Randomised Evaluation of COVID-19 Therapy

ConditionPneumonia

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age0+

SponsorUniversity of Oxford

About this trial

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)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Confirmed influenza A or B infection (including patients with SARS-CoV-2 co-infection)

Disqualifiers

None

Trial design

Design model

Factorial

Treatments tested in this trial

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/Vaccine
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/Vaccine
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)

Treatment groups

70,000 Participants

are divided into 23 treatment groups

Treatment groups

See each treatment group below.

Group A: Standard CareNo intervention 0 interventions

Group B: CorticosteroidsActive comparator 1 intervention

Group C: HydroxychloroquineActive comparator 1 intervention

Group D: Lopinavir-RitonavirActive comparator 1 intervention

Group E: AzithromycinActive comparator 1 intervention

Group F: Convalescent plasmaActive comparator 1 intervention

Group G: TocilizumabActive comparator 1 intervention

Group H: Intravenous ImmunoglobulinActive comparator 1 intervention

Group I: Synthetic neutralising antibodiesActive comparator 1 intervention

Group J: AspirinActive comparator 1 intervention

Group K: ColchicineActive comparator 1 intervention

Group L: BaricitinibActive comparator 1 intervention

Group M: AnakinraActive comparator 1 intervention

Group N: Dimethyl fumarateActive comparator 1 intervention

Group O: High Dose CorticosteroidsActive comparator 1 intervention

Group P: EmpagliflozinActive comparator 1 intervention

Group Q: SotrovimabActive comparator 1 intervention

Group R: MolnupiravirActive comparator 1 intervention

Group S: PaxlovidActive comparator 1 intervention

Group T: Baloxavir marboxilActive comparator 1 intervention

Group U: OseltamivirActive comparator 1 intervention

Group V: Corticosteroids (dexamethasone) (influenza arm)Active comparator 1 intervention

Group W: Corticosteroids (dexamethasone) (community-acquired pneumonia arm)Active comparator 1 intervention

Trial outcomes

Primary outcomes

Community-acquired pneumonia: All-cause mortality (with subsidiary analyses of cause of death and of death at various timepoints following discharge)

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.

Time frame

Within 28 days after randomisation

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