Kinetics of INF-γ Production in Intensive Care Patients (IGREY)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Intensive Care
• Intervention / Treatment: Other: blood sampling

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Jean-michel Constantin, MD, PhD; Phone Number: 33142161936; Email: jean-michel.constantin@aphp.fr

Study Locations

• France
  • Annecy, France, 74370
    • Not yet recruiting
    • Reanimation department, Annecy Genevois hospital
    • Contact: Noémie ZUCMAN, MD; Phone Number: 04 50 63 60 30; Email: nzucman@ch-annecygenevois.fr
  • Clermont-Ferrand, France, 63000
    • Not yet recruiting
    • Reanimation department, Clermont-Ferrand Hospital
    • Contact: Camille HAUMONT, MD; Email: chaumont@chu-clermontferand.fr
  • Lyon, France, 69003
    • Not yet recruiting
    • Reanimation department, Lyon hospital
    • Contact: Anne Claire LUKASZEWICZ, MD, PhD; Phone Number: +33 04 72 11 96 86; Email: anne-claire.lukaszewicz@chu-lyon.fr
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75013
      • Recruiting
      • Réanimation cardio-chirurgicale - Pitié-Salpêtrière hospital
      • Contact: Adrien BOUGLE, Pr; Phone Number: +33 6 64 82 56 29; Email: adrien.bougle@aphp.fr
    • Paris, Île-de-France Region, France, 75013
      • Recruiting
      • Réanimation chirurgicale Gaston Cordier - Pitié-Salpêtrière hospital
      • Contact: Jean-Michel CONSTANTIN, Pr; Phone Number: +331 42 16 19 36; Email: jean-michel.constantin@aphp.fr
      • Contact: Rayan BRAIK, Dr; Phone Number: +33 1 84 82 83 62; Email: rayan.braik@aphp.fr
    • Paris, Île-de-France Region, France, 75013
      • Not yet recruiting
      • Réanimation chirurgicale Husson Mourrier - Pitié-Salpêtrière hospital
      • Contact: Antoine MONSEL, Pr; Phone Number: +33 1 84 82 73 99; Email: antoine.monsel@aphp.fr
    • Paris, Île-de-France Region, France, 75013
      • Not yet recruiting
      • Réanimation neuro-chirurgicale - Pitié-Salpêtrière hospital
      • Contact: Alice JACQUENS, MD, PhD; Phone Number: +33 01 84 82 76 02; Email: alice.jacquens@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adults in Intensive care; Patient included will be adult patients admitted to intensive care after severe trauma, high-risk surgery, or presenting with acute respiratory distress

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
INF-γ production in patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress	The measurement of INF-γ production will be conducted using a fully automated Interferon Gamma Realease Assay (IGRA) test.	Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU discharge Vital status	Vital status at discharge from ICU	at ICU discharge, and at the latest Day 28
Incidence of nosocomial infections	Incidence of nosocomial infections occurring in the ICU : number, type, and duration of antibiotic therapy	From ICU-admission to ICU-discharge, and at the latest Day 28
Incidence of viral reactivations for CMV and HSV	Incidence of viral reactivations as detected by PCR for CMV (Cytomegalovirus) and HSV (Herpes Simplex Virus) in the ICU	From ICU-admission to ICU-discharge, and at the latest Day 28
Length of mechanical ventilation	Duration of mechanical ventilation in ICU	From ICU-admission to ICU-discharge, and at the latest Day 28
Presence of septic shock	Presence of septic shock in the ICU	From ICU-admission to ICU-discharge, and at the latest Day 28
Renal impairment	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.	From ICU-admission to ICU-discharge, and at the latest Day 28
mHLA-DR expression	mHLA-DR expression by flow cytometry	Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28).
Length of ICU stay	Length of stay in intensive care	at ICU discharge, and at the latest day 28

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2025
• Primary Completion (Estimated): October 24, 2026
• Study Completion (Estimated): October 24, 2026

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: August 9, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; immunostimulation; INF-γ
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Inflammation; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: APHP240860

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No