Randomised Evaluation of COVID-19 Therapy (RECOVERY)
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ClinicalTrials.gov Identifier: NCT04381936 |
Recruitment Status :
Recruiting
First Posted : May 11, 2020
Last Update Posted : January 5, 2024
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RECOVERY is a randomised trial of treatments to prevent death in patients hospitalised with pneumonia.
The treatments being investigated are:
COVID-19: Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin, Colchicine, IV Immunoglobulin (children only), Convalescent plasma, Casirivimab+Imdevimab, Tocilizumab, Aspirin, Baricitinib, Empagliflozin, Sotrovimab, Molnupiravir, Paxlovid or Anakinra (children only)
Influenza: Baloxavir marboxil, Oseltamivir, Low-dose corticosteroids - Dexamethasone
Community-acquired pneumonia: Low-dose corticosteroids - Dexamethasone
Condition or disease | Intervention/treatment | Phase |
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Severe Acute Respiratory Syndrome | Drug: Lopinavir-Ritonavir Drug: Corticosteroid Drug: Hydroxychloroquine Drug: Azithromycin Biological: Convalescent plasma Drug: Tocilizumab Biological: Immunoglobulin Drug: Synthetic neutralising antibodies Drug: Aspirin Drug: Colchicine Drug: Baricitinib Drug: Anakinra Drug: Dimethyl fumarate Drug: High Dose Corticosteroid Drug: Empagliflozin Drug: Sotrovimab Drug: Molnupiravir Drug: Paxlovid Drug: Baloxavir Marboxil Drug: Oseltamivir Drug: Low-dose corticosteroids: Dexamethasone | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 70000 participants |
Allocation: | Randomized |
Intervention Model: | Factorial Assignment |
Intervention Model Description: | RECOVERY participants are randomly allocated between one or more treatment arms. Not all treatments are available in all countries. COVID-19: Parts A to D, and the arm for children with PIMS-TS, have been discontinued. Part E: randomisation between no additional treatment vs high dose corticosteroids Part F: discontinued Part J: randomisation between no additional treatment vs sotrovimab Part K: discontinued Part L: discontinued Influenza: Part G: randomisation between no additional treatment vrs baloxavir marboxil Part H: randomisation between no additional treatment vrs oseltamivir Part I: randomisation between no additional treatment vrs Low-dose corticosteroids: Dexamethasone Community-acquired pneumonia: Part M: randomisation between no additional treatment vrs Low-dose corticosteroids: Dexamethasone |
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 : | June 30, 2026 |
Estimated Study Completion Date : | June 30, 2036 |
Arm | Intervention/treatment |
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No Intervention: Standard Care
Patient receives usual hospital care
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Active Comparator: Low dose corticosteroids
First (main) randomisation part A [This arm is now closed to 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 [This arm is now closed to recruitment] |
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 [This arm is now closed to recruitment] |
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 randomisation between Tocilizumab and no additional treatment. (Children with COVID-19 pneumonia are not eligible for this comparison). [This arm is now closed to recruitment] |
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 (children only) [This arm is now closed to recruitment] |
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. [This arm is now closed to recruitment] |
Drug: Synthetic neutralising antibodies
Patients ≥12 years only with COVID-19 pneumonia: 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 Names:
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Active Comparator: Aspirin
First (main) randomisation part C [This arm is now closed to recruitment] |
Drug: Aspirin
150 mg by mouth (or nasogastric tube) or per rectum once daily until discharge, for adults ≥18 years old. |
Active Comparator: Colchicine
First (main) randomisation part A [This arm is now closed to recruitment] |
Drug: Colchicine
1 mg after randomisation followed by 500mcg 12 hours later and then 500 mcg twice daily by mouth or nasogastric tube for 10 days in total, for men ≥18 years old and women ≥55 years old only |
Active Comparator: Baricitinib
First (main) randomisation part D [This arm is now closed to recruitment] |
Drug: Baricitinib
UK [age ≥2 years with COVID pneumonia] and India [age ≥18 years with COVID-19 pneumonia]: 4 mg once daily by mouth or nasogastric tube for 10 days in total. |
