Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19
In March 2020, the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone (a steroid treatment). Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK.
On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit. A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone.
Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).
Had the drug had been used to treat patients in the UK from the start of the pandemic, up to 5,000 lives could have been saved, researchers say.
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. This is an extremely welcome result. The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients. Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.’
Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, one of the Chief Investigators, said: ‘Since the appearance of COVID-19 six months ago, the search has been on for treatments that can improve survival, particularly in the sickest patients. These preliminary results from the RECOVERY trial are very clear – dexamethasone reduces the risk of death among patients with severe respiratory complications. COVID-19 is a global disease – it is fantastic that the first treatment demonstrated to reduce mortality is one that is instantly available and affordable worldwide.’
The UK Government’s Chief Scientific Adviser, Sir Patrick Vallance, said: ‘This is tremendous news today from the Recovery trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine. ‘This is a ground-breaking development in our fight against the disease, and the speed at which researchers have progressed finding an effective treatment is truly remarkable. It shows the importance of doing high-quality clinical trials and basing decisions on the results of those trials.’
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 over 175 hospitals across the whole of the UK, supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, Public Health Scotland, Department of Health & Social Care, and the NHS in England, Scotland, Wales and Northern Ireland.
RESULTS FROM THE HYDROXYCHLOROQUINE TRIAL:
Professor Peter Horby and Professor Martin Landray, chief investigators of the RECOVERY Trial, said ‘In March this year, RECOVERY was established as a randomised clinical trial to test a range of potential drugs for COVID-19, including hydroxychloroquine.
‘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. 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.
Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Deputy Chief Investigator, 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.’
Source: Oxford University News Release/Recoverytrial.net
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