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

Prevention of Secondary Infections by Interferon Gamma in ICU-acquired Sustained Immune-suppression: a Randomized Trial

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

Study Overview

• Status: Recruiting
• Conditions: Sustained Immunosuppression
• Intervention / Treatment: Drug: Interferon Gamma 1-b; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 326
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49100
    • Recruiting
    • Angers university hospial
    • Principal Investigator: Pierre ASFAR, MD
    • Contact: Pierre ASFAR, MD; Phone Number: +33241353815; Email: pierre.asfar@univ-angers.fr
  • Argenteuil, France, 95107
    • Recruiting
    • Argenteuil Hospital
    • Principal Investigator: gaetan PLANTEFEVE, MD
    • Contact: Gaetan PLANTEFEVE, MD; Phone Number: +33134231445; Email: gaetan.plantefeve@ch-argenteuil.fr
  • Belfort, France, 90015
    • Recruiting
    • Franche-comté north Hospital
    • Contact: Julio BADIE, MD; Phone Number: +33384981970; Email: Julio.BADIE@hnfc.fr
    • Principal Investigator: julio BADIE, MD
  • Brive-la-Gaillarde, France, 19100
    • Recruiting
    • Brive Hospital
    • Principal Investigator: Nicolas PICHON, MD
    • Contact: Nicolas PICHON, MD; Phone Number: +33555926013; Email: nicolas.pichon@ch-brive.fr
  • Chalon-sur-Saône, France, 71100
    • Recruiting
    • Chalon sur saone Hospital
    • Contact: Thomas MALDINEY, MD; Phone Number: +33385910111; Email: thomas.maldiney@ch-chalon71.fr
    • Principal Investigator: Thomas MALDINEY, MD
  • Dijon, France, 21000
    • Recruiting
    • Dijon University Hospital
    • Principal Investigator: Jean-Pierre QUENOT, MD
    • Contact: Jean-Pierre QUENOT, MD; Phone Number: +33380293685; Email: jean-pierre.quenot@chu-dijon.fr
  • Garches, France, 92380
    • Recruiting
    • APHP - Raymond Poincaré
    • Principal Investigator: Djillali ANNANE, MD
    • Contact: Djillali ANNANE, MD; Phone Number: +33147107787; Email: djillali.annane@rpc.aphp.fr
  • Le Chesnay, France, 78157
    • Recruiting
    • Versailles Hospital
    • Principal Investigator: Stéphane LEGRIEL, MD
    • Contact: Stéphane LEGRIEL, MD; Phone Number: +33139639717; Email: slegriel@ch-versailles.fr
  • Le Mans, France, 72000
    • Recruiting
    • Le Mans Hospital
    • Contact: Christophe GUITTON; Phone Number: MD; Email: cguitton@ch-lemans.fr
    • Principal Investigator: Christophe GUITTON, MD
  • Lens, France, 62300
    • Recruiting
    • CH de Lens
    • Contact: Nicolas VAN GRUNDEBEECK, MD; Phone Number: +33 0321691088; Email: nvangrunderbeeck@ch-lens.fr
    • Principal Investigator: Nicolas VAN GRUNDERBEECK, MD
  • Limoges, France, 87042
    • Recruiting
    • Limoges University Hospital
    • Contact: Bruno FRANCOIS, MD; Phone Number: +33 0555058841; Email: bruno.francois@chu-limoges.fr
    • Principal Investigator: Bruno Francois, MD
  • Lyon, France, 69002
    • Not yet recruiting
    • Lyon Civils Hospices
    • Contact: Anne-Claire LUKASZEWICZ, MD; Phone Number: +33472111327; Email: anne-claire.lukaszewicz@chu-lyon.fr
    • Principal Investigator: Anne-Claire LUKASZEWICH, MD
  • Marseille, France, 13915
    • Recruiting
    • APHM
    • Contact: Sami HRAIECH, MD; Phone Number: +33491965836; Email: sami.hraiech@ap-hm.fr
    • Principal Investigator: Sami HRAIECH, MD
  • Melun, France, 77000
    • Recruiting
    • Melun Hospital
    • Principal Investigator: Mehran MONCHI, MD
    • Contact: Mehran MONCHI, MD; Phone Number: +33181742258; Email: mehran.monchi@ghsif.fr
  • Nancy, France, 54035
    • Recruiting
    • Nancy University Hospital
    • Contact: Sébastien GIBOT, MD; Phone Number: +33383852123; Email: s.gibot@chru-nancy.fr
    • Principal Investigator: Sébastien GIBOT, MD
  • Nantes, France, 44000
    • Recruiting
    • Nantes University Hospital
    • Principal Investigator: Antoine ROQUILLY, MD
    • Contact: Antoine ROQUILLY, MD; Phone Number: +33240582230; Email: antoine.roquilly@chu-nantes.fr
  • Orléans, France, 45100
    • Recruiting
    • Orléans Hospital
    • Contact: François BARBIER, MD; Phone Number: +33238514446; Email: francois.barbier@chr-orleans.fr
    • Principal Investigator: François BARBIER, MD
  • Paris, France, 75010
    • Recruiting
    • APHP - Laroiboisière
    • Contact: Nicolas DEYE, MD; Phone Number: +33149956347; Email: nicolas.deye@lrb.aphp.fr
    • Principal Investigator: nicolas DEYE, MD
  • Paris, France, 75014
    • Recruiting
    • Aphp - Hegp
    • Contact: Jean-Luc DIEHL, MD; Phone Number: +33156093204; Email: jean-luc.diehl@aphp.fr
    • Principal Investigator: Jean-Lus DIEHL, MD
  • Paris, France, 75015
    • Recruiting
    • APHP - Cochin
    • Contact: Jean-Paul MIRA, MD; Phone Number: +33158412501; Email: jean-paul.mira@aphp.fr
    • Principal Investigator: Jean-Paul MIRA, MD
  • Rennes, France, 35000
    • Recruiting
    • Rennes University Hospital
    • Principal Investigator: Jean-Marc TADIE, MD
    • Contact: Jean-Marc TADIE, MD; Phone Number: +33299284248; Email: jeanmarc.tadie@chu-rennes.fr
  • Strasbourg, France, 67091
    • Recruiting
    • Strasbourg University Hospital
    • Contact: Louise-Marie JANDEAUX, MD; Phone Number: +33369551212; Email: Louise-marie.jandeaux@chru-strasbourg.fr
    • Principal Investigator: Louise-Marie JANDEAUX, MD
  • Tours, France, 37000
    • Recruiting
    • Tours University Hospital
    • Contact: Antoine GUILLON, MD; Phone Number: +33139639717; Email: antoine.guillon@univ-tours.fr
    • Principal Investigator: Antoine GUILLON, MD

