PROMISE II: Percutaneous Deep Vein Arterialization for the Treatment of Late-Stage Chronic Limb-Threatening Ischemia

Percutaneous Deep Vein Arterialization for the Treatment of Late-Stage Chronic Limb-Threatening Ischemia: the PROMISE II Trial

The LimFlow System is intended for endovascular, minimally invasive procedures in patients who have a clinical diagnosis of chronic limb-threatening ischemia and who have been determined to have no surgical or endovascular treatment option (i.e., "no option").

The objective of this US pivotal trial is to investigate the safety and effectiveness of The LimFlow System for creating an AV connection in the Below The Knee (BTK) vascular system using an endovascular, minimally invasive approach to arterialize the pedal veins for the treatment of chronic limb-threatening ischemia (CLTI) in subjects ineligible for conventional endovascular or surgical limb salvage procedures.

Inclusion Criteria:

1. Subject must be ≥18 and ≤ 95 years of age

2. Clinical diagnosis of chronic limb-threatening ischemia, defined as any of the following clinical assessments: previous angiogram or hemodynamic evidence of severely diminished arterial inflow of the index limb (e.g., ABI ≤ 0.39, TP / TcPO2 < 30 mm Hg) and

   1. Rutherford Classification 5, ischemic ulceration or
   2. Rutherford Classification 6, ischemic gangrene

3. Subject has been assessed by the principal investigator, reviewed by the Independent Review Committee (IRC), and determined that no conventional distal bypass surgical or endovascular therapy for limb salvage is feasible due to either a) absence of a usable pedal artery target (endovascular or surgical approach), or b) the presence of a pedal artery target with absence of a viable single-segment vein in either lower extremity or either arm that could be used for autogenous vein conduit.

4. Proximally, the Target In-flow Artery at the cross-over point must fall within the recommended vessel diameter ranges for the LimFlow stent graft by visual estimation.

5. Prior stent(s) to the infrainguinal arteries (e.g. iliac, SFA, and popliteal) are allowed.

6. Planned minor amputation (e.g. partial toe, ray or proximal foot/transmetatarsal) of target extremity within 30 days after the index procedure is allowed.

7. Subject is willing and able to sign the informed consent form.

8. Subject is enrolled in an acceptable wound care network and has an adequate support network to ensure that subject is compliant with medication regimen and follow-up study visits.

9. Prior to enrollment (7-day window), women of childbearing potential must have a negative pregnancy test.

10. Primary wound is stable (e.g. not rapidly deteriorating and/or showing signs of healing)

11. Stable glycemic control, HbA1C < 10% (<269mg/dL)

12. Subjects requiring dialysis may be included, provided they meet all the following requirements:

    • On dialysis for > 6 months
    • Autologous arteriovenous (AV) fistula or peritoneal access used for hemodialysis
    • Serum albumin > 30 g/liter
    • BMI > 20

Exclusion Criteria:

1. Subjects will be excluded from participating in this study if they meet any of the following criteria prior to initiation of the endovascular procedure: Concomitant hepatic insufficiency, thrombophlebitis in the target limb, or non-treatable coagulation disorder within the past 90 days.
2. Active immunodeficiency disorder or currently receiving immunosuppressant therapy for an immunodeficiency disorder.
3. Prior peripheral arterial bypass procedure above or below the knee which would inhibit proximal inflow to the stent graft or interventional revascularization procedure within 30 days.
4. Previous major amputation of the target limb or presence of a wound requiring a free flap or absence of adequate viable tissue.
5. Life expectancy less than 12 months.
6. Documented myocardial infarction or stroke within previous 90 days.
7. Active infection (e.g. fever, significantly elevated WBC count >20.0 x 109/L, and/or positive blood culture) at the time of the index procedure that may preclude insertion of a prosthesis or require major amputation (e.g. osteomyelitis proximal to metatarsals).
8. Known or suspected allergies or contraindications to aspirin or P2Y12 inhibitors, heparin, stainless steel, nitinol or contrast agent that cannot be adequately pre-treated.
9. Subject is currently taking anti-coagulants, which in the opinion of the investigator, interferes with the subject's ability to participate in the study (i.e., intermittent interruption of therapy for procedure may compromise subject's safety).
10. Lower extremity vascular disease that may inhibit the procedure and/or jeopardize wound healing (e.g. vasculitis, Buerger's disease, significant edema in the target limb, deep venous thrombus in the target vein, hyperpigmentation, or medial ulceration above the ankle).
11. Significant acute or chronic kidney disease with a serum creatinine of > 2.5 mg/dl in subjects not undergoing dialysis.
12. Severe heart failure (e.g. NYHA Class IV), which in the opinion of the investigator may compromise subject's ability to safely undergo a percutaneous procedure.
13. Any significant concurrent medical, psychological, or social condition, which may significantly interfere with the subject's optimal participation in the study, in the opinion of the investigator.
14. The subject is currently participating in another investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the endpoints of this study.
15. 15) Subject is unwilling, or unable, or unlikely for cognitive or social reasons to comply with any of the protocol or follow-up requirements.