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

Conditions

• Febrile Infection-Related Epilepsy Syndrome (FIRES)
• New Onset Refractory Status Epilepticus
• New-Onset Refractory Status Epilepticus

Eligibility Criteria

Sex

ALL

Age

2 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Anakinra — DRUG
  SOC will be followed , Suggested Dose: 10 mg/kg/day IV, divided into 4 daily doses (q6h) Maximum dose: 400 mg/day
• Tocilizumab — DRUG
  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
• Standard medical treatment — OTHER
  For patients who could not be randomized by day 7, standard clinical care will be followed and patients will be followed prospectively and observationally.

Study Details

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.

Key Dates

Start date

Jul 1, 2026

Status verified

May 2026

Primary completion

Mar 31, 2030

Completion

Sep 30, 2030

Study Design

Enrollment

438 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Randomized Controlled Trial (RCT) Cohort
  A randomized controlled cohort (RCT) of anakinra vs. tocilizumab (targeted immunotherapies) started up to and including 7 days after the onset of status epilepticus (SE)
• Other: Observational Cohort
  An observational cohort enrolling patients with acute cryptogenic NORSE who cannot be randomized or who are identified too late to be randomized by the end of day 7 .

Primary Outcome Measure

Glasgow Outcome Scale - Extended (GOS-E) [ Time Frame: 12 months ]

Central Contacts

• Camalene Chrysostoum
  2037375851
  [email protected]
• Tara McPartland
  2037375851
  [email protected]

Locations (25)

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