Hydrocortisone in Severe Community-Acquired Pneumonia.

Adult Humans Anti-Inflammatory Agents / adverse effects Community-Acquired Infections / drug therapy Double-Blind Method Hydrocortisone / adverse effects Pneumonia / drug therapy Respiration, Artificial Treatment Outcome

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
25 May 2023

Historique:

medline: 26 5 2023

pubmed: 22 3 2023

entrez: 21 3 2023

Statut: ppublish

Résumé

Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Sections du résumé

BACKGROUND BACKGROUND

Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear.

METHODS METHODS

In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days.

RESULTS RESULTS

A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment.

CONCLUSIONS CONCLUSIONS

Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Identifiants

DOI: 10.1056/NEJMoa2215145 PMID: 36942789

pubmed: 36942789

doi: 10.1056/NEJMoa2215145

doi:

Substances chimiques

Anti-Inflammatory Agents 0

Hydrocortisone WI4X0X7BPJ

Banques de données

ClinicalTrials.gov

['NCT02517489']

Types de publication

Randomized Controlled Trial Multicenter Study Clinical Trial, Phase III Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1931-1941

Subventions

Organisme : Ministère des Affaires Sociales et de la Santé

ID : Programme Hospitalier de Recherche Clinique 2014

Investigateurs

Laetitia Bodet-Contentin (L)

Walid Darwiche (W)

Stephan Ehrmann (S)

Denis Garot (D)

Antoine Guillon (A)

Youenn Jouan (Y)

Annick Legras (A)

Julie Mankikian (J)

Emmanuelle Mercier (E)

Marlène Morisseau (M)

Yonatan Perez (Y)

Emmanuelle Rouve (E)

Charlotte Salmon-Gandonnière (C)

Julie Helms (J)

Hassene Rahmani (H)

Alexandra Monnier (A)

Hamid Merdji (H)

Raphaël Clere-Jehl (R)

Laure Stiel (L)

Antoine Studer (A)

Pascal Andreu (P)

Jean-Baptiste Roudaut (JB)

Marie Labruyère (M)

Marine Jacquier (M)

François Barbier (F)

Dalila Benzekri (D)

Thierry Boulain (T)

Sophie Jacquier (S)

Armelle Mathonnet (A)

Grégoire Muller (G)

Mai-Anh Nai (MA)

Isabelle Runge (I)

Sophie Tollec (S)

Damien Roux (D)

Jonathan Messika (J)

Constance Vuillard (C)

Louis-Marie Dumont (LM)

Laura Federici (L)

Noémie Zucman (N)

Marc Amouretti (M)

Fernando-Daniel Berdaguer Ferrari (FD)

Sylvain Malfroy (S)

Charlotte Bourgoin (C)

Nahila Himer (N)

Djillali Annane (D)

Pierre Moine (P)

Paris Meng (P)

Rania Bounab (R)

Damien Contou (D)

Hervé Mentec (H)

Olivier Pajot (O)

Jo-Anna Tirolien (JA)

Elsa Logre (E)

Jean-Pierre Laforêt (JP)

Radj Cally (R)

Megan Fraisse (M)

Muriel-Sarah Fartoukh (MS)

Michel Djibre (M)

Alexandre Elabbadi (A)

Marie-Ange Azaïs (MA)

Konstantinos Bachoumas (K)

Arthur Bailly (A)

Rémi Bernardon (R)

Gauthier Blonz (G)

Luc Desmedt (L)

Brian Emonet (B)

Maud Fiancette (M)

Matthieu Henry (M)

Jean-Claude Lacherade (JC)

Jean-Baptiste Lascarrou (JB)

Christine Lebert (C)

Julien Lorber (J)

Laurent Martin-Lefevre (L)

Caroline Pouplet (C)

Isabelle Vinatier (I)

Aihem Yehia (A)

Arnaud W Thille (AW)

René Robert (R)

Florence Boissier (F)

Rémi Coudroy (R)

Delphine Chatellier (D)

Anne Veinstein (A)

Florent Joly (F)

Faustine Reynaud (F)

Angeline Jamet (A)

Damien Marie (D)

Grégoire Monseau (G)

Marie-Anne Hoppe (MA)

Julien Maréchal (J)

Sarah Benghanem (S)

Julien Charpentier (J)

Clara Vigneron (C)

François Legay (F)

Pierre Fillatre (P)

Claire Lhommet (C)

Matthieu Debarre (M)

Arnaud Mari (A)

Nicolas Massart (N)

Anne Courte (A)

Julien Letheulle (J)

François Mateos (F)

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Eric Magalhaes (E)

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