Absorb IV Randomized Controlled Trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring Absorb™ BVS, Angioplasty, Bioabsorbable, BVS, Coronary Artery Disease, Coronary Artery Endothelial Responsiveness, Coronary artery restenosis, Coronary artery stenosis, Coronary scaffold, Coronary Stent, Drug eluting stents, Everolimus, Myocardial ischemia, Stent thrombosis, Stents Read More

General Inclusion Criteria:

1. Subject must be at least 18 years of age.
2. Subject or a legally authorized representative must provide written Informed Consent prior to any study related procedure, per site requirements.

3. Subject must have evidence of myocardial ischemia (e.g., silent ischemia, stable or unstable angina, non-ST-segment elevation MI (NSTEMI), OR recent ST-segment elevation MI (STEMI). Patients with stable coronary syndromes can be enrolled any time after symptom onset if eligibility criteria are otherwise met. Patients with acute coronary syndrome can be enrolled under the following conditions:

   1. Unstable angina or NSTEMI within 2 weeks of the index procedure.
   2. STEMI > 72 hours ≤ 2 weeks prior to the index procedure.

   Note: Subjects with Unstable angina (UA) or NSTEMI or STEMI occurring > 2 weeks of the index procedure can be included in the trial but should be categorized based on their current angina class.

4. Subjects must be suitable for PCI. Subjects with stable angina or silent ischemia and < 70% diameter stenosis must have objective signs of ischemia as determined by one of the following: abnormal stress echocardiogram, nuclear scan, electrocardiogram (ECG), positron emission tomography (PET), magnetic resonance imaging (MRI), and/or fractional flow reserve (FFR).

   (Note: subject with silent ischemia must have a prior history of typical angina, angina-equivalent symptoms, or atypical angina within the past year to be included in the trial.)

5. Subject must be an acceptable candidate for coronary artery bypass graft (CABG) surgery.
6. Female subject of childbearing potential who 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 7 days prior to the index procedure per site standard.
7. Female subject is not breast-feeding at the time of the screening visit and will not be breast-feeding for at least 1 year following the index procedure.
8. Subject agrees to not participate in any other investigational or invasive clinical study for a period of 5 years following the index procedure.

Angiographic Inclusion Criteria:

Treatment of up to three de novo lesions in a maximum of two epicardial vessels, with a maximum of two lesions per epicardial vessel. If only a single lesion is to be treated, it must be a target lesion. Up to one non-target lesion can be treated. Non-target lesion treatment can occur only in a non-target vessel.

If there are two target lesions within the same epicardial vessel, the two target lesions must be at least 15 mm apart per visual estimation; otherwise this is considered as a single target lesion for lesion (and stent) length determination and must be treated with a single study device.

1. Target lesion(s) 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 ≤0.80 AND/OR a positive stress test), or presentation with an acute coronary syndrome (unstable angina or NSTEMI within 2 weeks of index procedure, or STEMI >72 hours but ≤ 2 weeks prior to the index procedure).

1. Target lesion(s) must be located in a native coronary artery with reference vessel diameter (RVD) by visual estimation of ≥ 2.50 mm and ≤ 3.75 mm.
2. Target lesion(s) must be located in a native coronary artery with length by visual estimation of ≤ 24 mm.

Note: Subjects with Unstable angina (UA) or NSTEMI or STEMI occurring > 2 weeks of the index procedure can be included in the trial but should be categorized based on their current angina class.

Note: To exclude enrollment of excessively small vessels, if the operator believes that based on visual angiographic assessments, the distal reference vessel diameter is ≤ 2.75 mm such that the plan is to implant a 2.5 mm device (stent or scaffold) in a target lesion, it is strongly recommended that either on-line QCA or intravascular imaging (ultrasound or optical coherence tomography) is used and demonstrates that the measured distal RVD for this target lesion is ≥ 2.50 mm (by at least one of these imaging modalities). This measurement may be performed before or after pre-dilatation, but before randomization. If the distal RVD measures <2.5 mm, that lesion IS NOT ELIGIBLE for randomization. Such a lesion may be treated as a non-target lesion.

General Exclusion Criteria:

1. Any surgery requiring general anesthesia or discontinuation of aspirin and/or a P2Y12 receptor inhibitor is planned within 12 months after the procedure.
2. Subject has known hypersensitivity or contraindication to device material and its degradants (everolimus, poly (L-lactide), poly (DL-lactide), lactide, lactic acid) and cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoro polymers that cannot be adequately pre-medicated. Subject has a known contrast sensitivity that cannot be adequately pre-medicated.
3. Subject has known allergic reaction, hypersensitivity or contraindication to any of the following: aspirin; or clopidogrel and prasugrel and ticagrelor; or heparin and bivalirudin, and therefore cannot be adequately treated with study medications.
4. Subject had an acute STEMI (appropriate clinical syndrome with ≥1 mm of ST-segment elevation in ≥2 contiguous leads) within 72 hours of the index procedure.

