Clinical Evaluation of a Vascular Venous Anastomotic Connector [InterGraft VIG-only Study]

Clinical Evaluation of a Vascular Venous Anastomotic Connector for Minimally Invasive Connection of an Arteriovenous Graft for Hemodialysis [InterGraft VIG-only Study]

The InterGraft™ Venous Anastomotic Connector provides an endovascular, minimally invasive means for attachment of an arteriovenous graft to a vein in the upper extremity. The InterGraft™ Venous Anastomotic Connector facilitates creation of the arteriovenous graft connection to a vein in support of hemodialysis in subjects with End Stage Renal Disease. The InterGraft™ Venous Anastomotic Connector is used together with conventional suturing of the arterial anastomosis to facilitate creation of an arteriovenous graft in support of hemodialysis in subjects with End Stage Renal Disease.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Device: Venous InterGraft Connector; Procedure: sutured arterial anastomosis of an implanted vascular graft for hemodialysis; Procedure: hemodialysis

Detailed Description

The InterGraft™ Venous Anastomotic Connector (VIG) was developed for endovascular, minimally invasive venous anastomosis of a standard arteriovenous graft (AVG) for hemodialysis. This study will evaluate the safety and performance of the VIG for anastomosis of a commercially available, 6 mm diameter, synthetic AVG. Anastomoses with the VIG may potentially reduce venous vessel trauma, improve the local vessel wall shear stresses and promote laminar flow, thereby improving patency.

While recognizing that a native fistula is the recommended access for hemodialysis, AVGs remain a frequently used access type. This study focuses on subjects who have a failed fistula, cannot have a fistula or are better suited for an AVG, as determined by the physician. The implant procedural outcomes, the number and type of major adverse events, and patency throughout a six-month follow-up period will be evaluated. The six-month patency rate will be compared with a pre-specified patency performance goal drawn from surgical AVG literature and published performance standards.

This is a pivotal, multicenter, prospective, non-randomized design study. All enrolled subjects will receive the VIG device and will have a standard sutured arterial anastomosis.

A total of 158 evaluable subjects will be enrolled, defined as primary analysis population of 146 subjects plus allowance for 12 subjects lost-to-follow up.

The study includes10 participating clinical centers. Study site investigators are physicians skilled in AVG placement and interventional techniques. Study data will be collected up to the point at which each subject has completed the six-month endpoint or experienced a terminal study endpoint.

The study will be conducted in compliance with the Investigational Plan, Investigational Device Exemption regulations, Good Clinical Practice guidelines, and other applicable regulatory requirements.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Triad of Alabama/Flowers Hospital
  • Georgia
    • Cartersville, Georgia, United States, 30120
      • Cartersville Medical Center, LLC
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia - Navicent Health
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System- Dept of Surgery
  • Missouri
    • Saint Louis, Missouri, United States, 63103
      • Saint Louis University
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Surgical Specialists of Charlotte
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Physician Associates II
    • Orangeburg, South Carolina, United States, 29118-1498
      • Regional Medical Center of Orangeburg and Calhoun Counties
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject is ≥ 18 years of age.
2. Subject requires the creation of a vascular access graft for hemodialysis, secondary to a diagnosis of End Stage Renal Disease.
3. Subject is able to have the vascular access graft placed in an upper extremity.
4. Baseline imaging shows suitable vascular anatomy/ vessel size for the InterGraft™ Venous Connector and an artery at least 3.5 mm in diameter that is suitable for creating the arterial anastomosis.
5. Subject has a reasonable expectation of remaining on hemodialysis for at least 6 months.
6. Subject or his/her legal guardian understands the study and is willing and able to comply with the dialysis schedule and follow-up requirements.
7. Subject or his/her legal guardian provides written informed consent. NOTE: In accordance with the requirements of some Institutional Review Boards, where applicable, only those subjects with capacity to consent for themselves will be included. Thus, where required by the Institutional Review Board, adult individuals who lack capacity to consent for themselves will be excluded from the study.
8. Physician's examination at time of surgery shows no significant vessel lesions, calcification(s), anatomic structures or abnormalities that may limit ability to safely deploy the InterGraft Connectors or create a sutured arterial anastomosis.

Exclusion Criteria:

1. Subject has a documented and unsuccessfully treated ipsilateral central venous stenosis as determined by imaging.
2. Subject currently has a known or suspected bacterial, fungal, or HIV infection. NOTE: Patients with hepatitis B or C may be included in the study.

3. Subject has a known hypercoagulable or bleeding disorder or requires treatment with warfarin or heparin.

   NOTE: The intent of this criterion is to exclude patients with high risk for bleeding or clotting complications. As such, patients who are taking oral anticoagulants (blood thinners) including, but not limited to, Xarelto® (rivaroxaban) or Eliquis® (apixaban) should also be excluded from the study. Patients may receive anticoagulation therapy any time after the study AV graft implant procedure, at their physician's discretion. This should be driven by an indication unrelated to the vascular access.

