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Randomised Evaluation of COVID-19 Therapy (RECOVERY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04381936
Recruitment Status : Recruiting
First Posted : May 11, 2020
Last Update Posted : September 29, 2020
Sponsor:
Collaborators:
UK Research and Innovation
National Institute for Health Research, United Kingdom
Wellcome
Bill and Melinda Gates Foundation
Department for International Development, United Kingdom
Health Data Research UK
Medical Research Council Population Health Research Unit
NIHR Clinical Trials Unit Support Funding
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections
Information provided by (Responsible Party):
University of Oxford

Brief Summary:
RECOVERY is a randomised trial investigating whether treatment with either Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin, Convalescent plasma, Synthetic neutralizing antibodies or Tocilizumab prevents death in patients with COVID-19.

Condition or disease Intervention/treatment Phase
Severe Acute Respiratory Syndrome Drug: Lopinavir-Ritonavir Drug: Corticosteroid Drug: Hydroxychloroquine Drug: Azithromycin Biological: Convalescent plasma Drug: Tocilizumab Biological: Immunoglobulin Drug: Synthetic neutralising antibodies Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15000 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:

Main randomisation (part A): Eligible patients will be randomly allocated between the available treatment arms.

Main randomisation (part B): Simultaneously, eligible patients will be randomly allocated between convalescent plasma, synthetic neutralizing antibodies or no additional treatment.

Subsequent randomisation: Participants with progressive COVID-19 (as evidenced by hypoxia and an inflammatory state) may undergo an optional second randomisation.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomised Evaluation of COVID-19 Therapy
Actual Study Start Date : March 19, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2031

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Standard Care
Patient receives usual hospital care
Active Comparator: Low dose corticosteroids
First (main) randomisation part A [This arm is now closed to adult recruitment]
Drug: Corticosteroid
Corticosteroid in the form of dexamethasone administered as an oral (liquid or tablets) or intravenous preparation 6 mg once daily for 10 days. In pregnancy or breastfeeding women, prednisolone 40 mg administered by mouth (or intravenous hydrocortisone 80 mg twice daily) should be used instead of dexamethasone. Corticosteroid (in children ≤44 weeks gestational age, or >44 weeks gestational age with PIMS-TS only) in the form of Hydrocortisone or Methylprednisolone sodium succinate (see Protocol for timing and dosage)

Active Comparator: Hydroxychloroquine
First (main) randomisation part A [This arm is now closed to recruitment]
Drug: Hydroxychloroquine
Hydroxychloroquine by mouth for a total of 10 days (see Protocol for timing and dosage).

Active Comparator: Lopinavir-Ritonavir
First (main) randomisation part A [This arm is now closed to recruitment]
Drug: Lopinavir-Ritonavir
Lopinavir 400mg-Ritonavir 100mg by mouth (or nasogastric tube) every 12 hours for 10 days.

Active Comparator: Azithromycin
First (main) randomisation part A
Drug: Azithromycin
Azithromycin 500mg by mouth (or nasogastric tube) or intravenously once daily for 10 days.

Active Comparator: Convalescent plasma
First (main) randomisation part B
Biological: Convalescent plasma
Single unit of ABO compatible convalescent plasma (275mls +/- 75 mls) intravenous per day on study days 1 (as soon as possible after randomisation) and 2 (with a minimum of 12 hour interval between 1st and 2nd units).

Active Comparator: Tocilizumab
Participants with progressive COVID-19 (as evidenced by hypoxia and an inflammatory state) may undergo an optional subsequent randomisation between Tocilizumab and no additional treatment.
Drug: Tocilizumab
Tocilizumab by intravenous infusion with the dose determined by body weight (see Protocol for dosage)

Active Comparator: Intravenous Immunoglobulin
First (main) randomisation part A (open to children only)
Biological: Immunoglobulin
Intravenous immunoglobulin (IVIg) for children >44 weeks gestational age and <18 years with PIMS-TS only (see Protocol for dosage)

Active Comparator: Synthetic neutralising antibodies
First (main) randomisation part B
Drug: Synthetic neutralising antibodies
For participants ≥12 years only: A single dose of REGN10933 + REGN10987 8 g (4 g of each monoclonal antibody) in 250ml 0.9% saline infused intravenously over 60 minutes +/- 15 minutes as soon as possible after randomisation
Other Name: REGN-COV2




Primary Outcome Measures :
  1. All-cause mortality [ Time Frame: Within 28 days after randomisation ]
    For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.


