Clinical trial NCT02532621: Clinical Evaluation of a Vascular Venous Anastomotic Connector [InterGraft VIG-only Study]
Official title: Clinical Evaluation of a Vascular Venous Anastomotic Connector for Minimally Invasive Connection of an Arteriovenous Graft for Hemodialysis [InterGraft VIG-only Study]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Lead sponsor: Phraxis, Inc.
Sponsor class: INDUSTRY
First posted: 2015-08-26
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative Patency at 6 Months
timeFrame: Six months of clinical follow-up following treatment assignment (enrollment)
Secondary outcomes:
measure: Acute Device Success
timeFrame: 24 hours
measure: Primary Unassisted Patency
timeFrame: Six months
measure: Time to First Cannulation
timeFrame: Six months
measure: Interventions Required to Maintain Patency
timeFrame: Six months
measure: Serious Adverse Events (Secondary Endpoint Defined SAEs)
timeFrame: Six months
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Triad of Alabama/Flowers Hospital
state: Alabama
city: Cartersville
country: United States
facility: Cartersville Medical Center, LLC
state: Georgia
city: Macon
country: United States
facility: Medical Center of Central Georgia - Navicent Health
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Health System- Dept of Surgery
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Charlotte
country: United States
facility: Surgical Specialists of Charlotte
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Florence
country: United States
facility: McLeod Physician Associates II
state: South Carolina
city: Orangeburg
country: United States
facility: Regional Medical Center of Orangeburg and Calhoun Counties
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
Study officials:
affiliation: Phraxis, Inc.
name: Cindy M Setum, Ph.D
role: STUDY_DIRECTOR
affiliation: Regional Medical Center
name: John R Ross, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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
citation: 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.
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citation: 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.
citation: 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.
citation: Saran R, Robinson B, Abbott KC, Agodoa LY, Albertus P, Ayanian J, Balkrishnan R, Bragg-Gresham J, Cao J, Chen JL, Cope E, Dharmarajan S, Dietrich X, Eckard A, Eggers PW, Gaber C, Gillen D, Gipson D, Gu H, Hailpern SM, Hall YN, Han Y, He K, Hebert H, Helmuth M, Herman W, Heung M, Hutton D, Jacobsen SJ, Ji N, Jin Y, Kalantar-Zadeh K, Kapke A, Katz R, Kovesdy CP, Kurtz V, Lavalee D, Li Y, Lu Y, McCullough K, Molnar MZ, Montez-Rath M, Morgenstern H, Mu Q, Mukhopadhyay P, Nallamothu B, Nguyen DV, Norris KC, O'Hare AM, Obi Y, Pearson J, Pisoni R, Plattner B, Port FK, Potukuchi P, Rao P, Ratkowiak K, Ravel V, Ray D, Rhee CM, Schaubel DE, Selewski DT, Shaw S, Shi J, Shieu M, Sim JJ, Song P, Soohoo M, Steffick D, Streja E, Tamura MK, Tentori F, Tilea A, Tong L, Turf M, Wang D, Wang M, Woodside K, Wyncott A, Xin X, Zang W, Zepel L, Zhang S, Zho H, Hirth RA, Shahinian V. US Renal Data System 2016 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2017 Mar;69(3 Suppl 1):A7-A8. doi: 10.1053/j.ajkd.2016.12.004. No abstract available.
citation: 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. 2024 Jul;25(4):1244-1251. doi: 10.1177/11297298231159691. Epub 2023 Mar 9.