Phase III Clinical Trial of Y-2 Sublingual Tablets in the Treatment of Acute Ischemic Stroke

Study Overview
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Brief Summary
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At present, the treatment of acute ischemic stroke includes intravenous thrombolysis, intravascular interventional therapy (including arterial thrombolysis, mechanical thrombectomy, angioplasty and stent implantation), antiplatelet therapy, anticoagulant therapy, defibrasion therapy, volume expansion therapy, and neuroprotective therapy. Y-2 sublingual tablet is an innovative drug developed by Yantai yinuoyi Biomedical Technology Co., Ltd. with independent intellectual property rights. This product is a free radical scavenger and inflammatory protein expression inhibitor. It can clear hydroxyl free radical (COH), nitric oxide free radical (no) and peroxynitrite ion (onoa), and inhibit the expression of tumor necrosis factor-A (TNF-a), interleukin IP (IL-1 (3), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and other inflammatory related proteins induced by cerebral ischemia. By clearing the excessive free radicals produced in the brain tissue during ischemia and reperfusion and inhibiting the secondary inflammatory reaction, we can reduce the damage of free radicals and inflammatory reaction to the brain tissue, block the pathological change process caused by cerebral ischemia from two ways, and play a synergistic therapeutic role in cerebral ischemia injury.

Detailed Description
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At present, the treatment of acute ischemic stroke includes intravenous thrombolysis, intravascular interventional therapy (including arterial thrombolysis, mechanical thrombectomy, angioplasty and stent implantation), antiplatelet therapy, anticoagulant therapy, defibrasion therapy, volume expansion therapy, and neuroprotective therapy. Y-2 sublingual tablet is an innovative drug developed by Yantai Yinuoyi Biomedical Technology Co., Ltd. with independent intellectual property rights. This product is a free radical scavenger and inflammatory protein expression inhibitor. It can clear hydroxyl free radical (COH), nitric oxide free radical (no) and peroxynitrite ion (onoa), and inhibit the expression of tumor necrosis factor-A (TNF-a), interleukin IP (IL-1 (3), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and other inflammatory related proteins induced by cerebral ischemia. By clearing the excessive free radicals produced in the brain tissue during ischemia and reperfusion and inhibiting the secondary inflammatory reaction, we can reduce the damage of free radicals and inflammatory reaction to the brain tissue, block the pathological change process caused by cerebral ischemia from two ways, and play a synergistic therapeutic role in cerebral ischemia injury.

Official Title
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Phase III Clinical Trial of Y-2 Sublingual Tablet in the Treatment of Acute Ischemic Stroke - a Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase III Clinical Trial

Conditions
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Stroke

Intervention / Treatment
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* Drug: Y-2 sublingual tablets
* Drug: d-borneol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Those who meet all of the following requirements: Age ≥ 18 years old and ≤ 80 years old, regardless of gender; After the onset of the disease, the National Institutes of Stroke Scale score: 6 ≤ NIHSS ≤ 20, and the sum of the fifth upper limb score and the sixth lower limb score was ≥2; The onset time is within 48 hours (including 48 hours); Patients diagnosed as ischemic stroke according to key points for diagnosis of all kinds of major cerebrovascular diseases in China 2019, with good prognosis after the first attack or the last attack (MRS score ≤ 1 before this attack); The informed consent approved by the ethics committee was voluntarily signed by the patient or his legal representative. Exclusion Criteria: - Those who meet any of the following items: Intracranial hemorrhagic diseases seen in head imaging: hemorrhagic stroke, epidural hematoma, intracranial hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, etc; If it is only oozing blood, the researcher can judge whether it is suitable for inclusion; Severe disturbance of consciousness: the item score of La consciousness level of NIHSS was more than 1; Transient ischemic attack (TIA); Systolic blood pressure was still higher than 220mmhg or diastolic blood pressure was higher than 120mmhg after blood pressure control; Patients with severe mental disorders and dementia; Severe active liver diseases have been diagnosed, such as acute hepatitis, chronic active hepatitis, cirrhosis, etc; Or ALT or AST > 2.0 × ULN; Severe active kidney disease and renal insufficiency have been diagnosed; Or serum creatinine > 1.5 × ULN; After the onset of the disease, the drugs with neuroprotective effect in the manual have been used; Embolectomy or interventional therapy has been used or planned after the onset of the disease; Complicated with malignant tumor or undergoing anti-tumor treatment; For the subjects diagnosed with malignant tumor after enrollment, whether to continue to participate in the study can be judged by the researcher and the willingness of the subjects; Suffering from severe systemic diseases, the estimated survival time is less than 90 days; Allergic to d-borneol or edaravone or excipients; Patients during pregnancy, lactation and planned pregnancy; Major operation history within 4 weeks before enrollment; Have participated in other clinical studies or are participating in other clinical studies within 30 days before randomization; The researcher thinks that it is not suitable to participate in this clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Y-2 sublingual test group<br>Y-2 sublingual tablets: Edaravone 30mg and d-borneol 6mg. | Drug: Y-2 sublingual tablets<br>* 30mg Edaravone+6mg d-borneo OR， Bid<br>|
| Sham Comparator: placebo group<br>60 μg d-borneol | Drug: d-borneol<br>* 60 μg d-borneol OR， Bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mRS score ≤ 1 | Whether patients with mRS(Modified Rankin Scale) score ≤ 1. Used to calculate the proportion of patients with mRS score ≤ 1. | 90 days after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patients' mRS score | patients' modified Rankin score | 90 days after treatment initiation | 
| Good functional outcome | Whether patients with mRS score ≤ 2. Used to calculate the proportion of good functional outcome (mRS ≤2) | 90 days after treatment initiation | 
| change of NIHSS score | Change of NIHSS (National Institute of Health stroke scale) score from baseline to day 14 after randomization | 14 after treatment initiation | 
| NIHSS score≤1 on 14 day | Whether NIHSS (National Institute of Health stroke scale) score≤1 on 14 day. Used to calculate the proportion of NIHSS score≤1 on 14 day. | 14 after treatment initiation | 
| NIHSS score≤1 on 30 day | Whether NIHSS (National Institute of Health stroke scale) score≤1 on 30 day. Used to calculate the proportion of NIHSS score≤1 on 30 day. | 30 after treatment initiation | 
| NIHSS score≤1 on 90 day | Whether NIHSS (National Institute of Health stroke scale) score≤1 on 90 day. Used to calculate the proportion of NIHSS score≤1 on 90 day. | 90 after treatment initiation |