Arterial Disease, Arterial Occlusion, Arterial Occlusive Diseases, Chronic Limb-Threatening Ischemia, Critical Limb Ischemia, Critical Lower Limb Ischemia, Peripheral Arterial Disease, Peripheral Artery Disease, Peripheral Artery Occlusion, Peripheral Ischemia, Peripheral Vascular Disease, Vascular Diseases
Conditions
Keywords
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
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).
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.
Interventions
DEVICELimFlow System
Creation of an AV fistula in below-the-knee vasculature for the treatment of critical limb ischemia
Sponsors
LimFlow, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, multi-center pivotal study
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amputation Free Survival (AFS) | 6 months post-procedure | freedom from major amputation and death at 6 months, compared to a historical performance goal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary Assisted Patency | 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. |
| Secondary Patency | 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. |
| Limb Salvage | 30 days post-procedure | The percentage of subjects with freedom from above-ankle amputation of the index limb. |
| Change in Rutherford Classification | 30 days post-procedure | A decrease in Rutherford class number (i.e.: from Rutherford class 5 to 4) is clinical improvement |
| Technical Success | Immediately post-procedure | The successful creation of an arteriovenous fistula in the desired limb location with immediate morphological success. |
| Procedure Success | 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. |
| Primary Patency | 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. |
| All Wound Healing | 30 days post-procedure | Complete healing of the patient's wounds. |
| Freedom From Contrast-Induced Nephropathy | 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. |
| Procedure Time | Immediately post-procedure | Time from the first puncture (venous or arterial) to when the last catheter is removed |
| Radiation Exposure | During the procedure | Patient radiation exposure (measured in milligray) |
| Contrast Volume | During the procedure | Total volume of contrast media (measured in milliliters) |
| All Wound Area Reduction | 30 days post-procedure | Defined as reduction in area of the patient's wounds |
| Target Wound Healing | 30 days post-procedure | Complete healing of the patient's target wound |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm Treated with the LimFlow System
LimFlow System: Creation of an AV fistula in below-the-knee vasculature for the treatment of critical limb ischemia | 105 |
| Total | 105 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Continuous | 69 years STANDARD_DEVIATION 10.4 |
| Baseline Rutherford Class 5 | 68 Participants |
| Baseline Rutherford Class 6 | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants |
| Race (NIH/OMB) White | 64 Participants |
| Region of Enrollment United States | 105 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 105 |
| other Total, other adverse events | 98 / 105 |
| serious Total, serious adverse events | 68 / 105 |
Outcome results
Primary
Amputation Free Survival (AFS)
freedom from major amputation and death at 6 months, compared to a historical performance goal.
Time frame: 6 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Amputation Free Survival (AFS) | 66 Percentage of participants |
Secondary
All Wound Area Reduction
Defined as reduction in area of the patient's wounds
Time frame: 12 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Area Reduction | 27 Percentage of participants |
Secondary
All Wound Area Reduction
Defined as reduction in area of the patient's wounds
Time frame: 6 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Area Reduction | 41 Percentage of participants |
Secondary
All Wound Area Reduction
Defined as reduction in area of the patient's wounds
Time frame: 3 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Area Reduction | 30 Percentage of participants |
Secondary
All Wound Area Reduction
Defined as reduction in area of the patient's wounds
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Area Reduction | 11 Percentage of participants |
Secondary
All Wound Area Reduction
Defined as reduction in area of the patient's wounds
Time frame: 9 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Area Reduction | 33 Percentage of participants |
Secondary
All Wound Healing
Complete healing of the patient's wounds.
Time frame: 12 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Healing | 42 Percentage of participants |
Secondary
All Wound Healing
Complete healing of the patient's wounds.
Time frame: 3 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Healing | 6 Percentage of participants |
Secondary
All Wound Healing
Complete healing of the patient's wounds.
Time frame: 6 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Healing | 28 Percentage of participants |
Secondary
All Wound Healing
Complete healing of the patient's wounds.
Time frame: 9 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Healing | 41 Percentage of participants |
Secondary
All Wound Healing
Complete healing of the patient's wounds.
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | All Wound Healing | 4 Percentage of participants |
Secondary
Change in Rutherford Classification
A change of one Rutherford class or greater.
Time frame: 3 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Change in Rutherford Classification | 32 Percentage of participants |
Secondary
Change in Rutherford Classification
A decrease in Rutherford class number (i.e.: from Rutherford class 5 to 4) is clinical improvement
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Change in Rutherford Classification | 18 Percentage of participants |
Secondary
Change in Rutherford Classification
A change of one Rutherford class or greater.
Time frame: 6 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Change in Rutherford Classification | 42 Percentage of participants |
Secondary
Contrast Volume
Total volume of contrast media (measured in milliliters)
Time frame: During the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Contrast Volume | 138 milliliter | Standard Deviation 80 |
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.
Time frame: Within the first 72 hours post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Freedom From Contrast-Induced Nephropathy | 103 Participants |
Secondary
Limb Salvage
The percentage of subjects with freedom from above-ankle amputation of the index limb.
Time frame: 6 months days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Limb Salvage | 76 Percentage of participants |
Secondary
Limb Salvage
The percentage of subjects with freedom from above-ankle amputation of the index limb.
Time frame: 3 months days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Limb Salvage | 85 Percentage of participants |
Secondary
Limb Salvage
The percentage of subjects with freedom from above-ankle amputation of the index limb.
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Limb Salvage | 94 Percentage of participants |
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.
Time frame: 6 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Primary Assisted Patency | 45 Percentage of participants |
Secondary
Primary Patency
Absence of occlusion of the endovascular intervention that is maintained without the need for additional or secondary surgical or endovascular procedures.
Time frame: 30 days post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Primary Patency | 68 percentage of participants |
Secondary
Primary Patency
Absence of occlusion of the endovascular intervention that is maintained without the need for additional or secondary surgical or endovascular procedures.
Time frame: 6 months post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Primary Patency | 26 Percentage of participants |
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.
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Procedure Success | 77 Percentage of participants |
Secondary
Procedure Time
Time from the first puncture (venous or arterial) to when the last catheter is removed
Time frame: Immediately post-procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Procedure Time | 217 minutes | Standard Deviation 87.77 |
Secondary
Radiation Exposure
Patient radiation exposure (measured in milligray)
Time frame: During the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Radiation Exposure | 263 Milligray | Standard Deviation 265 |
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.
Time frame: 6 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Secondary Patency | 64 Percentage of participants |
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.
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Secondary Patency | 95 Percentage of participants |
Secondary
Target Wound Healing
Complete healing of the patient's target wound
Time frame: 3 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Target Wound Healing | 8 Percentage of participants |
Secondary
Target Wound Healing
Complete healing of the patient's target wound
Time frame: 9 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Target Wound Healing | 37 Percentage of participants |
Secondary
Target Wound Healing
Complete healing of the patient's target wound
Time frame: 12 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Target Wound Healing | 45 Percentage of participants |
Secondary
Target Wound Healing
Complete healing of the patient's target wound
Time frame: 6 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Target Wound Healing | 25 Percentage of participants |
Secondary
Target Wound Healing
Complete healing of the patient's target wound
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Target Wound Healing | 4 Percentage of participants |
Secondary
Technical Success
The successful creation of an arteriovenous fistula in the desired limb location with immediate morphological success.
Time frame: Immediately post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Technical Success | 104 Participants |