Prophylactic Phenobarbital After Resolution of Neonatal Seizures

描述（由申请人提供）：新生儿癫痫发作消退后预防性苯巴比妥（PRO-PHE-NO）新生儿癫痫发作消退后使用抗癫痫药物治疗婴儿的差异很大，存在争议。婴儿通常在癫痫发作消退后用苯巴比妥治疗，以防止复发。支持这种做法的数据缺乏，但动物模型表明，新生儿的大脑容易受到反复发作。然而，发育中的大脑长时间暴露于苯巴比妥可能会产生有害的后果。我们正在提出一项多中心、随机、临床试验（RCT），以确定继续使用苯巴比妥治疗是否会减少癫痫复发而不会对神经发育结果产生不良影响，或者如果不给予预防性药物，婴儿的结局是否会改善。我们将确定在第一周内开始癫痫发作并在7天内消退的婴儿，并将他们随机分为每天接受苯巴比妥或安慰剂治疗，持续4个月。通过前六个月的访问和频繁的电话联系，我们将确定癫痫复发率。主要结局，神经发育状态，将在18-22个月时使用贝利婴儿发育量表进行评估。计划进行额外的亚组分析，以确定癫痫病因对结果的贡献和初始EEG分类的预测价值。本试验将在18家研究中心进行，选择这些研究中心是因为其在该特定人群中的入组和保留方面的经验和良好记录。本试验将由罗切斯特大学临床试验协调中心协调，并由指导委员会监督，指导委员会由经验丰富的临床试验专家组成，代表神经病学和儿科神经病学、生物统计学和临床试验管理。从儿童热性惊厥后苯巴比妥预防的RCT结果推断，苯巴比妥可能对大脑发育产生不良影响，并且可能对预防惊厥无效。基于这一导致实践中几乎普遍变化（消除单纯性热性惊厥后长期使用苯巴比妥）的既往RCT，我们预计我们生成的数据可能对新生儿惊厥婴儿的护理标准产生类似的影响。 公共卫生相关性：婴儿癫痫发作停止后的药物治疗非常多变。没有人知道持续几个月的苯巴比妥治疗是有益还是有害。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.