The RECOVERY trial (which stands for ‘Randomised Evaluation of COVid-19 thERapY’) was funded by UKRI as part of the UKRI/DHSC/NIHR COVID-19 rapid research response.
To provide real-time information in the pandemic, the results have been announced as quickly as possible, so it should be noted that the findings have not yet been peer-reviewed and accepted in a journal.
A range of potential treatments have been suggested for COVID-19 but nobody knows if any of them will turn out to be more effective in improving survival than the usual standard of hospital care which all patients will receive.
The RECOVERY trial is a large, randomised controlled trial of possible treatments for patients admitted to hospital with COVID-19. Over 11,000 patients have been randomised to several treatment arms, or no additional treatment - find out more on the RECOVERY website.
Professor Peter Horby, of the Nuffield Department of Medicine at the University of Oxford, and chief investigator for the trial, said: “Hydroxychloroquine and chloroquine have received a lot of attention and have been used very widely to treat COVID patients despite the absence of any good evidence. The RECOVERY trial has shown that hydroxychloroquine is not an effective treatment in patients hospitalised with COVID-19. Although it is disappointing that this treatment has been shown to be ineffective, it does allow us to focus care and research on more promising drugs."
Professor Fiona Watt, Executive Chair of the Medical Research Council, which helped fund the trial, said: “We don’t yet know which drugs will be effective in treating COVID-19 because it is a new disease. It is very important that we test potential therapies in randomised clinical trials so that we can find out, for the benefit of everyone, whether particular drugs work or not. The UK’s RECOVERY trial is the world’s largest randomised trial of potential COVID-19 treatments and has worked with unprecedented speed to start delivering the answers we need."
The chief investigators of the RECOVERY trial, Professor Peter Horby and Professor Martin Landray, said in a statement: ‘In March this year, RECOVERY was established as a randomised clinical trial to test a range of potential drugs for COVID-19, including hydroxycholoroquine.
'The trial has proceeded at unprecedented speed, enrolling over 11,000 patients from 175 NHS hospitals in the UK. Throughout this time, the independent Data Monitoring Committee has reviewed the emerging data about every two weeks to determine if there is evidence that would be strong enough to affect national and global treatment of COVID-19.
'On Thursday 4 June, in response to a request from the UK Medicines and Healthcare Products Regulatory Agency (MHRA), the independent Data Monitoring Committee conducted a further review of the data. Last night, the Committee recommended the chief investigators review the unblinded data on the hydroxychloroquine arm of the trial.
'We have concluded that there is no beneficial effect of hydroxychloroquine in patients hospitalised with COVID-19. We have therefore decided to stop enrolling participants to the hydroxychloroquine arm of the RECOVERY trial with immediate effect. We are now releasing the preliminary results as they have important implications for patient care and public health.
'A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes.
'These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19. Full results will be made available as soon as possible.'
For this particular analysis, follow-up is complete for just over 80% of participants. The lower bound of the confidence interval rules out any meaningful benefit.
Professor Martin Landray, from the Nuffield Department of Population Health at the University of Oxford, and deputy chief investigator on the trial, said: “There has been huge speculation and uncertainty about the role of hydroxychloroquine as a treatment for COVID-19, but an absence of reliable information from large randomised trials.
"Today’s preliminary results from the RECOVERY trial are quite clear - hydroxychloroquine does not reduce the risk of death among hospitalised patients with this new disease. This result should change medical practice worldwide and demonstrates the importance of large, randomised trials to inform decisions about both the efficacy and the safety of treatments."
The RECOVERY trial is conducted by the registered clinical trials units with the Nuffield Department of Population Health in partnership with the Nuffield Department of Medicine. The trial is supported by a grant to the University of Oxford from UK Research and Innovation/National Institute for Health Research (NIHR) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill and Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, and NIHR Clinical Trials Unit Support Funding.
The RECOVERY trial involves many thousands of doctors, nurses, pharmacists, and research administrators at 175 NHS Trusts across the whole of the UK, supported by staff at the NIHR Clinical Research Network, Public Health England, Department of Health & Social Care, and the NHS in England, Scotland, Wales and Northern Ireland.
This article is based on content provided by the University of Oxford.