NYU Langone Health Med-Lit Review
Clinical Question: In adults admitted to intensive care with severe community-acquired pneumonia (CAP), does treatment with a seven-day course of intravenous hydrocortisone (50 mg every six hours) compared to control (no corticosteroids) improve mortality at 90 days?
Background: CAP remains a leading cause of mortality and use of ICU resources. Corticosteroids in severe CAP may reduce mortality. Possible benefits from corticosteroids include anti-inflammatory properties that reduce end-organ damage from excessive host inflammatory responses, as well as alleviating septic shock via the renin-angiotensin-aldosterone axis. Recent guideline updates from the American Thoracic Society now conditionally recommend steroids in severe CAP, largely based on the CAPE COD trial, though other studies, including the ESCAPE trial, have not yielded the same results. Uncertainty regarding optimal patient population, corticosteroid type, and duration persists.
Study Design: Open-label, international, response-adaptive randomized, platform trial
Setting: 101 sites across 18 countries, including Australia, Europe, North America, and Asia
Synopsis: 658 patients (536 hydrocortisone, 122 control) were randomized into the intervention arm (50 mg intravenous hydrocortisone every six hours for seven days) or the control arm, then further grouped into four strata based on the presence of shock and influenza. The trial terminated early for futility: 15% of patients in the hydrocortisone arm died compared to 9.8% in the control. Median adjusted odds ratio was 1.56, giving a probability of superiority of 10% and a probability of harm of 90%. Pooled treatment effect across strata showed a 3.4% probability of greater than 20% reduction in odds of death by 90 days.
Limitations include the unblinded design and imbalanced randomization, including a coding error that randomized more patients into the intervention arm. Approximately 23% of control patients received corticosteroids for alternative reasons. Patients in this study were sicker than in comparable trials, with nearly 50% in shock. Discordance may result from the heterogeneity of severe CAP and differing populations. These results are unlikely to refute guideline recommendations, though clinicians should use judgment in deciding who benefits from corticosteroids in severe CAP.
Bottom Line: In this platform trial of intensive care patients, fixed-dose hydrocortisone for seven days in severe CAP patients did not likely improve mortality at 90 days. Possible harm could not be excluded.
Citation: Angus DC. Effect of hydrocortisone on mortality in patients with severe community-acquired pneumonia: The REMAP-CAP corticosteroid domain randomized clinical trial. Intensive Care Med. 2025;51(4):665-680. doi: 10.1007/s00134-025-07861-w. (Erratum in: Intensive Care Med. 2025;51(7):1415. doi: 10.1007/s00134-025-07954-6.)
Video: View Dr. Cruz’s video review.
Dr. Cruz, a hospitalist in the division of hospital medicine at NYU Langone Medical Center and a clinical assistant professor of medicine at NYU Grossman School of Medicine, both in New York, shares his thoughts on this literature.