Tailored Versus Coventional AntiPlaTelet Strategy Intended After OPTIMIZEd Drug Eluting Stent

Study Overview
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Brief Summary
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Objectives: To assess the safety of tailored antiplatelet therapy (short DAPT followed by P2Y12 inhibitor alone strategy) in patients who received optimized DES implantation guided by intravascular imaging (IVUS or OCT) Hypothesis: Tailored antiplatelet strategy (short DAPT followed by P2Y12 inhibitor alone) is superior to conventional antiplatelet strategy in terms of clinically relevant bleeding and noninferior for ischemic composite adverse events in patients who received intravascular imaging-guided optimized DES implantation. (Optimized stent evaluated by on-site IVUS/OCT could act as an essential criterion for decision making for tailored antithrombotic strategy)

Detailed Description
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Objective: To assess the safety of tailored antiplatelet strategy (short DAPT followed by P2Y12 inhibitor alone) in patients who received optimized DES implantation guided by intravascular imaging (IVUS or OCT) Design: Prospective, open label, multi-center, dual arm, randomized trial Number of Subjects 3,944 subjects (1972:1972) Study Population: Patients with coronary artery disease undergoing imaging-guided PCI Study Design: Eligible subjects will be randomized 1:1 to a) conventional DAPT strategy or b) tailored anti-platelet strategy (short DAPT followed by P2Y12 inhibitor alone) after optimized DES implantation guided by intravascular imaging. All subjects will be clinically followed at 1, 6, and 12 months Co-primary Endpoints: Clinically relevant bleeding (BARC 2, 3, or 5) at 12 months post-PCI Ischemic composite adverse events of all-cause death, MI, ischemia-driven TVR, stent thrombosis at 12 months post-PCI Net clinical outcome (NACE) of all-cause death, MI, ischemia-driven TVR, stent thrombosis, BARC 2,3,5 bleeding at 12 months post-PCI Statistics and Analysis: The study was designed to test the hypothesis that tailored antithrombotic strategy, as compared to the conventional DAPT, would be superior for clinically relevant bleeding, noninferior to the ischemic composite adverse events and NACE. The primary analysis would be evaluated by intention-to-treat analysis. With 3756 (each 1,878) patients, this study has >80% power to detect noninferiority of tailored antiplatelet strategy for ischemic composite adverse event, >85% power to detect noninferiority of tailored antiplatelet strategy for NACE, and >85% power to detect superiority of the tailored antiplatelet arm on clinically relevant bleeding. To compensate for 5% attrition rate, 3,944 (each 1,972) patients will be randomized.

Official Title
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Tailored Versus Coventional AntiPlaTelet Strategy Intended After OPTIMIZEd Drug

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥19 years Typical chest pain or objective evidence of myocardial ischemia suitable for PCI Significant de novo coronary artery lesions suitable for DES implantation Patients who underwent optimized stent implantation either by IVUS or OCT Using IVUS MSA >5.5 mm2, or MSA >90% of the MLA at the distal reference segment Plaque burden <50% with 5 mm of both stent edge No edge dissection, thrombus or plaque protrusion/stent area <10% Using OCT MSA >4.5 mm2, or MSA >90% of the MLA at the distal reference segment No significant malapposition No significant edge dissection, thrombus or plaque protrusion/stent area <10% The patient or guardian agrees to the study protocol and the schedule of clinical follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site Exclusion Criteria: Angiographic exclusion criteria: any of the followings 1. Bypass graft lesions 2. Lesions in which impaired delivery of imaging catheters is expected: Extreme angulation (≥90°) proximal to or within the target lesion. Excessive tortuosity (≥ two 45° angles) proximal to or within the target lesion. Heavy calcification proximal to or within the target lesion. In-stent restenosis Hypersensitivity or contraindication to device material and its degradants and cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoro polymers that cannot be adequately pre-medicated. Persistent thrombocytopenia (platelet count <80,000/l) Any history of hemorrhagic stroke or intracranial hemorrhage / TIA or ischemic stroke within the past 6 months A known intolerance or hypersensitivity to a study drug (aspirin, clopidogrel or ticagrelor) or heparin Patients requiring long-term oral anticoagulants or cilostazol Any surgery requiring general anesthesia or discontinuation of aspirin and/or an ADP antagonist is planned within 12 months after the procedure. A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study. History of liver cirrhosis (Child-Pugh B or C) or biliary tract obstruction Life expectancy < 1 years for any non-cardiac or cardiac causes Cardiogenic shock at the index admission Patient's pregnant or breast-feeding Active bleeding or extreme-risk for major bleeding (e.g. active peptic ulcer disease, gastrointestinal pathology with a high risk for bleeding, malignancies with a high risk for bleeding) Unwillingness or inability to comply with the procedures described in this protocol.

Ages Eligible for Study
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Minimum Age: 19 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: Eligible subjects will be randomized 1:1 to a) conventional DAPT strategy or b) tailored anti-platelet strategy (short DAPT followed by P2Y12 inhibitor alone) after optimized DES implantation guided by intravascular imaging. All subjects will be clinically followed at 1, 6, and 12 months
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional Arm<br>After PCI, patients are prescribed aspirin at a daily dose of 100 mg PO plus a P2Y12 inhibitor [clopidogrel or ticagrelor or prasugrel according to the clinical diagnosis] for 12 months after the index PCI. | Drug: aspirin<br>* DAPT strategy<br>* Other names: ticagrelor;|
| Experimental: Tailored Arm<br>The antiplatelet regimens post-PCI are 1-month DAPT (aspirin plus clopidogrel) followed by 11-months clopidogrel alone for CCS, and 3-months DAPT (aspirin plus P2Y12 inhibitor [ticagrelor, prasugrel]) followed by 9-months P2Y12 inhibitor alone for ACS. | Drug: aspirin<br>* DAPT strategy<br>* Other names: ticagrelor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1) clinically relevant bleeding [Bleeding Academic Research Consortium (BARC) 2, 3, or 5] | 1) clinically relevant bleeding [Bleeding Academic Research Consortium (BARC) 2, 3, or 5] | 12 month | 
| 2) net clinical outcome defined as a composite of all-cause death, MI, ischemia-driven target vessel revascularization (TVR), definite/probable stent thrombosis (ST), and clinically relevant bleeding [BARC 2, 3, or 5] | 2) net clinical outcome defined as a composite of all-cause death, MI, ischemia-driven target vessel revascularization (TVR), definite/probable stent thrombosis (ST), and clinically relevant bleeding [BARC 2, 3, or 5] | 12 month | 
| 3) ischemic composite adverse event of all-cause death, MI, ischemia-driven target vessel revascularization (TVR), definite/probable stent thrombosis (ST) | 3) ischemic composite adverse event of all-cause death, MI, ischemia-driven target vessel revascularization (TVR), definite/probable stent thrombosis (ST) | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1) Major or minor bleeding according to definitions from TIMI and International Society of Thrombosis or Hemostasis (ISTH) | 1) Major or minor bleeding according to definitions from TIMI and International Society of Thrombosis or Hemostasis (ISTH) | 12 month | 
| 2) % difference of strut coverage on FU OCT between optimal vs. suboptimal DES implantation group | 2) % difference of strut coverage on FU OCT between optimal vs. suboptimal DES implantation group | 1 or 3 month |