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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Critical Limb Ischemia, Critical Lower Limb Ischemia, Peripheral Artery Disease, Peripheral Arterial Disease, Chronic Limb-Threatening Ischemia, Arterial Occlusive Diseases, Arterial Occlusion, Arterial Disease, Peripheral Artery Occlusion, Peripheral Vascular Disease, Peripheral Ischemia, Vascular Diseases

Intervention / Treatment
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* Device: LimFlow System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥18 and ≤ 95 years of age 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 Rutherford Classification 5, ischemic ulceration or Rutherford Classification 6, ischemic gangrene 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. 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. Prior stent(s) to the infrainguinal arteries (e.g. iliac, SFA, and popliteal) are allowed. Planned minor amputation (e.g. partial toe, ray or proximal foot/transmetatarsal) of target extremity within 30 days after the index procedure is allowed. Subject is willing and able to sign the informed consent form. 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. Prior to enrollment (7-day window), women of childbearing potential must have a negative pregnancy test. Primary wound is stable (e.g. not rapidly deteriorating and/or showing signs of healing) Stable glycemic control, HbA1C < 10% (<269mg/dL) 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: 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. Active immunodeficiency disorder or currently receiving immunosuppressant therapy for an immunodeficiency disorder. 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. Previous major amputation of the target limb or presence of a wound requiring a free flap or absence of adequate viable tissue. Life expectancy less than 12 months. Documented myocardial infarction or stroke within previous 90 days. 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). Known or suspected allergies or contraindications to aspirin or P2Y12 inhibitors, heparin, stainless steel, nitinol or contrast agent that cannot be adequately pre-treated. 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). 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). Significant acute or chronic kidney disease with a serum creatinine of > 2.5 mg/dl in subjects not undergoing dialysis. 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. 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. 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) Subject is unwilling, or unable, or unlikely for cognitive or social reasons to comply with any of the protocol or follow-up requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 94 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, multi-center pivotal study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Treated with the LimFlow System | Device: LimFlow System<br>* Creation of an AV fistula in below-the-knee vasculature for the treatment of critical limb ischemia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amputation Free Survival (AFS) | freedom from major amputation and death at 6 months, compared to a historical performance goal. | 6 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency | Absence of occlusion of the endovascular intervention that is maintained without the need for additional or secondary surgical or endovascular procedures. | 30 days and 6 months post-procedure | 
| Primary Assisted Patency | Absence of occlusion of the endovascular intervention maintained with the use of additional or secondary surgical or endovascular procedures, as long as occlusion of the primary treated site has not occurred. | 30 days and 6 months post-procedure | 
| Secondary Patency | Absence of occlusion of the endovascular intervention that is maintained with the use of additional or secondary surgical endovascular procedures after occlusion occurs. | 30 days and 6 months post-procedure | 
| Limb Salvage | The percentage of subjects with freedom from above-ankle amputation of the index limb. | 30 days, 3 and 6 months post-procedure | 
| Change in Rutherford Classification | A change of one Rutherford class or greater. | 30 days, 3 and 6 months post-procedure | 
| Technical Success | The successful creation of an arteriovenous fistula in the desired limb location with immediate morphological success. | Immediately post-procedure | 
| Procedure Success | Combination of Technical Success, and absence of all-cause death, above-ankle amputation or clinically driven major re-intervention of the stent graft. | 30 days post-procedure | 
| Target Wound Healing | Complete healing of the patient's target wound | 30 days, 3, 6, 9, and 12 months post-procedure | 
| All Wound Healing | Complete healing of the patient's wounds. | 30 days, 3, 6, 9, and 12 months post-procedure | 
| Freedom from Contrast-Induced Nephropathy | Subjects without acute (within 72 hours after intravenous contrast administration) impairment of renal function, measured as an absolute ≥0.5 mg/dL (44 µmol/L) increase compared to baseline SCr value that results in a value above the upper limit of the normal range. | Within the first 72 hours post-procedure | 
| Procedure Time | Time from the first puncture (venous or arterial) to when the last catheter is removed | Immediately post-procedure | 
| Radiation Exposure | Patient radiation exposure (measured in milligray) | During the procedure | 
| Contrast Volume | Total volume of contrast media (measured in milliliters) | During the procedure | 
| All Wound Area Reduction | Defined as reduction in area of the patient's wounds | 30 days, 3, 6, 9, and 12 months post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLI, CLTI, Amputation, Desert Foot, PAD, Peripheral Artery Disease, Critical Limb Ischemia, Chronic Limb-Threatening Ischemia