Prevention of secondary infections by interferon gamma in ICU-acquired sustained immune-suppression: a randomized trial

Phase 3

Not yet recruiting

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

• Registration Number: 2024-516780-93-00
• Lead Sponsor: Centre Hospitalier Et Universitaire De Limoges

Brief Summary

To demonstrate the benefit of a standardized immunotherapy with IFN-γ versus placebo on the incidence of secondary infections at three months (Day 90) in ICU patients with documented sustained immunosuppression.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2025-04-22
• Last Update Posted: 2025-05-27

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 326

Inclusion Criteria

Adult patient hospitalized in the ICU for at least 1week

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 weeks of ICU hospitalization

Immunosuppression defined as an HLA-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

Chemotherapy / radiation therapy within the last 6 weeks

Acute ECG abnormality such as myocardial infarction or any acute life-threatening ECG abnormalities (e.g: ventricular fibrillation, ventricular tachycardia…)

Apache II ≥ 30

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

History of autoimmune disease

Organ or bone marrow transplant

History of hematologic malignancy

History of hepatitis C

Severe chronic renal failure (eGFR<10 ml/min/1.73m2 CKP-EPI method)

HIV stage C within the last 12 months

Hepatic cytolysis with AST/ALT > 5 times ULN (local laboratory)

Suspected acute pancreatitis with lipase or amylase > 3 times ULN (local laboratory)

Patient with thrombocytopenia below 50,000/mm3

Patient with traumatic brain and spinal injury

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 ( see appendix 1)

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

Participation in another research clinical trial within 30 days

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 at three months (Day 90) validated by an independent adjudication committee based on the current standardized definitions (CDC surveillance definitions, January 2024)		Incidence of secondary infection episodes at three months (Day 90) validated by an independent adjudication committee based on the current standardized definitions (CDC surveillance definitions, January 2024)

Secondary Outcome Measures

Name	Time	Method
All-cause ICU mortality and at Day 90		All-cause ICU mortality and at Day 90
Length of stay in the ICU and in the hospital at Day 90		Length of stay in the ICU and in the hospital at Day 90
Antibiotic and antifungal consumption at Day 90		Antibiotic and antifungal consumption at Day 90
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		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 at Day 90, cost per secondary infection avoided and cost per additional survivor, isolation requirement and antibiotic resistance		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) at D90		Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR) at D90

Trial Locations

Locations (20)

Assistance Publique Hopitaux De Paris; 🇫🇷 Garches, France

Centre Hospitalier De Versailles; 🇫🇷 Le Chesnay Rocquencourt, France

Centre Hospitalier Universitaire De Nantes; 🇫🇷 Nantes, France

Centre hospitalier de Melun-Sénart; 🇫🇷 Melun, France

Centre Hospitalier Victor Dupouy; 🇫🇷 Argenteuil Cedex, France

Centre Hospitalier Universitaire De Rennes; 🇫🇷 Rennes, France

Centre hospitalier de Lens; 🇫🇷 Lens, France

Centre Hospitalier Universitaire D'Angers; 🇫🇷 Angers, France

Centre Hospitalier Universitaire D Orleans; 🇫🇷 Orleans Cedex 2, France

Centre Hospitalier Et Universitaire De Limoges; 🇫🇷 Limoges, France

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Assistance Publique Hopitaux De Paris

🇫🇷Garches, France

Jean Luc DIEHL

Site contact

0156093201

jean-luc.diehl@aphp.fr

Nicolas DEYE

Site contact

0149958442

nicolas.deye@lrb.aphp.fr

Jean Paul MIRA

Site contact

0158412517

jean-paul.mira@aphp.fr

Djillali ANNANE

Site contact

0147107778

djillali.annane@rpc.aphp.fr