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

Peripheral Arterial Disease Clinical Trial

— PROMISE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03970538
• Other study ID #: LF-CA-PR-3
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 6, 2019
• Est. completion date: February 28, 2025

Study information

• Verified date: January 2024
• Source: LimFlow, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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").

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: February 28, 2025
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Device:
• LimFlow System
Creation of an AV fistula in below-the-knee vasculature for the treatment of critical limb ischemia

Locations

Country	Name	City	State
Puerto Rico	Ponce Medical School	Ponce
United States	New Mexico Heart Institute	Albuquerque	New Mexico
United States	Seton Heart	Austin	Texas
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Atrium Health	Charlotte	North Carolina
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Prisma Health -- Midlands	Columbia	South Carolina
United States	Unitypoint Health	Des Moines	Iowa
United States	The Cardiac and Vascular Institute	Gainesville	Florida
United States	University of Florida	Gainesville	Florida
United States	Prisma Health -- Upstate	Greenville	South Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Ochsner Health System	Kenner	Louisiana
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Luke's Hospital	Lee's Summit	Missouri
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	University of California San Francisco	San Francisco	California
United States	Harbor-UCLA Medical Center	Torrance	California
United States	Coastal Carolina Surgical Associates	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
LimFlow, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

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. 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amputation Free Survival (AFS)	freedom from major amputation and death at 6 months, compared to a historical performance goal.	6 months post-procedure
Secondary	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
Secondary	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	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
Secondary	Limb Salvage	The percentage of subjects with freedom from above-ankle amputation of the index limb.	30 days post-procedure
Secondary	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
Secondary	Technical Success	The successful creation of an arteriovenous fistula in the desired limb location with immediate morphological success.	Immediately post-procedure
Secondary	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
Secondary	Target Wound Healing	Complete healing of the patient's target wound	30 days post-procedure
Secondary	All Wound Healing	Complete healing of the patient's wounds.	30 days post-procedure
Secondary	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
Secondary	Procedure Time	Time from the first puncture (venous or arterial) to when the last catheter is removed	Immediately post-procedure
Secondary	Radiation Exposure	Patient radiation exposure (measured in milligray)	During the procedure
Secondary	Contrast Volume	Total volume of contrast media (measured in milliliters)	During the procedure
Secondary	All Wound Area Reduction	Defined as reduction in area of the patient's wounds	30 days post-procedure
Secondary	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	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
Secondary	Limb Salvage	The percentage of subjects with freedom from above-ankle amputation of the index limb.	3 months days post-procedure
Secondary	Limb Salvage	The percentage of subjects with freedom from above-ankle amputation of the index limb.	6 months days post-procedure
Secondary	Change in Rutherford Classification	A change of one Rutherford class or greater.	3 months post-procedure
Secondary	Change in Rutherford Classification	A change of one Rutherford class or greater.	6 months post-procedure
Secondary	Target Wound Healing	Complete healing of the patient's target wound	3 months post-procedure
Secondary	Target Wound Healing	Complete healing of the patient's target wound	6 months post-procedure
Secondary	Target Wound Healing	Complete healing of the patient's target wound	9 months post-procedure
Secondary	Target Wound Healing	Complete healing of the patient's target wound	12 months post-procedure
Secondary	All Wound Area Reduction	Defined as reduction in area of the patient's wounds	3 months post-procedure
Secondary	All Wound Area Reduction	Defined as reduction in area of the patient's wounds	6 months post-procedure
Secondary	All Wound Area Reduction	Defined as reduction in area of the patient's wounds	9 months post-procedure
Secondary	All Wound Area Reduction	Defined as reduction in area of the patient's wounds	12 months post-procedure
Secondary	All Wound Healing	Complete healing of the patient's wounds.	3 months post-procedure
Secondary	All Wound Healing	Complete healing of the patient's wounds.	6 months post-procedure
Secondary	All Wound Healing	Complete healing of the patient's wounds.	9 months post-procedure
Secondary	All Wound Healing	Complete healing of the patient's wounds.	12 months post-procedure