Established Status Epilepticus Treatment Trial (ESETT) - SDMC

描述（由申请人提供）：苯二氮卓类难治性癫痫持续状态（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。没有对照、随机、盲法临床试验来比较目前可用的ESE治疗的疗效和耐受性。本申请和随附的统计和数据管理中心（SDMC）申请描述了ESE治疗试验（ESETT），该试验旨在通过比较三组（磷苯妥英（FOS）、左乙拉西坦（LEV）和丙戊酸（VPA））来确定2岁以上患者中最有效和/或最无效的ESE治疗。这是一项多中心、随机、双盲、贝叶斯自适应、III期比较有效性试验。最初将以1：1：1的比例对最多795例患者进行随机化，招募300例患者后将进行缓解适应性随机化。随机化将按3个年龄组分层，2-18岁、19-65岁和66岁及以上。主要结局指标为研究药物给药后60分钟临床癫痫发作活动停止和精神状态改善，无严重不良反应或进一步干预。将对每例受试者进行随访，直至出院或入组后30天。本试验将包括早期成功和无效的中期分析。对于任何治疗，如果治疗最有效的概率大于0.975或治疗最无效的概率大于0.975，则认为本试验成功。这将是ESE在儿童和成人中的第一个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.