EVOLVE Short DAPT Study

Study Overview
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Brief Summary
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The EVOLVE Short DAPT Study is a prospective, multicenter, single-arm study designed to assess the safety of 3-month DAPT in subjects at high risk for bleeding undergoing PCI with a SYNERGY Stent System.

Detailed Description
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The primary objective of the EVOLVE Short DAPT Study is to assess the safety of 3-month dual antiplatelet therapy (DAPT) in subjects at high risk for bleeding undergoing percutaneous coronary intervention (PCI) with the SYNERGY Stent System. The study will be conducted up to 120 sites worldwide in the United States, Europe, Japan, and Brazil with planned enrollment of up to 2,250 subjects. Clinical follow-up will be required at the following time points: 3 months, 6 months, 12 months and 15 months post index procedure. Subjects must be treated with one of the following P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor) for 3 months following the index procedure. Subjects must be treated with aspirin for the duration of the trial. The minimum daily maintenance dose of aspirin should be 75-100 mg. Subjects are eligible for discontinuation of P2Y12 inhibitor at 3 months if they meet both of the following criteria: subject was treated with 3 months of study required antiplatelet therapy post index procedure; and subject was free from events (stroke, MI, PCI, coronary artery bypass graft [CABG], and stent thrombosis) between the index procedure and the 3 month visit. Subjects are not eligible for discontinuation of P2Y12 inhibitor at 3 months if any of the following criteria are met: subject who experiences a stroke, MI, PCI, CABG and/or stent thrombosis, during the 0-3 month period (between the date of the index procedure and the date of the 3-month follow-up visit); or subject who is non-compliant with study required antiplatelet therapy during the 0-3 month period (between the date of the index procedure and the date of the 3-month follow-up visit); or subject judged inappropriate for discontinuation from P2Y12 inhibitor use at 3 months due to another condition requiring chronic P2Y12 inhibitor use. All enrolled subjects who receive a SYNERGY stent must be followed at all milestones through 15-months, regardless of eligibility to discontinue P2Y12 inhibitor. Following the 3-month milestone, subjects who experience MI or stent thrombosis events should be treated per the investigator's discretion and should be followed through the 15-month visit.

Official Title
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A Prospective, Multicenter, Single-arm Study Designed to Assess the Safety of 3-month Dual Antiplatelet Therapy (DAPT) in Subjects at High Risk for Bleeding Undergoing Percutaneous Coronary Intervention (PCI) With the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: 3 months of dual antiplatelet therapy (DAPT)
* Device: SYNERGY Stent System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is considered at high risk for bleeding, defined as meeting one or more of the following criteria at the time of enrollment: ≥ 75 years of age and, in the opinion of the investigator, the risk of major bleeding associated with >3 months of DAPT outweighs the benefit, need for chronic or lifelong anticoagulation, history of major bleeding (severe/life threatening or moderate bleeding based on the GUSTO classification) within 12 months of the index procedure, history of stroke (ischemic or hemorrhagic), renal insufficiency (creatinine ≥2.0 mg/dl) or failure (dialysis dependent), platelet count ≤100,000/μL Subject must be at least 18 years of age Subject must have had implantation of at least one SYNERGY stent within the preceding 3 calendar days Subject must be able to take study required antiplatelet therapy (as required per protocol) Subject is willing to comply with all protocol requirements, including agreement to stop taking P2Y12 inhibitor at the 3-month milestone, if eligible per protocol Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any study-specific procedures are performed For subjects less than 20 years of age enrolled at a Japanese site, the subject/ the subject's legal representative must provide written informed consent before any study-specific tests or procedures are performed Exclusion Criteria: Subject with an indication for the index procedure of acute ST elevation MI (STEMI) Subject with an indication for the index procedure of Non ST elevation MI (NSTEMI), based on the 3rd Universal MI definition Subject with treatment with another coronary stent, other than SYNERGY, during the index procedure Subject with planned staged procedures. (Note: Planned staged procedures are allowed if performed within 7 days and with only SYNERGY stents). Subject has a known allergy to contrast (that cannot be adequately pre-medicated), the SYNERGY stent system or protocol-required concomitant medications (e.g., everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors and aspirin) Subject with implantation of a drug-eluting stent within 9 months prior to index procedure Subject previously treated at any time with intravascular brachytherapy Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding Subject is participating in an investigational drug or device clinical trial that has not reached its primary endpoint (Note: registry, observational, data collection studies are not exclusionary) Subject intends to participate in an investigational drug or device clinical trial within 15 months following the index procedure (Note: registry, observational, data collection studies are not exclusionary) Subject judged inappropriate for discontinuation from P2Y12 inhibitor use at 3 months, due to another condition requiring chronic P2Y12 inhibitor use Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor within 3 months following index procedure Subject is a woman who is pregnant or nursing Subject with a current medical condition with a life expectancy of less than 15 months Target lesion(s) is located in the left main Target lesion(s) is located within 3 mm of the origin of the left anterior descending (LAD) coronary artery or left circumflex (LCx) coronary artery by visual estimate Subject has unprotected left main coronary artery disease ( > 50% diameter stenosis) Planned treatment of more than 3 lesion Planned treatment of lesions in more than 2 major epicardial vessels Target lesion(s) treated that involve complex bifurcation (i.e. bifurcation lesion requiring treatment with more than one stent) Target lesion(s) is restenotic from a previous stent implantation Target lesion(s) is located within a saphenous vein graft or an arterial graft Target lesion(s) with a TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing Thrombus, or possible thrombus, present in the target vessel (by visual estimate)

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYNERGY stent + 3 month DAPT<br>Subject with implantation of at least one SYNERGY stent within the preceding 3 calendar days that takes the required dual antiplatelet therapy (3 months of P2Y12 inhibitor, 15 months of aspirin) | Drug: 3 months of dual antiplatelet therapy (DAPT)<br>* 3 months of P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) plus 15-months of aspirin<br>Device: SYNERGY Stent System<br>* SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Death or Myocardial Infarction (MI) | Rate of death or myocardial infarction | 3 to 15 months | 
| Number of Participants Who Experienced Stent Thrombosis (ST) | Rate of stent thrombosis: definite + probable, using the Academic Research Consortium (ARC) definition Confirmed/Definite (is considered either angiographic confirmed or pathologic confirmed) Probable Clinical definition of probable stent thrombosis is considered to have occurred in the following cases: Any unexplained death within the first 30 days Irrespective of the time after the index procedure and MI in the absence of any obvious cause which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis Possible Clinical definition of possible stent thrombosis is considered to have occurred with any unexplained death beyond 30 days. | 3 to 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Major Bleeding | Rate of Bleeding, per Bleeding Academic Consortium definition (BARC2, 3a, 3b, 3c, 4, 5a and 5b) Type 0: No Bleeding Type 1: Bleeding that is not actionable and does not cause the patient to seek treatment Type 2: Any clinically overt sign of hemorrhage that is actionable and requires diagnostic studies, hospitalization, or treatment by a health care professional Type 3a: Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding Type 3b: Overt bleeding plus hemoglobin drop ≥5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents Type 3c: Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision Type 4: CABG-related bleeding within 48 hours Type 5a: Probable fatal bleeding Type 5b: Definite fatal bleeding | 3 to 15 months |