Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 770
- 试验地点
- 85
- 主要终点
- Termination of SE
研究概览
简要总结
The goal of this clinical trial is to determine if treatment of patients with two doses of ketamine plus levetiracetam versus levetiracetam alone leads to more effective control of status epilepticus.
详细描述
KESETT is a multicenter, randomized, blinded study to determine whether adding 1 mg/kg or 3 mg/kg dose of KET to 60 mg/kg LEV can terminate status epilepticus (SE) in a larger fraction of subjects with benzodiazepine-refractory SE than those treated with LEV (60 mg/kg) alone.
The primary outcome is termination of SE from 15 minutes after starting the study drug infusion, sustained until 60 minutes from enrollment without using additional anti-seizure medication. Termination of SE is determined by (1) improving consciousness and absence of clinically apparent seizures at 60 minutes or (2) absence of any electrographic SE after 15 minutes in those with EEG monitoring and no improvement in consciousness.
Secondary objectives include determining the relative safety of the treatment arms on defined safety outcomes and all adverse events, analysis of secondary/exploratory efficacy outcomes, and evaluation of both effectiveness and safety in the pediatric subpopulation.
The trial will initially allocate subjects equally (1:1:1) for the first 350 participants (burn-in period) before transitioning to response-adaptive randomization. Interim analyses will be conducted for efficacy and futility beginning when 350 subjects have been randomized, and will occur every 100 subjects thereafter. A maximum of 770 participants will be enrolled.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient was witnessed to have a convulsive seizure for greater than 5-minute duration
- •The patient received an adequate dose of benzodiazepines. The doses may be divided.
- •The last dose of a benzodiazepine was administered 5-30 minutes before study drug administration.
- •Continued or recurring seizures in the Emergency Department.
- •Age 1 years or older
- •Known or estimated weight ≥10 Kg
排除标准
- •Known pregnancy
- •Opt-out identification or otherwise known to be previously enrolled in KESETT
- •Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital, or other agents defined in the MoP) for this episode of SE
- •Treatment with sedatives with anticonvulsant properties other than benzodiazepines for this episode of SE(propofol, etomidate, ketamine or other agents defined in the MoP)
- •Endotracheal intubation prior to enrollment
- •Acute traumatic brain injury clearly precedes seizures
- •Scalp injury or burn preventing EEG placement
- •Known allergy or other known contraindication to KET or LEV
- •Hypoglycemia < 50 mg/dL
- •Hyperglycemia > 400 mg/dL
- •Cardiac arrest / post-anoxic seizures
研究组 & 干预措施
Levetiracetam
Levetiracetam (LEV) (60 mg/Kg)
干预措施: Levetiracetam (LEV) (60 mg/Kg) (Drug)
Levetiracetam + high dose Ketamine
LEV 60 mg/mL + 3 mg/mL KET increasing up to a weight of 75 kg
干预措施: Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET) (Drug)
Levetiracetam + low dose Ketamine
LEV 60 mg/mL + 1 mg/mL KET
干预措施: Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET) (Drug)
结局指标
主要结局
Termination of SE
时间窗: From 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication.
Termination of SE from 15 minutes after starting the study drug infusion, sustained for 60 minutes without using additional anti-seizure medication. Termination of SE is determined by (1) improving consciousness and absence of clinically apparent seizures at 60 minutes or (2) absence of any electrographic status epilepticus (ESE) after 15 minutes in those with EEG monitoring and no improvement in consciousness.
次要结局
- Desirability of response (DOOR) outcome(60 minutes after starting the study drug infusion)
- Endotracheal intubation(Within 60 minutes after start of the study drug infusion)
- ICU duration(Up to 30 days after enrollment)
- Hospital length-of-stay (LOS)(Up to 30 days after enrollment)
- Late recurrent seizure(Between 60 minutes and 4 hours after the start of the study drug infusion)
- Time to termination of seizures(From the start of infusion of study drug to the cessation of electrographic seizure assessed up to 60 minutes from study drug initiation)
- Late seizures after requiring an anesthetic(Between 60 minutes and 24 hours after start of study drug infusion)
- All cause mortality(From the start of study drug infusion to hospital discharge or day 30)
研究者
Jaideep Kapur, MD
Eugene Meyer III Professor of Neuroscience and Professor of Neurology
University of Virginia