A major clinical trial ongoing in the United Kingdom has fingered dexamethasone, a common anti-inflammatory drug used to treat arthritis and asthma, as the “first” treatment to actually reduce mortality among COVID-19 patients – by as much as one-third. 

The preliminary findings were announced by the trial’s principal investigators, Martin Landray and Peter Horby, both professors at Oxford University. The trial results were welcomed by a number of health experts, including those at the World Health Organization.

“This is the first treatment to be shown to reduce mortality in patients with COVID-19 requiring oxygen or ventilator support,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus in a press release. “This is great news and I congratulate the Government of the UK, the University of Oxford, and the many hospitals and patients in the UK who have contributed to this lifesaving scientific breakthrough.”

Low doses of dexamethasone, a 59-year old corticosterone drug, reduced deaths among COVID-19 patients on a ventilator by one third, and by 20% among patients on simpler forms of oxygen treatment.

Overall, dexamethasone reduced the 28-day mortality rate by 17%. However, the drug did not appear to have any benefits in patients that did not require respiratory support, and patients outside the hospital setting were not studied.

‘Dexamethasone is the first drug to be shown to improve survival in COVID-19. This is an extremely welcome result,” said Peter Horby, Professor of Emerging Infectious Diseases at the University of Oxford, also a principal investigator of the trial.

The randomized clinical trial, which is part of the WHO and Wellcome Trust co-sponsored  RECOVERY initiative, compared some 2100 patients receiving 6 mg of dexamethasone daily for ten days, either by mouth or by intravenous injection, and with 4321 patients that received standard care.

Given it is widely available, cheap and has a ‘large’ survival benefit, dexamethasone should already become the new standard of care, said Horby:

“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.”

“It’s going to be very hard for any drug really to replace this, given that for less than 50 pounds [$63.26],” eight patients on a ventilator can be treated and one life can be saved, said Landray in an online briefing. And for every 25 COVID-19 patients on oxygen support, one life would be saved by treating them with dexamethasone, said Landray.

Researchers explained that the anti-inflammatory drug can calm the cytokine storm that overwhelms the immune systems of seriously ill patients. 

While preliminary results demonstrate “very clearly” that dexamethasone can curb mortality in patients with severe COVID-19, researchers did not make available the full data set on the study, a move that was criticized by some:

“It is unacceptable to tout study results by press release without releasing the full paper,” said Atul Gawande, a public health researcher and surgeon, in a tweet.

Meanwhile, a WHO spokesperson said that the Organization would share a reaction once it had completed the initial review of the preliminary results.

Over 11,500 patients from over 175 National Health Service hospitals (NHS) have been enrolled in the UK’s RECOVERY to test five other treatments for COVID-19:

• lopinavir/ritonavir, an antiviral
• hydroxychloroquine, an anti-malarial
• azithromycin, an antibiotic
• tocilizumab, an anti-inflammatory
• convalescent plasma from recovered individuals

There is still no approved treatment or vaccine for COVID-19, apart from Gilead’s remdesivir, a failed Ebola drug that does not improve the odds of survival – though it speeds up recovery in patients with COVID-18 from 15 to 11 days. 

In a parallel development, the recently touted hydroxychloroquine was shown to be “useless” earlier this month by Landray’s group. And yesterday, the US Food and Drug Administration revoked their Emergency Use Authorization (EUA) for the drug.

“Based on its ongoing analysis of the EUA and emerging scientific data, the Food and Drug Administration determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” said the FDA on Monday.

Image Credits: Phillip Jeffrey.