Safety and Efficacy Study of the Amaranth Medical MAGNITUDE Bioresorbable Drug-Eluting Coronary Stent (RENASCENT III)

Restoring Endoluminal Narrowing Using Bioresorbable Scaffolds - Extended Trial III

The purpose of this study is to evaluate the safety and performance of a new version of a coronary artery stent for treating blockages in the arteries supplying blood to the heart muscle. The Amaranth Medical MAGNITUDE scaffold releases a drug (sirolimus) to reduce the likelihood of the treated blood vessel developing a new blockage. In addition, the scaffold dissolves away over time, leaving no permanent implant after the blood vessel has healed.

The objective of this study is to evaluate the safety and performance of the AmM MAGNITUDE Bioresorbable Drug-Eluting Coronary Scaffold for use in the treatment of up to two different de novo native coronary artery lesions in patients undergoing elective percutaneous coronary intervention. The scaffold is a single-use device comprised of a balloon-expandable, intracoronary drug coated scaffold pre-mounted on a rapid-exchange delivery catheter. The scaffold is made of Poly-L-Lactide (PLLA) and is coated with a polymer-antiproliferative drug (sirolimus) matrix. The scaffold provides mechanical support similar to a metallic stent to the vessel while it is healing, and then gradually breaks down over time leaving no permanent implant in the treated vessel. Compared to prior versions of the scaffold, the new device has a thinner strut design (a wall thickness of 100 µm rather than 120 µm or 150 µm), but is otherwise identical.

The study design is a prospective, non-randomized, multi-center, non-inferiority trial. It will enroll a maximum of 70 patients from up to 20 investigational centers in Colombia and the European Union. Eligible patients who are at least 18 years of age diagnosed with symptomatic ischemic disease due to up to two different, de novo, stenotic lesions in native coronary arteries will be asked to participate in this study. After treatment with the investigational device, subjects will be followed for five years. Safety of the device will be evaluated using the incidence of target vessel failure during the follow-up period. Performance (efficacy) will be assessed using the in-scaffold late lumen loss measured by quantitative coronary angiography at nine months.

Inclusion Criteria:

General

1. Subject is ≥ 18 years of age and < 85 years of age.

2. Subject agrees not to participate in any other investigational device or drug study for a period of two years following the index procedure. Questionnaire-based studies, or other studies that are non-invasive and do not require investigational devices or medications are allowed.

3. Subject (or their legally authorized representative) provides written informed consent prior to any study-related procedure, using the form approved by the local Ethics Committee.

4. Subject has:

   1. evidence of myocardial ischemia (e.g., stable angina [Canadian Cardiovascular Society 1, 2, 3, or 4] or unstable angina [Braunwald Class 1-3, B-C], or silent ischemia with supporting imaging studies [ETT, SPECT, stress echocardiography, or Cardiac CT]), or
   2. low or intermediate risk NSTEMI, or
   3. evidence of myocardial ischemia in a coronary territory previously affected by STEMI as long as the lesion fulfills the angiographic inclusion criteria and the intervention performed ≥ 3 months following the STEMI.

5. Subject is an acceptable candidate for coronary artery bypass graft (CABG) surgery.

6. Patient agrees to complete all protocol required follow-up visits, including angiograms.

Angiographic

1. Patient indicated for elective stenting of up to two de novo native coronary artery lesions.

2. If two lesions are to be treated, they must either be located in two separate epicardial vessels (side branches are considered separate vessels) or if located within a single epicardial vessel be separated by ≥ 15 mm of angiographically normal vessel.

3. If an elective percutaneous intervention for two different lesions is planned, one of the following situations must apply:

   1. If both lesions are suitable for stenting with the MAGNITUDE™ scaffold, both lesions can be treated during the same procedure. In case a staging strategy is chosen, no minimum period between the staged interventions is required. In either strategy, the distal lesion must be intended to be treated first and before the proximal lesion.

   2. If one lesion is intended to be treated with a litmus-based metallic DES and the second lesion is a study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold), the two lesions must be located in two different epicardial vessels (side branches are considered separate vessels). Both lesions can be treated during the same procedure. In case a staging strategy is chosen, no minimum period between the staged interventions is required. However, all of the following conditions must apply:

      • Non-study lesion must be successfully treated without clinically significant complications prior to treatment of the study lesion.
      • Non-study lesion must be ≤ 30 mm in length.
      • Reference vessel diameter for the non-study lesion must be ≥ 2.75 mm by QCA.
      • Non-study lesion does not involve left main stenting, bifurcation stenting, chronic total occlusion, or high thrombotic burden.

4. Each study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold) must measure ≤ 14 mm in length by on-line QCA.

5. Each study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold) must be located in a native coronary artery with a diameter (average of distal and proximal to lesion by IVUS) of 2.5 mm to 3.5 mm.

