一项在韩国开展的随机、开放标签、多中心对照临床试验，比较左乙拉西坦和托吡酯作为局灶性癫痫患者的附加治疗。

A randomized, open-label, multicenter comparative trial of levetiracetam and topiramate as adjunctive treatment for patients with focal epilepsy in Korea.

机构信息

Seoul National University Hospital, Seoul, Republic of Korea.

University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Epilepsy Behav. 2019 Aug;97:67-74. doi: 10.1016/j.yebeh.2019.05.014. Epub 2019 Jun 10.

DOI:10.1016/j.yebeh.2019.05.014

PMID:31195326

Abstract

OBJECTIVE

The objective of this trial was to compare the effectiveness of levetiracetam (LEV) and topiramate (TPM) as adjunctive treatment for patients with focal seizures in Korea.

METHODS

In this Phase IV, open-label, multicenter trial (NCT01229735), adults were randomized to treatment with LEV (1000-3000 mg/day) or TPM (200-400 mg/day). Only patients achieving LEV ≥1000 mg/day or TPM ≥100 mg/day after a 4-week up-titration entered the 20-week dose-finding and subsequent 28-week maintenance periods. The primary outcome was the 52-week retention rate; others included safety and exploratory efficacy outcomes.

RESULTS

Of 343 randomized patients (LEV 177; TPM 166), 211 (61.5%) completed the trial. In the full analysis set (FAS), retention rate was 59.1% with LEV vs 56.6% with TPM (p = 0.7007), while in the prespecified sensitivity analysis, based on data from patients who received drug doses in the recommended range (LEV 176; TPM 113), it was 59.1% with LEV vs 42.5% with TPM (p = 0.0086). In the FAS, median percent reduction in seizure frequency from baseline was 74.47% with LEV and 67.86% with TPM (p = 0.0665); ≥50% responder rate was 69.0% vs 64.8% (p = 0.4205), and the 6-month seizure-freedom rate was 35.8% vs 22.3% (p = 0.0061). In the sensitivity analysis, differences between groups were greater, favoring LEV. Incidences of treatment-emergent adverse events (TEAEs) were 70.6% with LEV vs 77.1% with TPM; most frequently somnolence (20.3%), dizziness (18.1%), and nasopharyngitis (13.6%) with LEV; and decreased appetite (15.7%), dizziness (14.5%), and headache (14.5%) with TPM. Discontinuations due to TEAEs were 7.9% with LEV and 12.7% with TPM.

CONCLUSIONS

In this open-label trial, the 52-week retention rate was not significantly different between LEV and TPM. However, LEV was associated with a substantially higher seizure freedom rate and a more favorable safety profile than TPM in this population of Korean patients with focal seizures.

摘要

目的

本试验旨在比较左乙拉西坦（LEV）和托吡酯（TPM）作为韩国局灶性癫痫患者辅助治疗的疗效。

方法

在这项 IV 期、开放标签、多中心试验（NCT01229735）中，成年患者被随机分配接受 LEV（1000-3000mg/天）或 TPM（200-400mg/天）治疗。只有在 4 周的滴定期后达到 LEV≥1000mg/天或 TPM≥100mg/天的患者才能进入 20 周剂量发现和随后的 28 周维持期。主要结局是 52 周的保留率；其他包括安全性和探索性疗效结局。

结果

在 343 名随机患者（LEV 177 名；TPM 166 名）中，211 名（61.5%）完成了试验。在全分析集（FAS）中，LEV 的保留率为 59.1%，TPM 为 56.6%（p=0.7007），而在基于接受推荐剂量药物的患者数据的预先指定敏感性分析中，LEV 为 59.1%，TPM 为 42.5%（p=0.0086）。在 FAS 中，LEV 的中位癫痫发作频率从基线的降低百分比为 74.47%，TPM 为 67.86%（p=0.0665）；≥50%应答率为 69.0%vs 64.8%（p=0.4205），6 个月无癫痫发作率为 35.8%vs 22.3%（p=0.0061）。在敏感性分析中，LEV 组的差异更大，有利于 LEV。LEV 的治疗中出现的不良事件（TEAEs）发生率为 70.6%，TPM 为 77.1%；最常见的是嗜睡（20.3%）、头晕（18.1%）和鼻咽炎（13.6%）；食欲减退（15.7%）、头晕（14.5%）和头痛（14.5%）。因 TEAEs 而停药的分别是 LEV 7.9%和 TPM 12.7%。