The ABSORB BTK (Below The Knee) Clinical Investigation

A Clinical Evaluation of the Everolimus Eluting Bioresorbable Vascular Scaffold System (BVS) for the Treatment of Subjects With Critical Limb Ischemia (CLI) From Occlusive Vascular Disease of the Tibial Arteries

The purpose of the ABSORB BTK Clinical Investigation is to evaluate the safety and efficacy of the Everolimus Eluting Bioresorbable Vascular Scaffold System (BVS) in subjects with critical limb ischemia (CLI) following percutaneous transluminal angioplasty (PTA) of the tibial arteries.

Inclusion Criteria:

1. Subject must be at least 18 and ≤ 80 years of age.
2. History of symptomatic critical limb ischemia (CLI) (Rutherford Becker Clinical Category 4 or 5).
3. Subject is able to take at least one type of thienopyridine (e.g. clopidogrel) and acetylsalicylic acid (eg. Aspirin/ASA).
4. The subject must have a life-expectancy of more than 1 year.
5. Female subjects of childbearing potential must have had a negative pregnancy test within 14 days before treatment, must not be nursing at the time of treatment, and must also agree at time of consent to use birth control during participation in this study up to and including the angiographic follow-up at 1 year.
6. Subject has been informed of the nature of the study, agrees to its provisions, and has signed the informed consent form prior to any study related procedure.
7. Subject must agree to undergo all protocol-required follow-up examinations and requirements at the investigational site.
8. Subject must agree not to participate in any other clinical investigation for a period of one year following the index procedure. This includes clinical trials of medications and invasive procedures. Questionnaire-based studies, or other studies that are non-invasive and do not require medication are allowed.

Anatomic Inclusion Criteria

1. Up to two de novo lesions, each located in a separate native infrapopliteal vessel, with angiographically visible above-the-ankle reconstitution (proximal to the inferior cortical margin of the talus bone), only one of which can be designated as the target lesion and is suitable to be treated with a single BVS.
2. Target lesion length is visually estimated to be ≤ 24 mm.
3. Target vessel diameter at the location of the target lesion is ≥ 2.5 mm and ≤ 3.3 mm, as assessed by on-line quantitative angiography as per core laboratory guidelines.
4. The non-target lesion (if applicable) must be located in a separate infrapopliteal vessel, estimated to be ≤ 24 mm, and suitable to be treated with non-study percutaneous transluminal angioplasty (PTA) balloon(s) and/or a non-study stent.
5. Inflow between the proximal iliac and distal popliteal is unobstructed (free from ≥ 50% stenosis) as confirmed by angiography. [Note: Assessment may be made after interventions proximal to the target lesion.]
6. Subjects with a significant lesion (≥ 50% stenosis) in the inflow artery(ies) must have the inflow artery(ies) treated successfully prior to enrollment and treatment of the target lesion.
7. If there is evidence of an ischemic lesion/ulcer on the foot, the distribution of the target vessel must supply the area of the lesion (angiosome), as confirmed by angiography.
8. At least one patent distal tibial outflow artery (< 50% stenosis) that will provide a straight line of blood flow to the distal foot and (if applicable) wound area after treating a target lesion in the tibio-peroneal trunk.
9. Patent pedal outflow artery (< 50% stenosis) that will provide a straight line of blood flow to the distal foot and (if applicable) wound area.

Exclusion Criteria:

