Effect of Interferon Gamma as a Treatment for Post-aggressive Immunosuppression in Intensive Care Units, a Randomized Bayesian Double-blind Controlled Trial Versus Placebo
Ориентир для пациента и семьи
Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: Interferon Gamma 1-b, Placebo.
- Кому может быть актуально
- Состояния в реестре: 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. Базовые параметры: от 18 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- Франция
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Обзор
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).
Подробное описание
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.
Вмешательства
- Препарат Interferon Gamma 1-b
interferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections) - Препарат Placebo
Patients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)
Первичные конечные точки
- number of days alive without mechanical ventilation [Срок оценки: on Day 28 after drug administration]
Вторичные конечные точки (9)
- 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 [Срок оценки: 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 [Срок оценки: Day 0, Day 3 and at Day 7 post randomization]
- mortality at Day 28 and Day 90 after randomization [Срок оценки: Day 28 and Day 90 after randomization]
- incidence of nosocomial infections during intensive care unit stay [Срок оценки: from Day 0 to Day 28 (or the discharge from intensive care)]
- number of days alive whithout antibiotic [Срок оценки: Day 28 after drug administration]
- length of stay in intensive care between patients [Срок оценки: 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 [Срок оценки: From inclusion to Day 7]
- 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 [Срок оценки: 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 [Срок оценки: Day 0 to Day 7 and at Day 28 post randomization]
Критерии участия
Критерии включения
- 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)
Критерии исключения
- 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
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Рандомизированное
- Модель
- Параллельные группы
- Маскирование
- Тройное слепое
- Основная цель
- Лечение
Центры проведения
Франция · 2 центра
- Dr de Roquetaillade — Paris
- Pr Dépret — Paris
Идентификаторы
NCT: NCT06694740 · APHP220672 · 2023-506725-11-00