Dexamethasone cuts risk of death by 35% in COVID-19 patients on ventilation

New preliminary results from the University of Oxford-led RECOVERY trial released Tuesday suggest that low-dose dexamethasone can reduce the risk of death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. Peter Horby, one of the study's chief investigators, said "it is a major breakthrough…dexamethasone is the first drug to be shown to improve survival in COVID-19," adding the "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."

RECOVERY has recruited over 11,500 patients from 175 NHS hospitals in the UK who were randomised to one of multiple arms testing potential treatments for COVID-19. Aside from low-dose dexamethasone, these include AbbVie's HIV drug Kaletra/Aluvia (lopinavir/ritonavir), Roche's IL-6 inhibitor Actemra/RoActemra (tocilizumab), the antibiotic azithromycin, convalescent plasma, standard care, and until recently, a hydroxychloroquine arm, which was stopped after the antimalarial was found to confer no clinical benefit to patients hospitalised with SARS-CoV-2.

Survival benefit in ventilated, oxygenated patients

In regards to the latest results, researchers said a total of 2104 patients were randomised to receive once-daily dexamethasone 6 mg, orally or via intravenous injection, for 10 days and were compared with 4321 patients treated with usual care alone. Among patients in the standard-care arm, 28-day mortality was 41% in those who required ventilation, 25% in those who required oxygen only and 13% for patients who did not require any respiratory intervention.

Overall, results demonstrated that dexamethasone lowered the 28-day mortality rate by 17%, with a highly significant trend showing greatest benefit among those patients requiring ventilation. When compared to usual care alone, dexamethasone reduced deaths by 35% among intubated patients and by 20% in those receiving oxygen only. The findings suggest that "one death would be prevented by treatment of around eight ventilated patients with dexamethasone, or around 25 patients requiring oxygen alone," according to the authors.

Meanwhile, no survival benefit was seen with dexamethasone among patients who did not require respiratory support, and the study did not evaluate COVID-19 patients outside the hospital setting.

'£35 to save a life'

Martin Landray, another of RECOVERY's chief investigators, noted that dexamethasone "costs about £5 ($6.32) per patient (on the NHS), so essentially it costs £35 ($44) to save a life." He also pointed out that the drug is globally available and costs "substantially less, probably less than $1, in other parts of the world, for example in India… It's going to be very hard for any drug really to replace this."

Health Secretary Matt Hancock indicated that the UK began stockpiling the drug when its potential first became apparent in March. Commenting on Tuesday, Hancock said "we now have 200,000 courses that are ready to go and we're working with the NHS so that the…standard treatment for COVID-19 will include dexamethasone from this afternoon."

In April, Gilead Sciences' antiviral remdesivir was found to shorten the time to recovery by 31% versus placebo in the US-led ACTT trial of hospitalised patients with advanced disease, with particular benefit in those requiring supplemental oxygen. Remdesivir was also associated with a 14-day mortality rate of 7.1%, versus 11.9% for placebo, although the difference was not statistically significant. Earlier this month, Gilead said a five-day course of its drug in patients suffering from moderate COVID-19 pneumonia led to faster clinical improvement versus standard care alone. 

For related analysis see, KOL Views: Dexamethasone works – impact for COVID-19 drug development?

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