NYU Comprehensive Epilepsy Center, 223 East 34th Street, New York, NY 10016, USA.
Neurology. 2011 May 3;76(18):1555-63. doi: 10.1212/WNL.0b013e3182194bd3. Epub 2011 Mar 30.
To evaluate the efficacy and safety of ezogabine (United States adopted name)/retigabine (international nonproprietary name) (EZG[RTG]) 1,200 mg/day as adjunctive treatment in adults with drug-resistant epilepsy with partial-onset seizures with or without secondary generalization.
RESTORE 1 was a multicenter, randomized, double-blind, parallel-group trial. Following a prospective 8-week baseline phase, patients entered an 18-week double-blind treatment period (6-week forced dose titration to EZG[RTG] 1,200 mg/day in 3 equally divided doses or placebo, followed by a 12-week maintenance phase). Results were analyzed on an intent-to-treat basis for the entire 18-week period and for patients reaching the maintenance phase.
In 306 patients randomized, 305 received EZG(RTG) 1,200 mg/day (n = 153) or placebo (n = 152). Median percent reduction in total partial-seizure frequency was 44.3% vs 17.5% (p < 0.001) for EZG(RTG) and placebo, respectively, during the 18-week double-blind period; responder rates (≥50% reduction in total partial-seizure frequency from baseline) were 44.4% vs 17.8% (p < 0.001). In 256 patients (EZG[RTG], 119; placebo, 137) entering the 12-week maintenance phase, median percent reduction in seizure frequency for EZG(RTG) vs placebo was 54.5% and 18.9% (p < 0.001), respectively; responder rates were 55.5% vs 22.6% (p < 0.001). The proportion of patients discontinuing due to treatment-emergent adverse events (TEAEs) was 26.8% (EZG[RTG]) vs 8.6% (placebo). Dizziness, somnolence, fatigue, confusion, dysarthria, urinary tract infection, ataxia, and blurred vision were the most common TEAEs reported by more patients treated with EZG(RTG) than placebo.
This study demonstrates that EZG(RTG) is effective as add-on therapy for reducing seizure frequency in patients with drug-resistant partial-onset seizures.
This study provides Class II evidence that EZG(RTG) 1,200 mg/day is effective as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.
评估依佐加滨（美国采用的名称）/瑞替加滨（国际非专利名称）（EZG[RTG]）1200mg/天作为伴有或不伴有继发全面性发作的耐药性部分发作性癫痫成人患者的辅助治疗的疗效和安全性。
RESTORE 1 是一项多中心、随机、双盲、平行分组试验。在 8 周前瞻性基线期后，患者进入 18 周双盲治疗期（6 周强制性剂量滴定至 EZG[RTG]1200mg/天，分 3 次等份剂量或安慰剂，随后是 12 周维持期）。结果根据整个 18 周期间和达到维持期的患者进行意向治疗分析。
在 306 名随机患者中，305 名患者接受了 EZG（RTG）1200mg/天（n=153）或安慰剂（n=152）。在 18 周双盲期内，EZG（RTG）和安慰剂分别使总部分发作频率的中位数降低了 44.3%和 17.5%（p<0.001）；应答率（总部分发作频率从基线降低≥50%）分别为 44.4%和 17.8%（p<0.001）。在 256 名进入 12 周维持期的患者（EZG[RTG]，119 名；安慰剂，137 名）中，EZG（RTG）与安慰剂相比，发作频率的中位数降低分别为 54.5%和 18.9%（p<0.001）；应答率分别为 55.5%和 22.6%（p<0.001）。因治疗出现的不良事件（TEAE）而停药的患者比例分别为 26.8%（EZG[RTG]）和 8.6%（安慰剂）。与安慰剂相比，更多接受 EZG（RTG）治疗的患者报告了头晕、嗜睡、疲劳、意识模糊、构音障碍、尿路感染、共济失调和视力模糊等最常见的 TEAEs。
这项研究表明，EZG（RTG）作为附加治疗，可有效减少耐药性部分发作性癫痫患者的发作频率。
这项研究提供了 II 级证据，表明 EZG（RTG）1200mg/天作为伴有或不伴有继发全面性发作的部分发作性癫痫成人患者的辅助治疗是有效的。
