University of Washington, Seattle, WA, USA.
Neurology. 2010 Mar 2;74(9):714-20. doi: 10.1212/WNL.0b013e3181d1cd4c. Epub 2010 Jan 20.
To evaluate the efficacy and safety of adjunctive topiramate (sprinkle capsules or oral liquid) in reducing daily rates of partial-onset seizures (POS) in infants with refractory POS.
In this double-blind, placebo-controlled, parallel-group, international study, infants (n = 149) with clinical or EEG evidence of refractory POS were randomly allocated (1:1:1:1) to receive adjunctive topiramate 5, 15, or 25 mg/kg/d or placebo for 20 days. The primary variable was the median percentage reductions in daily POS rate from baseline to final assessment as recorded on a 48-hour video-EEG.
Of the 149 infants (mean age 12 months) included in the intent-to-treat analysis set, 130 completed the study. Median percentage reduction from baseline in daily POS rate was not significantly different (p = 0.97) between topiramate 25 mg/kg (20.4%) and placebo (13.1%). Lower doses were not formally tested, but nominal p values for comparisons with placebo were not significant (15-mg/kg/d dose: p = 0.97; 5-mg/kg/d dose: p = 0.91). Treatment-emergent fever, diarrhea, vomiting, anorexia, weight decrease, somnolence, and viral infection occurred more frequently (> or = 10% difference) with topiramate than with placebo.
In infants aged 1-24 months, topiramate 5, 15, or 25 mg/kg/d was not effective as adjunctive treatment for refractory partial-onset seizures. No new safety concerns associated with topiramate use were noted.
This interventional study provides Class I evidence that topiramate 5, 15, or 25 mg/kg/d compared with placebo does not significantly reduce seizure rates in infants aged 1 month to 2 years with refractory partial-onset seizures.
评估添加托吡酯(撒粉胶囊或口服液)辅助治疗耐药性部分发作性癫痫(POS)患儿的疗效和安全性。
在这项双盲、安慰剂对照、平行分组、国际研究中,将有临床或 EEG 证据显示耐药性 POS 的婴儿(n=149)随机分为(1:1:1:1)接受添加托吡酯 5、15 或 25mg/kg/d 或安慰剂治疗 20 天。主要变量是从基线到最终评估记录的 48 小时视频-EEG 上每日 POS 率的中位数百分比降低。
在意向治疗分析组的 149 名婴儿(平均年龄 12 个月)中,有 130 名完成了研究。每日 POS 率从基线的中位数百分比降低在托吡酯 25mg/kg(20.4%)和安慰剂之间无显著差异(p=0.97)。较低剂量未进行正式测试,但与安慰剂相比,名义 p 值无显著差异(15mg/kg/d 剂量:p=0.97;5mg/kg/d 剂量:p=0.91)。与托吡酯相比,发热、腹泻、呕吐、厌食、体重减轻、嗜睡和病毒感染更频繁(>或=10%差异)。
在 1-24 个月大的婴儿中,托吡酯 5、15 或 25mg/kg/d 作为耐药性部分发作性癫痫的辅助治疗无效。未发现与托吡酯使用相关的新安全性问题。
这项干预性研究提供了 I 级证据,表明与安慰剂相比,托吡酯 5、15 或 25mg/kg/d 不会显著降低 1 个月至 2 岁耐药性部分发作性癫痫患儿的癫痫发作频率。