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

• ClinicalTrials.gov Identifier: NCT03970538
• Recruitment Status: Active, not recruiting
• First Posted: May 31, 2019
• Results First Posted: February 28, 2024
• Last Update Posted: February 28, 2024
• Sponsor: LimFlow, Inc.
• Information provided by (Responsible Party): LimFlow, Inc.

Study Description

Brief Summary:

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").

Condition or disease	Intervention/treatment	Phase
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	Device: LimFlow System	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 105 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Prospective, multi-center pivotal study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Percutaneous Deep Vein Arterialization for the Treatment of Late-Stage Chronic Limb-Threatening Ischemia: the PROMISE II Trial
• Actual Study Start Date: December 6, 2019
• Actual Primary Completion Date: September 9, 2022
• Estimated Study Completion Date: February 28, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Amputation Free Survival (AFS) [ Time Frame: 6 months post-procedure ]
   freedom from major amputation and death at 6 months, compared to a historical performance goal.

Secondary Outcome Measures :

1. Primary Patency [ Time Frame: 30 days post procedure ]
   Absence of occlusion of the endovascular intervention that is maintained without the need for additional or secondary surgical or endovascular procedures.
2. Primary Assisted Patency [ Time Frame: 6 months post-procedure ]
   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.
3. Secondary Patency [ Time Frame: 30 days post-procedure ]
   Absence of occlusion of the endovascular intervention that is maintained with the use of additional or secondary surgical endovascular procedures after occlusion occurs.
4. Limb Salvage [ Time Frame: 30 days post-procedure ]
   The percentage of subjects with freedom from above-ankle amputation of the index limb.
5. Change in Rutherford Classification [ Time Frame: 30 days post-procedure ]
   A decrease in Rutherford class number (i.e.: from Rutherford class 5 to 4) is clinical improvement
6. Technical Success [ Time Frame: Immediately post-procedure ]
   The successful creation of an arteriovenous fistula in the desired limb location with immediate morphological success.
7. Procedure Success [ Time Frame: 30 days post-procedure ]
   Combination of Technical Success, and absence of all-cause death, above-ankle amputation or clinically driven major re-intervention of the stent graft.
8. Target Wound Healing [ Time Frame: 30 days post-procedure ]
   Complete healing of the patient's target wound
9. All Wound Healing [ Time Frame: 30 days post-procedure ]
   Complete healing of the patient's wounds.
10. Freedom From Contrast-Induced Nephropathy [ Time Frame: Within the first 72 hours post-procedure ]
    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.
11. Procedure Time [ Time Frame: Immediately post-procedure ]
    Time from the first puncture (venous or arterial) to when the last catheter is removed
12. Radiation Exposure [ Time Frame: During the procedure ]
    Patient radiation exposure (measured in milligray)
13. Contrast Volume [ Time Frame: During the procedure ]
    Total volume of contrast media (measured in milliliters)
14. All Wound Area Reduction [ Time Frame: 30 days post-procedure ]
    Defined as reduction in area of the patient's wounds
15. Primary Patency [ Time Frame: 6 months post procedure ]
    Absence of occlusion of the endovascular intervention that is maintained without the need for additional or secondary surgical or endovascular procedures.
16. Secondary Patency [ Time Frame: 6 months post-procedure ]
    Absence of occlusion of the endovascular intervention that is maintained with the use of additional or secondary surgical endovascular procedures after occlusion occurs.
17. Limb Salvage [ Time Frame: 3 months days post-procedure ]
    The percentage of subjects with freedom from above-ankle amputation of the index limb.
18. Limb Salvage [ Time Frame: 6 months days post-procedure ]
    The percentage of subjects with freedom from above-ankle amputation of the index limb.
19. Change in Rutherford Classification [ Time Frame: 3 months post-procedure ]
    A change of one Rutherford class or greater.
20. Change in Rutherford Classification [ Time Frame: 6 months post-procedure ]
    A change of one Rutherford class or greater.
21. Target Wound Healing [ Time Frame: 3 months post-procedure ]
    Complete healing of the patient's target wound
22. Target Wound Healing [ Time Frame: 6 months post-procedure ]
    Complete healing of the patient's target wound
23. Target Wound Healing [ Time Frame: 9 months post-procedure ]
    Complete healing of the patient's target wound
24. Target Wound Healing [ Time Frame: 12 months post-procedure ]
    Complete healing of the patient's target wound
25. All Wound Area Reduction [ Time Frame: 3 months post-procedure ]
    Defined as reduction in area of the patient's wounds
26. All Wound Area Reduction [ Time Frame: 6 months post-procedure ]
    Defined as reduction in area of the patient's wounds
27. All Wound Area Reduction [ Time Frame: 9 months post-procedure ]
    Defined as reduction in area of the patient's wounds
28. All Wound Area Reduction [ Time Frame: 12 months post-procedure ]
    Defined as reduction in area of the patient's wounds
29. All Wound Healing [ Time Frame: 3 months post-procedure ]
    Complete healing of the patient's wounds.
30. All Wound Healing [ Time Frame: 6 months post-procedure ]
    Complete healing of the patient's wounds.
31. All Wound Healing [ Time Frame: 9 months post-procedure ]
    Complete healing of the patient's wounds.
32. All Wound Healing [ Time Frame: 12 months post-procedure ]
    Complete healing of the patient's wounds.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California San Francisco

