Low-dose hydrocortisone was not associated with a significant reduction in death or need for persistent respiratory support by day 21 of treatment compared with placebo in critically ill patients with coronavirus disease 2019 (COVID-19), according to study results published in the Journal of the American Medical Association.
The study was embedded in the Community-Acquired Pneumonia: Evaluation of Corticosteroids (CAPE COD; ClinicalTrials.gov Identifier: NCT02517489) trial. A total of 149 patients (mean age, 62.2 years) admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure from March 7 to June 1, 2020, were recruited into this French multicenter, randomized double-blind trial. Last available follow-up data were for June 29, 2020. Researchers planned to enroll up to 290 patients, but recommendations from the data and safety monitoring board resulted in early termination of the study.
Approximately 81.2% of patients in this cohort were mechanically ventilated. Patients were randomly assigned to either continuous infusion of low-dose hydrocortisone (n=76) or placebo (n=73). The initial dose of hydrocortisone was 200 mg/d and continued at this dose until day 7, after which the dose was decreased to 100 mg/d for 4 days and 50 mg/d for 3 days. A short treatment regimen comprising 200 mg/d for 4 days, followed by 100 mg/d for 2 days and then 50 mg/d for the next 2 days was administered if the patient’s respiratory and generally status sufficiently improved by 4 days of treatment.
The primary outcome was treatment failure by day 21, which was defined as mortality or persistent need for mechanical ventilation or high-flow oxygen therapy. A total of 69 treatment failure events were reported, including 11 deaths and 20 deaths in the hydrocortisone and placebo groups, respectively.
Treatment failure on day 21 was reported in 42.1% (n=32) of patients assigned to low-dose hydrocortisone vs 50.7% (n=37) of patients assigned to placebo (difference of proportions, -8.6%; 95.48% CI, -24.9% to 7.7%; P =.29). There were 3 serious adverse events during the treatment period, all of which occurred in the hydrocortisone group. None of these events were considered related to the study treatment.
A limitation of the study included the short treatment duration because of its early termination, which the investigators suggested resulted in an underpowered trial.
The researchers added that the use of hydrocortisone in this patient population did not correlate “with an increase in the rate of secondary infections, a concerning risk with corticosteroids, especially in mechanically ventilated patients with ventilator-associated pneumonia.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Dequin P-F, Heming N, Meziani F, et al; for the CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: a randomized clinical trial. Published online September 2, 2020. JAMA. doi:10.1001/jama.2020.16761