IN.PACT™ AV Access IDE Study

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of the IN.PACT™ AV Access Drug Coated Balloon (DCB) compared to percutaneous transluminal angioplasty (PTA) for treatment of subjects presenting with de novo or non-stented restenotic obstructive lesion of native arteriovenous dialysis fistulae (AVF) in the upper extremity.

Detailed Description
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This is a prospective, global, multi-center, single-blinded, 1:1 randomized clinical trial evaluating the IN.PACT™ AV Access Drug Coated Balloon (DCB) compared to percutaneous transluminal angioplasty (PTA) for treatment of subjects presenting with de novo or non-stented restenotic obstructive lesion of native arteriovenous dialysis fistulae (AVF) in the upper extremity. The trial will be conducted in up to 30 sites in the United States, Japan, and New Zealand.

Official Title
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Randomized Study of IN.PACT™ AV Access Paclitaxel-Coated Percutaneous Transluminal Angioplasty (PTA) Balloon vs. Standard PTA for the Treatment of Obstructive Lesions in the Native Arteriovenous Dialysis Fistulae (AVF)

Conditions
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Arteriovenous Fistula Stenosis, Arteriovenous Fistula Occlusion, Arteriovenous Fistula, Fistula

Intervention / Treatment
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* Device: IN.PACT AV DCB
* Device: Standard Balloon Angioplasty


Participation Criteria
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Eligibility Criteria
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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 the arteriovenous anastomosis and axillosubclavian junction with ≥50% stenosis. Note: If the lesion is located in the anastomosis, the treatment may be delivered up to 2 cm upstream on the arterial side. If the lesion is located in the cephalic arch, the treatment may be delivered up to 2 cm into the subclavian vein Patient has a target lesion or 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, and 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 guide wire and pre-dilatation with a high pressure PTA balloon defined as: residual stenosis of ≤ 30% and absence of a flow limiting dissection (Grade ≥ C) or perforation Patient provides written consent prior to enrollment in the study Patient is willing to comply with all follow-up evaluations at specified times Exclusion Criteria: Women who are breastfeeding, pregnant, or are intending to become pregnant, or men intending to father children Patient is receiving immunosuppressive therapy Patient is anticipating a kidney transplant within 6 months of enrollment into the study 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 or currently has a thrombosis 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 treatment at the lesion site Patient has presence of a stent located in the target AV access circuit Patients with known allergies or sensitivities to paclitaxel 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 biological study and has not completed the primary endpoint, or was previously enrolled in this study Patient has a comorbid-condition that, in the judgment of the Investigator, may cause him/her to be non-compliant with the protocol of confound data interpretation

