FLEX Vessel Prep Prior to Angioplasty in Native Arteriovenous Fistulae (AVF)

Study Overview
=================
Brief Summary
-----------------
A prospective, multi-center, randomized (1:1) clinical study evaluating the FLEX Vessel Prep device plus percutaneous angioplasty (PTA) (study arm) vs PTA alone (control arm) for the treatment of obstructive lesions in the native arteriovenous dialysis fistulae.

Detailed Description
-----------------
This is a prospective, multi- center, randomized (1:1) clinical study evaluating the FLEX Vessel Prep System followed with PTA (TEST arm) vs PTA alone (CONTROL arm) for the treatment of de novo or non-stented restenotic obstructive lesions up to 100 mm in length located in the arteriovenous dialysis fistulae in an upper extremity. The objective is to evaluate and compare the serious adverse event rate at 30 days and primary patency at 6 months when using FLEX Vessel Prep System prior to PTA vs. PTA alone for treatment of obstructive lesion of native arteriovenous fistulae in the upper extremity. Enrollment will continue until complete data sets are collected for up to 75 subjects from up to 7 sites in the US.

Official Title
-----------------
FLEX Vessel Prep Prior to the Treatment of Obstructive Lesions in the Native Arteriovenous Dialysis Fistulae

Conditions
-----------------
Arteriovenous Fistula Stenosis

Intervention / Treatment
-----------------
* Device: FLEX Vessel Prep System
* Device: Angioplasty