4. Subject has had a previous instance of Heparin Induced Thrombocytopenia type 2 (HIT-2) or has known sensitivity to heparin.
5. Subject has co-morbid conditions that may limit their ability to comply with study and follow-up requirements.
6. The patient has had >2 previous arteriovenous accesses in treatment arm.
7. Subject is currently taking Aggrenox®.
8. Subject is in need of, or is scheduled for any major surgery within 30 days of the study procedure.
9. Subject is currently taking maintenance immunosuppressant medication such as rapamycin, mycophenolate or mycophenolic acid, prednisone (>10 mg), cyclosporine, tacrolimus or cyclophosphamide.
10. Life expectancy is less than 12 months.
11. Subject is pregnant. NOTE: A negative urine pregnancy test within 24 hours of the study procedure is required in all female subjects with reproductive capacity.
12. Subject is a poor compliance risk (i.e. history of IV or oral drug abuse).
13. The subject is enrolled in another dialysis or vascular investigational study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Venous InterGraft Connector (VIG); This is a nonrandomized, single-arm study: All enrolled patients are assigned to the same treatment: AVG implantation using a VIG (study device) to create the venous anastomosis and standard suturing to create the arterial anastomosis of the implanted AVG.

Device: Venous InterGraft Connector; The device is designed for transcatheter delivery within a vein and connection to an AVG that has been tunneled under the skin in a standard manner. The connection is made via a small skin incision.; Other Names: VIG; Procedure: sutured arterial anastomosis of an implanted vascular graft for hemodialysis; The arterial anastomosis of the implanted vascular graft for hemodialysis is formed using standard suturing technique.; Procedure: hemodialysis; The implanted vascular graft is intended as a vascular access for performing hemodialysis treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Patency	Percentage of subjects free from loss of access of the study graft for hemodialysis	Six Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute device success	AV graft flow at end of implant procedure	24 hours
Primary unassisted patency	Percentage of subjects free from the occurrence of either access thrombosis or an access procedure performed to maintain access patency	Six months
Time to first cannulation	Time from initial access placement to first graft cannulation for hemodialysis	Six months
Interventions required to maintain patency	Number and type of interventions required to maintain secondary patency	Six months
Serious Adverse Events	Number and type of serious adverse events- death, emergent surgery, significant bleeding,graft infection, pseudoaneurysm	Six months

Collaborators and Investigators

• Sponsor: Phraxis, Inc.
• Investigators: Study Director: Cindy M Setum, Ph.D, Phraxis, Inc.; Principal Investigator: John R Ross, M.D., Regional Medical Center

Publications and helpful links

General Publications

• Lee T, Roy-Chaudhury P. Advances and new frontiers in the pathophysiology of venous neointimal hyperplasia and dialysis access stenosis. Adv Chronic Kidney Dis. 2009 Sep;16(5):329-38. doi: 10.1053/j.ackd.2009.06.009.
• Dember LM, Beck GJ, Allon M, Delmez JA, Dixon BS, Greenberg A, Himmelfarb J, Vazquez MA, Gassman JJ, Greene T, Radeva MK, Braden GL, Ikizler TA, Rocco MV, Davidson IJ, Kaufman JS, Meyers CM, Kusek JW, Feldman HI; Dialysis Access Consortium Study Group. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA. 2008 May 14;299(18):2164-71. doi: 10.1001/jama.299.18.2164.
• U.S. Renal Data System. USRDS 2011 Annual Data Report: Volume 2. Atlas of End Stage Renal Disease in the United States. Bethesda, MD, National Institutes of Health, National Institutes of Diabetes, and Digestive and Kidney Diseases; 2011
• Akoh JA. Prosthetic arteriovenous grafts for hemodialysis. J Vasc Access. 2009 Jul-Sep;10(3):137-47. doi: 10.1177/112972980901000301.
• Roy-Chaudhury P, Kelly BS, Zhang J, Narayana A, Desai P, Melham M, Duncan H, Heffelfinger SC. Hemodialysis vascular access dysfunction: from pathophysiology to novel therapies. Blood Purif. 2003;21(1):99-110. doi: 10.1159/000067863.
• Lok CE, Allon M, Moist L, Oliver MJ, Shah H, Zimmerman D. Risk equation determining unsuccessful cannulation events and failure to maturation in arteriovenous fistulas (REDUCE FTM I). J Am Soc Nephrol. 2006 Nov;17(11):3204-12. doi: 10.1681/ASN.2006030190. Epub 2006 Sep 20.
• Lee HW, Allon M. When should a patient receive an arteriovenous graft rather than a fistula? Semin Dial. 2013 Jan-Feb;26(1):6-10. doi: 10.1111/sdi.12040. Epub 2012 Nov 22.
• Burgess JS, Beaver JD, London M, Rohan V, Orland P, Yevzlin A, Setum C, Ross J; InterGraft Study Investigators. Prospective multicenter study of a novel endovascular venous anastomotic procedure and device for implantation of an arteriovenous graft for hemodialysis. J Vasc Access. 2023 Mar 9:11297298231159691. doi: 10.1177/11297298231159691. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2018
• Primary Completion (Actual): January 19, 2022
• Study Completion (Actual): January 19, 2022

Study Registration Dates

• First Submitted: August 19, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (Estimated): August 26, 2015

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: Venous Anastomotic Connector

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