Secondary Outcome Measures :
  1. Duration of hospital stay [ Time Frame: Within 28 days and up to 6 months after the main randomisation ]
    To assess the effects of study treatment on number of days stay in hospital

  2. Composite endpoint of death or need for mechanical ventilation or ECMO [ Time Frame: Within 28 days and up to 6 months after the main randomisation ]
    Among patients not on invasive mechanical ventilation at baseline, the number of patients with a composite endpoint of death or need for invasive mechanical ventilation or ECMO.


Other Outcome Measures:
  1. Need for (and duration of) ventilation [ Time Frame: Within 28 days and up to 6 months after the main randomisation ]
    To assess the effects of study treatment on number of patients who needed ventilation and the number of days it was required

  2. Need for renal replacement [ Time Frame: Within 28 days and up to 6 months after the main randomisation ]
    To assess the effects of study treatment on number of patients who needed renal replacement therapy

  3. Development of new major cardiac arrythmias [ Time Frame: Within 28 days and up to 6 months after the main randomisation ]
    To assess the effects of study treatment on number of patients who develop new major cardiac arrythmias



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • (i) Hospitalised
  • (ii) SARS-CoV-2 infection (clinically suspected or laboratory confirmed)
  • (iii) No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial

Exclusion Criteria:

  • If the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms (see Protocol Appendix 2; section 8.2 and Appendix 3; section 8.3 for children) or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient. For patients who lack capacity, an advanced directive or behaviour that clearly indicates that they would not wish to participate in the trial would be considered sufficient reason to exclude them from the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04381936


Contacts
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Contact: Richard Haynes +44 (0)1865 743743 recoverytrial@ndph.ox.ac.uk

Locations
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United Kingdom
Nuffield Department of Population Health, University of Oxford Recruiting
Oxford, United Kingdom, OX3 7LF
Contact: Peter W Horby       recoverytrial@ndph.ox.ac.uk   
Principal Investigator: Peter W Horby         
Principal Investigator: Martin Landray         
Principal Investigator: Wei Shen Lim         
Principal Investigator: Kenneth Baillie         
Principal Investigator: Richard Haynes         
Principal Investigator: Ed Juszczak         
Principal Investigator: Thomas Jaki         
Sponsors and Collaborators
University of Oxford
UK Research and Innovation
National Institute for Health Research, United Kingdom
Wellcome
Bill and Melinda Gates Foundation
Department for International Development, United Kingdom
Health Data Research UK
Medical Research Council Population Health Research Unit
NIHR Clinical Trials Unit Support Funding
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections
Investigators
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Principal Investigator: Peter W Horby University of Oxford
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT04381936    
Other Study ID Numbers: NDPHRECOVERY
2020-001113-21 ( EudraCT Number )
ISRCTN50189673 ( Registry Identifier: ISRCTN )
First Posted: May 11, 2020    Key Record Dates
Last Update Posted: September 29, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data-sharing plans for this study will be made available at a later date.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Access Criteria: Proposals for substudies must be approved by the Trial Steering Committee. Procedures for accessing the data for this study are available on https://www.ndph.ox.ac.uk/data-access
URL: https://www.ndph.ox.ac.uk/data-access

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Oxford:
COVID-19
SARS-CoV-2
SARS coronavirus 2
SARS
Additional relevant MeSH terms:
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Severe Acute Respiratory Syndrome
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Ritonavir
Lopinavir
Azithromycin
Hydroxychloroquine
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Immunologic Factors
Physiological Effects of Drugs
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents
Antimalarials
Antiprotozoal Agents