Phase 2 Study of Levetiracetam for Neonatal Seizures

描述（由申请人提供）： 该项目旨在改善新生儿癫痫发作的治疗。目前的治疗方法效果不佳，而且有明显的副作用。左乙拉西坦（LEV）具有治疗新生儿癫痫发作的潜力，但未被批准用于2岁以下的儿童。本研究旨在获得左乙拉西坦在这一脆弱和研究不足的人群中的有效性和安全性数据，并同时开发脑电图（EEG）监测系统，以促进癫痫发作的检测和研究。 具体目的是：1）确定静脉注射作为一线治疗终止新生儿癫痫发作的疗效。2)通过研究额外剂量在无应答者中的额外疗效获得剂量递增数据。3)获得额外的药代动力学数据，以证实我们既往药代动力学研究的结果。4)获得左乙拉西坦在新生儿中的进一步安全性数据。5)证明集中式远程的可行性 通过互联网监测新生儿重症监护室（NICU）中的连续脑电图（EEG）监测，并测试自动新生儿癫痫发作检测算法。 拟定的研究设计是一项II期、随机化、设盲、对照研究。将招募被确定为有新生儿癫痫发作风险的受试者并获得知情同意。 将使用连续EEG监测来检测癫痫发作。本项目将通过互联网对来自6个不同新生儿病房的连续视频EEG监测进行远程集中审查。如果检测到癫痫发作，受试者将以6：4的比例随机接受左乙拉西坦（40 mg/kg）或苯巴比妥（PHB）（20 mg/kg）。如果电描记癫痫发作在负荷结束时仍然明显或如果复发，新生儿将根据治疗组接受20 mg/kg负荷的左乙拉西坦或10 mg/kg负荷的苯巴比妥。研究的主要终点将是左乙拉西坦治疗后的癫痫发作停止率。将获得临床和实验室安全性数据以及药代动力学数据。将评估远程连续EEG监测系统的功能，并将自动癫痫发作检测器的性能与两名经验丰富的新生儿脑电图学家的解释进行比较。

DESCRIPTION (provided by applicant): This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects. Levetiracetam (LEV) has potential as a treatment for neonatal seizures but is not approved for use in children less than 2 years of age. This study aims to obtain data regarding the efficacy and safety of levetiracetam in this vulnerable and under researched population, and to simultaneously develop electroencephalograph (EEG) monitoring systems that facilitate seizure detection and research. The specific aims are: 1) To determine the efficacy of intravenous in terminating neonatal seizures when given as first line therapy. 2) To obtain dose escalation data by studying the additional efficacy of an additional dose in non responders. 3) To obtain additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study. 4) To obtain further safety data of levetiracetum in neonates. 5) To prove the feasibility of centralized remote monitoring of continuous electroencephalograph (EEG) monitoring in the neonatal intensive care unit (NICU) via the internet and to test an automated neonatal seizure detection algorithm. The proposed study design is a phase 2, randomized, blinded, controlled study. Subjects identified as being at risk of neonatal seizures will be recruited and consent will be obtained. Continuous EEG monitoring will be used to detect seizures. This project will utilize remote centralized review via the internet of continuous video EEG monitoring from 6 different neonatal units. If seizures are detected, subjects will be randomized in a 6:4 ratio to receive either levetiracetum (40mg/kg) or phenobarbital (PHB) (20mg/kg). If electrographic seizures are still apparent at end of the load or if they recur, the newborn will receive a further 20mg/kg load of levetiracetum or 10mg/kg load of phenobarbital depending on the treatment arm. The primary endpoint studied will be seizure cessation rate following treatment with levetiracetum. Clinical and laboratory safety data and pharmacokinetic data will be obtained. The functionality of the remote continuous EEG monitoring system will be assessed, and the performance of the automated seizure detector will be compared with interpretation by two experienced neonatal encephalographers.