The Efficacy, Safety and Pharmacokinetic of Antiplatelet Therapy for Vicagrel

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, triple-dummy, parallel-controled, dose-exploration phase II trial. Patients with coronary atherosclerotic heart disease and planned percutaneous coronary intervention （PCI） will be randomized after informed consent, in a 1:1:1:1 ratio to the following treatment groups: Experimental group 1 : Vicagrel 20mg loading followed by 5mg/day for 28 days; Experimental group 2 : Vicagrel 24mg loading followed by 6mg/day for 28 days; Experimental group 3 : Vicagrel 30mg loading followed by 7.5mg/day for 28 days; Control group : Clopidogrel 300mg loading followed by 75mg/day for 28 days. The primary purpose of this trial is to evaluate the efficacy, safety of vicagrel antiplatelet therapy and explore dose in patients with coronary atherosclerotic heart disease during and after PCI compared with clopidogrel.

Official Title
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The Efficacy, Safety and Pharmacokinetic of Antiplatelet Therapy for Vicagrel in Patients With Coronary Atherosclerotic Heart Disease and Planned Percutaneous Coronary Intervention: a Multi-center, Randomized, Double-blind, Triple-dummy , Parallel-controlled, Dose-exploration Phase II Trial

Conditions
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Coronary Artery Disease, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors

Intervention / Treatment
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* Drug: Vicagrel 5mg
* Drug: Vicagrel 6mg
* Drug: Vicagrel 7.5mg
* Drug: Clopidogrel 75mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female aged 18-75. Weight ≥ 50 kg Patients with coronary atherosclerotic heart disease diagnosed clinically and planned percutaneous coronary intervention Patients with ability and willingness to sign informed consent and adherence to trial protocol. Exclusion Criteria: Hemorrhagic symptoms (such as hematemesis, melena, severe or recurrent epistaxis, hemoptysis, marked hematuria, gastrointestinal bleeding, or intracranial hemorrhage), or suspected vascular malformations (such as aneurysms), or abnormal bleeding history (such as abnormal hemorrhage attributed to tooth extraction), himself or his immediate family with coagulation or bleeding disorders (such as hemophilia); Non-ST-segment elevation acute coronary syndrome (<2h emergency PCI), or ST-segment elevation myocardial infarction within 7 days; Patients with suspected aortic dissection; Patients with negative coronary Computed Tomography angiography（CTA）(coronary CTA depending on investigator); Patients with severe disease and life expectancy <1 year; Patients with acute peptic ulcer; History of hemorrhagic stroke or history of ischemic stroke within 6 months before screening and a definite diagnosis of structural abnormalities in the central nervous system; Patients with uncontrolled high blood pressure (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg) after drug treatment during screening; One of the following conditions: cardiogenic shock, chronic congestive heart with failure New York Heart Association (NYHA) grade ≥ III grade or left ventricular ejection fraction determined by echocardiography < 35%, hypotension (systolic pressure < 90 mmHg and or diastolic pressure < 60 mmHg), severe arrhythmias (including high-degree atrioventricular block, sick sinus syndrome, persistent ventricular tachycardia), severe pulmonary insufficiency, pulmonary embolism, and hepatic insufficiency (ALT or AST caused by non-cardiac diseases exceeding the upper limit of normal by more than 3 times), severe renal insufficiency (eGFR < 30 ml/min), cirrhosis; Patients Received P2Y12 receptor antagonist and Ⅱb/IIIa receptor inhibitor, oral anticoagulant (warfarin, rivaroxaban, dabigatran, etc.) within 14 days before screening; Prolonged cardiopulmonary resuscitation (more than 10 minutes) or severe trauma within 2 weeks before screening; Patients plan to undergo another surgery within 1 month after participating in this trial，or plan to undergo PCI procedure performed several times during the test (except for the end of the safety follow-up); History of severe allergies, non-allergic drug reactions or allergies to 2 or more drugs (including contrast agents), or known allergies to the similar drugs (clopidogrel, ticagrelor) as the study drug or contraindication of aspirin; Patients with mental disorders or alcohol dependence; Patients being receiving any experimental medicine or experimental medical devices; Prothrombin time (PT)> 1.3 times the upper limit of normal or international normalized ratio (INR)> 2.0; Platelet count (PLT) < 100×10^9/L or > 600×10^9/L; Hemoglobin < 10g/dL; Patients who cannot tolerate dual antiplatelet therapy for 28 days; Female of reproductive age with positive blood pregnancy test; Female with gestational intention or in lactation; Other unsuitable conditions considered by investigators.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group 1<br>Experimental group 1: Vicagrel 20mg loading followed by 5mg/day for 28 days | Drug: Vicagrel 5mg<br>* Experimental group 1 : Vicagrel 20mg loading followed by 5mg/day for 28 days<br>|
| Experimental: Experimental group 2<br>Experimental group 2: Vicagrel 24mg loading followed by 6mg/day for 28 days | Drug: Vicagrel 6mg<br>* Experimental group 2 : Vicagrel 24mg loading followed by 6mg/day for 28 days<br>|
| Experimental: Experimental group 3<br>Experimental group 3: Vicagrel 30mg loading followed by 7.5mg/day for 28 days | Drug: Vicagrel 7.5mg<br>* Experimental group 3 : Vicagrel 30mg loading followed by 7.5mg/day for 28 days<br>|
| Active Comparator: Control group<br>Control group: Clopidogrel 300mg loading followed by 75mg/day for 28 days | Drug: Clopidogrel 75mg<br>* Control group : Clopidogrel 300mg loading followed by 75mg/day for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of platelet aggregation | Inhibition of platelet aggregation will be assessed by Verifynow System | 28 days after treatment |