12 mg vs 6 mg of Dexamethasone in Adults With COVID-19 and Severe Hypoxemia
COVID STEROID 2 trial design and results
Design
Multicentre, blinded randomised clinical trial
Treatment
Dexamethasone 12 mg daily
Control
Dexamethasone 6 mg daily
Population
982 patients with COVID-19 and severe hypoxaemia, median age 65, 31% women
Follow-up
90 days
Primary endpoint
Days alive without life support at 28 days
Result
12 mg did not produce statistically significantly more days alive without life support at 28 days than 6 mg. Serious adverse reactions including septic shock and invasive fungal infection occurred in 11.3% versus 13.4% (adjusted relative risk 0.83, 99% CI 0.54 to 1.29). The authors note the trial may have been underpowered. Mortality at 28 days was 27.1% with 12 mg and 32.3% with 6 mg — adjusted relative risk 0.86 (99% CI 0.68 to 1.08), a difference the trial was not powered to detect.
Secondary endpoints
Mortality at 28 and 90 days, serious adverse reactions
Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
The trial authors, in the published abstract
How it has aged
Confirms that the RECOVERY dexamethasone dose was the right one, and that the temptation to escalate steroids in sicker patients has no support. The authors' own admission of possible underpowering is the honest caveat.
Publications
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
Munch MW, Myatra SN, Vijayaraghavan BKT, et al. 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 Nov 9;326(18):1807-1817.
No significant increase in days alive without life support
No excess of serious adverse reactions at the higher dose