Daily 12 mg dexamethasone not superior to 6 mg for severe COVID-19 infection

1. This multi-centered, randomized controlled trial demonstrated that 12 mg and 6 mg dexamethasone daily had similar efficacy for days alive without life support and safety at 28 days for patients hospitalized with severe COVID-19.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Recent clinical trials have demonstrated that systemic glucocorticoids reduce short-term mortality in patients with a severe COVID-19 infection. Some of these trials showed that higher doses of dexamethasone are effective in patients with acute respiratory distress syndrome outside of a COVID-19 infection. Currently, 6 mg of dexamethasone daily is recommended to treat severe and critical COVID-19. This multi-centred, randomized controlled trial (COVID STEROID 2) investigated whether a higher dose of dexamethasone (12 mg) improves clinical outcomes compared to 6 mg in critical COVID-19 patients with hypoxemia. Patients were included if they were hospitalized with COVID-19 and required: supplemental oxygen at a rate of a minimum of 10L/min, non-invasive ventilation with continuous positive airway pressure for hypoxemia, or invasive mechanical ventilation. Patients were randomly assigned 12 mg (461/497 included in the analysis) or 6 mg (446/485 included in the analysis) of dexamethasone daily. The primary outcome was the number of days living without life support (invasive mechanical ventilation, circulatory support, kidney replacement therapy) at 28 days post-randomization. The duration of treatment was similar between both groups (median: 7 days [IQR: 5.0-9.0] vs. median 7 days [IQR: 6.0-9.0] in the 12-mg and 6-mg cohorts, respectively). The median number of days alive without life support at 28 days was similar between groups (22.0 days [IQR:6.0-28.0] vs. 20.5 days [IQR: 4.0-28.0] in the 12-mg and 6-mg cohorts, respectively; adjusted mean difference: 1.3 days [95% CI: 0-2.6 days]; p= 0.07). Additionally, serious adverse events (septic shock, invasive fungal infection, significant gastrointestinal bleeding) were similar between cohorts (11.3% in the 12-mg group vs. 13.4% in the 6-mg group; adjusted relative risk: 0.83 [99% CI: 0.54-1.29]). Overall, 12 mg of dexamethasone daily demonstrated no significantly short-term clinical improvement compared to 6 mg. Notably, treatment for COVID-19 changed in the middle of this trial (use of IL-6 receptor antagonists) which could have interfered with the outcomes of this study.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Dexamethasone in hospitalized patients with Covid-19

Image: PD

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