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

Assistance Publique - Hôpitaux de Paris

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Adult Patients Admitted to Intensive Care with Initial Severity (SOFA of the First 24 Hours Post-admission ≥ 6; Post-aggressive Immunosuppression; Adult Under Mechanical Ventilation, and Presenting an MHLA-DR Less Than 8,000AB/C

Treatments: Drug: Placebo; Drug: Interferon Gamma 1-b

Study type: Interventional

Funder types: Other

Identifiers

NCT06694740

2023-506725-11-00 (EU Trial (CTIS) Number)

APHP220672

Details and patient eligibility

About

The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).

Full description

The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).

This immunological adaptation, initially implemented as a host defense mechanism to protect against an overwhelming systemic reaction, can, if prolonged, lead to multiple complications resulting in significant delayed morbidity and mortality. Diagnosis is based on the use of immuno-inflammatory biomarkers, the most widely studied of which is monocyte expression of major histocompatibility complex type II molecules (mHLA-DR).

We have recently confirmed that PAIS can affect all types of patients admitted to the intensive care unit, but mainly occurs in the most severe patients. We also showed that the occurrence of PAIS was strongly associated with the subsequent occurrence of secondary infection and excess mortality.

Currently, there is no treatment with proven efficacy for PAIS, but several drugs have been shown to restore leukocyte function in-vitro. Several teams have reported the use of immunostimulatory molecules in patients with treatment failure, with a good safety profile and encouraging results. We believe that earlier treatment of patients with proven PAIS could improve their clinical outcome.

Enrollment: 170 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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170 participants in 2 patient groups, including a placebo group

interferon gamma-1b injection

Experimental group

Description:

Patients randomized to the experimental arm will receive : Recombinant human interferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)

Treatment:

Drug: Interferon Gamma 1-b

Placebo injection

Placebo Comparator group

Description:

Patients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)

Treatment:

Drug: Placebo