Safety of 6-month Duration of Dual Antiplatelet Therapy After Acute Coronary Syndromes (SMART-DATE)

Study Overview
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Brief Summary
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Objective : To test the safety of 6 month-duration of dual antiplatelet therapy (DAPT) compared to conventional 12-month-or-longer duration after second-generation drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS). Hypothesis : A 6-month duration of DAPT is non-inferior to a conventional 12-month-or longer duration of DAPT at preventing the occurrence of major adverse cardiac and cerebrovascular events (MACCE) at 18-month after second-generation DES implantation in patients with ACS.

Detailed Description
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Primary endpoint - MACCE, defined as a composite of all-cause mortality, myocardial infarction, and cerebrovascular events at 18 months after the index procedure. Secondary endpoint Individual components of the primary endpoint at 18-month after the index procedure Definite/probable stent thrombosis, defined by the Academic Research Consortium (ARC) at 18-month after the index procedure. Bleeding complication, defined by Bleeding Academic Research Consortium (BARC) type 2 to 5 at 18-month after the index procedure.

Official Title
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Smart Angioplasty Research Team: Safety of 6-month Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndromes (SMART-DATE)

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥ 20 years. Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving percutaneous coronary intervention and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure. Subject must have a culprit lesion in a native coronary artery with significant stenosis (>50% by visual estimate) eligible for stent implantation. Subject must have clinical diagnosis of ACS that includes unstable angina and MI. The specific definitions of ACS, as follows; 1) ST-segment elevation MI (STEMI) : elevation of ST-segment more than 0.1 mV in 2 or more contiguous electrocardiographic (ECG) leads or new left bundle-branch block with elevated biomarkers of myocardial necrosis 2) Non-ST-segment elevation MI (NSTEMI) : Elevated biomarkers of myocardial necrosis (troponin or CK-MB > upper reference limit) with one of the following; (a) Transient ST-segment elevation or depression, or T-wave changes consistent with myocardial ischemia, (b) Identification of a culprit lesion at coronary angiography 3) Unstable angina : An accelerating pattern or recurrent episodes of chest pain at rest or with minimal effort and new ST-segment depression of at least 0.05 mV, or T wave inversion of at least 0.3 mV in at least 2 leads. The ECG criteria for unstable angina were based on the TACTICS-TIMI 18 trial. Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥ 2.25 mm and ≤ 4.25 mm. Target lesion(s) must be amenable for percutaneous coronary intervention Exclusion Criteria: The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Biolimus, Everolimus, Zotarolimus, and Contrast media (Patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine [e.g. rash] may be enrolled. Those with true anaphylaxis to prior contrast media, however, should not be enrolled.) Patients with active pathologic bleeding Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months. Systemic (intravenous) Biolimus, everolimus, zotarolimus use within 12 months. Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study. History of bleeding diathesis, known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions Noncardiac comorbid conditions are present with life expectancy <1 year or that may result in protocol noncompliance (per site investigator's medical judgment). An elective surgical procedure is planned that would necessitate interruption of clopidogrel during the first 12 months post enrollment. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.

Ages Eligible for Study
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Minimum Age: 20 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6 months group<br>6 months duration of P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel) treatment | Drug: P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel)<br>* P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel)<br>|
| Experimental: 12 months or longer group<br>12 months or longer duration of P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel) treatment | Drug: P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel)<br>* P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of all-cause mortality, spontaneous myocardial infarction (MI), and cerebrovascular event | defined as MACCE | at 18-month after the index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Individual component of MACCE | at 18-month after the index procedure | 
| Spontaneous MI | Individual component of MACCE | at 18-month after the index procedure | 
| Cerebrovascular event | Individual component of MACCE | at 18-month after the index procedure | 
| Stent thrombosis | Definite or probable stent thrombosis defined by Academic Research Consortium (ARC) | at 18-month after the index procedure | 
| Bleeding | Bleeding Academic Research Consortium (BARC) type 2 to 5 | at 18-month after the index procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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duration of DAPT