Clinical trial NCT06774235: Prevention of Secondary Infections by Interferon Gamma in ICU-acquired Sustained Immune-suppression
Official title: Prevention of Secondary Infections by Interferon Gamma in ICU-acquired Sustained Immune-suppression: a Randomized Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Sustained Immunosuppression
Keywords: ICU
Immuno-restauration
Secondary infections
Prevention
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2025-01-14
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of secondary infection episodes
timeFrame: Day 90
Secondary outcomes:
measure: Cause of mortality of participant
timeFrame: Day 90
measure: Length of stay in the ICU and in the hospital
timeFrame: Day 90
measure: Antibiotic consumption
timeFrame: Day 90
measure: Biological immune restoration
timeFrame: Day 10
measure: Healthcare costs
timeFrame: Day 90
measure: Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR)
timeFrame: Day 90
measure: Antifungal consumption
timeFrame: Day 90
measure: Antifungal consumption
timeFrame: Day 90
measure: Antifungal consumption
timeFrame: Day 90
measure: Antibiotic consumption
timeFrame: Day 90
measure: Antibiotic consumption
timeFrame: Day 90
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers university hospial
city: Argenteuil
country: France
facility: Argenteuil hospital
city: Belfort
country: France
facility: Franche-comté north Hospital
city: Brive la gaillarde
country: France
facility: Brive Hospital
city: Chalon-sur-saone
country: France
facility: Chalon sur saone Hospital
city: Dijon
country: France
facility: Dijon University Hospital
city: Garches
country: France
facility: APHP - Raymond Poincaré
city: Le Chesnay
country: France
facility: Versailles Hospital
city: Le Mans
country: France
facility: Le mans Hospital
city: Lens
country: France
facility: CH de Lens
city: Limoges
country: France
facility: Limoges University Hospital
city: Lyon
country: France
facility: Lyon Civils Hospices
city: Marseille
country: France
facility: APHM
city: Melun
country: France
facility: Melun Hospital
city: Nancy
country: France
facility: Nancy University Hospital
city: Nantes
country: France
facility: Nantes University Hospital
city: Orleans
country: France
facility: Orléans Hospital
city: Paris
country: France
facility: APHP - Laroiboisière
city: Paris
country: France
facility: Aphp - Hegp
city: Paris
country: France
facility: APHP - Cochin
city: Rennes
country: France
facility: Rennes University Hospital
city: Strasbourg
country: France
facility: Strasbourg University Hospital
city: Tours
country: France
facility: Tours University Hospital
Study officials:
References: