2450, Luxembourg

Location

Akershus Unniversity Hospital

Oslo, Norway

Location

Lovisenberg Diaconal Hospital

Oslo, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

Hospital de Cascais

Cascais, Portugal

Location

CHULN- Hospital de Santa Maria

Lisbon, Portugal

Location

Centro Hospitalar Universitário de São João, EPE

Porto, Portugal

Location

Related Publications (25)

• 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.

  PMID: 32958495 BACKGROUND

• EU-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.

  PMID: 34763056 BACKGROUND

• Troseid 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.

  PMID: 35623577 BACKGROUND

• Terzic 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.

  PMID: 36680782 BACKGROUND

• Amstutz 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.

  PMID: 36828006 BACKGROUND

• Le 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.

  PMID: 32473020 BACKGROUND

• Le 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.

  PMID: 33089306 BACKGROUND

• Mercier 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.

  PMID: 37269068 BACKGROUND

• Fougerou-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.

  PMID: 37302469 BACKGROUND

• Beaulieu 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.

  PMID: 39236218 BACKGROUND

• Siempos 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.

  PMID: 38361992 BACKGROUND

• WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernandez Garcia C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, Garcia PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portoles A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Rottingen JA, Swaminathan S. Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2021 Feb 11;384(6):497-511. doi: 10.1056/NEJMoa2023184. Epub 2020 Dec 2.

  PMID: 33264556 RESULT

• Ader F, Peiffer-Smadja N, Poissy J, Bouscambert-Duchamp M, Belhadi D, Diallo A, Delmas C, Saillard J, Dechanet A, Mercier N, Dupont A, Alfaiate T, Lescure FX, Raffi F, Goehringer F, Kimmoun A, Jaureguiberry S, Reignier J, Nseir S, Danion F, Clere-Jehl R, Bouiller K, Navellou JC, Tolsma V, Cabie A, Dubost C, Courjon J, Leroy S, Mootien J, Gaci R, Mourvillier B, Faure E, Pourcher V, Gallien S, Launay O, Lacombe K, Lanoix JP, Makinson A, Martin-Blondel G, Bouadma L, Botelho-Nevers E, Gagneux-Brunon A, Epaulard O, Piroth L, Wallet F, Richard JC, Reuter J, Staub T, Lina B, Noret M, Andrejak C, Le MP, Peytavin G, Hites M, Costagliola D, Yazdanpanah Y, Burdet C, Mentre F; DisCoVeRy study group. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-beta-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clin Microbiol Infect. 2021 Dec;27(12):1826-1837. doi: 10.1016/j.cmi.2021.05.020. Epub 2021 May 26.

  PMID: 34048876 RESULT

• Ader F, Bouscambert-Duchamp M, Hites M, Peiffer-Smadja N, Poissy J, Belhadi D, Diallo A, Le MP, Peytavin G, Staub T, Greil R, Guedj J, Paiva JA, Costagliola D, Yazdanpanah Y, Burdet C, Mentre F; DisCoVeRy Study Group. 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. Lancet Infect Dis. 2022 Feb;22(2):209-221. doi: 10.1016/S1473-3099(21)00485-0. Epub 2021 Sep 14.

  PMID: 34534511 RESULT

• Lingas G, Neant N, Gaymard A, Belhadi D, Peytavin G, Hites M, Staub T, Greil R, Paiva JA, Poissy J, Peiffer-Smadja N, Costagliola D, Yazdanpanah Y, Wallet F, Gagneux-Brunon A, Mentre F, Ader F, Burdet C, Guedj J, Bouscambert-Duchamp M. Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial. J Antimicrob Chemother. 2022 Apr 27;77(5):1404-1412. doi: 10.1093/jac/dkac048.

  PMID: 35233617 RESULT

• Ader F, Bouscambert-Duchamp M, Hites M, Peiffer-Smadja N, Mentre F, Burdet C; DisCoVeRy Study Group. Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19. Lancet Infect Dis. 2022 Jun;22(6):764-765. doi: 10.1016/S1473-3099(22)00295-X. No abstract available.

  PMID: 35643099 RESULT

• Ader F; DisCoVeRy Study Group. An open-label randomized, controlled trial of the effect of lopinavir and ritonavir, lopinavir and ritonavir plus interferon-beta-1a, and hydroxychloroquine in hospitalized patients with COVID-19: final results. Clin Microbiol Infect. 2022 Sep;28(9):1293-1296. doi: 10.1016/j.cmi.2022.04.016. Epub 2022 May 7. No abstract available.

  PMID: 35533972 RESULT

• Neant N, Lingas G, Gaymard A, Belhadi D, Hites M, Staub T, Greil R, Paiva JA, Poissy J, Peiffer-Smadja N, Costagliola D, Yazdanpanah Y, Bouscambert-Duchamp M, Gagneux-Brunon A, Ader F, Mentre F, Wallet F, Burdet C, Guedj J; DisCoVeRy study group. Association between SARS-CoV-2 viral kinetics and clinical score evolution in hospitalized patients. CPT Pharmacometrics Syst Pharmacol. 2023 Dec;12(12):2027-2037. doi: 10.1002/psp4.13051. Epub 2023 Oct 11.

