A Clinical Evaluation of Absorb™ Bioresorbable Vascular Scaffold (Absorb™ BVS) System in Chinese Population ~ ABSORB CHINA Randomized Controlled Trial (RCT)

A Clinical Evaluation of Absorb™ BVS, the Bioresorbable Vascular Scaffold, in the Treatment of Subjects With de Novo Native Coronary Artery Lesions in Chinese Population

To evaluate the safety and efficacy of the Absorb BVS System compared to the XIENCE V Everolimus Eluting Coronary Stent System (EECSS) in the treatment of subjects with ischemic heart disease caused by up to two de novo native coronary artery lesions in separate epicardial vessels.

Inclusion Criteria:

1. Subject must be at least 18 years of age at the time of signing the informed consent form.
2. Subject or a legally authorized representative must provide written Informed Consent prior to any study related procedure.
3. Subject must have evidence of myocardial ischemia (e.g., stable angina, unstable angina, post-infarct angina or silent ischemia) suitable for elective percutaneous coronary intervention (PCI). Subjects with stable angina or silent ischemia and < 70% diameter stenosis must have objective sign of ischemia as determined by one of the following, echocardiogram, nuclear scan, ambulatory ECG or stress ECG. In the absence of noninvasive ischemia, fractional flow reserve (FFR) must be done and indicative of ischemia.
4. Subject must be an acceptable candidate for coronary artery bypass graft (CABG) surgery.
5. Female subject of childbearing potential does not plan pregnancy for up to 1 year following the index procedure. For a female subject of childbearing potential, a pregnancy test must be performed with negative results known within 14 days (≤14 days) prior to the index procedure per site standard test.
6. Female subject is not breast-feeding at the time of the screening visit and will not be breast-feeding for up to 1 year following the index procedure.
7. Subject agrees to not participate in any other investigational clinical studies for a period of 1 year following the index procedure.

Exclusion Criteria:

1. Any surgery requiring general anesthesia or discontinuation of aspirin and/or P2Y12 inhibitor is planned within 12 months after the index procedure.

2. Subject has a known hypersensitivity or contraindication to device material (cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers) and its degradants (everolimus, poly (L-lactide), poly (DL-lactide), lactide, lactic acid). Subject has a known contrast sensitivity that cannot be adequately pre-medicated.

3. Subject has a known allergic reaction, hypersensitivity or contraindication to:

   1. Aspirin; or
   2. All P2Y12 inhibitors (including clopidogrel and ticlopidine, and prasugrel and ticagrelor when they become available); or
   3. Heparin and bivalirudin.

4. Subject had an acute myocardial infarction (AMI) within 7 days of the index procedure and both creatine kinase (CK) and creatine kinase myocardial-band isoenzyme (CK-MB) have not returned to within normal limits at the time of index procedure.

5. Subject is currently experiencing clinical symptoms consistent with new onset AMI, such as nitrate-unresponsive prolonged chest pain with ischemic ECG changes.

6. Subject has a cardiac arrhythmia as identified at the time of screening which at least one of the following criteria is met:

   1. Subject requires coumadin or any other agent for chronic oral anticoagulation.
   2. Subject likely to become hemodynamically unstable due to their arrhythmia.
   3. Subject has poor survival prognosis due to their arrhythmia.

7. Subject has a known left ventricular ejection fraction (LVEF) < 30% assessed by any quantitative method. LVEF may be obtained within 6 months prior to the procedure for subjects with stable coronary artery disease (CAD). For subjects presenting with acute coronary syndrome (ACS), LVEF must be assessed during the index hospitalization (which may include during the index procedure by contrast left ventriculography) but prior to randomization in order to confirm the subject's eligibility.

8. Subject has received CABG at any time in the past.

9. Subject has undergone prior PCI within the target vessel during the last 12 months or undergone prior PCI within the non-target vessel within 30 days before the index procedure.

10. Subject requires future staged PCI either in target or non-target vessels.

11. Subject has received any solid organ transplants or is on a waiting list for any solid organ transplants.

12. At the time of screening, the subject has a malignancy that is not in remission.

13. Subject is receiving immunosuppressant therapy or has known immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.). Note: corticosteroids are not included as immunosuppressant therapy.

14. Subject has previously received or is scheduled to receive radiotherapy to coronary artery (vascular brachytherapy), or chest/mediastinum.

15. Subject is receiving or will receive chronic anticoagulation therapy (e.g., coumadin or any other anticoagulation agents).

