Best Endovascular vs. Best Surgical Therapy in Patients With Critical Limb Ischemia

Male and female subjects aged 18 years or older will be randomized to receive either open
surgical treatment or endovascular treatment. They will be followed for at least 2 years and
up to 4 years and 2 months after treatment to primarily assess survival and major adverse
limb events in the index or treated limb, and secondarily, to determine clinical and cost
effectiveness outcomes after treatment. These outcomes (survival-free of major limb events
and clinical, functional and cost effectiveness) will be compared within two cohorts of
subjects: those with an available single-segment great saphenous vein, and those with an
alternative conduit. The null hypotheses for both cohorts is that there will be no difference
in MALE-free survival between best endovascular therapy and best surgical therapy.

Inclusion Criteria:

1. Male or female, age 18 years or older.

2. Infrainguinal PAOD (occlusive disease of the arteries below the inguinal ligament).

3. CLI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or
rest pain consistent with Rutherford categories 4-6.

4. Candidate for both endovascular and open infrainguinal revascularization as judged by
the treating investigators

5. Adequate aortoiliac inflow.

6. Adequate popliteal, tibial or pedal revascularization target defined as an
infrainguinal arterial segment distal to the area of stenosis/occlusion which can
support a distal anastomosis of a surgical bypass.

7. Willingness to comply with protocol, attend follow-up appointments, complete all study
assessments, and provide written informed consent.

Exclusion Criteria:

1. Presence of a popliteal aneurysm (>2 cm) in the index limb.

2. Life expectancy of less than 2 years due to reasons other than PAOD.

3. Excessive risk for surgical bypass (as determined by the operating surgeon and the CLI
Team)

4. Planned above ankle amputation on ipsilateral limb within 4 weeks of index procedure.

5. Active vasculitis, Buerger's disease, or acute limb-threatening ischemia

6. Any prior index limb infrainguinal stenting or stent grafting associated with
significant restenosis within 1 cm of stent or stent-graft, unless the
occlusion/restenosis site is outside the intended treatment zone (i.e.,. a tibial
vessel that is not currently intended to be revascularized as a part of the treatment
for CLI).

7. Any of the following procedures performed on the index limb within 3 months prior to
enrollment:

1. Infrainguinal balloon angioplasty, atherectomy, stent, or stentgraft;

2. Infrainguinal bypass with either venous or prosthetic conduit

8. Open surgical inflow procedure (aortofemoral, axillofemoral, iliofemoral,
thoracofemoral or femorofemoral bypass) within 6 weeks prior to enrollment

9. Current chemotherapy or radiation therapy.

10. Absolute contraindication to iodinated contrast due to prior near-fatal anaphylactoid
reaction (laryngospasm, bronchospasm, cardiorespiratory collapse, or equivalent) which
would preclude patient participation in angiographic procedures.

11. Pregnancy or lactation.

12. Administration of an investigational drug for PAD within 30 days of randomization.

13. Participation in a clinical trial (except observational studies) within the previous
30 days.

14. Prior enrollment or randomization into BEST-CLI.