Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia
Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
BMJ Open. 2021 May 10;11(5):e043488. doi: 10.1136/bmjopen-2020-043488.
Stroke is a common cause of epilepsy that may be mediated via glutamate dysregulation. There is currently no evidence to support the use of antiseizure medications as primary prevention against poststroke epilepsy. Perampanel has a unique antiglutamatergic mechanism of action and may have antiepileptogenic properties. This study aims to evaluate the efficacy and safety of perampanel as an antiepileptogenic treatment in patients at high risk of poststroke epilepsy.
Up to 328 patients with cortical ischaemic stroke or lobar haemorrhage will be enrolled, and receive their first treatment within 7 days of stroke onset. Patients will be randomised (1:1) to receive perampanel (titrated to 6 mg daily over 4 weeks) or matching placebo, stratified by stroke subtype (ischaemic or haemorrhagic). Treatment will be continued for 12 weeks after titration. 7T MRI will be performed at baseline for quantification of cerebral glutamate by magnetic resonance spectroscopy and glutamate chemical exchange saturation transfer imaging. Blood will be collected for measurement of plasma glutamate levels. Participants will be followed up for 52 weeks after randomisation.The primary study outcome will be the proportion of participants in each group free of late (more than 7 days after stroke onset) poststroke seizures by the end of the 12-month study period, analysed by Fisher's exact test. Secondary outcomes will include time to first seizure, time to treatment withdrawal and 3-month modified Rankin Scale score. Quality of life, cognitive function, mood and adverse events will be assessed by standardised questionnaires. Exploratory outcomes will include correlation between cerebral and plasma glutamate concentration and stroke and seizure outcomes.
This study was approved by the Alfred Health Human Research Ethics Committee (HREC No 44366, Reference 287/18).
ACTRN12618001984280; Pre-results.
中风是癫痫的常见病因，其可能通过谷氨酸失调介导。目前尚无证据支持使用抗癫痫药物作为中风后癫痫的一级预防。吡仑帕奈具有独特的抗谷氨酸作用机制，可能具有抗癫痫发生的特性。本研究旨在评估吡仑帕奈作为皮质性缺血性中风或大脑半球出血后癫痫高危患者的抗癫痫发生治疗的疗效和安全性。
多达 328 名皮质性缺血性中风或大脑半球出血患者将被纳入研究，并在中风发作后 7 天内接受首次治疗。患者将按 1:1 随机分为吡仑帕奈（4 周内滴定至 6 毫克/天）或匹配安慰剂组，按中风亚型（缺血性或出血性）分层。滴定后将继续治疗 12 周。基线时将进行 7T MRI 以通过磁共振波谱和谷氨酸化学交换饱和传递成像定量测定脑内谷氨酸。将采集血液以测量血浆谷氨酸水平。参与者将在随机分组后随访 52 周。主要研究终点为在 12 个月研究期间结束时，各组中无晚期（中风发作后 7 天以上）中风后发作的参与者比例，通过 Fisher 精确检验进行分析。次要终点包括首次发作时间、治疗停药时间和 3 个月改良 Rankin 量表评分。通过标准问卷评估生活质量、认知功能、情绪和不良事件。探索性终点包括脑内和血浆谷氨酸浓度与中风和癫痫结局的相关性。
本研究得到了阿尔弗雷德健康人体研究伦理委员会（HREC No 44366，参考 287/18）的批准。
ACTRN12618001984280；预结果。