1. Subject is unable to understand or unwilling to cooperate with study procedures.
2. The subject is mentally ill or belongs to a vulnerable population.
3. Subject is currently breast-feeding, pregnant, or intends to become pregnant prior to completion of the 1 year angiographic follow-up.
4. Subject has had any type of amputation to the ipsilateral or contralateral extremity.
5. Subject is unable to walk. (with assistance is accepted)
6. Subject has had recent major surgery (requiring general or regional anesthesia or impacting major organ systems) within the last 3 months.
7. Subject has received, or is on the waiting list for a major organ transplant.
8. Subject is diagnosed as Rutherford Becker Clinical Category 0, 1, 2, 3 or 6.
9. Subject has any type of infection, until treated successfully.
10. Subject has osteomyelitis present in the distal ipsilateral extremity.
11. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions.
12. The subject has a history of prior life-threatening contrast media reaction.
13. Subject is receiving or scheduled to receive anticancer therapy for malignancy within 1 year prior to or after the procedure.
14. Subject is receiving immunosuppression therapy, or has known serious immunosuppressive disease (e.g., human immunodeficiency virus), or has severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., systemic lupus erythematosus, etc.).
15. Subject is receiving or will receive inhibitors of CYP3A or inducers of CYP3A within 30 days prior to or following the procedure.
16. Subject is receiving Phenprocoumon (Marcumar) or is scheduled to receive chronic anticoagulation therapy.
17. Subject has severe liver impairment as defined by total bilirubin > 3 mg/dl or two times increase over the normal level of serum glutamic oxaloacetic transminase(SGOT) or serum glutamic pyruvic transminase (SGPT).
18. Subject has platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3, a WBC < 3,000 cells/mm3, or hemoglobin < 10.0 g/dl.
19. Subject has elevated serum creatinine > 2.0 mg/dl or > 150μmol/L.
20. Subject has uncontrolled diabetes mellitus (DM) (glucose > 400 mg/dl).
21. Subject has had a myocardial infarction (MI) within the previous 30 days or has unstable angina (defined as rest angina with ECG changes).
22. Subject has had a stroke within the previous 30 days and/or has deficits from a prior stroke that limits the subject's mobility.
23. Subject has acute thrombophlebitis or deep vein thrombosis in either extremity
24. Subject has known allergies to the following: aspirin, thienopyridines, heparin, contrast agent (that cannot be adequately treated with pre-medication or substitution for an alternate thienopyridine), poly (L-lactide), poly (DL-lactide), or drugs similar to everolimus (i.e. tacrolimus, sirolimus, zotarolimus), or other macrolides.
25. Subject requires any planned procedure that would necessitate the discontinuation of thienopyridines following the procedure. If the subject is enrolled into the study and then requires a medical procedure, which would necessitate the discontinuation of these medications, then the subject is to resume protocol recommended medications as soon as possible.
26. Subject has other known medical illnesses (e.g., cancer or congestive heart failure) that may cause the subject to be non-compliant with protocol requirements, confound the data interpretation, or is associated with limited life-expectancy (i.e., less than 1 year).
27. Subject is already participating in another clinical investigation that has not yet reached its primary endpoint.

Anatomic Exclusion Criteria

1. The target lesion can only be accessed via popliteal or pedal approach.
2. The target vessel diameter at the location of the target lesion is not suitable for available BVS size.
3. Unsuccessfully treated proximal inflow limiting arterial stenosis or inflow-limiting arterial lesions left untreated.
4. No angiographic evidence of a patent pedal artery.
5. Significant (> 50% stenosis) lesion in a distal outflow artery that requires treatment at the time of the index procedure.
6. More than a single significant lesion (> 50% stenosis) in the target vessel.
7. Target or (if applicable) non-target lesion location requiring bifurcation treatment method.
8. Target or (if applicable) non-target lesion lies within or adjacent to an aneurysm.
9. A segment/portion of the study scaffold will be deployed distal to the inferior cortical margin of the talus bone or in a pedal vessel.
10. Subject has previously had, or requires, bypass surgery, endarterectomy or other vascular surgery on any vessel of the ipsilateral extremity.
11. Subject has moderate to severe calcium in the target lesion or in the artery immediately adjacent to the target lesion, or the investigator is unable to pre-dilate the lesion according to vessel diameter.
12. Target or (if applicable) non-target vessel contains visible thrombus as indicated in the angiographic images.
13. Subject has angiographic evidence of thromboembolism or atheroembolism in the ipsilateral extremity. (Pre and post-angiographic images must confirm the absence of emboli in the distal anatomy.)
14. Target or (if applicable) non-target lesion has a high probability that a procedure other than pre-dilatation, implantation of the scaffold, and post-dilatation (as applicable) will be required at the time of index procedure for treatment of the target vessel (e.g., atherectomy, cutting balloon, etc.).
15. Subject has lesions in the target vessel that were treated or will require treatment < 1 year pre-or post- study procedure.
16. Subject has lesions in any other vascular anatomy, other than those treated at the time of the study procedure, that were treated or will require treatment < 30 days pre-or post- study procedure.
17. Subject has had or will require treatment with a drug-eluting/coated stent or drugcoated balloon in any vessel < 90 days pre-or post-study procedure.