Study of Urinary Kallikrein to Enhance Collateral Circulation in Symptomatic Intracranial Atherosclerosis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Urinary Kallikrein has an additional effect on enhancing collateral circulation in symptomatic intracranial atherosclerotic patients under clopidogrel and aspirin dual antiplatelet therapy.

Official Title
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Study of Urinary Kallikrein to Enhance Collateral Circulation in Symptomatic Intracranial Atherosclerosis: a Study Based on Whole-brain CTP

Conditions
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Collateral Circulation, Intracranial Arteriosclerosis, Anterior Cerebral Circulation Infarction

Intervention / Treatment
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* Drug: Urinary Kallikrein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke or TIA within 72 hours; Intracranial ICA, MCA M1 segment stenosis (>70%) Exclusion Criteria: >70% Stenosis in an intracranial artery other than the culprit artery. >50% Stenosis of an extracranial carotid or vertebral artery on the ipsilateral side. Perforator strokes based on MRI. Non-atherosclerotic lesion, for example, moyamoya disease, vascular inflammatory disease due to infection, autoimmunity diseases, developmental or genetic abnormalities, for example, fibromuscular dysplasia, sickle-cell anaemia, suspected vasospasm. Potential cardiac embolism as cause. Intracranial haemorrhage within 6 weeks. Concomitant intracranial tumour, aneurysm or arteriovenous malformation. Known contraindications for heparin, aspirin, clopidogrel or contrast. Haemoglobin <10 g/dL, blood platelet count <100 000, international normalisation ratio >1.5, or other uncorrectable coagulopathies.Impaired liver function (alanine aminotransferase or glutamic oxalacetic transaminase ≥ 3×upper limit of normal) or renal function (serum creatinie ≥ 1.5mg/dl); A baseline modified Rankin Score of ≥3. Life expectancy of <1 year due to the concomitant illness. Pregnant or lactating women. long-term statins users. History of mental instability or dementia.

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Urinary Kallikrein group<br>Urinary Kallikrein for injection, 0.15PNA IU,qd, for 2 weeks, administered within 96 hours after TIA or acute ischemic stroke, with basic therapies like dual antiplatelet therapy, blood pressure-lowering therapy and lipid-lowering therapy. | Drug: Urinary Kallikrein<br> <br> * Other names: Urinary Kallidinogenase;|
| No Intervention: control group<br>with basic therapies like dual antiplatelet therapy, blood pressure-lowering therapy and lipid-lowering therapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the percentage of patients with modified Rankin Score (mRS) equivalent to or less than 2 |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rLMC scale of Collateral circulation | We use regional leptomeningeal score(rLMC) score to measure collateral circulation.rLMC score is based on scoring pial and lenticulostriate arteries in 6 ASPECTS regions(M1-6) plus anterior cerebral artery region and basal ganglia. Pial arteries in the Sylvian sulcus are scored 0,2, or 4. | 2 weeks, 1 month | 
| NIHSS score |  | 2 weeks, 1month | 
| Hemorrhageic complications | Hemorrhageic complications including intracranial, digestive tract | 2 weeks, 1 month, 3 months, 6 months | 
| New stroke or transient ischemic attack(TIA) |  | 6 months |