Nelonemdaz and Patients With Acute Ischemic Stroke and Mechanical Reperfusion: The RODIN Randomized 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.

Figure 1.. Trial Flowchart

IP, investigational product; ITT, intention-to-treat; mRS, modified Rankin scale; PP, per protocol.

Figure 2.. Distribution of Modified Rankin Scale (mRS) at 12 Weeks

Figure 3.. Subgroup Analysis

No multiplicity correction was applied. ASPECTS indicates Alberta Stroke Program Early Computed Tomography Scores; CT, computed tomography; eTICI, extended thrombolysis in cerebral infarction; MRI, magnetic resonance imaging; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; TOAST, Trial of Org 10172 in Acute Stroke Treatment.