The RECOVERY trial is the world’s largest clinical trial into treatments for COVID-19, with more than 40,000 participants across 185 trial sites in the UK.
It was founded by UK Research and Innovation (UKRI)’s Medical Research Council (MRC) and the National Institute of Health Research (NIHR) with a joint investment of £2.1 million in March 2020. It is led by the University of Oxford.
The trial was up and running within six weeks of funding and found one of the world’s first COVID-19 treatments, dexamethasone. This cheap, readily available steroid was shown to reduce deaths of hospitalised COVID-19 patients by one third.
It’s estimated that dexamethasone saved the lives of around 22,000 COVID-19 patients in the UK and one million lives globally by March 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 trial expanded in early 2021 to Indonesia and Nepal, where it initially focused on the treatments aspirin and colchicine, since those were 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 2020, 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, reduced 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.
Colchicine and aspirin added to RECOVERY trial
The RECOVERY team added aspirin and colchicine to the trial in November 2020.
By March 2021, the trial closed the colchicine arm of the trial, as it had no benefits for patients.
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, which made it a good candidate for the trial.
As co-chief investigator Professor Martin Landray noted, one of the roles of clinical trials is to find negative results.
We do large randomised trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those.
In March 2021, the trial closed the colchicine arm of the trial, as it had found no benefit to patients.
Professor Landray noted that finding negatives is part of the trial process, and that as colchicine is used to treat gout and other inflammatory conditions, it had been a promising candidate.
Aspirin was added to the trial because it is used to prevent blood clots, patients with COVID-19 are at higher risk of blood clots forming in their blood vessels. It is also cheap and widely available, which make it a good candidate.
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 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.
Baricitinib reduces deaths in hospitalised patients
In March 2022, the RECOVERY trial reported that baricitinib reduces the risk of death when given to hospitalised patients with severe COVID-19.
Baricitinib is an anti-inflammatory drug normally used to treat rheumatoid arthritis.
The RECOVERY team found that treatment with baricitinib reduced deaths by 13%. It also reduced the chance of progressing to invasive mechanical ventilation.
Sir Martin Landray said the results show not only that:
…treatment with baricitinib improves the chances of survival for patients with severe COVID-19, but that this benefit is additional to that from other treatments that dampen down the over-active immune response, such as dexamethasone and tocilizumab.
This opens up the possibility of using combinations of anti-inflammatory drugs to further drive down the risk of death for some of the sickest patients.
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 NIHR.
Last updated: 26 May 2022