In patients with COVID-19 and severe hypoxemia, treatment with dexamethasone 12 mg/day compared with dexamethasone 6 mg/day is not associated with any statistically significant days alive without life support at 28 days. These were among the findings of COVIDSTEROID2, a multicenter, randomized clinical trial (ClinicalTrials.gov identifier: NCT04509973) conducted from August 2020 through May 2021 at 26 hospitals in Europe and India. Results of the analysis were published in JAMA.
In COVIDSTEROID2, the investigators sought to evaluate the effects of 2 different doses of dexamethasone in patients with COVID-19 who also had severe hypoxemia. The primary study outcome was the number of days alive without life support (ie, invasive mechanical ventilation [MV], circulatory support, or kidney replacement therapy) at 28 days. Secondary outcomes included number of days alive without life support at 90 days, number of days alive when out of the hospital at 90 days, mortality at 28 days, mortality at 90 days, and 1 or more serious adverse reactions at 28 days.
The study analysis included 982 patients with COVID-19 who required at least 10 L/minute of oxygen or MV. The median participant age was 65 years (range, 55 to 73 years); 31% of participants were women. Primary outcome data were available for 971 participants, 491 in the dexamethasone 12-mg group and 480 in the dexamethasone 6-mg group.
Results of the study showed that the median number of days alive without the use of life support was 22.0 days (range, 6.0 to 28.0 days) in the 12-mg arm and 20.5 days (range, 4.0 to 28.0 days) in the 6-mg arm (adjusted mean difference, 1.3 days; 95% CI, 0-2.6 days; P =.07). At 28 days, mortality was 27.1% in the 12-mg group and 32.3% in the 6-mg group (adjusted relative risk, 0.86; 99% CI, 0.68-1.08). At 90 days, the mortality rate was 32.0% in the dexamethasone 12-mg/day arm vs 37.7% in the dexamethasone 6-mg/day arm (adjusted relative risk, 0.87; 99% CI, 0.70-1.07).
Serious adverse reactions, which included septic shock and invasive fungal infections, were reported among 11.3% of participants in the 12-mg dexamethasone group and 13.4% of those in the 6-mg dexamethasone group (adjusted relative risk, 0.83; 99% CI, 0.54-1.29).
The investigators concluded that although the higher 12-mg/day dose of dexamethasone evaluated did not result in a statistically significant number of additional days alive in patients with COVID-19 and severe hypoxemia compared with the lower 6-mg/day dose, this result could have been the result of the study being insufficiently powered to detect a significant difference.
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Munch MW, Myatra SN, Vijayaraghavan BKT, et al; COVID STEROID 2 Trial Group. Effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia: the COVID STEROID 2 randomized trial. JAMA. 2021;326(18):1807-1817. doi:10.1001/jama.2021.18295