Active Comparator: Anakinra
Randomisation for children only with PIMS-TS (Children with COVID-19 pneumonia are not eligible for this comparison). [This arm is now closed to recruitment] |
Drug: Anakinra
For children ≥1 <18 years old only: subcutaneously or intravenously once daily for 7 days or discharge (if sooner). NB Anakinra will be excluded from the randomisation of children <10 kg in weight. |
Active Comparator: Dimethyl fumarate
First (main) randomisation part A (UK adults only; early phase assessment) [This arm is now closed to recruitment] |
Drug: Dimethyl fumarate
Early phase assessment. UK adults ≥18 years old only (excluding those on ECMO). 120 mg every 12 hours for 4 doses followed by 240 mg every 12 hours by mouth for 8 days (10 days in total). |
Active Comparator: High Dose Corticosteroids
First (main) randomisation part E
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Drug: High Dose Corticosteroid
Adults ≥18 years old with hypoxia only. Dexamethasone 20 mg (base) once daily by mouth, nasogastric tube or intravenous infusion for 5 days follow by dexamethasone 10 mg (base) once daily by mouth, nasogastric tube or intravenous infusion for 5 days. |
Active Comparator: Empagliflozin
First (main) randomisation part F [This arm is now closed to recruitment] |
Drug: Empagliflozin
Adults ≥18 years old only. 10 mg once daily by mouth for 28 days (or until discharge, if earlier). |
Active Comparator: Sotrovimab
First (main) randomisation part J
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Drug: Sotrovimab
UK patients ≥12 years old. 1000 mg in 100 mL 0.9% sodium chloride or 5% dextrose by intravenous infusion over 1 hour as soon as possible after randomisation. |
Active Comparator: Molnupiravir
First (main) randomisation part K [This arm is now closed to recruitment] |
Drug: Molnupiravir
Patients ≥18 years old. 800 mg twice daily for 5 days by mouth. |
Active Comparator: Paxlovid
First (main) randomisation part L [This arm is now closed to recruitment] |
Drug: Paxlovid
UK patients ≥18 years old. 300/100 mg twice daily for 5 days by mouth.
Other Name: nirmatrelvir/ritonavir |
Active Comparator: Baloxavir marboxil
Randomisation part G (influenza)
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Drug: Baloxavir Marboxil
Patients ≥12 years old in the UK (or ≥18 years old in other countries), with or without SARS-CoV-2 co-infection. 40mg (or 80mg if weight ≥80kg) once daily by mouth or nasogastic tube to be given on day 1 and day 4. Other Name: Xofluza |
Active Comparator: Oseltamivir
Randomisation part H (influenza)
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Drug: Oseltamivir
Any age in the UK (or ≥18 years old in other countries), with or without SARS-CoV-2 co-infection. 75mg twice daily by mouth or nasogastric tube for five days. (See Protocol for detailed dosage information) Other Name: Tamiflu |
Active Comparator: Low-dose corticosteroids: Dexamethasone (influenza arm)
Randomisation part I (influenza)
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Drug: Low-dose corticosteroids: Dexamethasone
Any age in the UK (or ≥18 years old in other countries), without suspected or confirmed SARS-CoV-2 infection, and with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturations <92% on room air) 6mg once daily given orally or intravenously for ten days or until discharge (whichever happens earliest) |
Active Comparator: Low-dose corticosteroids: Dexamethasone (pneumonia arm)
Randomisation part M (community-acquired pneumonia)
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Drug: Low-dose corticosteroids: Dexamethasone
≥18 years old) with a diagnosis of community-acquired pneumonia (with planned antibiotic use and without suspected or confirmed SARS-CoV-2, influenza, active pulmonary tuberculosis, or Pneumocystis jirovecii infection) 6mg once daily given orally or intravenously for ten days or until discharge (whichever happens earliest) |
- 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.
- Influenza co-primary outcome: All-cause mortality (with subsidiary analysis of cause of death and death at various timepoints following discharge) [ Time Frame: Within 28 days after randomisation ]
- Influenza co-primary outcome: Time to discharge alive from hospital [ Time Frame: Within the first 28-days ]
- COVID-19 & community-acquired pneumonia: 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
- COVID-19 & community-acquired pneumonia: 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.
- Influenza: 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.
