The RECOVERY trial is the world’s largest clinical trial into treatments for COVID-19, with more than 30,000 participants across 177 trial sites in the UK.
It was founded by UK Research and Innovation (UKRI)’s Medical Research Council and the National Institute of Health Research (NIHR) with a joint investment of £2.1million in March 2020 and is led by the University of Oxford.
The trial, which was up and running within six weeks of funding, has found one of the world’s first COVID-19 treatments, dexamethasone. This cheap, readily available steroid was shown to reduce deaths of patients in hospital with COVID-19 by one third.
It’s been estimated that dexamethasone has saved the lives of around 12,000 COVID-19 patients in the UK and approximately 650,000 lives globally so far (predictions up to Jan 2021).
In February 2021, new preliminary findings revealed that tocilizumab, an anti-inflammatory drug often used to treat rheumatoid arthritis, also reduces the risk of death for hospitalised patients with severe COVID-19.
The RECOVERY trial has now been expanded internationally to Indonesia and Nepal, where it will initially focus on the treatments aspirin and colchicine, since those are readily available and affordable. Like RECOVERY in the UK, new drugs will be added over time.
The RECOVERY trial continues to assess a range of potential treatments. Here’s RECOVERY’s journey so far.
Hydroxychloroquine has no clinical benefits
In June, the RECOVERY trial concluded that hydroxychloroquine had no beneficial effect in patients hospitalised with COVID-19, and stopped enrolling participants to that arm of the trial immediately.
Hydroxychloroquine and chloroquine had received a lot of media attention in early 2020 and was used widely to treat COVID patients, despite the absence of any good evidence.
The RECOVERY trial team issued its preliminary findings due to their important implications for patient care and public health.
The trial team said it was “disappointing” that the treatment was ineffective, but noted it allowed them to “focus care and research on more promising drugs.”
Dexamethasone reduces deaths by up to one third
Just a few weeks later, the trial published further preliminary results. This time showing that dexamethasone, a low-cost steroid treatment, reduces deaths of hospitalised COVID-19 patients with severe respiratory complications by up to one third.
Speaking at the time, Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and one of the chief investigators for the trial, said:
Dexamethasone is the first drug to be shown to improve survival in COVID-19. It is inexpensive, on the shelf, and can be used immediately to save lives worldwide.
No significant mortality impact for lopinavir
Further preliminary results showed lopinavir, an antiviral drug commonly used in combination with ritonavir to treat HIV, had no significant mortality benefit (The RECOVERY Trial) in hospitalised COVID-19 patients.
The treatment had previously shown promising activity against SARS and MERS coronaviruses.
Speaking at the time, Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Deputy Chief Investigator, said:
These are clear results and once again emphasise the value of large randomised clinical trials in differentiating drugs we hope work from treatments we know do work.
Potential new COVID-19 treatments on trial
In October 2020, it was announced that RECOVERY would evaluate Regeneron Pharmaceuticals’ investigational antiviral antibody cocktail, REGN-COV2.
REGN-COV2 is the first specifically designed COVID-19 therapy to be evaluated by the trial.
Peter Horby, acting as chief investigator of the trial, said:
The RECOVERY trial was specifically designed so that when promising investigational drugs such as REGN-COV2 became available they can be tested quickly.
Aspirin and colchicine added to RECOVERY trial
The RECOVERY team added aspirin and colchicine to the trial in November.
Patients with COVID-19 are at higher risk of blood clots forming in their blood vessels. Aspirin is used to prevent blood clots in many other conditions, like heart attack and pre-eclampsia, and it is cheap and widely available, which made it a good candidate for the trial.
It is anticipated that at least 2,000 patients will be randomly allocated to receive aspirin 150mg daily plus the usual standard-of-care.
Colchicine is a commonly used anti-inflammatory treatment. Inflammation is a key component of severe COVID-19 and can lead to lung damage, the need for mechanical ventilation and death.
The drug is well understood, inexpensive and widely available, and it will take several months to find out whether it has benefits for the trial’s patients.
Professor Peter Horby said:
If it works it would be another COVID-19 treatment that could be used immediately worldwide, even in the poorest countries.
Azithromycin has no clinical benefits
Azithromycin is a widely-used antibiotic that also reduces inflammation, a key feature of severe COVID-19.
In December 2020, the RECOVERY team released preliminary results showing it has no effect on clinical outcomes in COVID-19.
Professor Horby said:
Azithromycin has been widely used to treat COVID patients because of its theoretical potential to reduce lung inflammation.
Our results show very clearly that for patients hospitalised with COVID-19 azithromycin is not an effective treatment.
Professor Fiona Watt, Executive Chair of the MRC , said:
Although it is disappointing that azithromycin isn’t an effective treatment for hospitalised COVID-19 patients, negative results are important so that clinicians can focus patient care on drugs that have been shown to work.
This is particularly vital for antibiotics like azithromycin, because inappropriate use of antibiotics contributes to bacteria in the body becoming resistant.
Tocilizumab reduces deaths in patients hospitalised with COVID-19
In February 2021 the trial reported that tocilizumab, an intravenous drug used to treat rheumatoid arthritis, is an effective treatment for COVID-19.
The team reported that the drug reduces the risk of death for hospitalised patients with severe COVID-19.
The study also showed that tocilizumab shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator.
The trial was one of a round of projects to receive funding as part of the rapid research response (National Archives) funded by UKRI and the Department of Health and Social Care through the National Institute for Health Research.
Last updated: 2 March 2021