Prevention of Secondary Infections by Interferon Gamma in ICU-acquired Sustained Immune-suppression

Phase 3

Not yet recruiting

• Conditions: Sustained Immunosuppression
• Interventions: Drug: Interferon Gamma 1-b; Drug: Placebo

• Registration Number: NCT06774235
• Lead Sponsor: University Hospital, Limoges

Brief Summary

The goal of this clinical trial is to demonstrate the benefit of a standardized immunotherapy (Interferon gamma) on the incidence of secondary infections. . It will also learn about the safety of Interferon-gamma. The main questions it aims to answer are:

Does Interferon-gamma:

* reduces the Incidence of secondary infection episodes at three months

* reduces the ICU mortality and at Day 90

* reduces the ICU and hospital length of stay

* induces Biological immune restoration at Day 10

* has cost-consequence and cost-effectiveness

Researchers will compare Interferon-gamma to a placebo (a look-alike substance that contains no drug) to see if Interferon-gamma works to treat sustained immunosuppression .

Participants will:

* Take Interferon-Gamma or a placebo for a maximum of 5 times between day 1 and day 9

* be monitored evety day until their ICU discharge and at day 30, 60 and 90

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-06
• Study First Submitted QC: 2025-01-13
• Study First Posted: 2025-01-14
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-11
• Study Start: 2025-07-01
• Primary Completion: 2028-10-01
• Study Completion: 2028-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 326

Inclusion Criteria

• Adult patient hospitalized in the ICU for at least 1 week
• Expected length of stay in the ICU greater than 10 days at screening
• At least 1 episode of multiple organ failure, defined as a SOFA ≥ 6 (excluding the respiratory component when related to a neurological failure), during the first 1 week of ICU hospitalization
• Immunosuppression defined as an mHLA-DR < 8000 Ab/c and a lymphopenia < 1000/mm3 within a 96 hours time window
• Patient or the legal representative giving consent must be able to understand the trial in its entirety
• Patient affiliated to the social security system
• For female participants of childbearing potential, agreement to use dual methods of contraception until Day 90
• For male participants with female partners of childbearing potential, agreement to use barrier method of contraception until Day 90.

Exclusion Criteria

• Uncontrolled secondary infections ongoing at the time of screening
• Participation in another research clinical trial within 30 days
• Chemotherapy / radiation therapy within the last 6 weeks
• Apache II ≥ 30 at screening
• History of autoimmune disease
• Organ or bone marrow transplant
• History of hematologic malignancy
• History of hepatitis C
• HIV stage C within the last 12 months
• Patients under legal protection
• History of or ongoing tuberculosis
• Chronic hepatitis B
• Patients receiving immunosuppressive medications including patient receiving a steroid dose greater than 1mg/kg/day of prednisone equivalent for more than 1 week and patient that have been on corticosteroid for more than 3 months
• Patient with thrombocytopenia below 50,000/mm3
• Patient with traumatic brain and spinal injury
• Pregnancy or breast feeding
• Subjects with a history hypersensitivity to interferon gamma or excipient (Mannitol, Sodium succinate dibasic hexahydrate, Succinic acid, polysorbate 20), known latex hypersensitivity or other interferon
• Hepatic cytolysis with AST/ALT > 5 times ULN (local laboratory)
• Suspected acute pancreatitis with lipase or amylase > 3 times ULN (local laboratory)
• Severe chronic renal failure (eGFR<10 ml/min/1.73m2 CKP-EPI method)
• Acute ECG abnormality such as myocardial infarction or any acute life-threatening ECG abnormalities (e.g: ventricular fibrillation, ventricular tachycardia...)
• Mental state rendering the person giving consent incapable of understanding the trial
• Patient deprived of liberty by judicial or administrative decision
• Patient being the investigator, or any member of the team or relative of the investigator directly involved in the trial, including assistant doctors, pharmacists, nurses, trial coordinators

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Interferon-gamma	Interferon Gamma 1-b	Injections of Interferon gamma-1b are sub-cutaneous and preferably in the deltoid region left or right or on the anterior part of the thigh. 5 injections between day 1 and day 9
Placebo	Placebo	The comparative treatment will be a placebo, consisting in 0.5 ml of 0.9% sodium chloride solution only (same volume for interferon gamma-1b)

Primary Outcome Measures

Name	Time	Method
Incidence of secondary infection episodes	Day 90	Number of episodes divided by the follow-up length, in days, validated by an independent adjudication committee based on the current definitions.

Secondary Outcome Measures

Name	Time	Method
Cause of mortality of participant	Day 90	All-cause ICU mortality and at Day 90
Length of stay in the ICU and in the hospital	Day 90	Number of days spent in the ICU and in the hospital at Day 90
Antibiotic consumption	Day 90	Duration of antibiotics taken at Day 90
Antifungal consumption	Day 90	Duration of antifungals taken at Day 90
Biological immune restoration	Day 10	Percentage of biological immune restoration (defined as an HLA-DR \> 13 500 Ab/c \[Antibodies bound per cell\] and an absolute lymphocyte count \> 1200 mm3) at Day 10
Healthcare costs	Day 90	Healthcare costs at Day 90, cost per secondary infection avoided and cost per additional survivor, isolation requirement and antibiotic resistance
Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR)	Day 90	Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR) at D90 according to sponsor causality assessment

Trial Locations

Locations (23)

CH de Lens; 🇫🇷 Lens, France

Angers university hospial; 🇫🇷 Angers, France

APHP - Laroiboisière; 🇫🇷 Paris, France

Argenteuil hospital; 🇫🇷 Argenteuil, France

Franche-comté north Hospital; 🇫🇷 Belfort, France

Brive Hospital; 🇫🇷 Brive la gaillarde, France

Chalon sur saone Hospital; 🇫🇷 Chalon-sur-saone, France

Dijon University Hospital; 🇫🇷 Dijon, France

APHP - Raymond Poincaré; 🇫🇷 Garches, France

Versailles Hospital; 🇫🇷 Le Chesnay, France

Le mans Hospital; 🇫🇷 Le Mans, France

Limoges University Hospital; 🇫🇷 Limoges, France

Lyon Civils Hospices; 🇫🇷 Lyon, France

APHM; 🇫🇷 Marseille, France

Melun Hospital; 🇫🇷 Melun, France

Nancy University Hospital; 🇫🇷 Nancy, France

Nantes University Hospital; 🇫🇷 Nantes, France

Orléans Hospital; 🇫🇷 Orleans, France

Aphp - Hegp; 🇫🇷 Paris, France

APHP - Cochin; 🇫🇷 Paris, France

Rennes University Hospital; 🇫🇷 Rennes, France

Strasbourg University Hospital; 🇫🇷 Strasbourg, France

Tours University Hospital; 🇫🇷 Tours, France