J Stroke.  2023 Jan;25(1):160-168. 10.5853/jos.2022.02453.

The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz (RODIN) Trial: Protocol for a Double-Blinded Clinical Trial of Nelonemdaz in Patients with Hyperacute Ischemic Stroke and Endovascular Thrombectomy

• Lee JS
• Lee JS
• Gwag BJ
• Choi DW
• An CS
• Kang HG
• Song TJ
• Ahn SH
• Kim CH
• Shin DI
• Kwon SU

• KMID: 2539069
• DOI: http://doi.org/10.5853/jos.2022.02453

Abstract

Background and Purpose
Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients. Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset. Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days.
Conclusion
This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).

Keyword

Ischemic stroke; Cerebral infarction; Reperfusion injury; Clinical trial; Protocols; Nelonemdaz

Figure

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  Figure 1. Trial flowsheet. NIHSS, National Institutes of Health Stroke Scale; ICA, internal carotid artery; M1, M1 segment of middle cerebral artery; M2, M2 segment of middle cerebral artery; ASPECTS, Alberta Stroke Program Early CT Score; MRI, magnetic resonance imaging.

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  Figure 2. Pathomechanism of acute cerebral infarction and pharmacological actions of nelonemdaz. (A) Excessive glutamates in the synaptic cleft activate N-methyl-D-aspartate (NMDA) receptor, and excitotoxicity subsequently occurs. Oxidative stress, also causing neuronal damage, is sustained especially by reperfusion injury. (B) Nelonemdaz noncompetitively blocks the 2B subunit of NMDA receptor, the activation of which causes fast excitotoxicity. This also results in scavenging free radicals, which are involved from slow oxidative stress. The first high dose of nelonemdaz targets the fast excitotoxicity and the successive moderate doses aids in decreasing oxidative stress during the Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz trial.

Reference

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