Human Recombinant Interferon Gamma-1b for the Prevention of Hospital-acquired Pneumonia in Critically Ill Patients: a Double-blind, International, Phase 2, Randomized, Placebo-controlled Trial - the PREV-HAP Study

Summary

PREV-HAP study is part of a larger project entitled 'Host-targeted Approaches for the Prevention and the treatment of Hospital-Acquired Pneumonia' (HAP2), funded by the European Union's H2020 research and innovation programme under grant agreement N°847782. HAP2 aims to develop stratified host-directed drugs and biomarkers to enhance the prevention and the treatment of HAP and develop precision medicine in infectious diseases. Its ambition is to revolutionize the management of HAP: capitalising on the novel concept of critical-illness related immunosuppression altering the host-pathogens interactions, the aim is to propose a complete reappraisal of the physiopathology of HAP based on the concept of respiratory dysbiosis. The main hypothesis of the PREV-HAP study is that human recombinant Interferon gamma 1b (rHuIFN-γ, Imukin) treatment can restore immunity in critically ill patients and prevent Hospital-Acquired Pneumonia. The hypothesesis is that the in vivo investigations of the host-pathogens interactions can be used for the stratification of patients into high/low risk and responders/non-responders to host-targeted prevention of hospital-acquired infections. The involvement of a state of critical-illness related immunosuppression in the susceptibility to hospital-acquired pneumonia is widely accepted, and an emerging trend is that the development of drugs for the treatment of this acquired immunosuppression will prevent infection and enhance outcomes of hospitalized patients. It has been demonstrated that the productions of IFN-γ by immune cells are decreased in critically ill patients, and that these defects are associated with the susceptibility to HAP. rHuIFN-γ has neither been tested nor is recommended as adjunctive treatment of patients with HAP. Based on these specific factors identified in the host response, it is proposed in this study to use rHuIFN-γ as novel preventive approach for HAP.

Timeline

Start

2021-03-29

Primary completion

2021-11-07

Completion

2023-06

Publications

• Petrier M, Sinha D, Martin FP, Poulain C, Flattres Duchaussoy D, Ziogas A, Novakovic B, Hurtado-Navarro L, Ferreira AV, Martens JHA, Koulenti D, Fernandez-Barat L, Torres A, Montassier E, Netea MG, Poschmann J, Roquilly A. Identification of a robust metabolic signature associated with hospital-acquired pneumonia and response to interferon-gamma treatment in critically ill patients. Crit Care. 2026 Mar 12;30(1):192. doi: 10.1186/s13054-026-05946-6.
• Anani H, Destras G, Regue H, Bulteau S, Bressollette-Bodin C, Roquilly A, Josset L. Metagenome-assembled complete genome of Bohxovirus, a virulent bacteriophage involved in the prediction of hospital-acquired pneumonia in intubated critically ill patients. Microbiol Resour Announc. 2025 Dec 11;14(12):e0059225. doi: 10.1128/mra.00592-25. Epub 2025 Oct 29.
• Bulteau S, Braud M, Petrier M, Castain L, Anani H, Peltier C, Mobuchon L, Bouras M, Flattres D, Poschmann J, Josset L, Roquilly A, Bressollette-Bodin C. Interferon Gamma Injection and Its Effect on the Respiratory Anelloviridae Population in ICU Ventilated Patients. J Med Virol. 2025 Oct;97(10):e70612. doi: 10.1002/jmv.70612.
• Anani H, Destras G, Bulteau S, Castain L, Semanas Q, Burfin G, Petrier M, Martin FP, Poulain C, Dickson RP, Bressollette-Bodin C, Roquilly A, Josset L. Lung virome convergence precedes hospital-acquired pneumonia in intubated critically ill patients. Cell Rep Med. 2025 Sep 16;6(9):102289. doi: 10.1016/j.xcrm.2025.102289. Epub 2025 Sep 5.
• Bouras M, Tessier P, Poulain C, Schirr-Bonnans S, Roquilly A. Three-month outcomes and cost-effectiveness of interferon gamma-1b in critically ill patients: a secondary analysis of the PREV-HAP trial. J Intensive Care. 2024 Oct 11;12(1):40. doi: 10.1186/s40560-024-00753-z.

Drugs

Indications

No indication recorded.