Nelonemdaz and Patients With Acute Ischemic Stroke and Mechanical Reperfusion
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Importance: Nelonemdaz selectively antagonizes the 2B subunit of the N-methyl-d-aspartate glutamate receptor and scavenges free radical species. Objective: To evaluate whether nelonemdaz enhances the clinical outcomes of patients with acute ischemic stroke undergoing emergent reperfusion therapy. Design, Setting, and Participants: This multicenter double-blind placebo-controlled randomized phase 3 trial (December 25, 2021, to June 30, 2023, in South Korea) recruited patients with acute ischemic stroke who met the following criteria: National Institutes of Health Stroke Scale score greater than or equal to 8, Alberta Stroke Program Early Computed Tomography score greater than or equal to 4, and endovascular thrombectomy within 12 hours after stroke onset. Intervention: Patients were assigned in a 1:1 ratio to receive intravenous infusions of nelonemdaz twice a day for 5 days or a matching placebo. Main Outcomes and Measures: The primary end point was a favorable shift in the modified Rankin scale (mRS) 12 weeks after stroke onset. The secondary end points included various composites of the mRS at 5 and 12 weeks, symptomatic intracranial hemorrhage, and infarct volume. Both intention-to-treat and per-protocol analyses were conducted. Results: A total of 496 patients were enrolled across 24 Korean stroke centers, of whom 39 dropped out (254 men [55.6%]; mean [SD] age, 72.9 [12.1] years). Baseline characteristics of study participants did not significantly differ. For the primary end point, the distribution of the mRS scores at 12 weeks did not significantly differ between the nelonemdaz and placebo groups (common odds ratio, 0.95; 95% CI, 0.69-1.31). For the secondary end points, a median of mRS at 5 weeks (3 vs 3) and mRS 0 at 12 weeks (18.1% vs 18.2%) did not differ substantially between groups. The occurrence of symptomatic intracranial hemorrhage (2.7% vs 0.9%) and infarct volume within 24 hours of the last trial drug infusion (42 vs 38 mL) did not differ significantly between groups. No serious adverse events were reported regarding the trial drug and placebo. Conclusions and Relevance: In this randomized clinical trial, nelonemdaz did not meet the primary efficacy end point compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT05041010.
Source: JAMA Network Open
Authors: Jin Soo Lee, Hyun Goo Kang, Seong Hwan Ahn, Tae-Jin Song, Dong-Ick Shin, Hee-Joon Bae, Chang Hun Kim, Sung Hyuk Heo, Jae-Kwan Cha, Yeong Bae Lee, Eung Gyu Kim, Man Seok Park, Hee-Kwon Park, Jinkwon Kim, Sungwook Yu, Heejung Mo, Sung Il Sohn, Jee Hyun Kwon, Jae Guk Kim, Young Seo Kim, Jay Chol Choi, Yang-Ha Hwang, Keun Hwa Jung, Soo-Kyoung Kim, Woo Keun Seo, Jung Hwa Seo, Joonsang Yoo, Jun Young Chang, Mooseok Park, Ji Sung Lee, Chun San An, Byoung Joo Gwag, Dennis W. Choi, Sun U. Kwon
Institutions: Asan Medical Center, University of Ulsan, Ajou University Medical Center, Ajou University, Jeonbuk National University Hospital, Jeonbuk National University, Chosun University, Chosun University Hospital, Ewha Womans University, Ewha Womans University Seoul Hospital, Chungbuk National University, Chungbuk National University Hospital, Seoul National University, Seoul National University Bundang Hospital, Gyeongsang National University, Gyeongsang National University Hospital, Kyung Hee University, Kyung Hee University Medical Center, Dong-A University Hospital, Dong-A University, Gachon University, Gachon University Gil Medical Center, Inje University, Inje University Busan Paik Hospital, Chonnam National University, Chonnam National University Hospital, Inha University, Inha University Hospital, Yonsei University, Daejeon Eulji Medical Center, Eulji University, Yongin Severance Hospital, Korea University Anam Hospital, Hallym University, Hallym University Dongtan Sacred Heart Hospital, Keimyung University Dongsan Hospital, Keimyung University, Ulsan University Hospital, Wonkwang University Hospital, Wonkwang University, Jeju National University Hospital, Jeju National University, Kyungpook National University Hospital, Kyungpook National University, Seoul National University Hospital, Samsung Medical Center, Sungkyunkwan University, Yongin Mental Hospital, Stony Brook University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
OpenAlex ID: W4406902191