6. Each study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold) must be in a major artery/branch with a visually estimated diameter stenosis of ≥ 50% and < 100% with a Thrombolysis in Myocardial Infarction (TIMI) flow of ≥ 1.

Exclusion Criteria:

General

1. Patient has known hypersensitivity or contraindication to aspirin, both heparin and bivalirudin, antiplatelet medication specified for use in the study (clopidogrel, prasugrel, and ticagrelor), sirolimus or its derivatives, poly (L-lactide), poly (D,L-lactide), platinum-iridium, or contrast sensitivity that cannot be adequately pre-medicated.
2. Patient has evolving ST segment elevation myocardial infarction (STEMI).
3. Patient has current unstable arrhythmias.
4. Patient has a left ventricular ejection fraction (LVEF) < 30%.
5. Patient has received a heart transplant or any other organ transplant, or is on a waiting list for any organ transplant.
6. Patient has any previous stent placements ≤ 15 mm (proximal or distal) of the study lesion(s) (e.g., suitable for stenting with the MAGNITUDE™ scaffold).
7. Patient is receiving or scheduled to receive chemotherapy for malignancy ≤ 30 days prior to or after the index procedure.
8. Patient is receiving immunosuppressant therapy and/or has known immunosuppressive or autoimmune disease (e.g. human immunodeficiency virus, systemic lupus erythematosus, rheumatoid arthritis, severe asthma requiring immunosuppressive medication, etc.).
9. Patient is receiving or scheduled to receive chronic anticoagulation therapy (e.g., heparin, Coumadin) that cannot be stopped and restarted according to local hospital standard procedures.
10. Elective surgery is planned ≤ 9 months after the index procedure that will require discontinuation of anti-platelet medications.
11. Patient has a platelet count < 100,000 cells/mm^3 or > 700,000 cells/mm^3, a WBC of < 3,000 cells/mm^3, or documented or suspected liver disease (including laboratory evidence of hepatitis).
12. Patient has known renal insufficiency (e.g., eGFR < 60 ml/kg/m^2 or serum creatinine level of > 2.5 mg/dL, or subject on dialysis).
13. Patient has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions.
14. Patient has had a cerebrovascular accident (CVA) or transient ischemic neurological attack (TIA) ≤ 6 months prior to the index procedure.
15. Patient has had a significant GI or urinary bleed ≤ 6 months prior to the index procedure.
16. Patient has extensive peripheral vessel disease that precludes safe introducer sheath insertion.
17. Patient has received brachytherapy in any epicardial vessel (including side branches).
18. Pregnant or nursing subjects and those who plan pregnancy ≤ 2 years following index procedure. (Note: Subjects of child-bearing potential must have a negative pregnancy test ≤ 28 days prior to the index procedure and agree to use contraception for 2 years.)
19. Patient has other medical illness (e.g., cancer or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin, etc.) that per physician judgment that may cause non-compliance with the protocol or confound the data interpretation or is associated with a life expectancy ≤ 1 year.
20. Subject belongs to a vulnerable population (e.g., subordinate hospital staff, mentally deficient, or unable to read or write).

Angiographic Exclusion

1. A study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold) meets any of the following criteria:

   1. Aorto-ostial location (within ≤ 3 mm of aorta junction).
   2. Left Main location.
   3. Located ≤ 3 mm of the origin of the left anterior descending (LAD) or left coronary circumflex (LCX).
   4. Located within an arterial or saphenous vein graft or distal to a diseased (defined as vessel irregularity per angiogram and > 20% stenosed lesion, by visual estimation) arterial or saphenous vein graft.
   5. Lesion involving a bifurcation > 2 mm in diameter and ostial lesion > 40% stenosed by visual estimation or side branch requiring predilatation.
   6. Total occlusion (TIMI flow 0) prior to wire crossing.
   7. Excessive tortuosity (≥ two 45° angles), or extreme angulation (≥ 90°) proximal to or within the target lesion.
   8. Restenotic from previous intervention.
   9. Moderate to severe superficial calcification (defined as calcium arch > 120°) proximal to or within the target lesion.

2. A study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold) involving a myocardial bridge.

3. A study vessel (e.g., having a lesion suitable for stenting with the MAGNITUDE™ scaffold) contains visible thrombus as indicated in the angiographic images.

4. Another clinically significant lesion is located in the same major epicardial vessel(s) (including side branches) as a study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold).

5. Inadequate pre-dilation (residual stenosis > 40% by visual assessment) of a study lesion (e.g., suitable for stenting with the MAGNITUDE™ scaffold).

6. Patient has a high probability of use of other ancillary devices (e.g., atherectomy or cutting balloon) will be required at the time of index procedure for treatment of a study vessel (e.g., having a lesion suitable for stenting with the MAGNITUDE™ scaffold).