San Francisco, California, United States, 94143

Harbor-UCLA Medical Center

Torrance, California, United States, 90502

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06519

United States, Florida

The Cardiac and Vascular Institute

Gainesville, Florida, United States, 32605

University of Florida

Gainesville, Florida, United States, 32608

United States, Iowa

Unitypoint Health

Des Moines, Iowa, United States, 50309

United States, Louisiana

Ochsner Health System

Kenner, Louisiana, United States, 70065

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Boston Medical Center

Boston, Massachusetts, United States, 02118

United States, Missouri

Saint Luke's Hospital

Lee's Summit, Missouri, United States, 64086

United States, New Hampshire

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03766

United States, New Mexico

New Mexico Heart Institute

Albuquerque, New Mexico, United States, 87102

United States, North Carolina

Atrium Health

Charlotte, North Carolina, United States, 28203

Coastal Carolina Surgical Associates

Wilmington, North Carolina, United States, 28401

United States, Ohio

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

United States, South Carolina

Prisma Health -- Midlands

Columbia, South Carolina, United States, 29203

Prisma Health -- Upstate

Greenville, South Carolina, United States, 29615

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Seton Heart

Austin, Texas, United States, 78723

Baylor College of Medicine

Houston, Texas, United States, 77030

Puerto Rico

Ponce Medical School

Ponce, Puerto Rico, 00731

Sponsors and Collaborators

LimFlow, Inc.

Investigators

• Principal Investigator: Daniel Clair, MD; Vanderbilt University
• Principal Investigator: Mehdi Shishehbor; University Hospital Cleveland

  Study Documents (Full-Text)

Documents provided by LimFlow, Inc.:

Study Protocol  [PDF] February 3, 2021

Statistical Analysis Plan  [PDF] February 2, 2022

More Information

Publications of Results:

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.

• Responsible Party: LimFlow, Inc.
• ClinicalTrials.gov Identifier: NCT03970538
• Other Study ID Numbers: LF-CA-PR-3
• First Posted: May 31, 2019
• Results First Posted: February 28, 2024
• Last Update Posted: February 28, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by LimFlow, Inc.:

CLI; CLTI; Amputation; Desert Foot; PAD; Peripheral Artery Disease; Critical Limb Ischemia; Chronic Limb-Threatening Ischemia; TADV - Transcatheter Arterialization of Deep Veins; DVA - Deep Vein Arterialization

Additional relevant MeSH terms:

Peripheral Arterial Disease; Peripheral Vascular Diseases; Vascular Diseases; Chronic Limb-Threatening Ischemia; Arterial Occlusive Diseases; Ischemia; Pathologic Processes; Atherosclerosis; Arteriosclerosis; Cardiovascular Diseases; Chronic Disease; Disease Attributes