ETOPOSIDE for Hemophagocytic lymphohistiocytosis (HLH)

Inclusion criteria

• {"criterion_text":"- Adult patient\n- Confirmed diagnosis of HLH: • Presence of 5 or more Henter criteria (HLH-04) out of the 6 achievable in routine care (fever, splenomegaly, cytopenias affecting 2 or 3 blood lineages, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis in bone marrow, spleen or lymph nodes, hyperferritinemia) • Diagnosis of HLH established by the multidisciplinary team caring for the patient\n- First episode of HLH\n- Admission to intensive care unit\n- Presence of one or more organ failures • Circulatory: mBP < 65 mmHg with lactate > 2 mmol/L, or treatment with catecholamines • Respiratory: oxygen therapy > 6L/min or need for non-invasive ventilation, high-flow nasal cannula oxygen therapy, or invasive mechanical ventilation • Renal: stage 2 or higher according to KDIGO criteria, either creatinine 2-2.9 times baseline, or urine output < 0.5 mL/kg/h for 12 hours • Neurological: GCS ≤ 13"}

Exclusion criteria

• {"criterion_text":"- Moribund patient with refractory distributive shock: multi-organ failure requiring noradrenaline >2.5 μg/kg/min and imminent risk of death\n- Recent vaccination with a live attenuated vaccine\n- Hypersensitivityor contraindication to dexamethasone or any of its excipients\n- Patients developing SAM within 15 days ofchemotherapy for cancer or malignant blood disease\n- Participation in another interventional research study\n- Inability to administer etoposide within 12 hours\n- Patient treated with etoposide prior to admission to the intensive care unit\n- Hypersensitivity to etoposide or any of its excipients\n- Patient not covered by social security\n- Patient under legal guardianship, tutelage, or curatorship\n- Minor patient\n- Pregnant or lactating woman"}

Primary endpoints

• {"endpoint_text":"- The occurrence of an event defined as the onset or worsening of organ failures, evaluated using the modified Sequential Organ Failure Assessment (SOFA) score (excluding the hematologic component). An event will be defined as an increase of at least 1 point for at least two organ systems compared to Day 0. In the delayed arm, the use of rescue etoposide treatment or in case of secondary aggravation during follow-up will also be considered an event.","definition_or_measurement_approach":"Evaluated using the modified SOFA score (excluding hematologic component). An event = increase ≥1 point for at least two organ systems vs Day 0. In delayed arm, rescue etoposide use or secondary aggravation during follow-up also counts as an event."}

Secondary endpoints

• {"endpoint_text":"- Time to death after inclusion (with a maximum follow-up duration of 60 days)","definition_or_measurement_approach":"Time from inclusion to death; follow-up censored at 60 days."}
• {"endpoint_text":"- Number of ventilator-free days between inclusion and Day 14","definition_or_measurement_approach":"Count of days alive and free from mechanical ventilation from inclusion to Day 14."}
• {"endpoint_text":"- Number of catecholamine-free days between inclusion and Day 14","definition_or_measurement_approach":"Count of days alive and free from catecholamine therapy from inclusion to Day 14."}
• {"endpoint_text":"- Proportion of patients receiving at least one session of renal replacement therapy between inclusion and Day 14","definition_or_measurement_approach":"Proportion receiving ≥1 renal replacement therapy session from inclusion to Day 14."}
• {"endpoint_text":"- Length of stay in the intensive care unit","definition_or_measurement_approach":"Duration of ICU stay (days)."}
• {"endpoint_text":"- Length of hospital stay","definition_or_measurement_approach":"Duration of hospital stay (days)."}
• {"endpoint_text":"- Proportion of patients receiving a dose of etoposide","definition_or_measurement_approach":"Proportion of patients who receive ≥1 dose of etoposide."}
• {"endpoint_text":"- Cumulative dose of etoposide over the first 14 days, within the total study population and among those receiving at least one dose of treatment","definition_or_measurement_approach":"Total etoposide dose accumulated over first 14 days; analyzed in overall population and among treated patients."}
• {"endpoint_text":"- Number of days between inclusion and initiation of etoposide treatment in patients who received etoposide","definition_or_measurement_approach":"Days from inclusion to first etoposide dose among those treated."}
• {"endpoint_text":"- Number of patients receiving another immunosuppressive treatment during the intensive care unit stay up to Day 14","definition_or_measurement_approach":"Count/proportion receiving other immunosuppressive therapies during ICU stay up to Day 14."}
• {"endpoint_text":"- Time from inclusion to normalization of fibrinogen (> 2 g/L), decrease in ferritin (< 2000 μg/L), and decrease in triglycerides (< 1.5 mg/dL) during the intensive care unit stay up to Day 14","definition_or_measurement_approach":"Time (days) from inclusion to reaching specified lab thresholds within ICU stay up to Day 14."}
• {"endpoint_text":"- HScore at Days 2, 7, and 14","definition_or_measurement_approach":"HScore measured at Days 2, 7 and 14."}
• {"endpoint_text":"- Proportion of patients experiencing healthcare-associated infections, acquired neutropenia after inclusion (defined by ANC < 500/mm³) and its duration if applicable, and post-inclusion bleeding event requiring transfusion and/or surgical intervention","definition_or_measurement_approach":"Proportions of patients with healthcare-associated infections, ANC <500/mm3 (neutropenia) and duration, and bleeding events post-inclusion requiring transfusion/surgery."}
• {"endpoint_text":"- Delta SOFA at Days 2 and 5, maximum SOFA score, including both SOFA and modified SOFA","definition_or_measurement_approach":"Change in SOFA (and modified SOFA) at Days 2 and 5 and maximum SOFA score during observation."}

France

Earliest CTIS Part Ii Submission Date

06-01-2026

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

52

Number Of Sites

27

Number Of Participants

176

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"French Ministry of Health (PHRC-IR 2022)","duties_or_roles":"Source of monetary support","organisation_type":""}