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

Starting soon · Phase 3

Conditions studied: New Onset Refractory Status Epilepticus, New-Onset Refractory Status Epilepticus, Febrile Infection-Related Epilepsy Syndrome (FIRES)

In brief

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 facts

Study ID

NCT07281027

Run by

Yale University

People needed

438

Starts

2026-07-01

Expected to finish

2030-09-30

Last updated by the study team

2026-05-12

Who can join

Age: 2 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Barrow Institute — Phoenix, Arizona, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Yale New Haven Hospital — New Haven, Connecticut, United States
• Children's National (DC) — Washington D.C., District of Columbia, United States
• University of Florida — Gainesville, Florida, United States
• University of Chicago — Chicago, Illinois, United States
• Northwestern University — Evanston, Illinois, United States
• Mass General (MGH) — Boston, Massachusetts, United States
• Beth Israel Deaconess — Boston, Massachusetts, United States
• Boston Children's Hospital — Boston, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• University of Nebraska — Lincoln, Nebraska, United States
• New York University — New York, New York, United States
• Columbia University — New York, New York, United States
• Mount Sinai (NY) — New York, New York, United States
• University of Cincinnati — Cincinnati, Ohio, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Children's Hospital Philadelphia (CHOP) — Philadelphia, Pennsylvania, United States
• University of Pennsylvania — Philadelphia, Pennsylvania, United States
• UT Southwestern Medical Center — Dallas, Texas, United States
• Baylor/Texas Children's — Houston, Texas, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• University of Wisconsin — Madison, Wisconsin, United States
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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