Prophylactic Phenobarbital After Resolution of Neonatal Seizures

描述(由申请人提供)：新生儿癫痫发作解决后的预防性苯巴比妥(Phe-NO)新生儿癫痫发作解决后，婴儿使用抗癫痫药物的治疗是高度可变和有争议的。婴儿通常在癫痫发作缓解后使用苯巴比妥治疗，以防止复发。缺乏支持这一做法的数据，但动物模型表明，新生儿的大脑容易反复癫痫发作。然而，发育中的大脑长期暴露在苯巴比妥中可能会产生有害的后果。我们建议进行一项多中心随机临床试验(RCT)，以确定继续使用苯巴比妥治疗是否在不对神经发育结果产生不利影响的情况下减少癫痫复发，或者如果不给予预防性药物，婴儿的结果是否得到改善。我们将确定从第一周开始癫痫发作并在7天内消失的婴儿，并随机选择他们在四个月内每天接受苯巴比妥或安慰剂治疗。通过前六个月的探访和频繁的电话联系，我们将确定癫痫复发的比率。主要结果，神经发育状况，将在18-22个月时使用贝利婴儿发育量表进行评估。还计划进行其他亚组分析，以确定癫痫病因对结果的贡献以及初始脑电分类的预测价值。试验将在18个地点进行，选择这些地点是因为他们在这一特定人群中的注册和保留方面的经验和经过证明的记录。这项试验将由罗切斯特大学的临床试验协调中心协调，并由一个指导委员会监督，该委员会由代表新生儿学和儿科神经病学、生物统计学和临床试验管理的经验丰富的试验专家组成。从儿童热性癫痫发作后苯巴比妥预防的随机对照试验结果推断，苯巴比妥可能会对大脑发育产生不利影响，在预防癫痫发作方面可能无效。基于这一导致实践中几乎普遍变化的先前随机对照试验(在单纯性发热性癫痫发作后取消长时间使用苯巴比妥)，我们预计我们产生的数据可能对新生儿癫痫发作婴儿的护理标准产生类似的影响。 与公共卫生相关：婴儿癫痫发作停止后用药治疗的情况非常不同。没有人知道继续使用苯巴比妥治疗几个月是有益的还是有害的。这项临床试验旨在帮助回答这个问题，并提供有助于确定这些儿童的护理标准的数据。

DESCRIPTION (provided by applicant): Prophylactic Phenobarbital after Resolution of Neonatal Seizures (PRO-PHE-NO) The treatment of infants with antiepileptic medications after the resolution of neonatal seizures is highly variable and controversial. Infants are commonly treated with phenobarbital after their seizures have resolved to prevent recurrence. Data to support this practice are lacking but animal models suggest that the neonatal brain is vulnerable to repeated seizures. Yet exposure of the developing brain to phenobarbital for prolonged periods may have deleterious consequences. We are proposing a multi- center, randomized, clinical trial (RCT) to determine if continued treatment with phenobarbital reduces seizure recurrence without adversely affecting neurodevelopmental outcome or if infants' outcomes are improved if no prophylactic medication is given. We will identify infants with seizures beginning in the first week that resolve within 7 days and randomize them to receive phenobarbital or placebo daily for four months. Via visits and frequent telephone contacts over the first six months, we will determine the rate of seizure recurrence. The primary outcome, neurodevelopmental status, will be assessed at 18-22 months using the Bayley Scales of Infant Development. Additional subgroup analyses are planned to determine the contribution of seizure etiology to outcome and predictive value of initial EEG classification. The trial will be conducted at 18 sites, chosen for their experience and proven track record for enrollment and retention in this specific population. The trial will be coordinated by the Clinical Trials Coordination Center at the University of Rochester and overseen by a Steering Committee composed of experienced trialists representing neonatology and pediatric neurology, biostatistics, and clinical trial administration. Extrapolation from the results of an RCT of phenobarbital prophylaxis after febrile seizures in children suggests that phenobarbital may adversely affect brain development and may be ineffective in preventing seizures. Based on this previous RCT that resulted in near universal change in practice (the elimination of prolonged use of phenobarbital after simple febrile seizures), we anticipate that the data we generate may have a similar impact on standard of care for infants with neonatal seizures. PUBLIC HEALTH RELEVANCE: The treatment of infants with medications after their seizures have stopped is very variable. No one knows if continuing treatment with phenobarbital for up to several months is helpful or harmful. This clinical trial is designed to help answer that question and provide data that will help determine standard of care for these children.