- 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 any ventilation and (for invasive mechanical ventilation) the number of days it was required
- 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
- Number of patients who had thrombotic events [ 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 had thrombotic events, defined as either (i) acute pulmonary embolism; (ii) deep vein thrombosis; (iii) ischaemic stroke; (iv) myocardial infarction; or (v) systemic arterial embolism.
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.
Ages Eligible for Study: | 0 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients are eligible for the study if all of the following are true:
(i) Hospitalised
(ii) Pneumonia syndrome
In general, pneumonia should be suspected when a patient presents with:
- typical symptoms of a new respiratory tract infection (e.g. influenza-like illness with fever and muscle pain, or respiratory illness with cough and shortness of breath); and
- objective evidence of acute lung disease (e.g. consolidation or ground-glass shadowing on X-ray or CT, hypoxia, or compatible clinical examination); and
- alternative causes have been considered unlikely or excluded (e.g. heart failure).
However, the diagnosis remains a clinical one based on the opinion of the managing doctor (the above criteria are just a guide).
(iii) One of the following diagnoses:
- Confirmed SARS-CoV-2 infection (including patients with influenza co-infection)
- Confirmed influenza A or B infection (including patients with SARS-CoV-2 co-infection)
- Community-acquired pneumonia with planned antibiotic treatment (excluding patients with suspected or confirmed SARS-CoV-2, influenza, active pulmonary tuberculosis or Pneumocystis jirovecii pneumonia)
Exclusion criteria:
(iv) 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
Participants will be excluded 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, and Appendix 4 for pregnant and breastfeeding women), 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.
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
Contact: Richard Haynes | +44 (0)1865 743743 | recoverytrial@ndph.ox.ac.uk |
Ghana | |
Kumasi Center for Collaborative Research in Tropical Medicine KNUST | Recruiting |
Kumasi, Ghana | |
Contact +233 278 364 389 | |
India | |
Indian Council of Medical Research, Division of Epidemiology and Communicable Diseases | Recruiting |
New Delhi, India, ICMR-110029 | |
Contact +91 996 840 8999 | |
Indonesia | |
Eijkman Oxford Clinical Research Unit (EOCRU), Eijkman Institute for Molecular Biology | Recruiting |
Jakarta, Indonesia | |
Nepal | |
Clinical Trial Unit, Oxford University Clinical Research Unit-Nepal, Patan Academy of Health Sciences | Recruiting |
Kathmandu, Nepal | |
South Africa | |
Wits Health Consortium | Recruiting |
Johannesburg, South Africa | |
Contact +27 11 274 9200 | |
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 | |
Vietnam | |
Oxford University Clinical Research Unit, Centre for Tropical Medicine | Recruiting |
Ho Chi Minh City, Vietnam | |
Contact +84 8 39241983 recoverytrial@oucru.org |
Principal Investigator: | Peter W Horby | University of Oxford |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: | January 5, 2024 |
Last Verified: | January 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | RECOVERY data will be made available via the Infectious Diseases Data Observatory (IDDO). Researchers will be able to apply via the IDDO Data Access process - https://www.iddo.org/covid19/data-sharing/accessing-data |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) |
Time Frame: | It is anticipated that some datasets will be available by Q1/2024. |
Access Criteria: | RECOVERY data will be made available via the Infectious Diseases Data Observatory (IDDO). Researchers will be able to apply via the IDDO Data Access process. |
URL: | https://www.iddo.org/covid19/data-sharing/accessing-data |
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 |
COVID-19 SARS-CoV-2 SARS coronavirus 2 SARS Viral pneumonia syndrome |
Community-acquired pneumonia Bacterial pneumonia syndrome Influenza A Influenza B |
COVID-19 Severe Acute Respiratory Syndrome Syndrome Disease Pathologic Processes Pneumonia, Viral Pneumonia Respiratory Tract Infections Infections Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases |
Respiratory Tract Diseases Aspirin Empagliflozin Ritonavir Lopinavir Azithromycin Hydroxychloroquine Oseltamivir Nirmatrelvir Nirmatrelvir and ritonavir drug combination Sotrovimab Molnupiravir Baloxavir Casirivimab and imdevimab drug combination Dexamethasone |