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IN.PACT AV DCB<br>PTA will be performed using the IN.PACT AV Access Drug Coated Balloon. IN.PACT AV Access DCB was the device name used during the clinical study. Medtronic has changed the name of the device to IN.PACT™ AV Paclitaxel-Coated Balloon Catheter (also referred as IN.PACT AV DCB). Hence, throughout posting, the study device will be referred to as the IN.PACT AV DCB. | Device: IN.PACT AV DCB<br>* IN.PACT™ AV Paclitaxel-Coated Percutaneous Transluminal Angioplasty (PTA) Balloon<br>|
| Active Comparator: Standard Balloon Angioplasty<br>PTA will be performed using a commercially available uncoated PTA balloon. | Device: Standard Balloon Angioplasty<br>* Standard PTA Balloon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Lesion Primary Patency Rate Through 6 Months | Freedom from clinically-driven target lesion revascularization (CD-TLR) or access circuit thrombosis measured through 6 months post-procedure. | 6 Months Post-Procedure | 
| Primary Safety Endpoint - Serious Adverse Event Rate | Serious Adverse Event (SAE) rate involving the AV access circuit | 30 days post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Access Circuit Primary Patency | Defined as freedom from re-intervention in the access circuit or access circuit thrombosis through 3 months, 6 months, 9 months,12 months, 18 months, and 24 months post-procedure. | 3, 6, 9, 12, 18, and 24 Months | 
| Target Lesion Primary Patency | Percentage of participants with freedom from clinically driven target lesion revascularization or access thrombosis occurring in the target lesion through 3 months, 9 months,12 months, 18 months, and 24 months post-procedure. | 3, 9, 12, 18, and 24 Months | 
| Cumulative Target Lesion Revascularizations | The number and percentage of participants with target lesion revascularizations through 3 months, 6 months, 9 months,12 months, 18 months, and 24 months post-procedure. | 3, 6, 9,12, 18, and 24 Months | 
| Total Number of Interventions Required to Maintain Target Lesion Patency | The number of target lesion revascularizations per treatment arm through 3 months, 6 months, 9 months, 12 months,18 months, and 24 months post-procedure. | 3, 6, 9, 12, 18, and 24 Months | 
| Total Number of Interventions Required to Maintain Access Circuit Patency | The number of re-interventions in the target lesion and/or access circuit through 3 months, 6 months, 9 months,12 months, 18 months, and 24 months. | 3, 6, 9, 12, 18, and 24 Months | 
| Cumulative Access Circuit Thromboses | The number and percentage of participants with access circuit thrombosis through 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months. | 3, 6, 9, 12, 18, and 24 Months | 
| Device Success | Device Success is defined as successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst at or below rated burst pressure (RBP) during the index procedure. | Time of Procedure | 
| Procedure Success | Maintenance of patency (≤30% residual stenosis) in the absence of peri-procedural serious adverse device effect (SADE). | Time of Procedure | 
| Clinical Success | Resumption of successful dialysis for at least one session after index procedure. | From the time of the index procedure to the first successful dialysis session after index procedure. Typically, this is within 1 week of index procedure. | 
| Rate of Device Related Adverse Events | Device Related Adverse Event Rate: defined as the number and percentage of participants with device related Adverse Events through 30 days, 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months. | 30 days, 3, 6, 9, 12, 18, and 24 Months. | 
| Procedure Related Adverse Event Rate | Procedure Related Adverse Event Rate: defined as the number and percentage of participants with procedure related Adverse Events reported post-index procedure until the first successful dialysis session through 30 days, 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months. | 30 Days, 3, 6, 9, 12, 18, and 24 Months | 
| Target Lesion Revascularizations (TLR) | Defined as the percentage of participants who had an event, the Kaplan-Meier method was used to estimate Cumulative Incidence up to 36 months post-index procedure. | 6, 9, 12, 18, 24, and 36 Months | 
| Clinically-Driven Target Lesion Revascularizations (CD-TLR) | Defined as the percentage of participants who had an event, the Kaplan-Meier method was used to estimate Cumulative Incidence with CD-TLR up to 36 months post index procedure | 6, 9, 12, 18, 24, and 36 Months | 
| Re-interventions in the Access Circuit | Defined as the percentage of participants who had a reinterventions occurring within the access circuit. The Kaplan-Meier method was used to estimate Cumulative Incidence up to 36 months post-index procedure. | 6, 9, 12, 18, 24, and 36 Months | 
| Abandonment of Target AVF | Defined as number of participants with abandonment of the target AV abandonment up to 36 months post-index procedure. | 6, 9, 12, 18, 24, and 36 Months | 
| Serious Adverse Event Rate | Serious Adverse Event Rate: defined as the number and percentage of participants with one or more Serious Adverse Events reported post-index procedure through 6 months, 12 months, 24 months, and 36 months. | 6, 12, 24, and 36 Months | 
| Rate of Freedom From All-Cause Mortality Post Vital Status Update | Percentage of participants who had all-cause death post vital status update. The Kaplan-Meier method was used to estimate survival probability up to 60 months post-index procedure through 6 months, 12 months, 24 months, 36 months, and 48 months. | 6, 12, 24, 36, and 48 Months |