Comparison of the efficacy of equivalent doses of dexamethasone, methylprednisolone, and hydrocortisone for treatment of COVID-19-related acute respiratory distress syndrome: a prospective three-arm randomized clinical trial

Abstract

Background: This prospective controlled clinical trial aimed to compare the efficacy of methylprednisolone, dexamethasone, and hydrocortisone at equivalent doses in patients with severe COVID-19.

Methods: In total, 106 patients with mild to moderate COVID-19-related acute respiratory distress syndrome (ARDS) were randomized to receive either dexamethasone (6 mg once a day), methylprednisolone (16 mg twice a day), or hydrocortisone (50 mg thrice a day) for up to 10 days. All participants received a standard of care for COVID-19. The primary and secondary efficacy outcomes included all-cause 28-day mortality, clinical status on day 28 assessed using the World Health Organization (WHO) eight-category ordinal clinical scale, number of patients requiring mechanical ventilation and intensive care unit (ICU) care, number of ventilator-free days, length of hospital and ICU stay, change in PaO₂:FiO₂ ratios during the first 5 days after treatment, and incidence of serious adverse events. P-values below 0.008 based on Bonferroni's multiple-testing correction method were considered statistically significant.

Results: According to the obtained results, there was a trend toward more favorable clinical outcomes in terms of needing mechanical ventilation and ICU care, number of ventilator-free days, change in PaO₂:FiO₂ ratios during the first 5 days after treatment, clinical status score at day 28, length of ICU and hospital stay, and overall 28-day mortality in patients receiving dexamethasone compared to those receiving methylprednisolone or hydrocortisone; however, likely due to the study's small sample size, the difference between groups reached a significant level only in the case of clinical status score on day 28 (p-value = 0.003). There was no significant difference in the incidence of serious adverse events between the study groups.

Conclusion: Based on the results, severe cases of COVID-19 treated with dexamethasone might have a better clinical status at 28-day follow-up compared to methylprednisolone and hydrocortisone at an equivalent dose. Larger multicenter trials are required to confirm our findings.

Keywords: Corticosteroids; Cytokine storm; Mechanical ventilation; Mortality; SARS-CoV-19 infection; Severe COVID-19 pneumonia.

Fig. 1

Flow diagram of the study

Fig. 2

a Comparison of the distribution of clinical status of the groups on day 28 using the eight-point ordinal scale of the World Health Organization (WHO; p-value = 0.240). b Comparison of the proportion of the patients who met recovery criteria on day 28 between the study groups, defined with the WHO clinical status 1, 2, or 3 (p-value = 0.024). P-values lower than 0.008 based on Bonferroni’s multiple-testing correction method were considered statistically significant

Fig. 3

Change in the mean ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂/FiO₂) through different timepoints for the study groups (p-value = 0.036). P-values lower than 0.008 based on Bonferroni’s multiple-testing correction method were considered statistically significant