Department of Paediatric Neurology, Starship Children's Health, Auckland, New Zealand.
Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California.
Pediatrics. 2020 Jun;145(6). doi: 10.1542/peds.2019-3182. Epub 2020 May 8.
There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures.
The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists.
Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam ( < .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant).
In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.
目前，美国食品和药物管理局尚未批准用于新生儿癫痫的治疗方法。苯巴比妥和苯妥英通常无法控制癫痫发作。人们对发育中的大脑中抗癫痫药物的安全性存在担忧。左乙拉西坦在老年患者中已被证实具有疗效和良好的安全性，因此，人们对其在新生儿中的应用非常感兴趣。但是，尚未进行随机研究。我们的目的是研究左乙拉西坦与苯巴比妥相比作为新生儿癫痫一线治疗的疗效和安全性。
该研究是一项多中心、随机、双盲、对照、Ⅱb 期临床试验，旨在研究左乙拉西坦与苯巴比妥相比作为任何病因新生儿癫痫的一线治疗的疗效和安全性。主要结局指标是通过 2 位神经生理学家对 EEG 进行独立评估，评估 24 小时内完全无癫痫发作的情况。
随机分配至苯巴比妥组的 80%（24/30）的患者在 24 小时内保持无癫痫发作，而随机分配至左乙拉西坦组的患者为 28%（15/53）（<.001；相对风险 0.35[95%置信区间：0.22-0.56]；修改后的意向治疗人群）。左乙拉西坦剂量从 40mg/kg 增加到 60mg/kg 可使疗效提高 7.5%。随机分配至苯巴比妥组的患者出现更多不良反应（但无统计学意义）。
在这项Ⅱb 期研究中，苯巴比妥治疗新生儿癫痫的效果优于左乙拉西坦。苯巴比妥治疗组的不良反应发生率较高。需要进一步研究左乙拉西坦的高剂量，并需要进行长期结局评估的确定性研究。
