Effect of Interferon Gamma as a Treatment for Post-aggressive Immunosuppression in Intensive Care Units, a Randomized Bayesian Double-blind Controlled Trial Versus Placebo
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 2
- 主要终点
- number of days alive without mechanical ventilation
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
interferon gamma-1b injection
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)
Placebo injection
Patients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)
干预措施: Placebo (Drug)
结局指标
主要结局
number of days alive without mechanical ventilation
时间窗: on Day 28 after drug administration
number of days alive without mechanical ventilation on day 28 after randomization or on discharge from intensive care if this occurs before the 28th day
次要结局
- mortality at Day 28 and Day 90 after randomization(Day 28 and Day 90 after randomization)
- incidence of nosocomial infections during intensive care unit stay(from Day 0 to Day 28 (or the discharge from intensive care))
- Evaluate, depending on the randomization arm, the kinetics of plasma inflammatory parameters and leucocyte count between patients treated with recombinant interferon gamma 1-b versus placebo(Day 1 to Day 7 and at Day 28 post randomization)
- number of days alive whithout antibiotic(Day 28 after drug administration)
- length of stay in intensive care between patients(from Day 0 to Day 28 (or the discharge from intensive care))
- - Compare organ failure score (SOFA) kinetics between patients treated with recombinant interferon gamma 1-b versus placebo(From inclusion to Day 7)
- Evaluate, depending on the randomization arm, the kinetics of plasma inflammatory parameters and leucocyte count between patients treated with recombinant interferon gamma 1-b versus placebo.(Day 1 to Day 7 and at Day 28 post randomization)
- Evaluate, depending on the randomization arm, the kinetics of plasma inflammatory parameters between patients treated with recombinant interferon gamma 1-b versus placebo(Day 0, Day 3 and at Day 7 post randomization)
- Evaluate, depending on the randomization arm, the transcriptomic profile of circulating peripheral blood mononuclear cells count between patients treated with recombinant interferon gamma 1-b versus placebo(Day 0, Day 3 and Day 7 after randomization)
- Evaluate, depending on the randomization arm the leucocyte count between patients treated with recombinant interferon gamma 1-b versus placebo(Day 0 to Day 7 and at Day 28 post randomization)
- Evaluate the efficacy of IFNy in correcting PAIS-defining biological abnormalities (re-ascension of mHLA-DR above 8,000 AB/C) between patients treated with recombinant interferon gamma 1-b versus placebo(Day 1 to Day 7 and at Day 28 post randomization)