A multicenter, randomized controlled trial (REMED trial) conducted in the Czech Republic investigated the effects of two different dexamethasone dosing regimens on ventilator-free days (VFDs) in patients with moderate to severe acute respiratory distress syndrome (ARDS) caused by COVID-19. The trial, involving nine centers, aimed to determine if a higher dose of dexamethasone could improve outcomes compared to the standard dose. However, the study was terminated prematurely due to futility, revealing no significant difference in the primary outcome between the two groups.
The study enrolled 234 patients between February 12, 2021, and March 9, 2022, who were then randomized into two groups. The intervention group received 20 mg of intravenous dexamethasone daily for the first five days, followed by 10 mg daily for the subsequent five days. The control group received the standard dose of 6 mg of intravenous dexamethasone daily for ten days. The primary outcome was the number of ventilator-free days at day 28 after randomization. Secondary outcomes included 60-day all-cause mortality, C-reactive protein (CRP) dynamics, WHO Clinical Progression Scale (WHO-CPS) score on day 14, adverse events related to corticosteroid use, and independence at 90 days assessed by the Barthel index (BI).
The results indicated no statistically significant difference in ventilator-free days at day 28 between the two groups. The study also found no significant differences in 60-day mortality rates or other secondary outcomes. A preplanned subgroup analysis was performed, considering factors such as age, sex, BMI, comorbidities, P/F ratio, length of dexamethasone treatment before enrollment, ECMO procedure, use of other corticosteroids, CRP at baseline and trial center. The study was terminated early due to a fall-off in recruitment and a recommendation from the Data and Safety Monitoring Board (DSMB) based on an unplanned second interim analysis, which suggested futility in achieving the primary outcome.
Eligible patients were adults (≥ 18 years) admitted to the ICU within 24 hours, with confirmed COVID-19 infection, requiring intubation/mechanical ventilation or high-flow nasal cannula (HFNC) therapy, and presenting with moderate or severe ARDS based on the Berlin criteria (PaO2:FIO2 ratio ≤ 200 mmHg). Key exclusion criteria included known hypersensitivity to dexamethasone, ARDS lasting more than 14 days prior to enrollment, pregnancy or breastfeeding, expected death within 24 hours, contraindications to corticosteroids, current hematological or generalized solid malignancy, cardiac arrest before ICU admission, participation in another interventional trial, or a history of immunosuppression.
The trial's premature termination and lack of significant difference between the two dexamethasone dosing regimens suggest that further research is needed to optimize corticosteroid treatment strategies for COVID-19-related ARDS. While dexamethasone remains a crucial component of COVID-19 management, the optimal dosing strategy requires further investigation.
