Contributors: Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Centre d’Investigation Clinique de Nantes (CIC Nantes); Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Centre d'Investigation Clinique de Limoges (CIC1435); CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM); Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT); CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST); Université de Limoges (UNILIM)-Université de Limoges (UNILIM); CHU Limoges; Centre Hospitalier Régional Universitaire de Brest (CHRU Brest); Optimisation des régulations physiologiques (ORPHY (EA 4324)); Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM); Université de Brest (UBO)-Université de Brest (UBO); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Université de Rennes (UR); Centre Hospitalier Universitaire d'Angers (CHU Angers); PRES Université Nantes Angers Le Mans (UNAM); Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Hôpital Beaujon AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Universitat de Barcelona (UB); Clinic Barcelona Hospital Universitari; Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES); MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie); Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); “Attikon” University Hospital; The University of Queensland (UQ All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations ); Atlanrea study group and the Société Française d’Anesthésie Réanimation (SFAR) Research Network: Nicolas Grillot, Karim Asehnoune, Alexandre Bourdiol, Dominique Demeure Dit Latte, Apostolos Armaganidis, Nicolas Nesseler, Philippe Seguin
نبذة مختصرة : International audience ; Purpose: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients.Methods: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients.Results: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment.Conclusions: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.
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