NCT07281027

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

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

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 438 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Anakinra	SOC will be followed , Suggested Dose: 10 mg/kg/day IV, divided into 4 daily doses (q6h) Maximum dose: 400 mg/day
DRUG	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
OTHER	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.

Timeline

• Start date: 2026-03-01
• Primary completion: 2030-03-31
• Completion: 2030-09-30
• First posted: 2025-12-15
• Last updated: 2025-12-15

Locations

33 sites across 7 countries: United States, Canada, France, Italy, South Korea, Sweden, United Kingdom

Regulatory

• FDA-regulated drug study