Ischemic Stroke
Conditions
Keywords
Neu2000KWL, Neuroprotection, endovascular therapy, glutamate, free radical
Brief summary
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.
Detailed description
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.
Interventions
DRUGNeu2000KWL High-does group
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
DRUGNeu2000KWL Low-does group
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
DRUGPlacebo
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
Sponsors
GNT Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults ≥19 years 2. Patients who were presented to hospitals after onset of brain ischemic symptoms from the base of last normal state and can start Endovascular therapy in accordance with standard practice guidelines within 8 hours after the symptom onset. 3. NIHSS scores on screening time point (admission) ≥ 8 points 4. Patients whose activity is possible without the help of others in the gen-eral condition one day before the ischemic stroke onset. and whose Barthel index scores exceed 90 points 5. Patients whose brain CT and CT angiography imaging confirmed acute ischemic stroke and symptomatic intracranial occlusion at screening and whose occlusion site considered the cause of acute ischemic stroke meets the following conditions: ① Carotid T or L type occlusion ② M1 MCA ③ M1-MCA equivalent (two or more M2-MCAs) However, anterior temporal artery is not regarded M2 6. Patients with ASPECTS on Brain CT without early imaging hyper-enhancement ≥ 6 7. Patients who spontaneously submitted a written informed consent to participation on this clinical study
Exclusion criteria
1. a medical history of hypersensitivity against aspirin (salicylates), sulfasalazine or (5-ASA) at screening. 2. Patients who meets the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportional Ratios of study subjects with mRS 0-2 scores at 12 weeks after Neu2000KWL treatment | 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 | 12weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratios of Barthel index >90 (≥ 95) at 1, 4 and 12 weeks vs baseline | 1week, 4weeks, 12weeks | — |
| Distribution changes of mRS scores at 1, 4 and 12 weeks vs baseline (shift analysis) | 1week, 4weeks, 12weeks | — |
| 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) | 4-5days | 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. |
| Occurrence rate of cerebral hemorrhagic transformation occurring within Day 4 or Day 5 (Day of the last treatment of the study drug) | 4-5days | based on parenchymal hematoma (PH) criteria by ECASS (European Co-operative Acute Stroke Study)-I and II |
| Ratios of NIHSS 0-2 scores at 1, 4 and 12 weeks vs baseline | 1week, 4weeks, 12weeks | — |
Countries
South Korea
Contacts
Primary ContactChun San An
Backup ContactSung Ig Cho
Outcome results
None listed