IN.PACT™ AV Access IDE Study

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)

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.

Study Overview

• Status: Completed
• Conditions: Fistula; Arteriovenous Fistula; Arteriovenous Fistula Stenosis; Arteriovenous Fistula Occlusion
• Intervention / Treatment: Device: IN.PACT AV DCB; Device: Standard Balloon Angioplasty

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Amagasaki, Japan
    • Kansai Rosai Hospital
  • Kamakura, Japan
    • Shonan Kamakura General Hospital
  • Kishiwada, Japan
    • Kishiwada Tokushukai Hospital
  • Saitama, Japan
    • Saitama Medical Center Saitama Medical University
  • Shizuoka, Japan
    • Shizuoka General Hospital
  • Tokyo, Japan
    • Tokyo Women's Medical University Hospital
• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital
  • Wellington, New Zealand
    • Capital and Coast District Health Board
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham (UAB) Hospital
  • Arizona
    • Tempe, Arizona, United States, 85281
      • SKI Vascular Center
  • California
    • Sacramento, California, United States, 95825
      • Capital Nephrology Medical Group
  • Florida
    • Gainesville, Florida, United States, 32605
      • Florida Research Network
    • Pensacola, Florida, United States, 32504
      • Coastal Vascular and Interventional
  • Illinois
    • Champaign, Illinois, United States, 61822
      • Christie Clinic Vein and Vascular Center
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Ashland, Kentucky, United States, 41101
      • King's Daughters Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • North Carolina Nephrology PA
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Dialysis Access Institute
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Sanford University of South Dakota Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • University Surgical Associates
  • Texas
    • Plano, Texas, United States, 75093
      • Dallas Nephrology Associates
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Vascular Specialists
    • North Chesterfield, Virginia, United States, 23236
      • Richmond Vascular Center
    • Woodbridge, Virginia, United States, 22193
      • Vascular Institute of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient is ≥21 years of age.
2. Patient has a life expectancy of ≥ 12 months
3. Patient has a native AV fistula created ≥ 60 days prior to the index procedure
4. The target AV fistula has undergone successful dialysis for at least 8 of 12 sessions during a four week period
5. 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
6. 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
7. Patient has a target vessel diameter of 4.0 - 12.0 mm (by visual estimate).
8. 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
9. Patient provides written consent prior to enrollment in the study
10. Patient is willing to comply with all follow-up evaluations at specified times

Exclusion Criteria:

1. Women who are breastfeeding, pregnant, or are intending to become pregnant, or men intending to father children
2. Patient is receiving immunosuppressive therapy
3. Patient is anticipating a kidney transplant within 6 months of enrollment into the study
4. Patient has undergone prior intervention of access site within 30 days of index procedure
5. Patient with anticipated conversion to peritoneal dialysis
6. Patient has an infected AV access or systemic infection
7. Patient has planned surgical revision of access site
8. Patient with secondary non-target lesion requiring treatment within 30-days post index procedure
9. Patient with hemodynamically significant central venous stenoses that cannot be successfully treated prior to treatment of the target lesion
10. Patient with target AVF or access circuit which previously had or currently has a thrombosis
11. Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the delivery system
12. Patient with target lesion located central to the axillosubclavian junction
13. Patient has significant arterial inflow lesion requiring treatment more than 2 cm upstream from the anastomosis in the AV access
14. Patient has presence of pseudoaneurysm or aneurysm requiring treatment at the lesion site
15. Patient has presence of a stent located in the target AV access circuit
16. Patients with known allergies or sensitivities to paclitaxel
17. Patient with known contraindication, including allergic reaction, or sensitivity to contrast material that cannot be adequately pre-treated
18. Patient who cannot receive recommended antiplatelet and/or anticoagulant therapy
19. Patient with clinically significant Steal Syndrome requiring treatment
20. 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
21. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IN.PACT AV DCB; 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; IN.PACT™ AV Paclitaxel-Coated Percutaneous Transluminal Angioplasty (PTA) Balloon
Active Comparator: Standard Balloon Angioplasty; PTA will be performed using a commercially available uncoated PTA balloon.	Device: Standard Balloon Angioplasty; Standard PTA Balloon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Endpoint - Serious Adverse Event Rate	Serious Adverse Event (SAE) rate involving the AV access circuit	30 days post procedure
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

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
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
Abandonment of Target AVF	Defined as number of participants with abandonment of the target AV up to 36 months post-index procedure.	6, 9, 12, 18, 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, 48 months, and 60 months.	6, 12, 24, 36, 48, and 60 Months

Collaborators and Investigators

• Sponsor: Medtronic Endovascular
• Investigators: Principal Investigator: Andrew Holden, MD, Auckland City Hospital; Principal Investigator: Robert Lookstein, MD, The Mount Sinai Hospital; Principal Investigator: Hiroaki Haruguchi, MD, Haruguchi Vascular Access Clinic

Publications and helpful links

General Publications

• Lookstein RA, Haruguchi H, Ouriel K, Weinberg I, Lei L, Cihlar S, Holden A; IN.PACT AV Access Investigators. Drug-Coated Balloons for Dysfunctional Dialysis Arteriovenous Fistulas. N Engl J Med. 2020 Aug 20;383(8):733-742. doi: 10.1056/NEJMoa1914617.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2017
• Primary Completion (Actual): December 6, 2018
• Study Completion (Actual): May 5, 2023

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (Estimated): February 2, 2017

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Pathological Conditions, Anatomical; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Fistula; Arteriovenous Fistula
• Other Study ID Numbers: APV-IN.PACT AV Access

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes