Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Republic of Korea (J.M.H., Jin Soo Lee).
Department of Neurology, Gachon University Gil Medical Center, Incheon, Republic of Korea (Y.-B.L., D.H.S.).
Stroke. 2022 Nov;53(11):3250-3259. doi: 10.1161/STROKEAHA.122.039649. Epub 2022 Sep 6.
Nelonemdaz is a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, as proven in preclinical ischemia-reperfusion studies. We aimed to evaluate the safety and efficacy of nelonemdaz in patients with acute ischemic stroke receiving endovascular reperfusion therapy.
This phase II randomized trial involved participants with large-artery occlusion in the anterior circulation at baseline who received endovascular reperfusion therapy <8 hours from symptom onset at 7 referral stroke centers in South Korea between October 29, 2016, and June 1, 2020. Two hundred thirteen patients were screened and 209 patients were randomly assigned at a 1:1:1 ratio using a computer-generated randomization system. Patients were divided into 3 groups based on the medication received-placebo, low-dose (2750 mg) nelonemdaz, and high-dose (5250 mg) nelonemdaz. The primary outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 12 weeks.
Two hundred eight patients were assigned to the placebo (n=70), low-dose (n=71), and high-dose (n=67) groups. The groups had similar baseline characteristics. The primary outcome was achieved in 183 patients, and it did not differ among the groups (33/61 [54.1%], 40/65 [61.5%], and 36/57 [63.2%] patients; =0.5578). The common odds ratio (90% CI) indicating a favorable shift in the modified Rankin Scale scores at 12 weeks was 1.55 (0.92-2.60) between the placebo and low-dose groups and 1.61 (0.94-2.76) between the placebo and high-dose groups. No serious adverse events were reported.
The study arms showed no significant difference in the proportion of patients achieving modified Rankin Scale scores of 0-2 at 12 weeks. Nevertheless, nelonemdaz-treated patients showed a favorable tendency toward achieving these scores at 12 weeks, without serious adverse effects. Thus, a large-scale phase III trial is warranted.
URL: https://clinicaltrials.gov; Unique identifier: NCT02831088.
Nelonemdaz 是一种多靶点神经保护剂，可选择性阻断 N-甲基-D-天冬氨酸受体并清除自由基，这已在临床前缺血再灌注研究中得到证实。我们旨在评估 Nelonemdaz 在接受血管内再灌注治疗的急性缺血性脑卒中患者中的安全性和疗效。
这是一项在韩国 7 家转诊卒中中心进行的 2 期随机试验，共纳入了基线时存在前循环大动脉闭塞且在症状发作后 8 小时内接受血管内再灌注治疗的患者。2016 年 10 月 29 日至 2020 年 6 月 1 日期间，共筛选了 213 名患者，采用计算机生成的随机分组系统以 1:1:1 的比例将 209 名患者随机分为 3 组，分别接受安慰剂、低剂量（2750mg）Nelonemdaz 和高剂量（5250mg）Nelonemdaz 治疗。主要结局为治疗 12 周后改良 Rankin 量表评分 0-2 的患者比例。
208 名患者被分配至安慰剂组（n=70）、低剂量组（n=71）和高剂量组（n=67）。3 组基线特征相似。主要结局在 183 名患者中达到，3 组间无差异（33/61[54.1%]、40/65[61.5%]和 36/57[63.2%]；=0.5578）。12 周时改良 Rankin 量表评分向有利方向转变的常见比值比（90%CI）分别为安慰剂与低剂量组之间 1.55（0.92-2.60），安慰剂与高剂量组之间 1.61（0.94-2.76）。未报告严重不良事件。
各组在治疗 12 周后改良 Rankin 量表评分 0-2 的患者比例无显著差异。然而，Nelonemdaz 治疗组患者在 12 周时达到这些评分的趋势较好，且无严重不良事件。因此，需要进行大规模的 3 期临床试验。
