Kinetics of INF-γ Production in Intensive Care Patients
- Conditions
- Intensive Care
- Interventions
- Other: blood sampling
- Registration Number
- NCT06549374
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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
- Expressed opposition from the patient, a relative (if applicable), or their legal representative (guardian, curator)
- Pregnant woman
- Hemoglobin less than 7g/dl at inclusion
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Adults in Intensive care blood sampling Patient included will be adult patients admitted to intensive care after severe trauma, high-risk surgery, or presenting with acute respiratory distress
- Primary Outcome Measures
Name Time Method INF-γ production in patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28). The measurement of INF-γ production will be conducted using a fully automated Interferon Gamma Realease Assay (IGRA) test.
- Secondary Outcome Measures
Name Time Method Presence of septic shock From ICU-admission to ICU-discharge, and at the latest Day 28 Presence of septic shock in the ICU
Incidence of nosocomial infections From ICU-admission to ICU-discharge, and at the latest Day 28 Incidence of nosocomial infections occurring in the ICU : number, type, and duration of antibiotic therapy
Incidence of viral reactivations for CMV and HSV From ICU-admission to ICU-discharge, and at the latest Day 28 Incidence of viral reactivations as detected by PCR for CMV (Cytomegalovirus) and HSV (Herpes Simplex Virus) in the ICU
Length of mechanical ventilation From ICU-admission to ICU-discharge, and at the latest Day 28 Duration of mechanical ventilation in ICU
mHLA-DR expression Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28). mHLA-DR expression by flow cytometry
ICU discharge Vital status at ICU discharge, and at the latest Day 28 Vital status at discharge from ICU
Renal impairment From ICU-admission to ICU-discharge, and at the latest Day 28 Renal impairment defined by a Kidney Disease Improving Global Outcomes (KDIGO) score \> 1.
Scale of 1 to 3, with 3 corresponding to severe acute kidney damage.Length of ICU stay at ICU discharge, and at the latest day 28 Length of stay in intensive care