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

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").

Study Overview

• Status: Active, not recruiting
• Conditions: Vascular Diseases; Arterial Occlusive Diseases; Peripheral Arterial Disease; Peripheral Vascular Disease; Peripheral Artery Disease; Critical Limb Ischemia; Arterial Disease; Arterial Occlusion; Critical Lower Limb Ischemia; Chronic Limb-Threatening Ischemia; Peripheral Artery Occlusion; Peripheral Ischemia
• Intervention / Treatment: Device: LimFlow System

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00731
    • Ponce Medical School
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Torrance, California, United States, 90502
      • Harbor-UCLA Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
    • Gainesville, Florida, United States, 32605
      • The Cardiac and Vascular Institute
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • UnityPoint Health
  • Louisiana
    • Kenner, Louisiana, United States, 70065
      • Ochsner Health System
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Missouri
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Heart Institute
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Atrium Health
    • Wilmington, North Carolina, United States, 28401
      • Coastal Carolina Surgical Associates
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health -- Midlands
    • Greenville, South Carolina, United States, 29615
      • Prisma Health -- Upstate
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78723
      • Seton Heart
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 94 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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
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
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
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 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.	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 post-procedure
Limb Salvage	The percentage of subjects with freedom from above-ankle amputation of the index limb.	30 days post-procedure
Change in Rutherford Classification	A decrease in Rutherford class number (i.e.: from Rutherford class 5 to 4) is clinical improvement	30 days post-procedure
Target Wound Healing	Complete healing of the patient's target wound	30 days post-procedure
All Wound Healing	Complete healing of the patient's wounds.	30 days 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
All Wound Area Reduction	Defined as reduction in area of the patient's wounds	30 days post-procedure
Primary Patency	Absence of occlusion of the endovascular intervention that is maintained without the need for additional or secondary surgical or endovascular procedures.	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.	6 months post-procedure
Limb Salvage	The percentage of subjects with freedom from above-ankle amputation of the index limb.	3 months days post-procedure
Limb Salvage	The percentage of subjects with freedom from above-ankle amputation of the index limb.	6 months days post-procedure
Change in Rutherford Classification	A change of one Rutherford class or greater.	3 months post-procedure
Change in Rutherford Classification	A change of one Rutherford class or greater.	6 months post-procedure
Target Wound Healing	Complete healing of the patient's target wound	3 months post-procedure
Target Wound Healing	Complete healing of the patient's target wound	6 months post-procedure
Target Wound Healing	Complete healing of the patient's target wound	9 months post-procedure
Target Wound Healing	Complete healing of the patient's target wound	12 months post-procedure
All Wound Area Reduction	Defined as reduction in area of the patient's wounds	3 months post-procedure
All Wound Area Reduction	Defined as reduction in area of the patient's wounds	6 months post-procedure
All Wound Area Reduction	Defined as reduction in area of the patient's wounds	9 months post-procedure
All Wound Area Reduction	Defined as reduction in area of the patient's wounds	12 months post-procedure
All Wound Healing	Complete healing of the patient's wounds.	3 months post-procedure
All Wound Healing	Complete healing of the patient's wounds.	6 months post-procedure
All Wound Healing	Complete healing of the patient's wounds.	9 months post-procedure
All Wound Healing	Complete healing of the patient's wounds.	12 months post-procedure

Collaborators and Investigators

• Sponsor: LimFlow, Inc.
• Investigators: Principal Investigator: Daniel Clair, MD, Vanderbilt University; Principal Investigator: Mehdi Shishehbor, University Hospital Cleveland

Publications and helpful links

General Publications

• Shishehbor MH, Powell RJ, Montero-Baker MF, Dua A, Martinez-Trabal JL, Bunte MC, Lee AC, Mugglin AS, Mills JL, Farber A, Clair DG; PROMISE II Investigators. Transcatheter Arterialization of Deep Veins in Chronic Limb-Threatening Ischemia. N Engl J Med. 2023 Mar 30;388(13):1171-1180. doi: 10.1056/NEJMoa2212754.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2019
• Primary Completion (Actual): September 9, 2022
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PAD; Peripheral Artery Disease; Amputation; CLI; Critical Limb Ischemia; CLTI; Desert Foot; Chronic Limb-Threatening Ischemia; TADV - Transcatheter Arterialization of Deep Veins; DVA - Deep Vein Arterialization
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Arteriosclerosis; Disease Attributes; Atherosclerosis; Chronic Disease; Vascular Diseases; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Arterial Occlusive Diseases; Chronic Limb-Threatening Ischemia
• Other Study ID Numbers: LF-CA-PR-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes