Background and objectives Recent randomized controlled trials (RCTs) have indicated potential therapeutic benefits with high-dose dexamethasone (HDD) or tocilizumab (TCZ) plus standard care in moderate to severe coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS). No study has compared these two against each other. We aimed to compare the efficacy and safety of HDD against TCZ in moderate to severe COVID-ARDS. Methods Patients admitted with moderate to severe COVID-19 ARDS with clinical worsening within 48 hours of standard care were randomly assigned to receive either HDD or TCZ plus standard care. The primary outcome was ventilator-free days (VFDs) at 28 days. The main secondary outcomes were 28-day all-cause mortality and the incidence of adverse events. Our initial plan was to perform an interim analysis of the first 42 patients. Results VFDs were significantly lower in the HDD arm (median difference: 28 days; 95% confidence interval (CI): 19.35-36.65; Cohen’s d = 1.14;p < 0.001). We stopped the trial at the first interim analysis due to high 28-day mortality in the HDD arm (relative risk (RR) of death: 6.5; p = 0.007; NNT (harm) = 1.91). The incidence of secondary infections was also significantly high in the HDD arm (RR: 5.5; p = 0.015; NNT (harm) = 2.33). Conclusions In our study population, HDD was associated with a very high rate of mortality and adverse events. We would not recommend HDD to mitigate the cytokine storm in moderate to severe COVID-19 ARDS. TCZ appears to be a much better and safer alternative.
【저자키워드】 COVID-19, Tocilizumab, Secondary infection, acute respiratory distress syndrome (ARDS), Fungal infection, Cytokine storms, high-dose dexamethasone, pulse dose steroids, 【초록키워드】 Dexamethasone, Randomized controlled trial, ARDS, Mortality, Trial, severe COVID-19, 28-day mortality, risk, adverse events, Efficacy and safety, incidence, moderate, patients, acute respiratory distress, Therapeutic benefit, High-dose, Primary outcome, 95% confidence interval, standard care, study population, severe coronavirus disease, worsening, all-cause mortality, syndrome, secondary outcome, interim analysis, significantly lower, Cohen’s d, mitigate, recent, Randomly, initial, Result, significantly, indicated, median, appear, assigned, receive, 48 hour, NNT, TCZ, the cytokine storm, ventilator-free day, VFD, 【제목키워드】 Controlled,