Efficacy and Safety Study of Neu2000KWL for Acute Ischemic Stroke Patients Within 6 Hours of Onset

Study Overview
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Brief Summary
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The purpose of the study is to explore safety and efficacy of Salfaprodil administration for patients with acute ischemic stroke within 6 hours of onset.

Detailed Description
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The present study is to investigate safety and efficacy of Neu2000, a multi-target neuroprotectant acting as a moderate NR2B-selective NMDA receptor antagonist and potent antioxidant, in acute ischemic stroke patients within 6 hours of onset. Compared to NMDA antagonists or antioxidants, improved efficacy and therapeutic time window of Neu2000 have been well documented in four animal models of stroke. Notable Safety of Neu2000 has been demonstrated in 168 human subjects conducted in the US and China as well as animals. In the present phase II study, patients with acute ischemic stroke within 6 hours of onset would be assigned randomly to one of four groups as follows: Group A receiving 2.75g Neu2000KWL for 5 days Group B receiving 5.25g Neu2000KWL for 5 days Group C receiving 6.00g Neu2000KWL for 5 days Group D receiving placebo for 5 days Patients will receive intravenous infusion of the clinical study drug twice a day at 12±1 hour intervals for 5 days.

Official Title
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A Phase II, Double-blind, Randomized, Placebo-controlled, Multi-center Study to Assess the Efficacy and Safety of the Salfaprodil for Injection in Patients With Acute Ischemic Stroke

Conditions
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Stroke, Cerebral Infarction

Intervention / Treatment
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* Drug: Neu2000KWL
* Drug: Neu2000KWL
* Drug: Neu2000KWL
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients aged between 35 and 75 years; acute ischemic stroke patients in internal carotid artery system within 6 hours of onset; patients with NIHSS scores of 4 to 22 and limb weakness including motor arm or motor leg score ≥2 of NIHSS; patients within 6 hours of onset or the last time known to be symptom free (within 6 hours of the start of sleep for ischemic stroke patients with onset during sleep), and who receive a CT test before the clinical study; Informed consent should be signed from the patient or patient's legally authorized representative; patients with premorbid mRS score of 0 1; patients with no history of myocardial infarction within last 3 months; patients with no heart, liver, kidney and lung function deficit; patients with no hemorrhagic diseases within last 3 months; patients with no haematological diseases. Exclusion Criteria: Any contraindication to CT and MRI (e.g., metal implants such as pacemakers, claustrophobia); Stroke caused by posterior circulation ischemia, or transient ischemic attack (TIA); Acute intracranial hemorrhage, intracranial neoplasm, cobweb hemorrhage, cerebritis or other non-acute ischemic stroke and cerebral arteriovenous malformation; Endovascular treatment within 6 hours of onset, such as mechanical embolectomy, stent angioplasty or arteriovenous bridge treatment; Pregnant or lactating women. Note: the pregnancy test of fertile women must be negative before randomization into groups, and female patients must take appropriate contraceptive methods at least for 3 weeks prior to the clinical study and over the next 7 days following the last injection of test drugs; Pre-existing medical, neurologic, or psychiatric diseases that would confound the neurologic, functional, or imaging evaluations, such as persistent deficit from previous ischemic stroke; Malignant tumor or other critical disease; Patients with a history of epilepsy or undergoing seizure on onset of the ischemic stroke A history of intracranial hemorrhage; Patients with low blood pressure, or showing blood pressure lower than 90/60mmHg in three consecutive times after admission; A history of severe injury and surgical operation within the last 3 months; Consciousness disorder as defined as NIHSS Ia score ≥2 ; Complete atrioventricular block bradycardia; Cardiac function rating above II level according to the New York heart association (NYHA) grade of cardiac function, history of congestive heart failure (CHF); With primary liver and kidney disease, AST or ALT 2 times greater than upper normal limit, serum creatinine >2.0 mg/dL or >176.8 µmol/L; International normalized ratio (INR) > 1.7 or current use of oral anticoagulants, except aspirin, clopidogrel, subcutaneous heparin or warfarin; With bleeding tendency disease (such as hemophilia), partial thromboplastin time (PTT) > 3 ×the upper limit of normal; A history of, or known current problems with, drug or alcohol abuse; A irritability experience of the study drugs or drugs with similar chemical structures; Participation in other clinical trials or studies before this study within the last 3 months; Researchers consider that patients don't suit for the study. Hepatitis B and C, HIV-positive patients Imaging exclusion criteria: patients with high density lesions associated with haemorrhage on CT scan after admission; patients with significant lower density lesions of 1/3 middle cerebral artery on CT scan after admission; patients with intracranial parenchymal tumors on CT scan after admission.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neu2000KWL 2750mg dose group<br>Low dose group | Drug: Neu2000KWL<br>* 1st infusion of 500mg in patients within 6 hours following ischemic stroke onset followed by 9 consecutive infusions of 250 mg at intervals of 12 hours<br>* Other names: Salfaprodil for injection;|
| Experimental: Neu2000KWL 5250mg dose group<br>Middle dose group | Drug: Neu2000KWL<br>* 1st infusion of 750mg in patients within 6 hours following ischemic stroke onset followed by 9 consecutive infusions of 500 mg at intervals of 12 hours<br>* Other names: Salfaprodil for injection;|
| Experimental: Neu2000KWL 6000mg dose group<br>High dose group | Drug: Neu2000KWL<br>* 1st infusion of 1500mg in patients within 6 hours following ischemic stroke onset followed by 9 consecutive infusions of 500 mg at intervals of 12 hours<br>* Other names: Salfaprodil for injection;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebos<br>* 1st infusion of the same volume of saline in patients within 6 hours following ischemic stroke onset followed by 9 consecutive infusions of the same volume of saline at intervals of 12 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratio of patients with NIHSS score of 0-1 or with reduction of NIHSS score of ≥4 than the baseline on 14 ± 2 day following the first injection. | The ratio of patients with NIHSS score of 0-1 or with reduction of NIHSS score of ≥4 than the baseline on 14 ± 2 day following the first injection. | days:14±2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from the baseline in NIHSS score on 14 ± 2, 30 ± 2 and 90 ± 7 days following the first injection. 1. Change from the baseline in NIHSS score on 14 ± 2, 30 ± 2 and 90 ± 7 days following the first injection. | Change from the baseline in NIHSS score on 14 ± 2, 30 ± 2 and 90 ± 7 days following the first injection. | days 14±2, 30±2 and 90±7 | 
| Change from the baseline in mRS score on 14 ± 2, 30 ± 2 and 90 ± 7 days following the first injection. | Change from the baseline in mRS score on 14 ± 2, 30 ± 2 and 90 ± 7 days following the first injection. | days 14±2, 30±2 and 90±7 | 
| Change from the baseline in Barthel Index (BI) score on 14 ± 2, 30 ± 2 and 90 ± 7 days following the first injection. | Change from the baseline in Barthel Index (BI) score on 14 ± 2, 30 ± 2 and 90 ± 7 days following the first injection. | days 14±2, 30±2 and 90±7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, the Salfaprodil for injection, Neu2000KWL, Neuroprotection, glutamate, free radical