JAK Inhibitor in Acquired Hemophagocytic synDrome in the Intensive Care Unit

Assistance Publique - Hôpitaux de Paris42 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophagocytic Syndromes

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Outcomes

Primary Outcomes

Survival with a decrease in SOFA score ≥ 3 points

Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.

Time frame: At day 7

Secondary Outcomes

Overall survival in HS critically ill patients

Time frame: At 6 months

SOFA score

Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.

Time frame: At day 1

SOFA score

Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.

Time frame: At day 14

SOFA score

Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.

Time frame: At day 28

Length of stay in Intensive Care Unit

number of days in the ICU from inclusion to ICU discharge or death

Time frame: Up to 6 months

Hospital length of stay

number of days in the hospital from inclusion to hospital discharge or death

Time frame: Up to 6 months

Measurement of clinical and biological manifestations

Measurements of temperature, ferritin level, CD25 soluble receptor dosage, fibrinogen level, triglycerides level, haemoglobin level, white blood cells count, platelets count

Time frame: At day 1

Measurement of clinical and biological manifestations

Measurements of temperature, ferritin level, CD25 soluble receptor dosage, fibrinogen level, triglycerides level, haemoglobin level, white blood cells count, platelets count

Time frame: At day 7

Measurement of temperature

Time frame: At day 14

Measurement of temperature

Time frame: At day 28

Measurement of ferritin level

Time frame: At day 14

Measurement of ferritin level

Time frame: At day 28

Measurement of CD25 soluble receptor dosage

Time frame: At day 14

Measurement of CD25 soluble receptor dosage

Time frame: At day 28

Measurement of fibrinogen level

Time frame: At day 14

Measurement of fibrinogen level

Time frame: At day 28

Measurement of triglycerides level

Time frame: At day 14

Measurement of triglycerides level

Time frame: At day 28

Measurement of haemoglobin level

Time frame: At day 14

Measurement of haemoglobin level

Time frame: At day 28

Measurement of white blood cells count

Time frame: At day 14

Measurement of white blood cells count

Time frame: At day 28

Platelets count

Time frame: At day 14

Platelets count

Time frame: At day 28

Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha

Time frame: At day 1

Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha

Time frame: At day 7

Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha

Time frame: At day 14

Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha

Time frame: At day 28

Incidence of nosocomial infections (viral and bacterial)

Time frame: Until day 28

Incidence of adverse event, severe adverse event

Intensity and frequency of adverse event and severe adverse event according to the CTCAE Toxicity Grading Scale for Determining The Severity of Adverse Events

Time frame: Until day 28

JAK Inhibitor in Acquired Hemophagocytic synDrome in the Intensive Care Unit

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts