多中心双盲、随、安慰剂对照的临床研究评价左乙拉西坦添加治疗.doc

多中心双盲、随机、安慰剂对照的临床研究评价左乙拉西坦添加治疗 难治性部分性癫痫发作的疗效及安全性 吴洵昳* 洪震 吴逊 吴立文 赵忠新 王学峰 周东 吕传真 [摘要] 目的 评价左乙拉西坦（LEV）作为添加用药治疗难治性部分性癫痫发作的临床疗效及安全性。 方法 双盲、随机、安慰剂对照、多中心平行设计添加治疗202例平均年龄32.8±12.7岁、确诊为有癫痫部分性发作的患者（ITT人群）被随机分配入LEV治疗组（N=102）与安慰剂组（N=100），回顾8周基线期的癫痫发作情况后，进入逐量加药期，初始研究用药剂量为500mg bid，2周后增加至1000mg bid，4周后加量至1500mg bid，随后维持该剂量治疗12周，最后逐渐减量并转入LEV开放治疗期。主要评价指标包括16周治疗期每周癫痫部分性发作频率的变化，药物治疗50%有效率，总体临床疗效评估及药物不良反应。 结果 16周治疗期内LEV组每周癫痫部分性发作频率明显减少，相对安慰剂组减少百分数为26.8%，每周部分性发作频率相对基线期下降的相对百分数在LEV组与安慰剂组的组间差异为42.2%，LEV组癫痫部分性发作的治疗50%有效率为55.9%，相对安慰剂组的OR值为3.6，LEV组有11例患者治疗后无发作，上述各项指标的组间差异均有显著统计学意义(p0.001)。LEV组与安慰剂组的不良事件发生率相当，LEV组的主要不良事件为嗜睡、头晕、无力、血小板减少。 结论 LEV作为添加用药治疗成人难治性部分性癫痫发作，可以显著减少癫痫发作频率，安全性好。 [关键词] 抗癫痫药物； 左乙拉西坦；癫痫；添加治疗 Multicenter Randomized, Double-Blind, Placebo-Controlled Trial of Levetiracetam as Add-on Therapy in Patients with Refractor Partial Seizures WU Xun-yi*, HONG Zhen1, WU Xun, Wu li-wen, ZHAO Zhong-xin, WANG Xue-feng, ZHOU Dong, LV Chuan-zhen *Institue of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China [Abstract] Purpose To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add-on therapy in patients with refractory partial seizures. Methods In this Chinese multicenter, double-blind, randomized ,placebo-controlled trial, LEV was compared with placebo as add-on therapy in 202 patients(intent-to treat (ITT) population) at least 16 years old ( mean, 32.8?2.7 years) with uncontrolled partial-onset seizures were enrolled .All patients entered an 8-week baseline period followed by a 4-week titration interval and a 12-week maintenance period. Patients initially received LEV 500mg bid, and increase to 1000mg bid after 2 weeks, and to 1500mg bid after another 2 weeks. The main outcome measure were reduction in seizure frequency, the 50% responder rate, globle evaluation scale (GES), and adverse events. Results During the 16 weeks of the trial, LEV significantly decreased the seizure frequency compared with placebo, with reduction over