Efficacy and Safety of Perampanel in the Treatment of Refractory Status Epilepticus
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Primary Outcomes
研究概览
简要总结
This project is aiming to better understand the use of perampanel as an appropriate standard-of-care therapy for treatment refractory status epilepticus (RSE), to identify determinants of outcomes, and establish safety. The study will recruit 25 patients at WSU. The study will last for about 96 weeks and will involve a screening visit and two in clinic visits at 3 and 6 months. If the subjects give written informed consent and meet all eligibility criteria they will be clinically evaluated and will be given the study drug. This study will involve recording of patients medical history, drug history and epilepsy history. A physical exam and a and neurological exam will also be performed to study the heath status of the participant. Results and patient information will be stored in a database for analysis to find commonality among key factors that have been seen in past research.
详细描述
ILAE (International league against epilepsy) defines status epilepticus (SE) as generalized tonic-clonic seizures > 5 minutes or focal impaired awareness seizure > 15 min or recurrent seizures with alteration of consciousness in between seizures.
Refractory status epilepticus (RSE) is defined as failure to respond to first line benzodiazepines and one antiepileptic drug (AED). It often requires treatment with anesthetic drugs and continuous EEG monitoring for diagnosis and titration of medications. Status epilepticus (SE) is estimated to be refractory in about 30 % of cases, associated with increased morbidity and mortality and requires continuous EEG monitoring to guide treatment [1]. It is seen across all ages, and around 200,000 cases are seen in the United States annually resulting in significant morbidity and mortality [2]. Morbidity and mortality of SE and especially RSE is due to prolonged stay in the ICU and at times treatment from IV anesthetics including hemodynamic instability, and related infections of the ICU stays.
Standard of Care treatment of SE and RSE
Rapid termination of the SE is the primary goals of SE treatment with evidence indicating that if left untreated, SE becomes harder to terminate [3,4]. In a patient with SE, the first AED should be started at the onset concomitantly with the first line benzodiazepine or soon after. The agents of choice are typically those available in IV (intravenous) formulation with purpose of fast and safe administration in a seizing patient. These include phenytoin (PHT)/fosphenytoin, valproic acid (VPA), levetiracetam (LEV); lacosamide (LCM) with no clear evidence that one drug is superior [5,6]. Beyond the introduction of a second seizure medication, there is no unified consensus or clear evidence to guide treatment at that stage of RSE.
Other AED are used as add-on therapy in the treatment of SE when benzodiazepine (1st agent) and IV AED (2nd agent) fail. These have been demonstrated to be efficacious in different cohorts and case series and include but not limited to clobazam, topiramate, oxcarbazepine and eslicarbazepine [7].
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults patients equal or greater than 18 years
- •Patients in RSE that require IV anesthetic infusions. Note: RSE is defined as status epilepticus that fails to terminate after an adequate dose of benzodiazepines (1st line agents) and an AED (2nd line agent). Adequate doses have been defined in the screening (below).
- •Patients taking oral contraception who will be on the study long term should be informed about additional alternative methods of contraception.
排除标准
- •Childbearing potential female who has a positive pregnancy test result or is otherwise known to be pregnant. Hypoglycemia or hyperglycemia induced seizures
- •Mild, moderate or severe hepatic impairment
- •Severe renal impairment or on hemodialysis
- •History of psychiatric illness or suicidal behavior/ideation
- •Previous or current use of PMP
- •Known severe allergy to any AED
- •Anoxic brain injury as etiology of status epilepticus
- •Use caution in patients taking moderate and strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin)
- •Patients on other forms of strong CYP3A4 (e.g. Rifampin, St John's Wart, etc).
研究组 & 干预措施
Single arm prospective study
- Adults patients equal or greater than 18 years
- Patients in RSE that require IV anesthetic infusions. Note: RSE is defined as status epilepticus that fails to terminate after an adequate dose of benzodiazepines (1st line agents) and an AED (2nd line agent). Adequate doses have been defined in the screening (below).
- Patients taking oral contraception who will be on the study long term should be informed about additional alternative methods of contraception.
干预措施: Perampanel (Drug)
结局指标
主要结局
Primary Outcomes
时间窗: Within 48 hours of stopping intravenous anesthetics
Successful wean of IV anesthetics without recurrence of status epilepticus. a. Determined by absence of clinical and electrographic seizure activity.
次要结局
- 5. Mortality rate(ICU and hospital discharge)
- Secondary Outcomes(3 months and 6 months)
- 3. The number of antiseizure medications used.(90 Days)
- 3. Total duration of intubation(90 days)
- 7. Favorable outcome(Hospital discharge, 3 months, 6 months)
- Seizure Control(Determined by percentages of the patients that do not experience seizure recurrence)
- 2. Total duration of intravenous anesthetic infusion.(90 Days)
- 6. Functional impairment(Hospital discharge, 3 months, 6 months)
- Total ICU and in-hospital length of stay(90 days)
- 8. Favorable discharge location(Hospital discharge)
研究者
Maysaa Basha
Principle Investigator
Wayne State University