Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial
Ji Man Hong, Jin Soo Lee, Yeong‐Bae Lee, Dong Hoon Shin, Dong‐Ick Shin, Yang‐Ha Hwang, Seong Hwan Ahn, Jae Guk Kim, Sung‐Il Sohn, Sun U. Kwon, Ji Sung Lee, Byoung Joo Gwag, Ángel Chamorro, Dennis W. Choi, Ángel Chammorro, Eung Yeop Kim, Jin Wook Choi, Min-Ju Yeo, Jae-Hyuk Kwak, Sung Eun Lee, Jeong‐Ho Hong, Sang Kil Lee, Yoon-Joo Lee, Min-Joo Lee
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: =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. CONCLUSIONS: 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. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02831088.