Human recombinant interferon gamma in the treatment of ventilator-acquired pneumonia in ICU patients. IGNORANT study

The primary objective of this study is to evaluate the efficacy of **recombinant human interferon gamma** in reducing the duration of mechanical ventilation during the first episode of **ventilator-acquired pneumonia** (VAP) in patients treated in intensive care. This is in addition to standard antibiotic treatment and is specifically targeted at patients with an mHLA-DR < 8000 AB/C. The clinical relevance of this objective lies in potentially decreasing the time patients require mechanical ventilation, which could lead to improved patient outcomes and reduced healthcare resource utilization.

Secondary objectives include assessing:

• Mortality
• Microbiological healing
• The occurrence of another episode of VAP before extubation
• Length of stay in the intensive care unit
• Length of stay at the hospital
• Prevention of infectious recurrences
• The host's immune response
• Evaluation of the economic efficiency of the administration of IFN-γ

The clinical trial focuses on evaluating the efficacy of recombinant human interferon gamma in patients with **ventilator-acquired pneumonia** (VAP). The study population comprises adult patients who are hospitalized in an intensive care unit and have been under mechanical ventilation for more than five days. Participants are experiencing their first episode of VAP, indicated by a Clinical Pulmonary Infection Score (CPIS) greater than six, and have a monocyte HLA-DR count of less than 8000 AB/C. Both male and female subjects are included, and the trial involves a vulnerable population. The age range of participants spans from young adults to older adults. The selection process requires written informed consent from a trusted support person or, in their absence, a representative, with an emergency certificate completed and signed by the investigator. Participants must also be affiliated with a social security scheme. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of **recombinant human interferon gamma** in reducing the duration of mechanical ventilation in patients with ventilator-acquired pneumonia (VAP) in an intensive care unit (ICU) setting. This is a randomized, double-blind, controlled trial involving adult patients who have been under mechanical ventilation for more than five days and are experiencing their first episode of VAP, characterized by a Clinical Pulmonary Infection Score (CPIS) greater than six and a monocyte HLA-DR count of less than 8000 AB/C. The trial will compare the effects of the investigational product, IMUKIN, administered subcutaneously, against a placebo, CHLORURE DE SODIUM PROAMP, administered via injection. The primary endpoint is the number of mechanical ventilation-free days from extubation through day 28, with secondary endpoints including all-cause mortality in the ICU at day 28, bacteriological sample results, and the occurrence of another VAP episode before extubation.

The trial is expected to last until May 2025, with recruitment having commenced in April 2023. Participants will be involved in the study for a maximum treatment period of five days. The sequence of study visits includes an initial screening visit to confirm eligibility based on the inclusion criteria, followed by regular follow-up visits to monitor the patient's response to treatment and any adverse events. The end-of-study visit will assess the primary and secondary endpoints and gather final data on the patient's health status. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise patient safety. The trial is conducted in accordance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants.

The clinical trial involves the administration of **IMUKIN**, a solution for injection containing **recombinant human interferon gamma 1b** as the active substance. This experimental medication is provided in a pharmaceutical form of a solution injectable, with a concentration of 2 x 10⁶ UI (0.1 mg). The medication is administered subcutaneously, with a maximum daily dose of 100 micrograms and a total maximum dose of 500 micrograms over a treatment period of up to 5 days. The administration schedule is designed to evaluate the efficacy of the drug in reducing the duration of mechanical ventilation in patients with ventilator-acquired pneumonia (VAP) in the intensive care unit (ICU). Compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, the study utilizes **CHLORURE DE SODIUM PROAMP 0.9%**, a solution for injection containing **sodium chloride** as the active substance. This non-experimental treatment serves as a placebo comparator in the trial. The sodium chloride solution is administered via injection, with a maximum daily dose of 0.5 milliliters and a total maximum dose of 2.5 milliliters over the same 5-day treatment period. The use of this placebo allows for the assessment of the experimental drug's efficacy against a standard control. Participant compliance with the administration of the placebo is also monitored to maintain the integrity of the study results.

The efficacy of recombinant human **interferon gamma** in the treatment of ventilator-acquired pneumonia (VAP) in ICU patients will be assessed through a series of primary and secondary endpoints. The primary endpoint is the number of mechanical ventilation-free days (VFD) from extubation through day 28 (D28). A statistically significant increase in VFD in patients receiving the study drug compared to those receiving placebo would indicate a beneficial effect.

Secondary endpoints include all-cause mortality in intensive care at D28, the negativity of bacteriological samples, the occurrence of another VAP episode before extubation, and the length of stay in both the intensive care unit and the hospital. Additionally, the trial will evaluate the evolution of monocytic HLA-DR and leukocyte kinetics, as well as the economic efficiency of interferon gamma administration.

These efficacy parameters will be measured and collected at specified timepoints, with the primary endpoint focusing on the duration of mechanical ventilation. The analysis will involve comparing the outcomes between the treatment group and the placebo group to determine the efficacy of the intervention.