PROMISE III: 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 III Trial

A prospective, single-arm, multi-center study designed to gather additional information on the LimFlow System.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease; Critical Limb Ischemia; Chronic Limb-Threatening Ischemia
• Intervention / Treatment: Device: LimFlow Stent Graft System

Detailed Description

The objective of this study is to provide additional information on 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 in subjects ineligible for conventional endovascular or surgical limb salvage procedures.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Erin Towery; Phone Number: 888-478-7705; Email: etowery@limflow.com

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Withdrawn
      • University of California, San Diego Health
    • Palo Alto, California, United States, 94304
      • Completed
      • Stanford University School of Medicine
    • San Francisco, California, United States, 94143
      • Completed
      • UCSF
    • Torrance, California, United States, 90502
      • Completed
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Completed
      • Yale University
  • Florida
    • Gainesville, Florida, United States, 32605
      • Recruiting
      • The Cardiac and Vascular Institute
      • Contact: Marti Roberson; Phone Number: 352-359-1561; Email: mroberson@tcavi.com
      • Principal Investigator: Arthur Lee, MD
    • Gainesville, Florida, United States, 32608
      • Completed
      • University of Florida
    • Tallahassee, Florida, United States, 32308
      • Withdrawn
      • Tallahassee Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Completed
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Anahita Dua, MD
      • Contact: Erin McSweeney; Phone Number: 617-726-2264; Email: emcsweeney@mgh.harvard.edu
    • Boston, Massachusetts, United States, 02118
      • Withdrawn
      • Boston Medical Center
    • Worcester, Massachusetts, United States, 01655
      • Completed
      • UMass Chan Medical School
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Withdrawn
      • Washington University / Barnes Jewish
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Recruiting
      • Dartmouth-Hitchcock Medical Center
      • Contact: Michelle Keyes; Phone Number: 603-650-7966; Email: Michelle.R.Keyes@hitchcock.org
      • Principal Investigator: Joceyln Beach, MD
  • New Jersey
    • Pomona, New Jersey, United States, 08240
      • Completed
      • Vascular Institute of Atlantic Medical Imaging
    • Teaneck, New Jersey, United States, 07666
      • Completed
      • Holy Name Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87113
      • Completed
      • Presbyterian Healthcare
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health Long Island Jewish Medical Center
      • Contact: Sally Kaplan; Phone Number: 516-233-3781; Email: skaplan2@northwell.edu
      • Principal Investigator: Yana Etkin
    • New York, New York, United States, 10016
      • Completed
      • NYU Langone Health
    • New York, New York, United States, 10029
      • Completed
      • Mount Sinai
    • New York, New York, United States, 10065
      • Completed
      • Cornell University
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Completed
      • Atrium Health
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Principal Investigator: Mehdi Shishehbor, MD
      • Contact: Amy McKnight; Phone Number: 216-983-4896; Email: amy.mcknight@uhhospitals.org
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Completed
      • Penn State Health
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Alice Chen; Phone Number: 267-521-7303; Email: Alice.Chen1@Pennmedicine.upenn.edu
      • Principal Investigator: Elizabeth Genovese
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Daniel Clair
      • Contact: Celia Nunez; Phone Number: 615-322-4559; Email: celia.m.nunez@vumc.org
  • Texas
    • Dallas, Texas, United States, 75390
      • Completed
      • UT Southwestern Medical Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Sentara Norfolk General Hospital
      • Contact: Sarah Havert; Phone Number: 757-388-2991; Email: sshavert@sentara.com
      • Principal Investigator: David Dexter
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Withdrawn
      • Ascension Columbia St. Mary's Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Withdrawn
      • The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 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 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. Subject is willing and able to sign the informed consent form.
6. 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.
7. Prior to enrollment (7-day window), women of childbearing potential must have a negative pregnancy test.
8. Primary wound is stable (e.g., not rapidly deteriorating and/or showing signs of healing).
9. Stable glycemic control, HbA1C < 10% (<269mg/dL)

10. 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. 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.
4. Absence of adequate viable tissue in target foot.
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. Subject is unwilling, 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: Treated with LimFlow; Treatment with the LimFlow Stent Graft System	Device: LimFlow Stent Graft System; Creation of an arteriovenous fistula in the desired limb location

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amputation Free Survival	Freedom from major (above-ankle) amputation and death (all-cause mortality)	6 Months

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
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
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
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
Secondary Patency	Absence of occlusion of the endovascular intervention that is maintained with the use of additional or secondary surgical or endovascular procedures after occlusion occurs	30 Days
Secondary Patency	Absence of occlusion of the endovascular intervention that is maintained with the use of additional or secondary surgical or endovascular procedures after occlusion occurs	6 Months
Limb Salvage	Percentage of subjects with freedom from above-ankle amputation of the index limb	30 Days
Limb Salvage	Percentage of subjects with freedom from above-ankle amputation of the index limb	3 Months
Limb Salvage	Percentage of subjects with freedom from above-ankle amputation of the index limb	6 Months
Change in Rutherford Classification	A change of one class or greater	30 Days
Change in Rutherford Classification	A change of one class or greater	3 Months
Change in Rutherford Classification	A change of one class or greater	6 Months
Technical Success	The successful creation of an arteriovenous fistula in the desired limb location with immediate morphological success	Intraprocedurally
Procedural Success	The 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
Target Wound Healing	Complete healing of the patient's target wound	30 Days
Target Wound Healing	Complete healing of the patient's target wound	3 Months
Target Wound Healing	Complete healing of the patient's target wound	6 Months
Target Wound Healing	Complete healing of the patient's target wound	12 Months
All Wound Healing	Complete healing of the patient's wounds	30 Days
All Wound Healing	Complete healing of the patient's wounds	3 Months
All Wound Healing	Complete healing of the patient's wounds	6 Months
All Wound Healing	Complete healing of the patient's wounds	12 Months
All Wound Area Reduction	Reduction in area of the patient's wounds	30 Days
All Wound Area Reduction	Reduction in area of the patient's wounds	3 Months
All Wound Area Reduction	Reduction in area of the patient's wounds	6 Months
All Wound Area Reduction	Reduction in area of the patient's wounds	12 Months
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.	72 hours
Procedure Time	The time of the first puncture (venous or arterial) to when the last catheter is removed	Intraprocedurally
Radiation Exposure	Patient radiation exposure (in milligray) during the procedure	Intraprocedurally
Contrast Volume	The total volume of contrast media (in milliliters) given during the procedure	Intraprocedurally

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 12, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: PAD; CLI; CLTI
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ischemia; Pathological Conditions, Signs and Symptoms; Chronic Limb-Threatening Ischemia; Peripheral Arterial Disease
• Other Study ID Numbers: LF-CA-PR-53

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share

Drug and device information, study documents

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