Dexamethasone
Maria G. Tanzi, PharmD
Use of dexamethasone resulted in lower 28-day mortality among hospitalized patients with COVID-19, according to data from the RECOVERY trial published online in the New England Journal of Medicine. The trial showed reduced mortality for patients who were receiving either invasive mechanical ventilation or oxygen alone at randomization, but not for patients receiving no respiratory support.
“Dexamethasone was the first drug to be shown to improve survival in patients with COVID-19,” said Martin Landray, professor of medicine and epidemiology at the Nuffield Department of Population Health, University of Oxford, and one of the chief investigators of the study. “Finding an existing treatment that reduces the risk of death among patients with severe respiratory complications was an extremely welcome result, particularly since dexamethasone is an inexpensive and readily available treatment.”
Within hours of announcing the results, the treatment became standard of care in the United Kingdom and is now provided to seriously ill COVID-19 patients worldwide, said Landry. “It’s not a treatment for everybody, and there is still more we need to do, which may include looking at dexamethasone in combination with other treatments,” he said.
Trial design and results
RECOVERY is a controlled, open-label trial designed to evaluate readily available potential treatments that may be effective for patients hospitalized with COVID-19 at 176 National Health Service organizations in the United Kingdom.
Researchers from the Nuffield Department of Population Health at the University of Oxford are assessing various treatments including low-dose dexamethasone (now only recruiting children), azithromycin, tocilizumab, and convalescent plasma collected from donors who have recovered from COVID-19 and contain antibodies against the SARS-CoV-2 virus.
The dexamethasone treatment arm assigned 2,104 patients to receive oral or I.V. dexamethasone at a dose of 6 mg once daily for up to 10 days and 4,321 patients to receive usual care. The patients’ mean age was 66.1 years, and 36% were female. At randomization, 16% of patients were receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, 60% were receiving oxygen only, and 24% were receiving neither.
The preliminary results showed that mortality at 28 days was significantly lower in the dexamethasone group compared with usual care (22.9% vs. 25.7%). The incidence of death was lowest in patients taking dexamethasone who were receiving invasive mechanical ventilation (29.3% vs. 41.4%) or oxygen (23.3% vs. 26.2%) compared with usual care. There was no clear effect in those not receiving any respiratory support.
“What we have achieved with RECOVERY is unprecedented, but it couldn’t have been done without the support and commitment of everyone involved—the participants, the doctors, nurses, and pharmacists at the 176 hospital sites, our coordinating center, and the regulators and funders who have helped to make this possible,” said Landray.
Clinical applicability
The National Institutes of Health released guidelines on prophylaxis use, testing, and management of patients with COVID-19, including the use of corticosteroids.
The agency recommended dexamethasone for patients who are mechanically ventilated and those who require supplemental oxygen. Alternative corticosteroids such as prednisone, methylprednisolone, or hydrocortisone can be used when dexamethasone is not available.
The total daily dose equivalencies to dexamethasone 6 mg (oral or I.V.) for these drugs are prednisone 40 mg, methylprednisolone 32 mg, and hydrocortisone 160 mg.
Since the half-life, duration of action, and frequency of administration varies among the corticosteroids, intermediate-acting corticosteroids such as prednisone and methylprednisolone may be administered once daily or in two divided doses daily; short-acting corticosteroids such as hydrocortisone should be administered in two to four divided doses daily.
When using dexamethasone or other corticosteroids for COVID-19, clinicians should closely monitor patients for adverse effects (e.g., hyperglycemia, secondary infections, psychiatric effects, avascular necrosis) and be aware that prolonged use of systemic corticosteroids may increase the risk of reactivation of latent infections (e.g., hepatitis B, herpesvirus infections, strongyloidiasis, tuberculosis).