• Byeong Jo Chun, Seok Ran Yeom, Sung Phil Chung, Young Hwan Lee, Jungsoo Lee, Yun-Hee Kim, Ji Sung Lee, Jin Soo Lee, Chun San An, Byoung Joo Gwag, and Jin-Ho Choi.
• Department of Emergency Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.
• Crit. Care Med. 2025 Jan 16.

ObjectivesNelonemdaz is a N-methyl d-aspartate receptor subtype 2B-selective N-methyl-D-aspartate receptor antagonist and a potent free-radical scavenger that might ameliorate hypoxic-ischemic brain injury after out-of-hospital cardiac arrest (OHCA). We investigated the efficacy of nelonemdaz for patients with OHCA.DesignA double-blind, placebo-controlled, randomized, multicenter phase II trial.SettingThis trial enrolled 105 patients at five sites in South Korea between November 18, 2018, and February 23, 2023.ParticipantsOHCA patients undergoing targeted temperature management.InterventionsPatients were randomly assigned to high-dose (5250 mg), low-dose (3250 mg), and placebo groups at a 1:1:1 ratio.Measurements And Main ResultsPatients with a median age of 61 years (82% male) were assigned to the high-dose (n = 37), low-dose (n = 35), and placebo (n = 33) groups. The primary outcome, the serum level of neuron-specific enolase (NSE) at 48-52 hours, was evaluated in 93 patients. There was no difference in serum NSE between high-dose (median and interquartile range; 23.7, 15.0-69.9) and placebo (17.5, 13.6-113.0) groups, or between low-dose (26.6, 16.2-83.4) and placebo groups (all p > 0.05). Brain MRI fractional anisotropy was significantly higher in the high-dose group compared with the placebo group (0.465, 0.449-0.485 vs. 0.441, 0.431-0.464; p = 0.028), but not between low-dose (0.462, 0.439-0.480) and placebo groups (p > 0.05). At day 90, the common odds ratio (95% CI) indicating a numerically favorable shift in the modified Rankin Scale was 1.25 (0.48-3.24) and 1.22 (0.47-3.20) in the high-dose and low-dose groups, respectively, compared with placebo group (all p > 0.05). No serious adverse events were reported.ConclusionsNelonemdaz treatment of patients after OHCA did not reduce serum NSE levels compared with controls. Patients treated with high-dose nelonemdaz showed higher brain MRI fractional anisotropy suggesting less cerebral white matter damage.Copyright © 2025 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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