The EVOLVE China Clinical Trial

The EVOLVE China clinical trial is designed 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) in native coronary arteries in China. The SYNERGY™ Stent System (Boston Scientific Corporation [BSC Corporation], Natick, Massachusetts, United States) is based on the well characterized Element™ stent platform and utilizes a bioabsorbable poly(DL-lactide-co-glycolide) (PLGA) polymer to deliver everolimus.

While SYNERGY is a new generation DES, the safety and effectiveness of the Element stent platform in combination with everolimus in the form of the PROMUS Element stent has been established in the PLATINUM Clinical Trial Program.The PROMUS Element Plus stent (control device) uses the same stent platform as PROMUS Element stent with a modified balloon component on the Stent Delivery System to improve overall system deliverability. In addition, the previous version of the SYNERGY stent, the SYNERGY First Human Use stent (SYNERGY FHU stent) has been investigated in the EVOLVE FHU trial which has completed its primary endpoint and demonstrated comparable safety and efficacy profile of SYNERGY FHU to PROMUS Element up to 1-year follow-up (28). SYNERGY has been approved by CE Mark.

Inclusion criteria

• CI1. Subject must be 18 -75 years of age
• CI2. 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
• CI3. Subject is eligible for percutaneous coronary intervention (PCI)
• CI4. Subject has symptomatic coronary artery disease with objective evidence of ischemia or silent ischemia
• CI5. Subject is an acceptable candidate for coronary artery bypass grafting (CABG)
• CI6. Subject is willing to comply with all protocol-required follow-up evaluation
• CI7. Subject has a left ventricular ejection fraction (LVEF) >30% as measured within 60 days prior to enrollment
• AI1. Target lesion(s) must be de novo lesion located in a native coronary artery with a visually estimated reference vessel diameter (RVD) ≥2.25 mm and ≤4.0 mm
• AI2. Target lesion(s) length must be ≤34 mm (by visual estimate)
• AI3. 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
• AI4. Coronary anatomy is likely to allow delivery of a study device to the target lesions(s)
• AI5. The first lesion treated must be successfully predilated/pretreated

Exclusion criteria

• CE1. Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute MI .
• CE2. Subject with unstable angina or recent MI (within 1 week) must have CK/CK-MB or troponin documented prior to the procedure and are excluded if any of the following criteria are met at the time of the index procedure:

• If CK MB >2× upper limit of normal (ULN), the subject is excluded regardless of the CK Total.
• If CK Total >2× ULN, either CK-MB or troponin must be drawn and the subject is excluded if either CK-MB or troponin is abnormal.
• If neither CK Total or CK MB is drawn but troponin is, the subject is excluded if troponin >1× ULN and the subject has at least one of the following:

• Subject has ischemic symptoms and ECG changes indicative of ongoing ischemia (e.g., >1 mm ST segment elevation or depression in consecutive leads or new left bundle branch block [LBBB])
• Development of pathological Q waves in the ECG or
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
• CE3. Subject has cardiogenic shock, hemodynamic instability requiring inotropic or mechanical circulatory support, or intractable ventricular arrhythmias or ongoing intractable angina
• CE4. Subject has received an organ transplant or is on a waiting list for an organ transplant
• CE5. Subject is receiving or scheduled to receive chemotherapy within 30 days before or after the index procedure
• CE6. Planned PCI or CABG after the index procedure
• CE7. Subject has a known allergy to 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, clopidogrel, or aspirin) and contrast (that cannot be adequately premedicated)
• CE8. Subject has a known condition(s) of the following (as assessed from the time of screening through the day of index procedure):

• Other serious medical illness (e.g., cancer, congestive heart failure) that may reduce life expectancy to 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
• CE9. Subject is receiving chronic (≥72 hours) anticoagulation therapy (i.e., heparin, Coumadin) for indications other than acute coronary syndrome
• CE10. Subject with out of range complete blood count (CBC) values that are determined by the study physician to be clinically significant.
• CE11. Subject has documented or suspected liver disease, including laboratory evidence of hepatitis
• CE12. Subject is on dialysis or has baseline serum creatinine level >2.0 mg/dL (177µmol/L)
• CE13. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions
• CE14. Subject has had a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months
• CE15. Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding
• CE16. Subject has signs or symptoms of active heart failure (i.e., NYHA class IV) at the time of the index procedure
• CE17. Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint
• CE18. Subject intends to participate in another investigational drug or device clinical trial within 12 months after the index procedure
• CE19. 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)
• CE20. 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)
• CE21. Target vessel has been treated with any type of PCI (e.g., balloon angioplasty, stent, cutting balloon, atherectomy) within 12 months prior to the index procedure
• AE1. Planned treatment of more than 2 lesions
• AE2. Planned treatment of lesions in more than 2 major epicardial vessels
• AE3. Planned treatment of a single lesion with more than 1 stent Note: Planned use of 2 overlapping stents will be allowed in subjects randomized to PROMUS Element Plus where lesion length is ≥28 mm and 2.25 mm stents are used.
• AE4. Target lesion meets any of the following criteria:

• Left main location
• Located within 3 mm of the origin of the left anterior descending (LAD) coronary artery or left circumflex (LCX) coronary artery by visual estimate
• Located within a saphenous vein graft or an arterial graft
• Will be accessed via a saphenous vein graft or an arterial graft
• TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing
• Thrombus, or possible thrombus, present in the target vessel
• Excessive tortuosity proximal to or within the lesion
• Excessive angulation proximal to or within the lesion
• Target lesion and/or the target vessel proximal to the target lesion is moderately to severely calcified by visual estimate
• Involves a side branch ≥2.0 mm in diameter by visual estimate or a side branch <2.0 mm in diameter by visual estimate which requires treatment
• AE5. Target lesion(s) treated during the index procedure that involves a complex bifurcation (e.g., bifurcation lesion requiring treatment with more than 1 stent)
• AE6. Target lesion(s) is restenostic from a previous stent implantation or study stent would overlap with a previous stent
• AE7. Subject has unprotected left main coronary artery disease (>50% diameter stenosis)
• AE8. Subject has protected left main coronary artery disease (>50% diameter stenosis in the LMCA with bypass graft(s) to the left coronary artery) and a target lesion in the LAD or LCX