Interferon gamma for post-aggressive immunosuppression in ventilated ICU adults

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

This test tries to see if giving interferon gamma helps adults on mechanical ventilation in the ICU with severe illness and low mHLA-DR recover immune function and avoid secondary infections.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 170 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: prednisone
• Locations: 2 sites (Paris and 1 other locations)
• Trial ID: NCT06694740 on ClinicalTrials.gov

What this trial studies

This is a randomized, Bayesian, double-blind, placebo-controlled Phase 2/3 trial comparing interferon gamma 1-b to placebo in adults with post-aggressive immunosuppression (PAIS) in intensive care. Eligible patients are invasively mechanically ventilated adults with high early severity (SOFA ≥ 6) and low monocyte HLA-DR (< 8,000 AB/C) measured between days 5 and 10 after ICU admission. Participants receive interferon gamma or placebo and are monitored for immune marker changes, occurrence of secondary infections, duration of organ support, and survival. The adaptive Bayesian design allows analysis across phases to identify clinically meaningful improvements in immune function and patient-centered outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) in the ICU who are invasively mechanically ventilated, had a SOFA score ≥ 6 in the first 24 hours, and have mHLA-DR < 8,000 AB/C measured between days 5 and 10 after admission, with consent provided by the patient or a proxy.

Not a fit: Patients with preexisting immunosuppression (recent cancer, hematologic disease, transplant, HIV), very limited life expectancy, predicted ICU stay under 72 hours, or those not meeting the low mHLA-DR biomarker threshold are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could restore immune function and reduce secondary infections and delayed mortality in severely ill ICU patients with PAIS.

How similar studies have performed: Small case series and compassionate-use reports of immunostimulatory agents including interferon gamma have shown acceptable safety and encouraging signals, but no large randomized trials have yet proven clinical benefit.

Eligibility criteria

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

Where this trial is running

Paris and 1 other locations

• Dr de Roquetaillade — Paris, France (Recruiting)
• Pr Dépret — Paris, France (Recruiting)

Study contacts

• Study coordinator: Charles De ROQUETAILLADE, MD

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; Critical care; ICU-acquired immune suppression; HLA-DR; immunity; sepsis