NCT06549374

Kinetics of INF-γ Production in Intensive Care Patients

Kinetics of INF-γ Production in Intensive Care Patients-Monitoring of INF-γ in Intensive Care

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Intensive Care

Interventions

Type	Name	Description
OTHER	blood sampling	After informing eligible patients (or their trusted support person, relative/guardian/curator where applicable) and in the absence of any opposition, they are included in the research. Blood samples from an arterial catheter already in place will be taken every day from D1 to D7, then every 72 hours until discharge from intensive care, or until D28. For each of these samples, a maximum volume of 4 ml will be collected in a heparinized tube. Samples will not be taken if the hemoglobin level is below 7g/dl. For patients undergoing controlled surgery, the D1 sample will be taken as soon as possible after induction of anaesthesia. Patients will be monitored until discharge from intensive care, or until D28 at the latest. Apart from the blood samples included in this study, all other examinations will be carried out as part of routine management. Data will be collected exclusively from medical records.

Timeline

• Start date: 2025-04-24
• Primary completion: 2026-04-24
• Completion: 2026-05-24
• First posted: 2024-08-12
• Last updated: 2025-12-11

Locations

7 sites across 1 country: France