  PMID: 37728045 RESULT

• WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet. 2022 May 21;399(10339):1941-1953. doi: 10.1016/S0140-6736(22)00519-0. Epub 2022 May 2.

  PMID: 35512728 RESULT

• Hites M, Massonnaud CR, Lapique EL, Belhadi D, Jamard S, Goehringer F, Danion F, Reignier J, de Castro N, Garot D, Lacombe K, Tolsma V, Faure E, Malvy D, Staub T, Courjon J, Cazenave-Roblot F, Dyrhol Riise AM, Leturnier P, Martin-Blondel G, Roger C, Akinosoglou K, Moing VL, Piroth L, Sellier P, Lescure X, Troseid M, Clevenbergh P, Dalgard O, Gallien S, Gousseff M, Loubet P, Vardon-Bounes F, Visee C, Belkhir L, Botelho-Nevers E, Cabie A, Kotanidou A, Lanternier F, Rouveix-Nordon E, Silva S, Thiery G, Poignard P, Carcelain G, Diallo A, Mercier N, Terzic V, Bouscambert-Duchamp M, Gaymard A, Trabaud MA, Destras G, Josset L, Billard N, Han TH, Guedj J, Couffin-Cadiergues S, Dechanet A, Delmas C, Esperou H, Fougerou-Leurent C, Mestre SL, Metois A, Noret M, Bally I, Dergan-Dylon S, Tubiana S, Kalif O, Bergaud N, Leveau B, Eustace J, Greil R, Hajdu E, Halanova M, Paiva JA, Piekarska A, Rodriguez Bano J, Tonby K, Trojanek M, Tsiodras S, Unal S, Burdet C, Costagliola D, Yazdanpanah Y, Peiffer-Smadja N, Mentre F, Ader F; DisCoVeRy study group. Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial. J Infect. 2024 Mar;88(3):106120. doi: 10.1016/j.jinf.2024.106120. Epub 2024 Feb 16. No abstract available.

  PMID: 38367705 RESULT

• Terzic V, Miantezila Basilua J, Billard N, de Gastines L, Belhadi D, Fougerou-Leurent C, Peiffer-Smadja N, Mercier N, Delmas C, Ferrane A, Dechanet A, Poissy J, Esperou H, Ader F, Hites M, Andrejak C, Greil R, Paiva JA, Staub T, Tacconelli E, Burdet C, Costagliola D, Mentre F, Yazdanpanah Y, Diallo A; DisCoVeRy Study Group. Cardiac Adverse Events and Remdesivir in Hospitalized Patients With COVID-19: A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial. Clin Infect Dis. 2024 Aug 16;79(2):382-391. doi: 10.1093/cid/ciae170.

  PMID: 38552208 RESULT

• Grundeis F, Ansems K, Dahms K, Thieme V, Metzendorf MI, Skoetz N, Benstoem C, Mikolajewska A, Griesel M, Fichtner F, Stegemann M. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2023 Jan 25;1(1):CD014962. doi: 10.1002/14651858.CD014962.pub2.

  PMID: 36695483 DERIVED

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

• Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD014962. doi: 10.1002/14651858.CD014962.

  PMID: 34350582 DERIVED

• Taccone FS, Gorham J, Vincent JL. Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base. Lancet Respir Med. 2020 Jun;8(6):539-541. doi: 10.1016/S2213-2600(20)30172-7. Epub 2020 Apr 15. No abstract available.

  PMID: 32304640 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19; Pneumonia

Interventions

remdesivir; Lopinavir; Interferon beta-1a; Hydroxychloroquine; Standard of Care; cilgavimab and tixagevimab drug combination

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Florence Ader, MD

  Hospices Civils de Lyon

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: * the treatment arm SOC + hydroxychloroquine has been ceased since May 24, 2020; * the treatment arm SOC + lopinavir / Ritonavir and lopinavir / ritonavir + interferon ß-1a has been ceased since June 29, 2020 * the treatment arm SOC + remdesivir has been ceased since January 19, 2021 * the treatment arm SOC + AZD7442
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: March 20, 2020
• Study Start: March 22, 2020
• Primary Completion: July 9, 2022
• Study Completion: September 25, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study protocol and statistical analysis plan will be available from September 2020 with no time limit. Other data will be available upon request after first publication of the results for at least 5 years
• Access Criteria: Study protocol and statistical analysis plan will be published. All requests for the trial's data will be considered by the French DisCoVeRy Trial Management Team that can be contacted via the principal investigator: florence.ader@chu-lyon.fr

Locations

LU (2); NO (3); PT (3); FR (45); GR (2); AU (3); BE (4)