Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
Department of Emergency and Critical Care Medicine, Tsukuba University Hospital, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Trials. 2021 May 2;22(1):317. doi: 10.1186/s13063-021-05269-7.
Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE.
This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is "continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance." In both groups, diazepam is initially administered at 1-20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000-3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes.
The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application.
Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019.
癫痫持续状态（SE）是一种紧急情况，迅速且安全地终止癫痫发作非常重要。苯妥英和苯妥英的前体药物磷苯妥英，因其不良反应较轻而被推荐作为二线治疗药物。然而，磷苯妥英会引起严重的不良反应，如低血压和心律失常。左乙拉西坦据报道对 SE 具有相似的疗效和更高的安全性；然而，缺乏其用于成人 SE 的证据。在本研究中，正在进行一项非劣效性设计的多中心随机对照试验（RCT），以比较地西泮后左乙拉西坦与磷苯妥英作为 SE 的二线治疗。
这项多中心、前瞻性、开放标签 RCT 在急诊科进行。2019 年 12 月 23 日至 2023 年 3 月 31 日，将 176 名送往急诊室的惊厥性 SE 患者随机分为磷苯妥英组和左乙拉西坦组，比例为 1:1。SE 的定义为“持续发作超过 5 分钟或离散发作超过 2 分钟并伴有意识障碍”。在两组中，均首先给予地西泮 1-20mg，然后给予静脉注射磷苯妥英 22.5mg/kg 或静脉注射左乙拉西坦 1000-3000mg。主要结局是 30min 内的癫痫发作停止率。24h 内癫痫复发、严重不良事件和 24h 内插管率为次要结局。
本研究经日本急救医学协会批准并作为一项倡议性研究进行。如果确定非劣效性，该协会将通过公开知识应用程序，为 SE 的左乙拉西坦申请国民健康保险覆盖范围。
日本临床试验注册中心 jRCTs031190160。注册于 2019 年 12 月 13 日。
