Critical Limb Ischemia
Conditions
Keywords
Desert foot, No-option patients, Venous arterialization
Brief summary
The objective of this post-market study is to evaluate the safety and effectiveness of the LimFlow System in creating a below-the-knee arterio-venous fistula for venous arterialization in subjects with critical limb ischemia.
Detailed description
This study will investigate the safety and effectiveness of the LimFlow System for creating an arterio-venous fistula in the below-the-knee vascular system using an endovascular, minimally invasive approach for the treatment of critical limb ischemia in subjects ineligible for conventional endovascular or surgical limb salvage procedures.
Interventions
Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach
DEVICELimFlow System
Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach
Sponsors
LimFlow SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Subject must be \> 21 and \< 95 years of age * Clinical diagnosis of symptomatic critical limb ischemia, defined as Rutherford category 5 or 6 * Assessment that no conventional surgical or endovascular treatment is possible * Proximally, the target in-flow artery at the cross-over point must be treatable with a 3.5 - 4.0 mm stent after pre-treatment (by visual estimate), and be \<50% stenosed * Subject is willing and has adequate support to comply with protocol requirements, including medication regimen and follow-up visits
Exclusion criteria
* Concomitant hepatic insufficiency, deep venous thrombus in target limb, uncorrected coagulation disorders, or current immunodeficiency disorder * Prior vein stripping surgery and/or vessel harvesting for CABG in the limb intended for study * Life expectancy less than 12 months * Patient currently taking coumarin/warfarin which, in the opinion of the attending physician, interferes with the patient's treatment * Any significant medical condition which, in the attending physician's opinion, may interfere with the patient's optimal treatment * Patient 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 treatment * Patient unable to give consent * Pregnant or breastfeeding women * Documented myocardial infarction or stroke within previous 90 days * Patients suffering from renal insufficiency (GFR value less than 30 ml/min/1.73 m²) who are not on hemodialysis * Patients with vasculitis and/or untreated popliteal aneurysms * Patients with acute limb ischemia * Prior peripheral arterial bypass procedure above or below the knee which could inhibit proximal inflow to the stent graft * Lower extremity venous disease with significant edema in the target limb that may inhibit the procedure and/or jeopardize wound healing, in the investigator's opinion * Known or suspected systemic or severe infection (e.g., WIfI foot Infection grade of 3) * Known or suspected allergies or contraindications to stainless steel, nickel, or contrast agent that cannot be adequately pre-treated, or patients who cannot receive anticoagulation or antiplatelet aggregation therapy * Severe heart failure, which in the opinion of the investigator may compromise subject's ability to safely undergo a percutaneous procedure (e.g., known ejection fraction of \< 40%, NYHA Classification III-IV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amputation-free Survival | Throughout one year | Freedom from death or major amputation as calculated using the Kaplan-Meier estimate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary and Secondary Patency as Assessed by Duplex Ultrasound | Throughout one year | Stent graft patency as assessed by duplex ultrasound and calculated using the Kaplan-Meier estimate |
| Limb Salvage | Throughout one year | Freedom from major amputation as calculated using the Kaplan-Meier estimate |
| Wound Healing | Throughout one year | Complete index wound healing as assessed by wound pictures |
| Interventions With Technical Success (Procedure Completion) | Immediately post-procedure | Procedure completion and immediate morphological success with successful placement of the arterial and venous catheters in the desired location in the limb, and ability to place the stent graft |
| Interventions With Procedural Success (Technical Success Without Death, Major Amputation, or Re-intervention) | One month post-procedure | Combination of technical success without death, major amputation, or re-intervention |
| Deterioration in Renal Function | One month and six months | Number of participants with deterioration in renal functionas assessed by changes in creatinine level |
Countries
Austria, Germany, Netherlands, New Zealand, Singapore
Participant flow
Recruitment details
There were 60 subjects screened at 10 sites in 4 countries resulting in 34 subjects enrolled between December 2017 and January 2022.
Pre-assignment details
Subjects were screened by site personnel and once it was deemed they met inclusion and exclusion criteria, consent was obtained and imaging of the target arterial and venous anatomy were uploaded for review by an independent review committee to confirm that the patients were no-option, i.e., with no capacity for standard endovascular or surgical treatment.
