Dexamethasone reduces mortality by one-third in ventilated patients with COVID-19
Low-dose dexamethasone used as a treatment for COVID-19 reduced the risk for death by one-third in ventilated patients and also lowered risk in patients receiving oxygen, according to early results from the RECOVERY trial.
RECOVERY was established as a randomized clinical trial to test a range of potential treatments for COVID-19, including the corticosteroid dexamethasone.
On June 8, recruitment in the dexamethasone arm of RECOVERY was halted, due to the trial’s steering committee decision that sufficient patients had been enrolled to establish whether dexamethasone had a meaningful clinical benefit, according to a press release.
Researchers randomly assigned 2,104 patients to dexamethasone 6 mg per day for 10 days and 4,321 patients to usual care alone.
Total 28-day mortality was 41% among patients requiring ventilation, 25% among patients requiring oxygen only and 13% among patients who did not require respiratory intervention, according to the release.
Low-dose dexamethasone decreased deaths by one-third in ventilated patients (RR = 0.65; 95% CI, 0.48-0.88; P = .0003) and by one-fifth in those receiving oxygen (RR = 0.8; 95% CI, 0.67-0.96; P = .0021), according to the release.
The researchers reported no benefit of dexamethasone 6 mg per day in patients who did not require respiratory support (RR = 1.22; 95% CI, 0.86-1.75; P = .014).
Based on these results, one death would be prevented by treatment of about eight ventilated patients or around 25 patients requiring oxygen alone.
Low-dose dexamethasone was administered by mouth or by IV injection.
“Since the appearance of COVID-19 6 months ago, the search has been on for treatments that can improve survival, particularly in the sickest patients,” Martin Landray, MB, ChB, PhD, FRCP, FHEA, FASN, FBPhS, FESC, professor of medicine and epidemiology at the Nuffield Department of Population Health at the University of Oxford and one of the chief investigators for the RECOVERY trial, said in the release. “These preliminary results from the RECOVERY trial are very clear — dexamethasone reduces the risk of death among patients with severe respiratory complications.”
Due to the importance of these promising results, the RECOVERY researchers are planning to publish the full details of the RECOVERY study as soon as possible.
“‘Dexamethasone is the first drug to be shown to improve survival in COVID-19. ... 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,” Peter Horby, professor of emerging infectious diseases in the Nuffield Department of Medicine at the University of Oxford and a chief investigator in the trial, said in the release. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.”
Full details of the study protocol and related materials are available at www.recoverytrial.net.
The RECOVERY trial, led by researchers at Oxford University, has randomly assigned more than 11,500 patients to the following treatment arms, or no additional treatment: lopinavir/ritonavir; low-dose dexamethasone; hydroxychloroquine (stopped due to lack of efficacy); azithromycin; tocilizumab (Actemra, Genentech); and convalescent plasma collected from donors who have recovered from COVID-19.
Perspective
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The RECOVERY trial is a pathbreaking randomized clinical trial that shines light on what treatments work and also what does not work. Clinicians in the last 6 months have administered several unproven, and potentially harmful therapies, and sometimes in combination with COVID-19 patients. This study restores some sanity to the treatment landscape.
The striking finding of reduction in 28-day mortality by more than 30% in mechanical ventilation patients with severe COVID-19 is impressive. Dexamethasone is the first drug to show improvement in survival and steroids will probably become the standard of care. Comparing the results from the ACTT-1 study preliminary report and supplemental information, dexamethasone helps the most where remdesivir (Gilead Sciences) was not helpful, especially those on mechanical ventilation. Remdesivir probably helped consistently in those for whom dexamethasone was not very effective — patients on room air or supplemental oxygen.
Dexamethasone is a known, cheap, safe — at the low dose and duration proposed — and very effective treatment that could now be used in both resource-rich and limited settings. The RECOVERY trial also put some of the final nails in the coffin of hydroxychloroquine, with early termination of the hydroxychloroquine arm. I look forward to reading the complete published article of this very compelling study.
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