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

   1. Subject requires coumadin or any other agent for chronic oral anticoagulation.
   2. Subject is likely to become hemodynamically unstable due to their arrhythmia.
   3. Subject has poor survival prognosis due to their arrhythmia.
6. Subject has a left ventricular ejection fraction (LVEF) < 30% assessed by any quantitative method, including but not limited to echocardiography, MRI, multiple-gated acquisition (MUGA) scan, contrast left ventriculography, PET scan, etc. LVEF may be obtained within 6 months prior to the procedure for subjects with stable CAD. For subjects presenting with acute coronary syndrome (ACS), LVEF must be assessed within 1 week of the index procedure and after ACS presentation, which may include contrast left ventriculography during the index procedure but prior to randomization in order to confirm the subject's eligibility.
7. Subject has undergone prior PCI within the target vessel during the last 12 months. Prior PCI within the non-target vessel or any peripheral intervention is acceptable if performed anytime >30 days before the index procedure, or between a minimum of 24 hours and 30 days before the index procedure if successful and uncomplicated.
8. Subject requires future staged PCI of any lesion other than a target lesion identified at the time of index procedure; or subject requires future peripheral vascular interventions < 30 days after the index procedure.
9. Subject has received any solid organ transplants or is on a waiting list for any solid organ transplants.
10. At the time of screening, the subject has a malignancy that is not in remission.
11. Subject is receiving immunosuppressant therapy or has known immunosuppressive or severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.). Note: corticosteroids are not included as immunosuppressant therapy.
12. Subject has previously received or is scheduled to receive radiotherapy to a coronary artery (vascular brachytherapy), or the chest/mediastinum.
13. Subject is receiving or will require chronic anticoagulation therapy (e.g., coumadin, dabigatran, apixaban, rivaroxaban, edoxaban or any other related agent for any reason).
14. Subject has a platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3.
15. Subject has a documented or suspected hepatic disorder as defined as cirrhosis or Child-Pugh ≥ Class B.
16. Subject has renal insufficiency as defined as an estimated glomerular filtration rate (GFR) < 30 ml/min/1.73m2 or dialysis at the time of screening.
17. Subject is high risk of bleeding for any reason; has a history of bleeding diathesis or coagulopathy; has had a significant gastrointestinal or significant urinary bleed within the past six months.
18. Subject has had a cerebrovascular accident or transient ischemic neurological attack (TIA) within the past six months, or any prior intracranial bleed, or any permanent neurologic defect, or any known intracranial pathology (e.g. aneurysm, arteriovenous malformation, etc.).
19. Subject has extensive peripheral vascular disease that precludes safe 6 French sheath insertion. Note: femoral arterial disease does not exclude the patient if radial access may be used.
20. Subject has a life expectancy <5 years for any non-cardiac or cardiac cause.
21. 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. This includes completion of Patient Reported Outcome instruments.
22. Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.
23. Subject is part of a vulnerable population who, in the judgment of the investigator, is unable to give Informed Consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include: Individuals with a mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.

Angiographic Exclusion Criteria:

All exclusion criteria apply to the target lesion(s) or target vessel(s).

1. Unsuccessful pre-dilatation, defined as the presence of one or more of the following (note: successful pre-dilatation of at least one target lesion is required prior to randomization):

   1. Residual %diameter stenosis (DS) after pre-dilatation is ≥ 40% (per visual estimation). Note: achieving a %DS ≤ 20% prior to randomization is strongly recommended.
   2. TIMI flow grade <3 (per visual estimation).
   3. Any angiographic complication (e.g. distal embolization, side branch closure).
   4. Any dissection NHLBI grade D-F.
   5. Any chest pain lasting > 5 minutes.
   6. Any ST-segment depression or elevation lasting > 5 minutes.
2. Lesion is located in left main or there is a ≥30% diameter stenosis in the left main (unless the left main lesion is a protected left main (i.e. a patent bypass graft to the LAD and/or LCX arteries is present), and there is no intention to treat the protected left main lesion).
3. Aorto-ostial right coronary artery (RCA) lesion (within 3 mm of the ostium).
4. Lesion located within 3 mm of the origin of the left anterior descending artery (LAD) or left circumflex artery (LCX).

5. Lesion involving a bifurcation with a:

   1. side branch ≥ 2 mm in diameter, or
   2. side branch with either an ostial or non-ostial lesion with diameter stenosis >50%, or
   3. side branch requiring dilatation

6. Anatomy proximal to or within the lesion that may impair delivery of the Absorb BVS or XIENCE stent:

   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. If intravascular ultrasound (IVUS) used, subject must be excluded if calcium arc in the vessel prior to the lesion or within the lesion is ≥ 180°.
7. Lesion or vessel involves a myocardial bridge.
8. Vessel has been previously treated with a stent and the target lesion is within 5 mm proximal or distal to a previously stented lesion.
9. Target lesion located within an arterial or saphenous vein graft or distal to any arterial or saphenous vein graft.