A Randomized Comparison of CLOpidogrel Monotherapy Versus Extended Dual-antiplatelet Therapy Beyond 12 Months After Implantation of Drug-eluting StEnts in High-risk Lesions or Patients; A-CLOSE Trial

Study Overview
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Brief Summary
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We hypothesized that clopidogrel mono-therapy will not be inferior to the extended DAPT in terms of the occurrence of both ischemic and bleeding events, for lesions or patients at high risk for either ischemic or bleeding complications 12 months after drug-eluting stent (DES) implantation.

Detailed Description
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Patients at high risk for either ischemic or bleeding complications, but who were stable without clinical evetns for 12 months after DES implantation will be included in this study. Eligible patients will be randomized to continue DAPT (aspirin plus clopidogrel) for further 24 months or to change to single antiplatelet therapy with clopidogrel (clopidogrel-alone). Randomization will be stratified according to 1) clinical presentation (acute coronary syndrome or stable coronary artery disease) and 2) age (≥75 or <75). Baseline clinical and angiographic characteristics, laboratory findings will be assessed at the time of randomization. All patients will provide informed consent on their own initiative. All of study subjects will be have an outpatient visit as scheduled in outpatient clinic. Occurrence of study endpoints will be documented at clinical visit or telephone interview every 6 months up to 24 months after randomization. Antiplatelet drugs will be open-label and prescribed by attending physician.

Official Title
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A Randomized Comparison of CLOpidogrel Monotherapy Versus Extended Dual-antiplatelet Therapy Beyond 12 Months After Implantation of Drug-eluting StEnts in High-risk Lesions or Patients; A-CLOSE Trial

Conditions
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Coronary Artery Disease, DES

Intervention / Treatment
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* Drug: Clopidogrel mono-therapy
* Drug: Dual-antiplatelet therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria (must all met) Patients >19 years old Patients who underwent DES implantation 12 months (-1 to +5 months) previously. High risk characteristics (clinical or lesion) for ischemic events (must at least one) High risk patients; clinical criteria Acute coronary syndrome Previous history of cerebrovascular accidents History of peripheral artery intervention Heart failure (left ventricular ejection fraction ≤40%) Diabetes treated with medication Chronic renal insufficiency including end-stage renal diseases High risk lesions; angiographic or procedural criteria Left main diseases Bifurcation lesions Chronic total occlusion In-stent restenotic lesions Graft lesions Diffuse long lesions requiring total stent length ≥28 mm Calcified lesions requiring atherectomy Multivessel coronary artery disease with multiple stents Small vessel disease requiring stent diameter of ≤2.5 mm Exclusion criteria Age> 80 years Pregnant women or women with potential childbearing Life expectancy < 1 year Refusal or inability to understand of informed consent Need for chronic oral anticoagulation History of major bleeding within 3 months prior to randomization

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: Patients will be assigned to continue DAPT (aspirin plus clopidogrel) or to change to single antiplatelet therapy with clopidogrel (clopidogrel-alone) for further 24 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clopidogrel mono-therapy<br>After randomization, patients will receive clopidogrel monotherapy after DES implantation for 24 months. | Drug: Clopidogrel mono-therapy<br>* Patients will receive clopidogrel (75 mg once daily) monotherapy without co-administration of aspirin for 24 months after randomization.<br>|
| Active Comparator: Dual-antiplatelet therapy<br>Patients will receive dual antiplatelet consisting of aspirin and clopidogrel. | Drug: Dual-antiplatelet therapy<br>* Patients will receive co-administration of aspirin (100 mg/day) and clopidogrel (75 mg/day) for 24 months after randomization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net Adverse Clinical Events (NACE) | The composite of all-cause of death, myocardial infarction (MI), stent thrombosis, stroke, or bleeding (BARC type 2, 3, or 5) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Each component of net adverse clinical events |  | 24 months | 
| All-cause or cardiovascular mortality |  | 24 months | 
| Major or minor bleeding | Major or minor bleeding would be defined by BARC and TIMI criteria | 24 months | 
| Major adverse cardiac event | Major Adverse Cardiac events includes all-cause of death, myocardial infarctions, stent thrombosis, or stroke. | 24 months | 
| Major adverse cardiac and cerebrovascular event | Major or minor bleeding would be defined by BARC and TIMI criteria Major Adverser Cardiac events includes all-cause of death, myocardial infarctionh, stent thrombosis, or ischemia-driven target vessel revascularization Major adverse cardiac and cerebrovascular event includes all-cause death, myocardial infarction, stent thrombosis, stroke, or ischemia-driven target vessel revascularization | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patients who underwent percutaneous coronary intervention with DES implantation carrying high risks for the recurrent major adverse events., anti platelet therapy, bleeding