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Higher Dose of Dexamethasone Likely Beneficial in Severe COVID-19

A multicenter, randomized trial of patients in Europe and India showed improvements in mortality among patients with COVID-19 who received a higher dose of dexamethasone.

A higher dose of dexamethasone may be safe and beneficial for patients with COVID-19 who have severe hypoxemia, a recent study found.

The international, multicenter, randomized trial, published inJAMA, included 1,000 patients hospitalized with COVID-19 at 26 hospitals in Europe and India between August 2020 and May 2021.

Participants required at least 10 liters per minute of supplemental oxygen or mechanical ventilation and were included in two groups, with 503 patients receiving 12 mg of intravenous dexamethasone daily for up to 10 days and 497 receiving 6 mg per day of intravenous dexamethasone.

“It’s likely that patients with COVID-19 needing intensive oxygen supplementation overall benefit from higher dose dexamethasone,” corresponding author Anders Perner, MD, PhD, professor of intensive care at Rigshospitalet in Copenhagen, Denmark, told Contagion.

At 28 days, the median number of days alive without life support was 22 (IQR, 6.0-28.0 days) among the group receiving 12 mg/day of dexamethasone compared with 20.5 (IQR, 4.0-28.0 days) in the lower-dose group.

At 28 days, mortality was 27.1% among those receiving the higher dose compared with 32.3% in the group receiving 6 mg/day of dexamethasone (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). At 90 days, mortality was 32% and 37.7% respectively (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]).

Serious adverse events were reported among 11.3% in the 12 mg/day group and 13.4% in the 6 mg/day group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]).

“The report by the COVID STEROID 2 Trial Group in this issue of JAMA adds important data to the evidence base of therapies for COVID-19, based on a well-executed trial conducted in multiple locations during the pandemic,” Steven A. Webb, MD, PhD; Alisa M. Higgins, PhD; and Colin J. McArthur, MBChB, wrote in an associated editorial. “The results raise the strong possibility that treatment outcomes for COVID-19 may be improved further by the use of higher doses of glucocorticoids; however, additional trials are needed to confirm this and determine what dose is optimal.”

The COVID STEROID 2 randomized trial was overseen by the Collaboration for Research in Intensive Care and the George Institute for Global Health with protocol approved by the Danish Medicines Agency, the ethics committee of the Capital Region of Denmark and participating hospitals and funding by Novo Nordisk Foundation.

“It was very positive to experience the readiness that funders, administrators, clinicians, patients and relatives had re. the preparation and conduct of a clinical trial under very challenging circumstances,” Perner said.

The results were not statistically significant to support change in practice, and the study may not have had sufficient power to detect statistically significant differences. More research is needed to confirm the results and determine optimal dose.

“We will analyze the effect of the higher dose (12 mg) vs the standard dose (6 mg) dexamethasone on mortality and quality of life at 180 days and also pool our data with those of similar trials to get an effect estimate from the totality of the evidence,” Perner said.