The EVOLVE II Clinical Trial To Assess the SYNERGY Stent System for the Treatment of Atherosclerotic Lesion(s)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and effectiveness of the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System for the treatment of subjects with atherosclerotic lesion(s) ≤ 34 mm in length (by visual estimate) in native coronary arteries ≥2.25 mm to ≤4.0 mm in diameter (by visual estimate).

Detailed Description
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A concurrent, non-randomized, single-arm, pharmacokinetic (PK) substudy and a consecutive, non-randomized, single-arm, Diabetes substudy will also enroll under the EVOLVE II protocol.

Official Title
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EVOLVE II: A Prospective Multicenter Trial to Assess the Safety and Effectiveness of the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System (SYNERGY Stent System) for the Treatment of Atherosclerotic Lesion(s)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: PROMUS Element Plus
* Device: SYNERGY


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 18 years of age Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific tests or procedures are performed For subjects less than 20 years of age enrolled at a Japanese site, the subject and the subject's legal representative must provide written informed consent before any study-specific tests or procedures are performed Subject is eligible for percutaneous coronary intervention (PCI) Subject has symptomatic coronary artery disease with objective evidence of ischemia or silent ischemia Subject is an acceptable candidate for coronary artery bypass grafting (CABG) Subject is willing to comply with all protocol-required follow-up evaluation Angiographic Inclusion Criteria (visual estimate): Target lesion(s) must be located in a native coronary artery with a visually estimated reference vessel diameter (RVD) ≥2.25 mm and ≤4.0 mm Target lesion(s) length must be ≤34 mm (by visual estimate) Target lesion(s) must have visually estimated stenosis ≥50% and <100% with thrombolysis in Myocardial Infarction (TIMI) flow >1 and one of the following: stenosis ≥70%, abnormal fractional flow reserve (FFR), abnormal stress or imaging stress test, or elevated biomarkers prior to the procedure Coronary anatomy is likely to allow delivery of a study device to the target lesions(s) The first lesion treated must be successfully predilated/pretreated Exclusion Criteria: Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation MI (STEMI) Subject has cardiogenic shock, hemodynamic instability requiring inotropic or mechanical circulatory support, intractable ventricular arrhythmias, or ongoing intractable angina Subject has received an organ transplant or is on a waiting list for an organ transplant Subject is receiving or scheduled to receive chemotherapy within 30 days before or after the index procedure Planned PCI (including staged procedures) or CABG after the index procedure Subject previously treated at any time with intravascular brachytherapy _ Subject has a known allergy to contrast (that cannot be adequately premedicated) and/or the trial stent system or protocol-required concomitant medications (e.g., platinum, platinum-chromium alloy, stainless steel, everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors, or aspirin) Subject has one of the following (as assessed prior to the index procedure): Other serious medical illness (e.g., cancer, congestive heart failure) with estimated life expectancy of less than 24 months Current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.) Planned procedure that may cause non-compliance with the protocol or confound data interpretation Subject is receiving chronic (≥72 hours) anticoagulation therapy (i.e., heparin, coumadin) for indications other than acute coronary syndrome Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3 Subject has a white blood cell (WBC) count < 3,000 cells/mm3 Subject has documented or suspected liver disease, including laboratory evidence of hepatitis Subject is on dialysis or has baseline serum creatinine level >2.0 mg/dL (177µmol/L) Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions Subject has had a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding Subject has severe symptomatic heart failure (i.e., NYHA class IV) Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint Subject intends to participate in another investigational drug or device clinical trial within 12 months after the index procedure Subject with known intention to procreate within 12 months after the index procedure (women of child-bearing potential who are sexually active must agree to use a reliable method of contraception from the time of screening through 12 months after the index procedure) Subject is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential) Angiographic Exclusion Criteria (visual estimate): Planned treatment of more than 3 lesions Planned treatment of lesions in more than 2 major epicardial vessels Planned treatment of a single lesion with more than 1 stent Subject has 2 target lesions in the same vessel that are separated by less than 15 mm (by visual estimate) 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 Target lesion(s) is located within a saphenous vein graft or an arterial graft Target lesion(s) will be accessed via a saphenous vein graft or arterial graft Target lesion(s) with a TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing Target lesion(s) treated during the index procedure that involves a complex bifurcation (e.g., bifurcation lesion requiring treatment with more than 1 stent) Target lesion(s) is restenotic from a previous stent implantation or study stent would overlap with a previous stent Subject has unprotected left main coronary artery disease (>50% diameter stenosis) Subject has been treated with any type of PCI (i.e., balloon angioplasty, stent, cutting balloon atherectomy) within 24 hours prior to the index procedure 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Promus Element Plus<br>PROMUS Element Plus is a device/drug combination product composed of two components, a device (coronary stent system including a platinum chromium stent platform) and a drug product (a formulation of everolimus contained in a polymer coating). | Device: PROMUS Element Plus<br>* A drug eluting coronary stent system<br>|
| Experimental: SYNERGY<br>SYNERGY is a device/drug combination product composed of two components, a device (coronary stent system including a platinum chromium stent platform) and a drug product (a formulation of everolimus contained in a bioabsorbable polymer coating). | Device: SYNERGY<br>* A drug eluting coronary stent system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Target Lesion Failure (TLF) at 12 Months | TLF is defined as any ischemia-driven revascularization of the target lesion, myocardial infarction (Q-wave and non-Q-wave) related to the target vessel, or cardiac death. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Target Lesion Revascularization (TLR) at 12 Months. | The TLR overall rate includes: TLR Percutaneous Coronary Intervention (PCI) & TLR Coronary Artery Bypass Graft (CABG). | 12 months | 
| Percentage of Participants With Target Vessel Revascularization (TVR) at 12 Months. | TVR overall includes: TVR PCI & TVR CABG. | 12 months | 
| Percentage of Participants With Target Vessel Failure (TVF) at 12 Month. | Target Vessel Failure is defined as any ischemic-driven revascularization of the target vessel, MI related to the target vessel, or any cardiac death. | 12 months | 
| Percentage of Participants With Myocardial Infarction at 12 Month. | The MI rate includes: MI's related to the Target Vessel, MI's with unknown relationship to the Target Vessel and MI's not related to the Target Vessel. | 12 months | 
| Percentage of Participants With Cardiac Death at 12 Month. |  | 12 months | 
| Percentage of Participants With Non-Cardiac Death at 12 Month. |  | 12 months | 
| Percentage of Patients That Died at 12 Months. | The Death rate includes Cardiac- & Non-Cardiac Death. | 12 months | 
| Percentage of Patients With Cardiac Death or Myocardial Infarction (MI) at 12 Month. |  | 12 months | 
| Percentage of Participants Who Died or Had an Myocardial Infarction (MI) at 12 Month. |  | 12 months | 
| Percentage of Participants Who Died, Had an Myocardial Infarction (MI) or a Target Vessel Revascularization (TVR) at12 Month. |  | 12 months | 
| Percentage of Participants With a ARC (Academic Research Consortium) Stent Thrombosis Rate at 12 Month. |  | 12 months | 
| Percentage of Patients With a Stroke at 12 Month. | The stroke rate includes: Ischemic- , Hemorraghic- & Undetermined Stroke. | 12 months | 
| Periprocedural Technical Success Rate. | Technical Success Rate is defined as successful delivery and deployment of the study stent to the target vessel, without balloon rupture or stent embolization, and post-procedure diameter stenosis less then 30% in 2 near-orthogonal projections with TIMI 3 flow in the target lesion. Technical success is lesion based. | Day 1 (periprocedure) | 
| Periprocedural Clinical Procedural Success Rate | Procedural Success Rate is defined as post-procedure diameter less then 30% in 2 near-orthogonal projections with TIMI 3 flow in all target lesions without occurrence of in-hospital cardiac death, MI, TVR. Procedural success rate is subject based. | Day 1 (periprocedure) | 
| Percentage of Participants With a Target Lesion Failure (TLF) at 12 Month. |  | 12 month | 
| Percentage of Patients With Revascularization (=All Revascularizations) at 12 Month. | All CEC adjudicated revascularization at 12 month (Intent to treat population). | 12 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-Eluting Stents