Participants by arm
| Arm | Count |
|---|---|
| Percutaneous Deep Vein Arterialization Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach
Percutaneous deep vein arterialization: Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach
LimFlow System: Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach | 34 |
| Percutaneous Deep Vein Arterialization Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach
Percutaneous deep vein arterialization: Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach
LimFlow System: Creation of an arterio-venous fistula in the below-the-knee vasculature using the LimFlow System endovascular, minimally invasive approach | 35 |
| Total | 69 |
Baseline characteristics
| Characteristic | Percutaneous Deep Vein Arterialization |
|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 10.1 |
| Body Mass Index (BMI) | 25.0 kg/m² STANDARD_DEVIATION 4.4 |
| Current or former smoker | 16 Participants |
| Diabetes | 22 Participants |
| Heart failure | 18 Participants |
| Hyperlipidaemia requiring medication | 23 Participants |
| Hypertension requiring medication | 26 Participants |
| Prior intervention to target limb | 31 Legs |
| Prior Myocardial Infarction (MI) | 10 Participants |
| Prior stroke | 6 Participants |
| Region of Enrollment Germany | 20 participants |
| Region of Enrollment Netherlands | 9 participants |
| Region of Enrollment New Zealand | 1 participants |
| Region of Enrollment Singapore | 4 participants |
| Renal insufficiency Any renal insufficiency | 11 Participants |
| Renal insufficiency Renal insufficiency requiring dialysis | 6 Participants |
| Rutherford classification Rutherford Class 5 | 31 Legs |
| Rutherford classification Rutherford Class 6 | 4 Legs |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 34 |
| other Total, other adverse events | 5 / 34 |
| serious Total, serious adverse events | 32 / 34 |
Outcome results
Primary
Amputation-free Survival
Freedom from death or major amputation as calculated using the Kaplan-Meier estimate
Time frame: Throughout one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Percutaneous Deep Vein Arterialization | Amputation-free Survival | 50.7 percentage of participants |
Secondary
Deterioration in Renal Function
Number of participants with deterioration in renal functionas assessed by changes in creatinine level
Time frame: One month and six months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Percutaneous Deep Vein Arterialization | Deterioration in Renal Function | Deterioration in renal function at 1 month | 0 Participants |
| Percutaneous Deep Vein Arterialization | Deterioration in Renal Function | Deterioration in renal function at 2 months | 2 Participants |
Secondary
Interventions With Procedural Success (Technical Success Without Death, Major Amputation, or Re-intervention)
Combination of technical success without death, major amputation, or re-intervention
Time frame: One month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Percutaneous Deep Vein Arterialization | Interventions With Procedural Success (Technical Success Without Death, Major Amputation, or Re-intervention) | 24 Participants |
Secondary
Interventions With Technical Success (Procedure Completion)
Procedure completion and immediate morphological success with successful placement of the arterial and venous catheters in the desired location in the limb, and ability to place the stent graft
Time frame: Immediately post-procedure
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Percutaneous Deep Vein Arterialization | Interventions With Technical Success (Procedure Completion) | 33 Interventions |
Secondary
Limb Salvage
Freedom from major amputation as calculated using the Kaplan-Meier estimate
Time frame: Throughout one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Percutaneous Deep Vein Arterialization | Limb Salvage | 66.6 percentage of legs |
Secondary
Primary and Secondary Patency as Assessed by Duplex Ultrasound
Stent graft patency as assessed by duplex ultrasound and calculated using the Kaplan-Meier estimate
Time frame: Throughout one year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Percutaneous Deep Vein Arterialization | Primary and Secondary Patency as Assessed by Duplex Ultrasound | Primary patency | 34.0 percentage of legs |
| Percutaneous Deep Vein Arterialization | Primary and Secondary Patency as Assessed by Duplex Ultrasound | Secondary patency | 67.4 percentage of legs |
Secondary
Wound Healing
Complete index wound healing as assessed by wound pictures
Time frame: Throughout one year
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Percutaneous Deep Vein Arterialization | Wound Healing | 10 Legs |