Efficacy and safety of Neu2000, a multi-target drug designed to prevent both NMDA receptor-mediated excitotoxicity and free radical toxicity, will be investigated in acute ischemic stroke patients receiving endovascular treatment to remove clot within 8 hours following stroke onset. Neu2000KWL will be administered before endovascular treatment.
Neu2000 was designed as a multi-target neuroprotectant preventing both the NMDA receptor, a Ca2+-permeable glutamate receptor, and free radicals, two major routes of brain cell death in stroke. Neu2000 is a moderate NR2B-selective NMDA receptor antagonist and spin trapping molecule (=free radical scavenger or antioxidant). Therapeutic potential of Neu2000 has been well demonstrated in four animal models of stroke with better efficacy and therapeutic time windows than either NMDA receptor antagonist or anti-oxidant advanced to clinical trials. In human phase I studies of 165 healthy subjects conducted in the United States and China, Neu2000KWL showed promising safety profiles without any serious adverse events up to a single intravenous infusion of 6000 mg that is far beyond the therapeutic target dose determined in animal models of transient ischemic stroke. Very recently, acute endovascular recanalization therapy has been introduced as the new standard care of care in acute ischemic stroke. The present study is aimed to examine efficacy and safety of Neu2000KWL in acute ischemic stroke patients receiving endovascular thrombectomy within 8 hours of stroke onset.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
210
1st infusion of 750mg in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of 500 mg at intervals of 12 hours
1st infusion of 500mg in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of 250 mg at intervals of 12 hours
1st infusion of the same volume of saline in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of same volume of saline at intervals of 12 hours
Chungbuk National University Hospital
Cheongju-si, South Korea
RECRUITINGKeimyung University Dongsan Medical Center
Daegu, South Korea
RECRUITINGKyungpook National University Hospital
Daegu, South Korea
Proportional Ratios of study subjects with mRS 0-2 scores at 12 weeks after Neu2000KWL treatment
Time frame: 12weeks
Occurrence rate of cerebral hemorrhagic transformation occurring within 48 hours based on parenchymal hematoma (PH) criteria by ECASS (European Co-operative Acute Stroke Study)-I and II
Time frame: 12weeks
Distribution changes of mRS scores at 1, 4 and 12 weeks vs baseline (shift analysis)
Time frame: 1week, 4weeks, 12weeks
Ratios of NIHSS 0-2 scores at 1, 4 and 12 weeks vs baseline
Time frame: 1week, 4weeks, 12weeks
Ratios of Barthel index >90 (≥ 95) at 1, 4 and 12 weeks vs baseline
Time frame: 1week, 4weeks, 12weeks
Occurrence rate of cerebral hemorrhagic transformation occurring within Day 4 or Day 5 (Day of the last treatment of the study drug)
based on parenchymal hematoma (PH) criteria by ECASS (European Co-operative Acute Stroke Study)-I and II
Time frame: 4-5days
Occurrence rate of symptomatic intracranial hemorrhage (SICH) described and defined by this study protocol occurring within Day 4 or Day 5 (Day of the last treatment of the study drug)
It is defined as SICH of intracranial hemorrhage by brain imaging is confirmed and any one of the following conditions is accompanied: A. in case that NIHSS scores become worse 2 points or more B. in case that NIHSS scores become worse 1 point or more, accompanying decreased consciousness C. in case that neurological deficits persist 24 hours or more (and), D. in case of recurrence of stroke and progress deterioration, or in case that other medical causes are not related.
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Chosun University Hospital
Gwangju, South Korea
RECRUITINGGachon University Gil Medical Center
Incheon, South Korea
RECRUITINGAjou University Hospital
Seoul, South Korea
RECRUITINGTime frame: 4-5days