JAK Inhibitor in Acquired Hemophagocytic synDrome in the Intensive Care Unit
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 42
- 主要终点
- Survival with a decrease in SOFA score ≥ 3 points
研究概览
简要总结
Hemophagocytic syndrome (HS) is a rare condition that can be responsible for severe organ failure. Therapeutic guidelines are mainly based on observational studies and expert opinions: no therapeutic advance has been developed for years, explaining why mortality in HS remains high (Intensive Care Unit mortality ranging from 40 to 70%). If etoposide remains the gold standard in critically ill HS patients, nearly 20% of patients are refractory to this therapy: treatment escalation is common, most often requiring the administration of intensive treatments generating high toxicity. Ruxolitinib is the first approved JAK inhibitor. It has been associated with improvement of HS manifestations and survival in a pre-clinical murine model. Data in humans are scarce but promising.
The aim is to demonstrate that ruxolitinib, in association with standard of care, may reverse organ failure (as represented by Sequential Organ Failure Assessment (SOFA) score) better than standard of care alone in critically ill patients with acquired HS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult patients older than 18 years
- •acquired hemophagocytic syndrome, regardless of etiology, defined by the presence of 5 or 6 HLH-2004 criteria or HScore ≥ 200
- •admission in the ICU
- •need for symptomatic treatment of HS in relation with organ failure, as defined by SOFA score ≥ 4
- •Informed consent signed:
- •by the patient,
- •Or informed consent signed by a family members/trustworthy person if his condition does not allow him to express his consent in written
- •Or in an emergency situation and in the absence of family members/trustworthy person, the patient can be enrolled. The consent to participate to the research will be requested as soon as the condition of the patient will allow).
- •The inclusion of women of childbearing potential requires the use of a highly effective contraceptive measure. Contraception should be maintained during treatment and one day after
排除标准
- •Moribund, defined by a life expectancy < 48 hours;
- •Pregnant or lactating patients (women of childbearing potential must have a negative urine or blood Human Chorionic Gonadotropin pregnancy test prior to trial entry);
- •No affiliation to health insurance;
- •Known hypersensitivity to ruxolitinib;
- •Lactose intolerance;
- •Hypersensitivity to cellulose, microcrystalline; magnesium stearate; silica, colloidal anhydrous; sodium starch glycolate (Type A); povidone K30; hydroxypropylcellulose 300 to 600 cps,
- •Pre-existing decisions of withholding/withdrawing care,
- •History of progressive multifocal leukoencephalopathy
- •Uncontrolled cutaneous cancer
- •Persons under psychiatric care that would impede understanding of informed consent and optimal treatment and follow-up
- •Adults subject to a legal protection measure (guardianship, curatorship and safeguard of justice)
- •Patients deprived of their liberty by a judicial or administrative decision
- •Participation in another interventional research
研究组 & 干预措施
Interventional medicinal product
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Survival with a decrease in SOFA score ≥ 3 points
时间窗: At day 7
Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.
次要结局
- Measurement of ferritin level(At day 28)
- Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha(At day 28)
- Measurement of CD25 soluble receptor dosage(At day 28)
- Measurement of fibrinogen level(At day 28)
- SOFA score(At day 28)
- Length of stay in Intensive Care Unit(Up to 6 months)
- Hospital length of stay(Up to 6 months)
- Measurement of temperature(At day 28)
- Measurement of triglycerides level(At day 28)
- Measurement of haemoglobin level(At day 28)
- Incidence of adverse event, severe adverse event(Until day 28)
- Overall survival in HS critically ill patients(At 6 months)
- Measurement of white blood cells count(At day 28)
- Incidence of nosocomial infections (viral and bacterial)(Until day 28)
- Measurement of clinical and biological manifestations(At day 7)
- Platelets count(At day 28)