16. Subject has a platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3.

17. Subject has a known or documented hepatic disorder as defined as cirrhosis or Child-Pugh ≥ Class B.

18. Subject has known renal insufficiency as defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 or dialysis at the time of screening.

19. Subject is high risk of bleeding; has a history of bleeding diathesis or coagulopathy; has had a significant gastro-intestinal or significant urinary bleed within the past six months; will refuse blood transfusions.

20. Subject has had a cerebrovascular accident or transient ischemic neurological attack (TIA) within the past six months or any prior intracranial bleed, any permanent neurologic defect, or any known intracranial pathology (e.g., aneurysm, arteriovenous malformation, etc.).

21. Subject has extensive peripheral vascular disease that precludes safe 6 French sheath insertion. Note: femoral arterial disease does not exclude the subject if radial or brachial access can be used.

22. Subject has life expectancy < 2 years for any non-cardiac cause or cardiac cause.

23. Subject is in the opinion of the Investigator or designee, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.

24. Subject is currently participating in another clinical trial that has not yet completed its primary endpoint or protocol-required medications or invasive procedures.

Angiographic Inclusion Criteria

Assessment of angiographic eligibility is per visual assessment by an investigator both for qualitative and quantitative variables. On-line QCA is recommended to be used for appropriately sizing of the vessel. If on-line QCA cannot be used, visual estimation is required.

1. One or two de novo target lesions:

   1. If there is one target lesion, a second non-target lesion may be treated but the non-target lesion must be present in a different epicardial vessel, and must be treated first with a successful, uncomplicated result prior to randomization of the target lesion.
   2. If two target lesions are present, they must be present in different epicardial vessels and both satisfy the angiographic eligibility criteria.
   3. The definition of epicardial vessels means the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA) and their branches. Thus, for example, the subject must not have lesions requiring treatment in both the LAD and a diagonal branch.

2. Target lesion must be located in a native coronary artery with a visually estimated or quantitatively assessed %DS of ≥ 50% and < 100% with a thrombolysis in myocardial infarction (TIMI) flow of ≥ 1 and one of the following: stenosis ≥ 70%, an abnormal functional test (e.g., fractional flow reserve, stress test), unstable angina or post-infarct angina.

3. Target lesion must have a Dmax (by on-line QCA) or reference vessel diameter (RVD) (by visual estimation) ≥ 2.50 mm and ≤ 3.75 mm (on-line QCA assessment is recommended).

4. Target lesion must have a lesion length ≤ 24 mm based on either visual estimation or on-line QCA.

Angiographic Exclusion Criteria

All exclusion criteria apply to the target lesion(s) or target vessel(s). All exclusion criteria are based on visual estimation.

1. Target lesion is located in left main.

2. Aorto-ostial RCA target lesion (within 3 mm of the ostium).

3. Target lesion located within 3 mm of the origin of the LAD or LCX.

4. Lesion involving a bifurcation with a:

   1. Side branch ≥ 2 mm in diameter, or
   2. Side branch with diameter stenosis ≥ 50%, or
   3. Side branch requiring protection guide wire, or
   4. Side branch requiring pre-dilatation

5. Anatomy proximal to or within the lesion that may impair delivery of the Absorb BVS or XIENCE V, including:

   1. Extreme angulation (≥ 90°) proximal to or within the target lesion
   2. Excessive tortuosity (≥ two 45° angles) proximal to or within the target lesion
   3. Moderate or heavy calcification proximal to or within the target lesion

6. Target lesion or target vessel involves a myocardial bridge.

7. Target vessel contains thrombus as indicated in the angiographic images.

8. Target vessel has been previously treated with a stent at any time prior to the index procedure such that the Absorb BVS or XIENCE V would need to cross the stent to reach the target lesion.

9. Target vessel has been previously treated with a stent and the target lesion is within 5 mm proximal to a previously treated lesion.

10. Target lesion which prevents complete balloon pre-dilatation, defined as full balloon expansion with the following outcomes:

    1. Residual %DS is < 40% (per visual estimation), ≤ 20% is strongly recommended.
    2. TIMI Grade-3 flow (per visual estimation).
    3. No angiographic complications (e.g. distal embolization, side branch closure).
    4. No dissections National Heart, Lung, and Blood Institute (NHLBI) grade D-F.
    5. No chest pain lasting > 5 minutes.
    6. No ST depression or elevation lasting > 5 minutes.