Randomised Evaluation of COVID-19 Therapy

Summary

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)

Conditions

• Pneumonia

Interventions

DRUG

Lopinavir-Ritonavir

Lopinavir 400mg-Ritonavir 100mg by mouth (or nasogastric tube) every 12 hours for 10 days.

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)

DRUG

Hydroxychloroquine

Hydroxychloroquine by mouth for a total of 10 days (see Protocol for timing and dosage).

DRUG

Azithromycin

Azithromycin 500mg by mouth (or nasogastric tube) or intravenously once daily for 10 days.

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).

DRUG

Tocilizumab

Tocilizumab by intravenous infusion with the dose determined by body weight (see Protocol for dosage)

BIOLOGICAL

Immunoglobulin

Intravenous immunoglobulin (IVIg) for children \>44 weeks gestational age and \<18 years with PIMS-TS only (see Protocol for dosage)

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

DRUG

Aspirin

150 mg by mouth (or nasogastric tube) or per rectum once daily until discharge, for adults ≥18 years old.

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

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.

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.

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).

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.

DRUG

Empagliflozin

Adults ≥18 years old only. 10 mg once daily by mouth for 28 days (or until discharge, if earlier).

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.

DRUG

Molnupiravir

Patients ≥18 years old. 800 mg twice daily for 5 days by mouth.

DRUG

Paxlovid

UK patients ≥18 years old. 300/100 mg twice daily for 5 days by mouth.

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.

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)

DRUG

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)

DRUG

Corticosteroids (dexamethasone)

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)

Sponsors & Collaborators

• UK Research and Innovation

  collaborator OTHER

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• Wellcome Trust

  collaborator OTHER

• Bill and Melinda Gates Foundation

  collaborator OTHER

• Department for International Development, United Kingdom

  collaborator OTHER_GOV

• Health Data Research UK

  collaborator UNKNOWN

• Medical Research Council Population Health Research Unit

  collaborator UNKNOWN

• NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

  collaborator UNKNOWN

• Flu Lab

  collaborator UNKNOWN

• University of Oxford

  lead OTHER

Principal Investigators

• Peter W Horby · University of Oxford

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

0 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-03-19

Primary Completion

2028-09-30

Completion

2038-09-30

Countries

• Belgium
• Estonia
• France
• Ghana
• India
• Indonesia
• Italy
• Nepal
• Netherlands
• Portugal
• Romania
• South Africa
• Spain
• Sweden
• United Kingdom
• Vietnam

Study Locations