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient is ≥21 years of age. Patient has a life expectancy of ≥12 months. Patient has a native AV fistula created ≥ 60 days prior to the index procedure. The target AV fistula has undergone successful dialysis for at least 8 of 12 sessions during a four-week period. Patient has a de novo and/or non-stented restenotic lesion located between approximately 2 cm proximal to the arteriovenous anastomosis and axillosubclavian junction with ≥50% stenosis. Patient has a target lesion (which may include a tandem lesion) that is ≤ 100 mm in length (by visual estimate). Note: Tandem lesions may be enrolled provided they meet all of the following criteria: Separated by a gap of ≤ 30mm (3 cm). Total combined lesion length, including 30 mm gap, ≤ 100 mm. Able to be treated as a single lesion. Patient has a target vessel diameter of 4.0 - 12.0 mm (by visual estimate) Patient underwent successful crossing of the target lesion with the guidewire. Patient provides written informed consent prior to enrollment in the study. Patient is willing to comply with all follow-up evaluations at specified times. Exclusion Criteria: Patient is pregnant or breastfeeding. Patient is receiving immunosuppressive therapy. Patient has undergone prior intervention of access site within 30 days of index procedure. Patient with anticipated conversion to peritoneal dialysis. Patient has an infected AV access or systemic infection. Patient has planned surgical revision of access site. Patient with secondary non-target lesion requiring treatment within 30 days post index procedure. Patient with hemodynamically significant central venous stenoses that cannot be successfully treated prior to treatment of the target lesion. Patient with target AVF or access circuit which previously had thrombectomy within last 30 days. Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the delivery system. Patient with target lesion located central to the axillosubclavian junction. Patient has significant arterial inflow lesion requiring treatment more than 2 cm upstream from the anastomosis in the AV access. Patient has presence of pseudoaneurysm or aneurysm requiring surgical revision at the target lesion site. Patient with known contraindication, including allergic reaction, or sensitivity to contrast material that cannot be adequately pre-treated. Patient who cannot receive recommended antiplatelet and/or anticoagulant therapy. Patient with clinically significant Steal Syndrome requiring treatment. Patient is enrolled in another investigational drug, device, or biologic study and has not completed the primary endpoint or was previously enrolled in this study. Patient has a co-morbid condition that, in the judgment of the Investigator, may cause him/her to be non-compliant with the protocol or confound the data interpretation. Patient has AV fistula created via endovascular technique.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FLEX Vessel Prep System followed with PTA (TEST arm)<br>FLEX Vessel Prep System is used to create circumferential, continuous micro-incisions along the length of the stenosis by performing a retrograde pullback through the lesion. Following FLEX, standard balloon angioplasty is performed with an uncoated PTA balloon sized to meet the reference vessel diameter, according to its corresponding instructions for use. Once advanced to the lesion, the balloon should be inflated according to the site's standard of care. | Device: FLEX Vessel Prep System<br>* The FLEX Vessel Prep System™ is an over-the-wire sheathed catheter with a three-strut treatment element near the distal tip. As the device is pulled back in a retrograde fashion through the target lesion, the Treatment Element flexes providing continuous engagement along the lesion to create controlled depth micro-incisions.<br>|
| Active Comparator: PTA only (CONTROL arm)<br>Standard Balloon angioplasty is performed with an uncoated PTA balloon sized to meet the reference vessel diameter, according to its corresponding instructions for use. Once advanced to the lesion, the balloon should be inflated according to the site's standard of care. | Device: Angioplasty<br>* The brand and type of PTA balloon(s) used will be at the discretion of the treating physician and used according to its Instructions for Use (IFU). PTA balloons consist of an over-the-wire catheter with a balloon fixed at the distal tip. Within the lesion the balloon is inflated to a pressure that allows full effacement.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Endpoint: Serious Adverse Event Rate | Defined as the Serious Adverse Event (SAE) rate involving the AV access circuit through 30 days post- procedure. | 30 Days | 
| Primary Efficacy Endpoint: Target Lesion Primary Patency Rate | Defined as freedom from clinically driven target lesion re-intervention (CD-TLR) or access circuit thrombosis measured through 6 months post-procedure. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Safety Endpoint: Serious Adverse Event Rate within 3 and 6 Months | Defined as the Serious Adverse Event (SAE) rate involving the AV access circuit through 3 months and 6 months post-procedure. | 3 and 6 Months | 
| Access Circuit Primary Patency through 3 Months and 6 Months Post-Procedure | Defined as freedom from re-intervention in the access circuit or access circuit thrombosis through 3 months and 6 months post-procedure. | 3 and 6 Months | 
| Target Lesion Primary Patency through 3 Months and 6 Months Post- Procedure | Defined as freedom from CD-TLR or access thrombosis occurring in the target lesion through 3 months and 6 months post-procedure. | 3 and 6 Months | 
| Cumulative Target Lesion Reinterventions Measured through 3 Months and 6 Months Post-Procedure | Defined as proportion of subjects with TLR through 3 months and 6 months post-procedure. | 3 and 6 Months | 
| Number of Interventions Required to Maintain Target Lesion Patency through 3 Months and 6 Months Post-Procedure | Defined as number of TLR through 3 months and 6 months post-procedure. | 3 and 6 Months | 
| Number of Interventions Required to Maintain Access Circuit Patency through 3 Months and 6 Months Post-Procedure | Defined as number of reinterventions in the target lesion and/or access circuit through 3 months and 6 months post-procedure. | 3 and 6 Months | 
| Cumulative Access Circuit Thromboses Measured through 3 Months and 6 months Post-Procedure. | Defined as proportion of subjects with access circuit thrombosis through 3 months and 6 months post-procedure. | 3 and 6 Months | 
| Device Success | Defined as successful delivery, treatment, and retrieval of the FLEX Vessel Prep device at index procedure. | Procedure | 
| Procedural Success | Defined as maintenance of patency (≤30% residual stenosis) in the absence of peri-procedural Serious Adverse Event (SAE). | Procedure | 
| Clinical Success | Defined as resumption of successful dialysis for at least one session after index procedure. | 30 Days | 
| Balloon opening pressure | Defined as minimum inflation pressure required to efface target lesion noting parallel balloon walls. | Procedure | 
| Maximum balloon pressure | Maximum pressure of angioplasty balloon(s) required during the interventional procedure to treat target lesion. | Procedure | 
| Patient Reported Pain | Patient Reported Pain during the interventional procedure reported via Numerical Rating Scale (NRS). | Procedure |