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Oxford scientists to test high dexamethasone doses in severely ill COVID-19 patients

Low doses of are already proven to significantly reduce deaths in hospital.

The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial at Oxford University has already identified a number of effictive drugs for Covid-19, but the aim now is to see if larger doses of dexamethasone might shorten hospital stays and save more lives.

The trial was set up as an emergency response in March 2020 and has since identified several effective treatments for patients hospitalised with COVID-19.

In June 2020, RECOVERY showed that a low dose (6 mg daily) of dexamethasone significantly reduced deaths from COVID-19 by up to one third in the sickest patients. 

It immediately became part of standard of care for patients admitted to hospital with COVID-19 in the UK, a move that was replicated all around the world, saving hundreds of thousands of lives.

However, the experts reckon that using a higher dose of dexamethasone might be even better. Other clinical trials of corticosteroids, some of which used higher doses, have since confirmed the benefit of suppressing the immune response to COVID-19 for patients with inadequate levels of oxygen (hypoxia). 

Meanwhile, the RECOVERY trial has shown that the addition of other anti-inflammatory treatments, such as the arthritis drug tocilizumab, to low dose dexamethasone further reduces the risk of death for these patients. It is therefore possible that higher doses of dexamethasone might provide an additional benefit over the low dose now used as standard practice. 

Higher doses of corticosteroids are used to control inflammatory processes in other illnesses, including bacterial meningitis, tuberculous meningitis, and community acquired pneumonia; they may be also beneficial for COVID-19 patients and could offer a better treatment option for clinicians.

Sir Martin Landray, Professor of Medicine and Epidemiology at Oxford Population Health and Joint Chief Investigator, said "Although the RECOVERY Trial showed clearly that low dose dexamethasone can greatly benefit critically ill COVID-19 patients, it is possible that using a higher dose could deliver an even greater benefit for these people, shortening hospital stays and saving more lives from COVID-19. The RECOVERY trial will now answer that question."

Sir Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine at Oxford, said "Given how quickly the Omicron variant is spreading, we can expect to see patients admitted to hospital with severe COVID-19 for a while to come. This makes it very important that we continue to explore ways to further improve the care of patients with severe COVID-19."

The high dose dexamethasone study is taking place across the 177 UK-wide NHS hospital sites involved in RECOVERY. 

All patients admitted to hospital with confirmed COVID-19 are eligible - patients with low oxygen levels will be eligible to take part in the higher dose dexamethasone comparison.

The RECOVERY Trial is continuing to investigate other treatments including empagliflozin, a routine treatment for diabetes that may help reduce the symptoms of severe COVID-19, and sotrovimab, an investigational monoclonal antibody that targets the coronavirus spike protein.

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