COMparison Between Anakinra and Tocilizumab in NORSE - "COMBAT-NORSE"

Официальное название

Comparing the Effects of Anakinra and Tocilizumab on Outcomes in Patients With New-Onset Refractory Status Epilepticus

Обзор

The goal of this clinical trial is to find out whether two existing medications-anakinra and tocilizumab-can effectively treat a rare and life-threatening brain condition called NORSE (New-Onset Refractory Status Epilepticus). NORSE causes continuous seizures in previously healthy children and adults and does not respond to standard treatments. It often leads to long-term disability or death. Doctors currently use anakinra and tocilizumab as second-line treatments when first-line therapies fail, but there is no clear evidence showing which drug works better or when it should be given. This study aims to answer those questions. The study will enroll patients across 33 hospitals in the United States, Canada, Europe, and Asia. It includes two groups: 1. Randomized Cohort Patients will be randomly assigned to receive either anakinra or tocilizumab within the first 7 days of their illness. Only patients whose doctors were already planning to use one of these medications as part of standard care will be eligible for randomization. Researchers will monitor their recovery and compare outcomes between the two treatments. 2. Observational Cohort Patients who cannot be randomized-usually because they were diagnosed too late-will still be followed to study how the timing of treatment affects recovery. Participants will: * Receive one of the two medications (depending on their group assignment). * Take part in follow-up assessments over the course of one year, including medical evaluations and surveys. Some participants may be followed annually beyond one year. * Optionally participate in a 60-minute interview to share their or their caregiver's experience with NORSE.

Вмешательства

• Препарат Anakinra
  SOC will be followed , Suggested Dose: 10 mg/kg/day IV, divided into 4 daily doses (q6h) Maximum dose: 400 mg/day
• Препарат Tocilizumab
  SOC will be followed, Suggested Dose: If \<30 kg: 12 mg/kg IV once every 2 weeks If ≥30 kg: 8 mg/kg IV once every 2 weeks Maximum dose: 800 mg per dose
• Другое Standard medical treatment
  For patients who could not be randomized by day 7, standard clinical care will be followed and patients will be followed prospectively and observationally.

Первичные конечные точки

• Glasgow Outcome Scale - Extended (GOS-E) [Срок оценки: 12 months]

Вторичные конечные точки (6)

• Time to resolution of status epilepticus (SE) [Срок оценки: 24 hours off anesthetic drips]
• Hospital length of stay [Срок оценки: 12 months]
• Mortality [Срок оценки: up to 12 months]
• Number of serious adverse events attributed to anakinra or tocilizumab [Срок оценки: From hospitalization to 1 month after stopping treatment, up to 12 months]
• Number of participants Post-NORSE epilepsy [Срок оценки: 12 months]
• Number of participants with Treatment success [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age 2 and older.
• In their usual state of health prior to their onset of SE.
• Presenting with NORSE as defined in the consensus criteria:

• Refractory SE (failed 2 appropriately used anti-seizure medications) in a patient without active epilepsy or other pre-existing relevant neurological disorder and without an acute or active structural, toxic, or metabolic cause found in the first 72 hours.
• Includes patients with any RSE, not just super-refractory SE.
• Includes patients who ultimately are discovered to have a known etiology (infectious, autoimmune, genetic, etc.), as well as those who remain cryptogenic.

• Additional Inclusion Criteria for the Randomized Arm:
• Anakinra and/or tocilizumab are being planned or considered as part of standard clinical care.
• The onset of SE was in the prior 7 days at the time of enrollment.

Критерии исключения

• Any acute or active systemic medical illness such as metastatic cancer, renal failure, hepatic failure, poorly controlled diabetes, etc., in the opinion of the investigators. If this is unclear, the study PI Dr. Hirsch will determine if this criterion is met.

Additional Exclusion Criteria for the Randomized Control Cohort:

• Contraindication to either anakinra or tocilizumab as listed in the prescribing information:

• Known hypersensitivity to E. Coli-derived proteins, anakinra, tocilizumab, or any component of the products
• Active serious infection at the time of initiation
• Concomitant use of TNF blocking agents; absolute neutrophil count < 2000; platelet count < 100,000 per mm³; or ALT or AST > 1.5 X the upper limit of normal
• Elevated risk of GI perforation.

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

Простое слепое

Основная цель

Лечение

Центры проведения

США · 25 центров

• Barrow Institute — Phoenix
• Children's Hospital Colorado — Aurora
• Yale New Haven Hospital — New Haven
• Children's National (DC) — Washington D.C.
• University of Florida — Gainesville
• University of Chicago — Chicago
• Northwestern University — Evanston
• Mass General (MGH) — Boston
• … и ещё 17 центров

Канада · 2 центра

• Western University — London
• Hospital for Sick Children — Toronto

Великобритания · 2 центра

• Great Ormond Street Hospital — London
• King's College — London

Франция · 1 центр

• Salpêtrière — Paris

Италия · 1 центр

• University of Modena — Modena

South Korea · 1 центр

• Seoul National University Hospital — Seoul

Швеция · 1 центр

• Karolinska Institute — Stockholm

Идентификаторы

NCT: NCT07281027 · 2000041289 · RD-2024C2-39648

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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