Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

ABSTRACT

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.