Clinical trial NCT06549374: Kinetics of INF-γ Production in Intensive Care Patients
Official title: Kinetics of INF-γ Production in Intensive Care Patients-Monitoring of INF-γ in Intensive Care
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Intensive Care
Keywords: INF-γ
Inflammation
immunostimulation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-08-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient included will be adult patients admitted to intensive care after severe trauma, high-risk surgery, or presenting with acute respiratory distress

Brief summary: Most patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress are frequently characterized by significant initial inflammation accompanied by a compensatory anti-inflammatory response, which can lead to profound post-aggressive immunosuppression. This immunosuppression is associated with an increased risk of nosocomial infections, viral reactivations, prolonged ICU stays, and ultimately, increased mortality. Consequently, immunostimulation with agents such as interferon gamma (IFN-γ) has been proposed as a means to restore immune defense in the most severe patients. However, in a recent study conducted on mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared to placebo did not significantly reduce the incidence of nosocomial pneumonia or 28-day mortality and was even associated with an increase in severe side effects, leading to the premature termination of the trial. These results, along with previous studies, suggest that for IFN-γ to be effective, it must be targeted at patients who have reached the immunosuppressive phase. In the absence of evident clinical signs, the use of biomarkers could guide clinicians in identifying the appropriate patients and the optimal timing for this therapy.

In a recent monocentric study, they evaluated a new automated IFN-γ assay on a cohort of 22 septic patients to monitor T lymphocyte functionality independently of antigen. As expected, the results showed a marked decrease in IFN-γ release, which correlated with altered classical cellular parameters (CD8+ T cells, mHLA-DR). Since the test is performed using whole blood, requires no technician intervention, and provides results within four hours, this project propose to characterize the evolution of the immune status of a large cohort of ICU patients, including those with severe trauma, high-risk surgery, or acute respiratory distress syndrome.

Detailed description: Most patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress are frequently characterized by significant initial inflammation accompanied by a compensatory anti-inflammatory response, which can lead to profound post-aggressive immunosuppression. This immunosuppression is associated with an increased risk of nosocomial infections, viral reactivations, prolonged ICU stays, and ultimately, increased mortality. Consequently, immunostimulation with agents such as interferon gamma (IFN-γ) has been proposed as a means to restore immune defense in the most severe patients. However, in a recent study conducted on mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared to placebo did not significantly reduce the incidence of nosocomial pneumonia or 28-day mortality and was even associated with an increase in severe side effects, leading to the premature termination of the trial. These results, along with previous studies, suggest that for IFN-γ to be effective, it must be targeted at patients who have reached the immunosuppressive phase. In the absence of evident clinical signs, the use of biomarkers could guide clinicians in identifying the appropriate patients and the optimal timing for this therapy.

Among the described immune alterations and associated biomarkers in critically ill patients, the decrease in Human Leukocyte Antigen (HLA-DR) expression on monocytes (mHLA-DR) has been studied more extensively and is now considered a reliable biomarker for guiding myeloid-targeted immunotherapies. While functional tests are the best means to explore acquired immunosuppression in the ICU, as they directly measure the capacity of a given cell population to respond to an in vitro stimulus, they present analytical obstacles to their deployment. Most protocols are "homemade" and lack standardization, which is a major obstacle to large-scale trials and their use in clinical practice.

In a recent monocentric study, they evaluated a new automated IFN-γ assay on a cohort of 22 septic patients to monitor T lymphocyte functionality independently of antigen. As expected, the results showed a marked decrease in IFN-γ release, which correlated with altered classical cellular parameters (CD8+ T cells, mHLA-DR). Since the test is performed using whole blood, requires no technician intervention, and provides results within four hours, this project propose to characterize the evolution of the immune status of a large cohort of ICU patients, including those with severe trauma, high-risk surgery, or acute respiratory distress syndrome.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older
* Patients admitted to intensive care after severe trauma, or presenting with acute respiratory distress, or undergoing cardiac, vascular, or digestive surgery with planned postoperative intensive care. Exclusion Criteria

Exclusion Criteria:

* Expressed opposition from the patient, a relative (if applicable), or their legal representative (guardian, curator)
* Pregnant woman
* Hemoglobin less than 7g/dl at inclusion

Primary outcomes:
measure: INF-γ production in patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress
timeFrame: Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28).
Secondary outcomes:
measure: ICU discharge Vital status
timeFrame: at ICU discharge, and at the latest Day 28
measure: Incidence of nosocomial infections
timeFrame: From ICU-admission to ICU-discharge, and at the latest Day 28
measure: Incidence of viral reactivations for CMV and HSV
timeFrame: From ICU-admission to ICU-discharge, and at the latest Day 28
measure: Length of mechanical ventilation
timeFrame: From ICU-admission to ICU-discharge, and at the latest Day 28
measure: Presence of septic shock
timeFrame: From ICU-admission to ICU-discharge, and at the latest Day 28
measure: Renal impairment
timeFrame: From ICU-admission to ICU-discharge, and at the latest Day 28
measure: mHLA-DR expression
timeFrame: Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28).
measure: Length of ICU stay
timeFrame: at ICU discharge, and at the latest day 28
Other outcomes:
Locations:
city: Paris
country: France
facility: Réanimation cardio-chirurgicale - Pitié-Salpêtrière hospital
state: Ile De France
city: Paris
country: France
facility: Réanimation chirurgicale Gaston Cordier - Pitié-Salpêtrière hospital
state: Ile De France
city: Paris
country: France
facility: Réanimation chirurgicale Husson Mourrier - Pitié-Salpêtrière hospital
state: Ile De France
city: Paris
country: France
facility: Réanimation neuro-chirurgicale - Pitié-Salpêtrière hospital
state: Ile De France
Study officials:
References: