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的治疗。目前的治疗方法效果不佳，副作用很大。左乙拉西坦(LEV)具有治疗新生儿癫痫的潜力，但未被批准用于2岁以下儿童。本研究旨在获得有关左乙拉西坦在这一脆弱和研究不足人群中的有效性和安全性的数据，并同时开发有助于癫痫发作检测和研究的脑电图仪(EEG)监测系统。 其具体目的是：1)确定静脉注射作为一线治疗时终止新生儿癫痫发作的疗效。2)通过研究额外剂量在无反应者中的额外疗效来获得剂量递增数据。3)获得更多的药代动力学数据，以证实我们先前的药代动力学研究结果。4)进一步获得左乙拉西汀在新生儿中的安全性数据。5)证明远程集中实施的可行性 通过互联网监测新生儿重症监护病房(NICU)的连续脑电图仪(EEG)监测，并测试自动化新生儿癫痫检测算法。 建议的研究设计为2期随机、盲法对照研究。被确定为有新生儿癫痫风险的受试者将被招募，并将获得同意。将使用持续的脑电监测来检测癫痫发作。该项目将通过互联网远程集中审查来自6个不同新生儿病房的连续视频脑电监测。如果检测到癫痫发作，受试者将按6：4的比例随机接受左乙拉西汀(40 mg/kg)或苯巴比妥(PHB)(20 mg/kg)。如果负荷结束时仍有明显的心电图癫痫发作或复发，新生儿将根据治疗臂的不同，再接受20 mg/kg负荷的左乙拉西汀或10 mg/kg负荷的苯巴比妥。研究的主要终点将是左乙拉西汀治疗后的癫痫停止率。将获得临床和实验室安全数据以及药代动力学数据。将评估远程连续脑电监测系统的功能，并将自动癫痫检测器的性能与两名经验丰富的新生儿脑图师的判读进行比较。

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.