A Multicenter, Randomized, Blinded, Comparative Effectiveness Study of Fosphenytoin, Valproic Acid, or Levetiracetam in the Emergency Department Treatment of Patients With Benzodiazepine-refractory Status Epilepticus.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 478
- 试验地点
- 65
- 主要终点
- Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat
研究概览
简要总结
The primary objective is to determine the most effective and/or the least effective treatment of benzodiazepine-refractory status epilepticus (SE) among patients older than 2 years. There are three active treatment arms being compared: fosphenytoin (FOS),levetiracetam (LEV), and valproic acid (VPA).
The second objective is comparison of three drugs with respect to secondary outcomes.
The final objective is to ensure that the trial is informative for treatment of established SE in children by describing the effectiveness, safety, and rate of adverse reactions of these drugs in children.
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
- Triple (Participant, Investigator, 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
- •Patient witnessed to seize for greater than 5 minute duration prior to treatment with study drug; Patient received adequate dose of benzodiazepines. The last dose of a benzo was administered in the 5-30 minutes prior to study drug administration. The doses may be divided.; continued or recurring seizure in the Emergency Department; Age 2 years or older
排除标准
- •Known pregnancy; Prisoner; Opt-out identification; 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 (propofol, etomidate, ketamine or other agents defined in the MoP); Endotracheal intubation; Acute traumatic brain injury; Known metabolic disorder; Known liver disease; Known severe renal impairment; Known allergy or other known contraindication to FOS, PHT, LEV, or VPA; Hypoglycemia < 50 mg/dL; Hyperglycemia > 400 mg/dL; Cardiac arrest and post-anoxic seizures
研究组 & 干预措施
Fosphenytoin (FOS)
Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes.
干预措施: Fosphenytoin (Drug)
Valproic acid
Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes.
干预措施: Valproic acid (Drug)
Levetiracetam
Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes.
干预措施: Levetiracetam (Drug)
结局指标
主要结局
Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat
时间窗: Within 60 minutes after the start of study drug infusion
Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat
Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis
时间窗: Within 60 minutes after the start of study drug infusion
Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. The Adjudicated outcomes analysis is different from Outcome measure 1 because a central clinical phenomenology core of four neurologists adjudicated from the medical records the time to seizure cessation, the time in status epilepticus before trial-drug initiation, and the cause of the seizure. For each enrollment, two neurologists from this core group conducted independent initial reviews and then determined a consensus or consulted a third adjudicator, as needed. Adjudicators were unaware of the treatment assignments and made determinations by medical record review.
Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis
时间窗: Within 60 minutes after the start of study drug infusion
Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis
次要结局
- Number of Participants With Admission to Intensive Care Unit(Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient)
- Length of ICU Stay(number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study)
- Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success(start of drug infusion to seizure cessation)
- Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success(within 20 minutes)
- Length of Hospital Stay(length of hospital stay)
研究者
Jaideep Kapur, MD
Professor of Neurology and Neuroscience
University of Virginia