Chiron Catherine, Tonnelier Sylvie, Rey Elisabeth, Brunet Marie-Lucie, Tran Agnes, d'Athis Philippe, Vincent Jean, Dulac Olivier, Pons Gerard
INSERM U663, Service de Neurologie et Metabolisme, Hôpital Necker-Enfants Malades, 149 Rue de Sevres, F-75015 Paris, France.
J Child Neurol. 2006 Jun;21(6):496-502. doi: 10.1177/08830738060210062101.
Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P < .025). Twelve patients experienced at least one adverse event on stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.
司替戊醇是一种新型抗癫痫药物，可抑制细胞色素P450酶，在一项针对儿童难治性部分性癫痫的开放性试验中，它与卡马西平联合使用时显示出一定疗效。我们的目的是在一项安慰剂对照试验中验证这些结果。为了限制纳入的患者数量，我们采用了富集和撤药设计。在1个月单盲安慰剂基线期后进行的为期4个月的司替戊醇开放性添加研究中纳入的67名儿童中，32名有反应者被随机分组，接受2个月的治疗，其中17名继续使用司替戊醇，15名撤药改用安慰剂。如果随机分组后癫痫发作次数与基线相比增加至少50%，患者退出试验（主要终点）：继续使用司替戊醇的患者中有6名，使用安慰剂的患者中有8名（无统计学意义）。然而，与基线相比癫痫发作频率降低（次要终点），使用司替戊醇的患者（-75%）比使用安慰剂的患者（-22%）更显著（P<0.025）。12名使用司替戊醇的患者（71%）至少经历了一次不良事件，而使用安慰剂的患者有4名（27%）；均无严重不良事件报告。尽管出于伦理原因，根据本研究选择的作为主要终点的退出标准，司替戊醇与卡马西平联合使用未能显示出显著影响，但该联合用药被证明可降低儿童难治性部分性癫痫的发作频率。
