The Randomised Evaluation of COVID-19 Therapy (RECOVERY Trial) is a large-enrollment clinical trial of possible treatments for people in the United Kingdom admitted to hospital with severe COVID-19 infection. The trial was later expanded to Indonesia, Nepal and Vietnam. The trial has tested ten interventions on adults: eight repurposed drugs, one newly developed drug and convalescent plasma.
Overview
The RECOVERY Trial is a large-scale, randomized controlled trial. It is an "open label" study: people receiving the treatment and the attending clinicians both know which treatment is being administered. It is a multi-arm adaptive clinical trial, meaning that new treatments can be added into the trial as it progresses, and other treatment "arms" closed to new enrolment when results have been produced.
The very fast setting up of the trial was crucial for the fast-developing COVID-19 pandemic. Martin Landray, one of the trial's creators, said in March 2021 "I think it has set a new standard for what can be delivered and not just for pandemics. It would be a travesty if we went back to a situation where it takes years sometimes to get a trial off the ground."
Enrollment
When people who have been hospitalised with COVID-19 are enrolled in the trial, they are automatically randomized to receive trial treatments. If any treatment is contra-indicated (or positively indicated) for that patient, or is not available, then that treatment is not included in the randomization process. The main randomization stage has three parts, so that patients might be allocated none, one, two or three of the trial treatments. If their disease progresses, there may also be a second randomization.
Goals
The primary objective of the trial is to "provide reliable estimates of the effect of study treatments on all-cause mortality at 28 days after first randomization".
The trial protocol was developed in March 2020. The design minimizes the administrative load on hospital staff, who at the time were facing the prospect of overwhelming numbers of COVID-19 admissions.
Treatments
As of 25 June 2021, the following treatments are allocated at random to hospitalized people with severe COVID-19 infection: Baricitinib (an immunomodulatory drug used in rheumatoid arthritis) Dimethyl fumarate (adults only, early phase assessment) Infliximab (adults only) High-dose dexamethasone (adults with hypoxia only)
Children with PIMS-TS may also be allocated the following: Low-dose dexamethasone (a steroid, which reduces inflammation) Intravenous immunoglobulin Tocilizumab (an anti-inflammatory) Anakinra (an anti-inflammatory)
The following treatments have previously been included in the trial and obtained positive results: Low-dose dexamethasone Tocilizumab REGN-COV2 (a cocktail of two anti-viral monoclonal antibodies) Baricitinib
The following treatments have previously been included in the trial and were closed to new entrants after being shown to be ineffective.: Lopinavir-Ritonavir (an HIV medication) Hydroxychloroquine (used to treat malaria and rheumatism) Azithromycin (an antibiotic) Convalescent plasma (blood plasma from people who have recovered from COVID-19 and which may contain antibodies against the SARS-CoV-2 virus) Aspirin (a commonly used blood thinner) Colchicine (a drug used for gout)
Operations
The trial is run by the Nuffield Departments of Population Health and of Medicine at the University of Oxford and supported by the National Institute for Health Research (NIHR). The study is led by Peter Horby and Martin Landray who serve as Co-Chief Investigators of the trial. By July 2020, the trial was in progress at 176 NHS hospitals in the UK, involving many thousands of health professionals.
The trial began in March 2020. As of March 2021 the trial had enrolled more than 40,000 COVID-19 participants admitted to hospitals in the UK; the estimated primary completion date was December 2021, and the estimated study completion date was December 2031.
Results
Dexamethasone
In June 2020, preliminary results were published in a preprint showing that low-dose dexamethasone treatment reduced the death rate by one third in hospitalized people needing ventilators due to severe COVID-19 infection, and by one fifth in people treated with oxygen therapy. There was no benefit (and the possibility of harm) among people who did not require oxygen. The preliminary report was subsequently published in The New England Journal of Medicine.