Clinical trials

Two clinical trials, involving 600 patients in three countries (France, Spain and Greece), will be conducted as part of the HAP2 project.

Rational

During infections, activated monocytes and dendritic cells (DCs), stimulated by bacterial and viral antigens, release IL-12 which, in turn, induces the production of IFN-γ by innate-like lymphocytes (notably Natural Killer (NK) cells). Several studies (in vitro and in mice) demonstrated the importance of the IL-12/IFN-γ axis in the susceptibility to HAP.

In critically ill patients, the IL-12/IFN-γ axis is defective: modifications of the epigenetic regulation and of the metabolic activity alter the production of IL-12 and IFN-γ. This dysfunction of the immune response (also called state of immunosuppression) leads to a higher risk of developing pneumonia and a decreased ability to cope with infection for these patients.

Our main hypothesis is that supplementing human recombinant Interleukin-12 (rHuIL-12, HemaMax®) or human recombinant Interferon gamma 1b (rHuIFN-γ, Imukin) can restore the IL-12/IFN-γ axis and therefore immune competence in critically ill patients and thereby i) prevent (PREV-HAP study) ii) enhance the treatment (TREAT-HAP study) of Hospital-Acquired Pneumonia.

We also hypothesize that the in vivo investigations of the host-pathogens interactions, using omics approaches, can be used for the stratification of patients into high/low risk and responders/non-responders to host-targeted prevention of hospital-acquired infections.

Objectives

The primary objective of the studies is to determine whether rHuIL-12 and/or rHu-IFNγ, as compared with placebo, could i) reduce the rate of hospital-acquired pneumonia and ii) improve outcomes in patients admitted to intensive care unit and requiring mechanical ventilation.

If both rHuIL-12 and rHuIFN-γ reduce the rate of HAP and improve outcomes in patients, we will then aim at determining which one is the most effective.

Quality of Life and the economic efficiency of the interventions will also be assessed.