Comparing anakinra and tocilizumab for new-onset refractory status epilepticus
Compares anakinra and tocilizumab in people with seizures that standard treatments do not stop.
Key facts
- Who runs it
- Yale University
- Where
- Paris, FranceSee the siteAlso in 6 other countries, 32 sites
- Trial code
- Registry title
- COMparison Between Anakinra and Tocilizumab in NORSE - "COMBAT-NORSE"
- Status
- Not yet recruiting
- Phase
- Phase 3
- People taking part
- 438 people, planned
- Starts
- 1 Dec 2026
- Expected to end
- 30 Sept 2030
- Type of study
- Interventional, 2 groupsOne group gets an existing treatment, for comparison.
- Treatments tested
- Anakinra
- Tocilizumab
- Standard medical treatment
- Record updated
- 19 August 2026
Who can take part
AI summary
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for children and adults aged 2 and older who were in their usual health before suddenly developing continuous seizures (NORSE) that did not respond to standard seizure medicines.
- Age
- 2 years and older
- Sex
- All sexes
- Disease stage
- New-onset refractory status epilepticus (NORSE): continuous seizures that failed 2 appropriately used anti-seizure medications, in a person without epilepsy or another relevant neurological disorder and without an acute or active structural, toxic, or metabolic cause found in the first 72 hours. For the randomized group, the seizures started in the prior 7 days.
- Earlier treatment
- For the randomized group, doctors must already be planning or considering anakinra and/or tocilizumab as part of standard care. Failure of 2 anti-seizure medications is part of the NORSE definition.
Main reasons for not taking part
- Any acute or active serious illness elsewhere in the body, such as metastatic cancer, renal failure, hepatic failure, or poorly controlled diabetes
- Randomized group: known allergy to E. Coli-derived proteins, anakinra, tocilizumab, or any component of the products
- Randomized group: active serious infection at the start of treatment
- Randomized group: 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
- Randomized group: elevated risk of GI perforation
The registry criteria, word for word
Show all 7 criteriaShow less
Who can take part
- 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
Who cannot take part
- 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 in France
Also in 6 other countries, 32 sites
- SalpêtrièreParis, FranceContact: Vincent NavarroNo longer taking part
About the trial
What the trial wants to find out
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.
Read full original descriptionShow less
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.
The 2 groups in the trial
- Randomized Controlled Trial (RCT) CohortExisting treatment, for comparison
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)
Treatment: Anakinra and Tocilizumab
- Observational CohortOther group
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 .
Treatment: Standard medical treatment
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov.
- Official title
- Comparing the Effects of Anakinra and Tocilizumab on Outcomes in Patients With New-Onset Refractory Status Epilepticus
- Plain-language title
- Comparing anakinra and tocilizumab for new-onset refractory status epilepticusGenerated from the registry record. The registry title is the official one.
- AI summary
- From the trial's eligibility criteria. Read by machine on 12 November 2026.
- Record updated
- 19 August 2026