Febrile Infection-Related Epilepsy Syndrome (FIRES), New Onset Refractory Status Epilepticus, New-Onset Refractory Status Epilepticus
Conditions
Keywords
refractory status epilepticus, NORSE, FIRES, anakinra, tocilizumab
Brief 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.
Interventions
DRUGAnakinra
SOC will be followed , Suggested Dose: 10 mg/kg/day IV, divided into 4 daily doses (q6h) Maximum dose: 400 mg/day
DRUGTocilizumab
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
OTHERStandard 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.
Sponsors
Yale University
Patient-Centered Outcomes Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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: 1. 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. 2. Includes patients with any RSE, not just super-refractory SE. 3. 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glasgow Outcome Scale - Extended (GOS-E) | 12 months | The Glasgow Outcome Scale - Extended (GOS-E) is an 8-point scale used to measure global functional outcome. Participants are scored into one of the 8 categories: 1. Death, 2. Vegetative State, 3. Lower Severe Disability, 4. Upper Severe Disability, 5. Lower Moderate Disability, 6. Upper Moderate Disability, 7. Lower Good Recovery, 8. Upper Good Recovery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to resolution of status epilepticus (SE) | 24 hours off anesthetic drips | Time (days) until discontinuation of anesthetic drips for 24h for the treatment of SE with no return of SE on EEG |
| Hospital length of stay | 12 months | Mean number of days during hospitalization from admission to discharge |
| Mortality | up to 12 months | Mortality, number of participants |
| Number of serious adverse events attributed to anakinra or tocilizumab | From hospitalization to 1 month after stopping treatment, up to 12 months | Number of serious adverse events attributed to anakinra or tocilizumab |
| Number of participants Post-NORSE epilepsy | 12 months | Number of participants with any unprovoked seizures after hospital discharge |
| Number of participants with Treatment success | 12 months | Combined measure of lack of need for another immunomodulator after the study drug was begun, plus good outcome at 1 year (GOS-E of 5-8) (Yes/No) |
Countries
Canada, France, Italy, South Korea, Sweden, United Kingdom, United States
Contacts
CONTACTCamalene Chrysostoum
CONTACTTara McPartland
PRINCIPAL_INVESTIGATORLawrence Hirsch, MD
Yale University
Outcome results
None listed