Comparing the Effects of Anakinra and Tocilizumab on Outcomes in Patients With New-Onset Refractory Status Epilepticus
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 438
- 试验地点
- 61
- 主要终点
- Glasgow Outcome Scale - Extended (GOS-E)
研究概览
简要总结
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:
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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 .
干预措施: Standard medical treatment (Other)
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)
干预措施: Tocilizumab (Drug)
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)
干预措施: Anakinra (Drug)
结局指标
主要结局
Glasgow Outcome Scale - Extended (GOS-E)
时间窗: 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.
Glasgow Outcome Scale - Extended (GOS-E)
时间窗: 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.
次要结局
- Number of participants Post-NORSE epilepsy(12 months)
- Number of serious adverse events attributed to anakinra or tocilizumab(From hospitalization to 1 month after stopping treatment, up to 12 months)
- Number of participants with Treatment success(12 months)
- Time to resolution of status epilepticus (SE)(24 hours off anesthetic drips)
- Hospital length of stay(12 months)
- Time to resolution of status epilepticus (SE)(24 hours off anesthetic drips)
- Hospital length of stay(12 months)
- Mortality(up to 12 months)
- Number of serious adverse events attributed to anakinra or tocilizumab(From hospitalization to 1 month after stopping treatment, up to 12 months)
- Number of participants Post-NORSE epilepsy(12 months)
- Number of participants with Treatment success(12 months)
研究者
Lawrence Hirsch
Professor of Neurology
Yale University