Participation Criteria

Eligibility Criteria

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

Description

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 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; 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	Drug: Interferon Gamma 1-b; injection of interferon gamma 1-b
Placebo Comparator: 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)	Drug: Placebo; Injection of placebo in the same condition of experimental traitment

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cause of mortality of participant	All-cause ICU mortality and at Day 90	Day 90
Length of stay in the ICU and in the hospital	Number of days spent in the ICU and in the hospital at Day 90	Day 90
Antibiotic consumption	Name of antibiotics taken at Day 90	Day 90
Biological immune restoration	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	Day 10
Healthcare costs	Healthcare costs at Day 90, cost per secondary infection avoided and cost per additional survivor, isolation requirement and antibiotic resistance	Day 90
Antifungal consumption	Name of antifungals taken at Day 90	Day 90
Antifungal consumption	Dosage of antifungals taken at Day 90	Day 90
Antifungal consumption	Duration of antifungals taken at Day 90	Day 90
Antibiotic consumption	Dosage of antibiotics taken at Day 90	Day 90
Antibiotic consumption	Duration of antibiotics taken at Day 90	Day 90
Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR)	Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR) at D90 according to sponsor causality assessment	Day 90

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2025
• Primary Completion (Estimated): October 9, 2028
• Study Completion (Estimated): October 9, 2028

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): January 14, 2025

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: ICU; Prevention; Immuno-restauration; Secondary infections
• Additional Relevant MeSH Terms: Infections; Coinfection; 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: 87RI24_0040 (PLATINIUM); 2024-516780-93-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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