Patients with severe COVID-19 may benefit from a fixed-dose or shock-dependent dosing of hydrocortisone, but early study termination hindered study researchers from making definitive conclusions. The trial results were recently reported in JAMA.
The ongoing REMAP-CAP trial (ClinicalTrials.gov Identifier: NCT02735707), which is evaluating multiple interventions for COVID-19, enrolled adults from more than 100 sites with presumed or confirmed SARS-CoV-2 infection that was classified as severe, meaning patients were admitted to the intensive care unit (ICU) to receive respiratory or cardiovascular organ support.
The final outcome analysis for the hydrocortisone portion of the trial included 379 patients who were randomized to receive a fixed-dose of hydrocortisone 50 mg every 6 hours for 7 days (137 patients), hydrocortisone 50 mg every 6 hours when clinically evident shock developed (141 patients), or standard of care (101 patients), which was no hydrocortisone.
The rationale for the shock-dependent dosing strategy, the study researchers explained, was that restricting hydrocortisone to when the patient had overt shock would maximize the risk-benefit ratio.
However, the portion of the trial evaluating hydrocortisone stopped enrollment early after a press release for the RECOVERY trial reported a mortality benefit with dexamethasone for COVID-19.
As a result, the study researchers wrote, “No treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.”
What the trial did show was that, for the primary outcome, patients on the fixed-dose hydrocortisone arm had a 93% probability of superiority regarding the odds of improvement in organ support–free days within 21 days compared with patients who received no hydrocortisone (median adjusted odds ratio=1.43; 95% credible interval, 0.91-2.27).
Similarly, patients on the shock-dependent hydrocortisone arm had an 80% probability of superiority compared with patients who received no hydrocortisone (median adjusted odds ratio=1.22; 95% credible interval, 0.76-1.94).
The frequency of serious adverse events was low, with 3% of patients in the fixed-dose arm, 3% in the shock-dependent arm, and 1% in the no hydrocortisone arm reporting serious adverse events.
The Writing Committee for the REMAP-CAP Investigators. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA. Published online September 2, 2020. doi:10.1001/jama.2020.17022