Effect of hydrocortisone on mortality in patients with severe community-acquired pneumonia
Author(s)
Type
Journal Article
Abstract
Purpose
To determine whether hydrocortisone improves mortality in severe community-acquired pneumonia (CAP).
Methods
In an international adaptive randomized controlled platform trial testing multiple interventions, adults admitted to the intensive care unit (ICU) with severe CAP were randomized to a 7-day course of intravenous hydrocortisone (50 mg every 6 h) or control (no corticosteroid). The primary end point was 90-day all-cause mortality, analyzed iteratively by a Bayesian hierarchical model estimating distinct treatment effects for patients presenting with influenza (Y/N) and shock (Y/N).
Results
Fixed 7-day course hydrocortisone enrollment was stopped for futility (< 5% probability of > 20% relative improvement). Of 658 patients enrolled, 536 were randomized to hydrocortisone and 122 to control. Vital status at day 90 was missing for 15 patients. Day 90 mortality was 15% (78/521) and 9.8% (12/122) for the hydrocortisone and control groups. The adjusted odds ratio ranged from 1.52 to 1.63 (with all 95% CrI crossing 1), while the probability of > 20% relative reduction of day 90 mortality ranged from 7.1 to 3.3% across influenza and shock strata. Results were consistent in sensitivity and pre-specified secondary outcomes. In exploratory analyses, the duration of shock appeared lower in the hydrocortisone group compared with control (median (IQR) of 2 (2–5) days compared to control 3 (2–6.75) days, p value = 0.05).
Conclusions
Among patients with severe CAP, treatment with a 7-day course of hydrocortisone, compared with no hydrocortisone, appears unlikely to yield a large reduction in mortality. Smaller benefits and possible harm are not excluded.
Trial registration
Clinicaltrials.gov identifier: NCT02735707 (registration date: November 4th, 2016).
To determine whether hydrocortisone improves mortality in severe community-acquired pneumonia (CAP).
Methods
In an international adaptive randomized controlled platform trial testing multiple interventions, adults admitted to the intensive care unit (ICU) with severe CAP were randomized to a 7-day course of intravenous hydrocortisone (50 mg every 6 h) or control (no corticosteroid). The primary end point was 90-day all-cause mortality, analyzed iteratively by a Bayesian hierarchical model estimating distinct treatment effects for patients presenting with influenza (Y/N) and shock (Y/N).
Results
Fixed 7-day course hydrocortisone enrollment was stopped for futility (< 5% probability of > 20% relative improvement). Of 658 patients enrolled, 536 were randomized to hydrocortisone and 122 to control. Vital status at day 90 was missing for 15 patients. Day 90 mortality was 15% (78/521) and 9.8% (12/122) for the hydrocortisone and control groups. The adjusted odds ratio ranged from 1.52 to 1.63 (with all 95% CrI crossing 1), while the probability of > 20% relative reduction of day 90 mortality ranged from 7.1 to 3.3% across influenza and shock strata. Results were consistent in sensitivity and pre-specified secondary outcomes. In exploratory analyses, the duration of shock appeared lower in the hydrocortisone group compared with control (median (IQR) of 2 (2–5) days compared to control 3 (2–6.75) days, p value = 0.05).
Conclusions
Among patients with severe CAP, treatment with a 7-day course of hydrocortisone, compared with no hydrocortisone, appears unlikely to yield a large reduction in mortality. Smaller benefits and possible harm are not excluded.
Trial registration
Clinicaltrials.gov identifier: NCT02735707 (registration date: November 4th, 2016).
Date Issued
2025-04-01
Date Acceptance
2025-03-09
Citation
Intensive Care Medicine, 2025, 51 (4), pp.665-680
ISSN
0342-4642
Publisher
Springer
Start Page
665
End Page
680
Journal / Book Title
Intensive Care Medicine
Volume
51
Issue
4
Copyright Statement
© 2025 The Author(s). Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
License URL
Subjects
REMAP-CAP Investigators
Humans
Community-Acquired Infections
Pneumonia
Hydrocortisone
Anti-Inflammatory Agents
Treatment Outcome
Bayes Theorem
Aged
Middle Aged
Intensive Care Units
Female
Male
Influenza, Human
Community-Acquired Pneumonia
Publication Status
Published
Date Publish Online
2025-04-22