Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial

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: 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; P=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.

Keywords: cerebral infarction; ischemic stroke; neuroprotective agent; odds ratio; reperfusion.

Figure 1.

Flowchart of the SONIC trial (Safety and Optimal Neuroprotection of Neu2000 in Acute Ischemic Stroke With Recanalization). FAS indicates full analysis set; ITT, intention-to-treat; mRS, modified Rankin Scale; and PP, per protocol.

Figure 2.

Distribution of the primary outcome at 12 wk according to group (n=183). mRS indicates modified Rankin Scale.

Figure 3.

Subgroup analysis of the primary outcome in the full analysis set (n=183). ASPECTS indicates Alberta Stroke Program Early CT Score; CT, computed tomography; ERT, endovascular reperfusion therapy; NIHSS, National Institutes of Health Stroke Scale; RR, relative risk; and tPA, tissue-type plasminogen activator.