Sustained Immunosuppression
Conditions
Keywords
ICU, Immuno-restauration, Secondary infections, Prevention
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
Interventions
injection of interferon gamma 1-b
DRUGPlacebo
Injection of placebo in the same condition of experimental traitment
Sponsors
University Hospital, Limoges
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of secondary infection episodes | Day 90 | Number of episodes divided by the follow-up length, in days, validated by an independent adjudication committee based on the current definitions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of stay in the ICU and in the hospital | Day 90 | Number of days spent in the ICU and in the hospital at Day 90 |
| Antibiotic consumption | Day 90 | Name of antibiotics taken at Day 90 |
| Biological immune restoration | 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 |
| Cause of mortality of participant | Day 90 | All-cause ICU mortality and at Day 90 |
| Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR) | Day 90 | Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR) at D90 according to sponsor causality assessment |
| Antifungal consumption | Day 90 | Name of antifungals taken at Day 90 |
| Healthcare costs | Day 90 | Healthcare costs at Day 90, cost per secondary infection avoided and cost per additional survivor, isolation requirement and antibiotic resistance |
Countries
France
Outcome results
None listed