• Antoine Roquilly, Bruno Francois, Olivier Huet, Yoann Launey, Sigismond Lasocki, Emmanuel Weiss, Melanie Petrier, Yannick Hourmant, Marwan Bouras, Karim Lakhal, Cecilia Le Bel, Delphine Flattres Duchaussoy, Laia Fernández-Barat, Adrian Ceccato, Laurent Flet, Alexandra Jobert, Jeremie Poschmann, Veronique Sebille, Fanny Feuillet, Despoina Koulenti, Antoni Torres, and Atlanrea study group and the Société Française d’Anesthésie Réanimation (SFAR) Research Network.
• Nantes Université, CHU Nantes, INSERM, Anesthesie Réanimation, CIC 1413, 44000, Nantes, France. antoine.roquilly@chu-nantes.fr.
• Intensive Care Med. 2023 May 1; 49 (5): 530544530-544.

PurposeWe aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients.MethodsIn 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.ResultsThe 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.ConclusionsAmong 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.© 2023. The Author(s).

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