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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Device: Venous InterGraft Connector
* Procedure: sutured arterial anastomosis of an implanted vascular graft for hemodialysis
* Procedure: hemodialysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 18 years of age. Subject requires the creation of a vascular access graft for hemodialysis, secondary to a diagnosis of End Stage Renal Disease. Subject is able to have the vascular access graft placed in an upper extremity. 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. Subject has a reasonable expectation of remaining on hemodialysis for at least 6 months. Subject or his/her legal guardian understands the study and is willing and able to comply with the dialysis schedule and follow-up requirements. 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. 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: Subject has a documented and unsuccessfully treated ipsilateral central venous stenosis as determined by imaging. 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. 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. Subject has had a previous instance of Heparin Induced Thrombocytopenia type 2 (HIT-2) or has known sensitivity to heparin. Subject has co-morbid conditions that may limit their ability to comply with study and follow-up requirements. The patient has had >2 previous arteriovenous accesses in treatment arm. Subject is currently taking Aggrenox®. Subject is in need of, or is scheduled for any major surgery within 30 days of the study procedure. Subject is currently taking maintenance immunosuppressant medication such as rapamycin, mycophenolate or mycophenolic acid, prednisone (>10 mg), cyclosporine, tacrolimus or cyclophosphamide. Life expectancy is less than 12 months. 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. Subject is a poor compliance risk (i.e. history of IV or oral drug abuse). The subject is enrolled in another dialysis or vascular investigational study.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venous InterGraft Connector (VIG)<br>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<br>* 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.<br>* Other names: VIG;Procedure: sutured arterial anastomosis of an implanted vascular graft for hemodialysis<br>* The arterial anastomosis of the implanted vascular graft for hemodialysis is formed using standard suturing technique.<br>Procedure: hemodialysis<br>* The implanted vascular graft is intended as a vascular access for performing hemodialysis treatments.<br>|

What is the study measuring?
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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 |