Hydrocortisone in Severe Community-Acquired Pneumonia

Pierre-François Dequin, Ferhat Meziani, Jean-Pierre Quenot, Toufik Kamel, Jean-Damien Ricard, Julio Badie, Jean Reignier, Nicholas Heming, Gaëtan Plantefève, Bertrand Souweine, Guillaume Voiriot, Gwenhaël Colin, Jean-Pierre Frat, Jean-Paul Mira, Nicolas Barbarot, Bruno François, Guillaume Louis, Sébastien Gibot, Christophe Guitton, Christophe Giacardi, Sami Hraiech, Sylvie Vimeux, Erwan L’Her, Henri Faure, Jean-Etienne Herbrecht, Camille Bouisse, Aurélie Joret, Nicolas Terzi, Arnaud Gacouin, Charlotte Quentin, Mercé Jourdain, Marie Leclerc, Carine Coffre, Hélène Bourgoin, Céline Lengellé, Caroline Caille-Fénérol, Bruno Giraudeau, Amélie Le Gouge

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 8 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.).