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. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-023-07065-0.

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23

“…Its use seems to improve immune functions, including an increase in monocyte HLA-DR expression, as well as the outcome and immune dysfunction in invasive fungal infections [ 123 ]. In a recent multicentre, placebo‑controlled trial, 109 critically ill patients with one or more acute organ failures and undergoing mechanical ventilation were randomised to receive interferon γ ‑1b or placebo [ 124 ]. Unfortunately, treatment with interferon did not significantly reduce the incidence of hospital-acquired pneumonia or mortality on day 28.…”

Optimal strategy for treatment of sepsis based on the host inflammatory reaction and immune response

“…The treatment did not significantly reduce either the incidence of hospital-acquired pneumonia or the 28-day mortality rate compared to those who received placebo. [33] Owing to the heterogeneity among patients with sepsis and dynamic alterations in immune status, biomarker-guided therapy may offer more satisfactory outcomes and safety; this is especially applicable to cases where treatment aims to modulate host innate immunity.…”

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection

“…Despite these promising results, in a clinical trial conducted by Roquilly and collaborators, the results indicated that interferon gamma-1b treatment (100 µg interferon gamma-1b every 48 hours for a period of 1 to 9 days) did not significantly reduce the incidence of disease or death in the first 28 days. In addition, the study was stopped due to safety concerns about interferon gamma-1b treatment ( 193 ). These divergent outcomes suggest that further research is needed to determine the efficacy of IFN-γ in both prophylaxis and treatment of COVID-19.…”