Optimal antiPlatelet Therapy for High Bleeding and Ischemic RISK Patients Trial

Study Overview
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Brief Summary
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Current guidelines recommend that patients with ACS undergoing stent implantation might be offered extended DAPT treatment for up to 30 months if necessary. Therefore, we designed a prospective, multicenter, randomized, placebo-controlled trial among ACS patients with high-risk on ischemic and bleeding who received a new generation of DES and received 9 to 12 months of DAPT, and evaluated whether clopidogrel monotherapy reduce the risk of bleeding compared with clopidogrel plus ASA in the following 9 months and achieved non-inferior outcomes in preventing ischemic risk.

Detailed Description
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Current guidelines recommend that patients with ACS undergoing stent implantation might be offered extended DAPT treatment for up to 30 months if necessary. For patients with high risk of both ischemic and hemorrhage, despite prolonged use of DAPT may bring antithrombotic benefit, it may also increase the risk of bleeding. There is an urgent need for specific guiding on intensive antiplatelet therapy in this population of patients to reduce the risk of ischemia and to avoid the risk of bleeding. Previous studies have shown that, after 12 months of DAPT treatment, continuation of clopidogrel monotherapy may further reduce the risk of ischemia and bleeding compared with aspirin. Therefore, we designed a prospective, multicenter, randomized, placebo-controlled trial among ACS patients with high-risk on ischemic and bleeding who received a new generation of DES and received 9 to 12 months of DAPT, and evaluated whether clopidogrel monotherapy reduce the risk of bleeding compared with clopidogrel plus ASA in the following 9 months and achieved non-inferior outcomes in preventing ischemic risk.

Official Title
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Extended Antiplatelet Therapy With Clopidogrel Alone Versus Clopidogrel Plus Aspirin After Completion of 9- to 12-month Dual Antiplatelet Therapy for ACS Patients With Both High Bleeding and Ischemic Risk.

Conditions
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Prolonged DAPT in ACS Patients With Hisk of Both Ischemic and Hemorrhage

Intervention / Treatment
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* Drug: Clopidogrel
* Drug: Clopidogrel+aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ACS patients undergoing PCI (New-Generation DES) and finishing 9-12 months of DAPT 18   85 years old adult patients Patients under the age of 65 must meet at least one of the following clinical criteria of high bleeding risk and at least one of the following clinical criteria of high ischemic risk; Patients aged 65-75 must meet one of the following clinical criteria of either high bleeding risk or high ischemic risk. Clinical criteria of high bleeding risk: ≥75 years old female Iron deficiency anemia history of stroke (hemorrhagic or ischemic) ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin) Chronic kidney disease (eGFR <60mL/min or creatinine clearance<60mL/min) Clinical criteria of high ischemic risk: ≥75 years old Multiple coronary lesions target lesions required for stent of total length> 30mm Thrombotic target lesions Bifurcation lesions are Medina 0, 1, 1 or 1, 1, and 1, with stents implanted in both main branch and side branch Left main coronary artery (≥50%) or proximal LAD (≥70%) lesions Calcified plaques requiring endovascular excision acute coronary syndrome with troponin positive Previous myocardial infarction, ischemic stroke, diagnosed peripheral arterial disease (PAD), or revascularization due to coronary artery disease (CAD) / PAD recurrent myocardial infarction, revascularization, stent thrombosis, stroke in the last 9 months ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin) Chronic kidney disease (eGFR<60 mL/min or creatinine clearance <60 mL/min) Exclusion Criteria: Discontinuation or termination of DAPT treatment during the past 6 months due to adverse events (bleeding or ischemia) or other conditions Surgery plan within 90 days Coronary Revascularization (Surgical or Intervention) Program within 90 days Dialysis-dependent renal failure Moderate or severe hepatic insufficiency (2 times the upper limit of normal for ALT or AST) Life expectancy <1 year Unable or unwilling to provide informed consent Women with childbearing potential Platelet count <100000/mm3 Subjects undergoing warfarin or similar anticoagulant therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Clopidogrel monotherapy<br>On the basis of 9-12 months of DAPT(aspirin+clopidogrel), continue clopidogrel monotherapy in the following 9 months. | Drug: Clopidogrel<br>* Additional 9 months of clopidogrel monotherapy after 9-12 months of DAPT (aspirin+clopidogrel)<br>|
| Active Comparator: Clopidogrel plus aspirin<br>On the basis of 9-12 months of DAPT(aspirin+clopidogrel), continue DAPT (aspirin+clopidogrel) in the following 9 months. | Drug: Clopidogrel+aspirin<br>* Additional 9 months of clopidogrel plus aspirin after 9-12 months of DAPT (aspirin+clopidogrel)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical relevant bleeding events | defined as BARC type 2-5 bleeding events | During 9-month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All bleeding events | defined all BARC type 1-5 bleeding events | During 9-month follow up | 
| Major adverse cardiovascular and cerebrovascular events(MACCE) | defined as a composite endpoints of all-cause death, myofarction, stroke and clinically indicated revascularization | During 9-month follow up |