End Stage Renal Disease
Conditions
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.
Interventions
DEVICEVenous 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.
PROCEDUREsutured 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.
PROCEDUREhemodialysis
The implanted vascular graft is intended as a vascular access for performing hemodialysis treatments.
Sponsors
Phraxis, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Patency at 6 Months | Six months of clinical follow-up following treatment assignment (enrollment) | Percentage of subjects free from loss of access of the study graft for hemodialysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Device Success | 24 hours | AV graft flow at end of implant procedure |
| Primary Unassisted Patency | Six months | Percentage of subjects free from the occurrence of either access thrombosis or an access procedure performed to maintain access patency |
| Time to First Cannulation | Six months | Time from initial access placement to first graft cannulation for hemodialysis |
| Interventions Required to Maintain Patency | Six months | Number of interventions required to maintain secondary patency |
| Serious Adverse Events (Secondary Endpoint Defined SAEs) | Six months | Number and type of serious adverse events- death, emergent surgery, significant bleeding,graft infection, pseudoaneurysm |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
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.
Hemodialysis: The implanted vascular graft is intended as a vascular access for performing hemodialysis treatments. | 158 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | implanted graft abandoned before 6 months | 12 |
| Overall Study | last follow up performed outside window (<166 days) -censored | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Venous InterGraft Connector (VIG) |
|---|---|
| Age, Continuous | 62.6 years |
| Cardiovascular Disease | 78 Participants |
| Current hemodialysis using a catheter | 134 Participants |
| Diabetes mellitus | 98 Participants |
| Duration of Hemodialysis >= 12 months | 59 Participants |
| Duration of Hemodialysis < 6 months | 69 Participants |
| Duration of Hemodialysis >= 6 months and <12 months | 15 Participants |
| Duration of Hemodialysis NA (no current hemodialysis) | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 154 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Hypertension | 89 Participants |
| Number of prior permanent vascular access(s) for hemodialysis 0 | 64 Participants |
| Number of prior permanent vascular access(s) for hemodialysis 1 | 66 Participants |
| Number of prior permanent vascular access(s) for hemodialysis 2 or more | 28 Participants |
| Obesity | 51 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 123 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Sex: Female, Male Female | 97 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 158 |
| other Total, other adverse events | 37 / 158 |
| serious Total, serious adverse events | 58 / 158 |
Outcome results
Primary
Cumulative Patency at 6 Months
Percentage of subjects free from loss of access of the study graft for hemodialysis
Time frame: Six months of clinical follow-up following treatment assignment (enrollment)
Population: Intention-to-treat analysis population (All patients assigned to treatment using the study device). Patients withdrawn for reasons other than loss of cumulative patency were included in the analysis up until the time of withdrawal and were considered censored in the analysis, after withdrawal.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Venous InterGraft Connector (VIG) | Cumulative Patency at 6 Months | 146 Participants |
Comparison: The primary endpoint was evaluated by comparison with a performance goal of 75% that was determined from medical literature.~The sample size of 158 patients was estimated as follows:~* Kaplan-Meier estimate of cumulative patency rate at 6 months (exact binomial estimation for sample size)~* Type I error (alpha): 0.025 (one-sided)~* 80% Statistical power~* 8% Lost-to-follow up ratep-value: <0.001one-sided binomial exact test
Secondary
Acute Device Success
AV graft flow at end of implant procedure
Time frame: 24 hours
Population: Intention-to-treat (all patients assigned to treatment using the study device)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Venous InterGraft Connector (VIG) | Acute Device Success | 158 Participants |
Secondary
Interventions Required to Maintain Patency
Number of interventions required to maintain secondary patency
Time frame: Six months
Population: intention to treat
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Venous InterGraft Connector (VIG) | Interventions Required to Maintain Patency | One intervention to maintain AVG patency | 33 Participants |
| Venous InterGraft Connector (VIG) | Interventions Required to Maintain Patency | Two interventions to maintain AVF patency | 14 Participants |
| Venous InterGraft Connector (VIG) | Interventions Required to Maintain Patency | Three or more interventions to maintain AVG patency | 8 Participants |
| Venous InterGraft Connector (VIG) | Interventions Required to Maintain Patency | No interventions to maintain AVG patency | 103 Participants |
Secondary
Primary Unassisted Patency
Percentage of subjects free from the occurrence of either access thrombosis or an access procedure performed to maintain access patency
Time frame: Six months
Population: Intention-to-treat (all patients assigned to treatment using the study device). Patients withdrawn for reasons other than loss of primary unassisted patency were included in the analysis up until the time of withdrawal and were considered censored in the analysis, according to usual convention, after withdrawal.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Venous InterGraft Connector (VIG) | Primary Unassisted Patency | 95 Participants |
Secondary
Serious Adverse Events (Secondary Endpoint Defined SAEs)
Number and type of serious adverse events- death, emergent surgery, significant bleeding,graft infection, pseudoaneurysm
Time frame: Six months
Population: Intention-to-treat
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Venous InterGraft Connector (VIG) | Serious Adverse Events (Secondary Endpoint Defined SAEs) | Death | 3 Participants |
| Venous InterGraft Connector (VIG) | Serious Adverse Events (Secondary Endpoint Defined SAEs) | AVG infection | 6 Participants |
| Venous InterGraft Connector (VIG) | Serious Adverse Events (Secondary Endpoint Defined SAEs) | significant bleeding | 0 Participants |
| Venous InterGraft Connector (VIG) | Serious Adverse Events (Secondary Endpoint Defined SAEs) | emergent surgery | 0 Participants |
| Venous InterGraft Connector (VIG) | Serious Adverse Events (Secondary Endpoint Defined SAEs) | pseudoaneurysm | 0 Participants |
| Venous InterGraft Connector (VIG) | Serious Adverse Events (Secondary Endpoint Defined SAEs) | No protocol-defined SAEs | 149 Participants |
Secondary
Time to First Cannulation
Time from initial access placement to first graft cannulation for hemodialysis
Time frame: Six months
Population: Intention-to-treat.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venous InterGraft Connector (VIG) | Time to First Cannulation | 20.1 days | Standard Deviation 23.5 |