Effect of Interferon Gamma as a Treatment for Post-aggressive Immunosuppression in Intensive Care Units, a Randomized Bayesian Double-blind Controlled Trial Versus Placebo (INFINITY)

The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).

Study Overview

• Status: Recruiting
• Conditions: Post-aggressive Immunosuppression; Adult Patients Admitted to Intensive Care With Initial Severity (SOFA of the First 24 Hours Post-admission ≥ 6; Adult Under Mechanical Ventilation, and Presenting an mHLA-DR Less Than 8,000AB/C
• Intervention / Treatment: Drug: Interferon Gamma 1-b; Drug: Placebo

Detailed Description

The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).

This immunological adaptation, initially implemented as a host defense mechanism to protect against an overwhelming systemic reaction, can, if prolonged, lead to multiple complications resulting in significant delayed morbidity and mortality. Diagnosis is based on the use of immuno-inflammatory biomarkers, the most widely studied of which is monocyte expression of major histocompatibility complex type II molecules (mHLA-DR).

We have recently confirmed that PAIS can affect all types of patients admitted to the intensive care unit, but mainly occurs in the most severe patients. We also showed that the occurrence of PAIS was strongly associated with the subsequent occurrence of secondary infection and excess mortality.

Currently, there is no treatment with proven efficacy for PAIS, but several drugs have been shown to restore leukocyte function in-vitro. Several teams have reported the use of immunostimulatory molecules in patients with treatment failure, with a good safety profile and encouraging results. We believe that earlier treatment of patients with proven PAIS could improve their clinical outcome.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Charles De ROQUETAILLADE, MD; Phone Number: +33 01 49 95 55 68; Email: charles.de-roquetaillade@aphp.fr
• Study Contact Backup: Name: Benjamin CHOUSTERMAN, Professor; Phone Number: +33 01 49 95 85 18; Email: benjamin.chousterman@aphp.fr

Study Locations

• France
  • Paris, France
    • Recruiting
    • Dr de Roquetaillade
    • Contact: Dr de Roquetaillade Charles, MD; Phone Number: +33 0149958442; Email: charles.de-roquetaillade@aphp.fr
  • Paris, France
    • Recruiting
    • Pr Dépret
    • Contact: Pr Dépret François, Professor; Phone Number: +33 01 42 49 95 70; Email: francois.depret@aphp.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient ≥ 18 years old
• SOFA score for first 24 hours post-admission ≥ 6
• Mechanically ventilated at the time of inclusion (non-invasive ventilation (NIV) and high-flow nasal oxygen excluded)
• mHLA-DR< 8,000 AB/C measured between the 5th and 10th day after admission to the intensive care unit
• Patient affiliated to a social security scheme
• Written consent (relative/trusted person)

Exclusion Criteria:

• Patient with estimated life expectancy of less than 3 months
• Patients with a predicted remaining stay in intensive care < 72 hours
• Patient with pre-existing immunosuppression: solid cancer active or in remission for < 5 years, active hemopathy or in remission for < 5 years, systemic disease (including in the absence of specific treatment), solid organ transplant or marrow allograft patient, patient suffering from a HIV infection
• Patients with an expected prolonged duration of mechanical ventilation: comatose or vegetative patients (admission for severe stroke with Glasgow score < 8, patient resuscitated from an arterial stroke,) patients with tracheotomy for ENT problems, patients suffering from muscular disease (e.g. myopathy), patients on long-term mechanical ventilation
• Pregnant or breast-feeding women
• Contraindication of Imukin (hypersensitivity to interferon gamma-1b or known hypersensitivity to related products, such as another interferon)
• Patients on immunosuppressive therapy, including long-term corticosteroid therapy (>2.5mg/d prednisone equivalent)
• Patients with severe hepatic or renal insufficiency
• Patient included in another interventional clinical trial
• People under court protection and protected adults

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: interferon gamma-1b injection; Patients randomized to the experimental arm will receive : Recombinant human interferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)	Drug: Interferon Gamma 1-b; interferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)
Placebo Comparator: Placebo injection; Patients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)	Drug: Placebo; Patients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of days alive without mechanical ventilation	number of days alive without mechanical ventilation on day 28 after randomization or on discharge from intensive care if this occurs before the 28th day	on Day 28 after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality at Day 28 and Day 90 after randomization	Mortality rate at Day 28 and Day 90 after randomization between patients treated with recombinant interferon gamma 1-b versus placebo	Day 28 and Day 90 after randomization
incidence of nosocomial infections during intensive care unit stay	The incidence of nosocomial infections during an ICU stay between patients treated with recombinant interferon gamma 1-b versus placebo	from Day 0 to Day 28 (or the discharge from intensive care)
number of days alive whithout antibiotic	Number of days alive without antibiotic assessed on day 28 after randomization between patients treated with recombinant interferon gamma 1-b versus placebo	Day 28 after drug administration
length of stay in intensive care between patients	Number of days in intensive care between patients treated with recombinant interferon gamma 1-b versus placebo	from Day 0 to Day 28 (or the discharge from intensive care)
- Compare organ failure score (SOFA) kinetics between patients treated with recombinant interferon gamma 1-b versus placebo	Kinetics of SOFA score assessed at inclusion and during the 7 days following inclusion between patients treated with recombinant interferon gamma 1-b versus placebo	From inclusion to Day 7
Evaluate the efficacy of IFNy in correcting PAIS-defining biological abnormalities (re-ascension of mHLA-DR above 8,000 AB/C) between patients treated with recombinant interferon gamma 1-b versus placebo	Evolution of mHLA-DR measured at Day 0, Day 1, Day 2, Day 3, Day 7 and Day 28 or at discharge from intensive care if earlier (Day 0 corresponding to the day of inclusion in the study) between patients treated with recombinant interferon gamma 1-b versus placebo.	Day 1 to Day 7 and at Day 28 post randomization
Evaluate, depending on the randomization arm, the kinetics of plasma inflammatory parameters between patients treated with recombinant interferon gamma 1-b versus placebo	Evolution of inflammation markers (IL-1, IL-2, IL-6, IL-8, TNFa, etc.) measured in plasma at Day 0, Day 3 and Day 7, or at discharge from intensive care if it occurs before (Day 0 corresponding to the day of inclusion in the study) between patients treated with recombinant interferon gamma 1-b versus placebo	Day 0, Day 3 and at Day 7 post randomization
Evaluate, depending on the randomization arm, the transcriptomic profile of circulating peripheral blood mononuclear cells count between patients treated with recombinant interferon gamma 1-b versus placebo	Evolution of the transcriptomic profile of circulating peripheral blood mononuclear cells (PBMCs) using scRNAseq analysis measured at Day 0, Day 3 and Day 7 or upon discharge from intensive care if this occurs earlier.	Day 0, Day 3 and Day 7 after randomization
Evaluate, depending on the randomization arm the leucocyte count between patients treated with recombinant interferon gamma 1-b versus placebo	Evolution and kenetics of the leucocyte count measured at Day 0, Day 1, Day 2, Day 3, Day 7 and Day 28 or at discharge from intensive care if earlier (Day 0 corresponding to the day of inclusion in the study) between patients treated with recombinant interferon gamma 1-b versus placebo	Day 0 to Day 7 and at Day 28 post randomization

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Charles De ROQUETAILLADE, MD, APHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Actual): November 19, 2024

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Critical care; sepsis; immunity; HLA-DR; ICU-acquired immune suppression
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interferons; Lymphokines; Macrophage-Activating Factors; Interferon-gamma
• Other Study ID Numbers: APHP220672; 2023-506725-11-00 (Ctis)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No