Randomised Evaluation of COVID-19 Therapy

Sponsor
University of Oxford
Study ID
NCT04381936
Phase
PHASE3
Status
Recruiting
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Conditions

  • Pneumonia

Eligibility Criteria

Sex
ALL
Age
0 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Lopinavir-Ritonavir — DRUG
    Lopinavir 400mg-Ritonavir 100mg by mouth (or nasogastric tube) every 12 hours for 10 days.
  • Corticosteroid — DRUG
    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)
  • Hydroxychloroquine — DRUG
    Hydroxychloroquine by mouth for a total of 10 days (see Protocol for timing and dosage).
  • Azithromycin — DRUG
    Azithromycin 500mg by mouth (or nasogastric tube) or intravenously once daily for 10 days.
  • Convalescent plasma — BIOLOGICAL
    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).
  • Tocilizumab — DRUG
    Tocilizumab by intravenous infusion with the dose determined by body weight (see Protocol for dosage)
  • Immunoglobulin — BIOLOGICAL
    Intravenous immunoglobulin (IVIg) for children \>44 weeks gestational age and \<18 years with PIMS-TS only (see Protocol for dosage)
  • Synthetic neutralising antibodies — DRUG
    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
  • Aspirin — DRUG
    150 mg by mouth (or nasogastric tube) or per rectum once daily until discharge, for adults ≥18 years old.
  • Colchicine — DRUG
    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
  • Baricitinib — DRUG
    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.
  • Anakinra — DRUG
    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.
  • Dimethyl fumarate — DRUG
    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).
  • High Dose Corticosteroid — DRUG
    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.
  • Empagliflozin — DRUG
    Adults ≥18 years old only. 10 mg once daily by mouth for 28 days (or until discharge, if earlier).
  • Sotrovimab — DRUG
    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.
  • Molnupiravir — DRUG
    Patients ≥18 years old. 800 mg twice daily for 5 days by mouth.
  • Paxlovid — DRUG
    UK patients ≥18 years old. 300/100 mg twice daily for 5 days by mouth.
  • Baloxavir Marboxil — DRUG
    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.
  • Oseltamivir — DRUG
    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)
  • Corticosteroids (dexamethasone) — DRUG
    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)
  • Corticosteroids (dexamethasone) — DRUG
    Patients ≥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)

Study Details

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, Corticosteroids (dexamethasone) Community-acquired pneumonia: Corticosteroids (dexamethasone)

Key Dates

Start date
Mar 19, 2020
Status verified
Apr 2026
Primary completion
Sep 30, 2028
Completion
Sep 30, 2038

Study Design

Enrollment
70,000 participants (estimated)
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT

Arms

  • No Intervention: Standard Care
    Patient receives usual hospital care
  • Active Comparator: Corticosteroids
    First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Hydroxychloroquine
    First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Lopinavir-Ritonavir
    First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Azithromycin
    First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Convalescent plasma
    First (main) randomisation part B (COVID-19) \[This arm is now closed to recruitment\]
  • 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). \[This arm is now closed to recruitment\]
  • Active Comparator: Intravenous Immunoglobulin
    First (main) randomisation part A (children only) \[This arm is now closed to recruitment\]
  • Active Comparator: Synthetic neutralising antibodies
    First (main) randomisation part B (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Aspirin
    First (main) randomisation part C (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Colchicine
    First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Baricitinib
    First (main) randomisation part D (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Anakinra
    Randomisation for children only with PIMS-TS (Children with COVID-19 pneumonia are not eligible for this comparison). \[This arm is now closed to recruitment\]
  • Active Comparator: Dimethyl fumarate
    First (main) randomisation part A (COVID-19) (UK adults only; early phase assessment) \[This arm is now closed to recruitment\]
  • Active Comparator: High Dose Corticosteroids
    First (main) randomisation part E (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Empagliflozin
    First (main) randomisation part F (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Sotrovimab
    First (main) randomisation part J (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Molnupiravir
    First (main) randomisation part K (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Paxlovid
    First (main) randomisation part L (COVID-19) \[This arm is now closed to recruitment\]
  • Active Comparator: Baloxavir marboxil
    Randomisation part G (influenza)
  • Active Comparator: Oseltamivir
    Randomisation part H (influenza)
  • Active Comparator: Corticosteroids (dexamethasone) (influenza arm)
    Randomisation part I (influenza)
  • Active Comparator: Corticosteroids (dexamethasone) (community-acquired pneumonia arm)
    Randomisation part M (community-acquired pneumonia)

Primary Outcome Measure

Community-acquired pneumonia: All-cause mortality (with subsidiary analyses of cause of death and of death at various timepoints following discharge) [ Time Frame: Within 28 days after randomisation ]

Central Contacts

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