Established Status Epilepticus Treatment Trial (ESETT) - SDMC

描述(申请人提供)：苯二氮卓-难治性癫痫持续状态(ESE)是一种相对常见的紧急情况，有几种广泛使用的治疗方法。目前还没有对照的、随机的、盲目的临床试验来比较目前可用的ESE治疗的有效性和耐受性。该应用程序和随附的统计和数据管理中心(SDMC)应用程序描述了ESE治疗试验(ESETT)，该试验旨在通过比较三种药物：磷苯妥因(FOS)、左乙拉西坦(LEV)和丙戊酸(VPA)来确定在两年以上的患者中治疗ESE的最有效和/或最无效的治疗方法。这是一项多中心、随机、双盲、贝叶斯适应性、第三阶段比较有效性试验。最初将对多达795名患者进行1：1：1的随机化，在招募了300名患者后，将进行响应自适应随机化。随机化将按三个年龄组进行分层，2-18岁，19-65岁，66岁及以上。主要结果是停止临床癫痫发作活动和改善精神状态，在服用研究药物60分钟后没有严重不良反应或进一步干预。每个科目都将被跟踪，直到出院或从入学起30天。这项试验将包括对早期成功和无效的中期分析。对于任何治疗，如果一种治疗最有效的概率大于0.975或一种治疗最不有效的概率大于0.975，该试验将被认为是成功的。这将是ESE在儿童和成人中的第一次III期临床试验。

DESCRIPTION (provided by applicant): Benzodiazepine-refractory status epilepticus (Established Status Epilepticus, ESE) is a relatively common emergency condition with several widely used treatments. There are no controlled, randomized, blinded clinical trials to compare the efficacy and tolerability of currently available treatments of ESE. This and the accompanying Statistical and Data Management Center (SDMC) application describe the ESE treatment trial (ESETT), which is designed to determine the most effective and/or the least effective treatment of ESE among patients older than two years by comparing three arms: fosphenytoin (FOS), levetiracetam (LEV), and valproic acid (VPA). This is a multicenter, randomized, double-blind, Bayesian adaptive, Phase III comparative effectiveness trial. Up to 795 patients will be randomized initially 1:1:1 and response-adaptive randomization will occur after 300 patients have been recruited. Randomization will be stratified by three age groups, 2-18, 19-65, and 66 years and older. The primary outcome measure is cessation of clinical seizure activity and improving mental status, without serious adverse effects or further intervention at 60 min after administration of study drug. Each subject will be followed until discharge or 30 days from enrollment. This trial will include interim analyses for early success and futility. This trial wil be considered a success if the probability that a treatment is the most effective is greater than 0.975 or the probability that a treatment is the least effective is greater than 0.975 for any treatment. This will be the first phase III clinical trial of ESE in children and adults.