High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-related Acute Respiratory Distress Syndrome: A Multicenter and Randomized Open-label Clinical Trial

Purpose: To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome due to coronavirus disease 2019 (C-ARDS) Materials: A multicenter randomized controlled trial in adults with C-ARDS. Patients received 16 mg/d of dexamethasone intravenously for five days followed by 8 mg/d of dexamethasone for five days, or 6 mg/d of dexamethasone intravenously for 10 days. Results: Data from 98 patients who received at least one dose of dexamethasone were analyzed. At 28 days after randomization, there was no difference between high and low-dose dexamethasone groups in VFD (median, 0 d [interquartile range (IQR) 0-14 d] versus 0 d [IQR 0-1 d]; P=0.231). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P<0.001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms. Conclusions: Among patients with C-ARDS, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator.