Continued Access Study of the InterGraft™ Venous Anastomotic Connector for Minimally Invasive Connection of an Arteriovenous Graft for Hemodialysis
Phase: NA
Conditions: Dialysis Access Malfunction
Sponsor: Phraxis, Inc.

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 1 of 25 
 
  
 
 
Continued Access Study of the InterGraft™ Venous Anastomotic Connector for  
Minimally Invasive Connection of an Arteriovenous Graft for Hemodialysis 
 
 
INVESTIGATIONAL PLAN 
 
 
 
Clinical Trial Registration:   
NCT05448950 
 
 
 
 
 
IDE # G140221 
 
Investigational Plan Revision History: 
 
Rev 1, March 15, 2022: Initial release. 
 
 
 
Sponsored by: 
 
Phraxis, Inc. 
2910 13th Terrace NW  
 
 
St. Paul, MN 55112 USA 
Telephone (study contact): (612) 801-6730  
 
 
 
Reviewed and Approved by:  
 
 
___________________________________________     
_____________________________ 
Site Principal Investigator 
 
 
 
 
Date 
 
 
___________________________________________     
_____________________________ 
Sponsor representative:   
 
 
 
 
Date 
Cindy Setum, PhD., Director of Clinical Affairs 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 2 of 25 
 
TABLE OF CONTENTS 
 
 
 
 
 
 
 
 
 
 
                        
Page 
ACRONYMS AND ABBREVIATIONS 
 
 
 
 
 
 
4 
 
 
 
1.0 GENERAL INFORMATION  
 
 
 
 
 
 
5 
 
 
2.0 INTRODUCTION AND BACKGROUND 
 
 
 
 
 
6 
 
3.0 STUDY DEVICE DESCRIPTION 
 
 
 
 
 
 
6 
        
Indication for Use 
 
 
 
 
 
 
 
7 
 
 
 
4.0 PRIOR STUDIES 
 
 
 
 
 
 
 
 
7 
        
Bench Testing 
 
 
 
 
 
 
 
 
7 
        
Pre-Clinical Studies 
  
 
               
 
 
 
7 
  
        
Clinical Studies  
 
 
 
 
 
 
 
8 
 
 
5.0 STUDY OBJECTIVE  
 
 
 
 
 
 
 
8 
 
6.0 STUDY DESIGN 
 
 
 
 
 
 
 
 
8 
7.0 SUBJECT SELECTION  
 
 
 
 
 
 
 
8 
        
Initial Inclusion Criteria 
 
 
 
 
 
 
 
9 
        
Final Inclusion Criteria 
 
 
 
 
 
 
 
9 
        
Exclusion Criteria 
 
 
 
 
 
 
 
9 
 
8.0 STUDY ENDPOINTS  
 
 
 
 
 
 
 
10 
 
 
9.0 SUBJECT SCREENING AND INFORMED CONSENT  
 
 
 
11 
Screening and Enrollment  
 
 
 
 
 
 
11 
        
Baseline Imaging  
 
 
 
 
 
 
 
11 
        
Informed Consent 
 
 
 
 
 
 
 
11 
 
10.0 STUDY PROCEDURE 
 
 
 
 
 
 
 
12 
  
General Procedure       
 
 
 
 
 
 
 
12 
 Use of Clamps  
 
 
 
 
 
 
 
12 
        
Additional Treatment 
 
 
 
 
 
 
 
12 
        
Vascular Grafts for Hemodialysis  
 
 
 
 
 
13 
        
Treatment of Ipsilateral Central Venous Stenosis Prior to Enrollment 
 
 
13 
        
Study Device Failure, Defect, or Suspected Device Problem 
 
 
 
13 
        
Bailout Procedure 
 
 
 
 
 
 
 
14 
 
        
Assessment of Graft Flow at End of Procedure 
 
 
 
 
14 
       
 Initial Use of the Graft for Hemodialysis 
 
 
 
 
 
14 
11.0 FOLLOW-UP PROCEDURES AND GRAFT INTERVENTIONS  
 
 
14 
        
Subject Management 
 
 
 
 
 
 
 
14 
        
Pharmacologic Regimen  
 
 
 
 
 
 
14 
        
Follow-up Evaluations 
 
 
 
 
 
 
 
15 
         
Telephone Follow-up for Subjects Who Miss Final Visit 
 
 
 
15 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 3 of 25 
 
 
 
Follow-up Considerations Related to COVID-19 Pandemic 
 
 
 
15 
        
Graft Interventions 
 
 
 
 
 
 
 
15 
       
Summary of Tests and Procedures  
 
 
 
 
 
16 
       
Final Events 
 
 
 
 
 
 
 
 
16 
12.0 POTENTIAL RISKS  
 
 
 
 
 
 
 
16 
       Steps to Minimize Risks 
 
 
 
 
 
 
 
17 
 
13.0 POTENTIAL BENEFITS 
 
 
 
 
 
 
 
17 
14.0 SUBJECT WITHDRAWAL FROM THE STUDY 
 
 
 
 
18 
15.0 CRITERIA FOR STUDY TERMINATION 
 
 
 
 
 
18 
16.0 STUDY DURATION 
 
 
 
 
 
 
 
18 
17.0 TRAINING  
 
 
 
 
 
 
 
 
18 
18.0 STATISTICAL ANALYSIS   
 
 
 
 
 
 
18 
19.0 DATA COLLECTION AND MANAGEMENT  
 
 
 
 
19 
        
Data Collection  
 
 
 
 
 
 
 
19 
       
Data Management 
 
 
 
 
 
 
 
19 
 
20.0 DATA MONITORING AND QUALITY ASSURANCE MEASURES 
 
 
20 
        
Sponsor Monitoring 
 
 
 
 
 
 
 
20 
        
Clinical Events Committee 
 
 
 
 
 
 
20 
21.0 ADVERSE EVENTS  
 
 
 
 
 
 
 
20 
        
Definitions 
 
 
 
 
 
 
 
 
20 
Review and Notification of UADEs 
 
 
 
 
 
21 
Investigator Evaluation of Adverse Events  
 
 
 
 
22 
Reporting and Review of Serious Adverse Events 
 
 
 
 
22 
Reporting Deaths  
 
 
 
 
 
 
 
22 
22.0 PROTOCOL VIOLATIONS  
 
 
 
 
 
 
23 
23.0 REGULATORY RESPONSIBILITIES AND CONSIDERATIONS 
 
 
23 
        
Investigator Responsibilities 
 
 
 
 
 
 
24 
        
Sponsor Responsibilities  
 
 
 
 
 
 
24 
        
Record Retention Policy  
 
 
 
 
 
 
25 
24.0 MEASURES TO AVOID BIAS 
 
 
 
 
 
 
25 
 
25.0 PUBLICATION POLICY 
 
 
 
 
 
 
 
25 
26.0 REFERENCES 
 
 
 
 
 
 
 
 
25 
 
 
Appendix A: 
InterGraft™ Venous Anastomotic Connector Instructions for Use 
Appendix B: 
Sample Informed Consent Form  
Appendix C: 
Case Report Form 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 4 of 25 
 
ACRONYMS AND ABBREVIATIONS 
 
AE 
 
Adverse Event 
AIG 
 
Arterial InterGraft Connector 
AV 
 
Arteriovenous 
AVG 
 
Arteriovenous graft 
CEC 
 
Clinical Events Committee 
CRF 
 
Case Report Form 
DCC 
 
Data Coordination Center 
EDC 
 
Electronic Data Capture 
GCP 
 
Good Clinical Practice 
IFU 
 
Instructions for Use 
IRB 
 
Institutional Review Board 
KDOQI 
Kidney Disease Outcomes Quality Initiative (National Kidney Foundation) 
ePTFE  
expanded Polytetrafluoroethylene 
UADE  
Unanticipated Adverse Device Effect 
VIG 
 
Venous InterGraft Connector 
VIG-CAS 
Venous InterGraft Continued Access Study 
 
 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 5 of 25 
 
1.0 GENERAL INFORMATION 
 
Study Name:  
Continued Access Study of the InterGraft™ Venous Anastomotic Connector for 
Minimally Invasive Connection of an Arteriovenous Graft for Hemodialysis  
 
 
Study Device:  
InterGraft™ Venous Anastomotic Connector  
   
Study Device  
Regulatory Status:  
Investigational Device. Limited by Federal (United States) law to investigational use.  
 
Indication for Use: 
(proposed) 
The InterGraft™ Venous Anastomotic Connector provides a minimally invasive, 
sutureless method 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 Design:  
Prospective, multicenter, non-randomized study 
 
Subjects:  
Up to 15 subjects with end stage renal disease who have a planned arteriovenous graft 
implant procedure for hemodialysis access and who meet the study selection criteria will 
be included.    
 
Sponsor: 
 
Phraxis, Inc. 
Saint Paul, MN 
 
 
 
Sponsor representative: Cindy Setum, Ph.D., Director of Clinical Affairs 
 
 
 
csetum@phraxis.com 
 
Data Coordination & 
Statistical Analysis 
Technical Resources International, Inc. 
Bethesda, MD  
Project Manager: Daniel Molina 
dmolina@tech-res.com 
 
Clinical Events  
Committee (Chair):  
Arif Asif, MD 
 
 
 
Neptune, NJ 
 
 
 
Arif.Asif@HackensackMeridian.org 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 6 of 25 
 
2.0 INTRODUCTION AND BACKGROUND 
The traditional sutured graft-to-vein anastomosis suffers from stenosis that subsequently develops due to 
neointimal hyperplasia. This pathology is thought to form due to surgical implant trauma to the vein and 
surrounding tissues, the sutures themselves, as well as turbulent flow across the anastomosis.  The novel 
InterGraft™ Venous Anastomotic Connector (VIG) is designed to provide a minimally invasive anastomosis for 
arteriovenous (AVG) implantation that may avoid the pathology and clinical problems currently associated with a 
sutured anastomosis.  
The recently completed ‘VIG-only’ pivotal study evaluated the safety and effectiveness of using the VIG for the 
venous anastomosis, together with traditional suturing of the arterial anastomosis for implantation of an AVG for 
hemodialysis.  The VIG-only study was approved by FDA (IDE G140221) and included 158 subjects contributed 
from 10 USA study sites.  Collected data included baseline characteristics, AVG patency and use for 
hemodialysis, AVG interventions, and adverse events throughout a six-month follow-up period. The primary 
study endpoint was cumulative graft patency at 6 months. Secondary endpoints included evaluation of primary 
unassisted patency at six months, the number and type of AVG interventions, and serious adverse events 
including rates of death, AVG infection, emergent surgery, significant bleeding and pseudoaneurysm.  
Results of the VIG-only study showed that the primary endpoint of cumulative graft patency at 6 months, 
assessed by comparison to a target Performance Goal of 75%, was met (P-value < .001). By Kaplan Meier 
survival analysis, the lower 95% Confidence Bound for cumulative patency at 180 days was 86.98%. Primary 
unassisted patency was 60.21%, with a lower 95% Confidence Bound at 180 days of 50.84%. There were four 
deaths (2.5%), none of which were related to the VIG study device.   Six subjects had AVG infections (3.8%) 
resulting in surgical excision of the graft. None of the AVG infections were related to the VIG study device. 
There were no reports of emergent surgery, significant bleeding or pseudoaneurysm.  These results provide 
evidence of VIG efficacy for creating a venous anastomosis during AVG implantation, with no significant safety 
concerns. 
Phraxis, Inc. (Sponsor) is currently preparing an application to FDA for marketing clearance of the VIG. The 
continued access study of the VIG (hereafter referred to as the ‘Venous InterGraft Continued Access Study, or 
‘VIG-CAS’) described in this investigational plan allows for continued enrollment of subjects while the 
marketing application is being prepared and subsequently review by FDA.  The VIG-CAS will include the same 
patient population, follow-up schedule, and study endpoints as the VIG-only study.  
The VIG-CAS will be conducted in compliance with the Investigational Plan, Investigational Device Exemption 
(IDE) regulations, Good Clinical Practice guidelines (GCP), and other applicable regulatory requirements.   
 
3.0 STUDY DEVICE DESCRIPTION 
 
The VIG is designed for transcatheter delivery within a 4 -7 mm diameter peripheral vein, and connection to an 6 
mm AVG that has been tunneled under the skin in a standard manner. The connection is made via a small skin 
incision. The VIG is constructed as a nitinol framework encapsulated with ePTFE in the midsection and uncoated 
at the ends (Figure 1). The VIG distal flared end is configured as a nitinol scaffold with anchoring barbs that 
extend into the vein wall, and the proximal ‘graft end’ is a stent-like framework for anchoring within the AVG.  

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 7 of 25 
 
The VIG is intended as a permanent implant. The VIG is delivered and deployed within the target vein using a 
customized transcatheter delivery system. A detailed description of the VIG and delivery system is provided in 
the Instructions for Use (Appendix A).   
 
Figure 1- InterGraft Venous Anastomotic Connector (VIG). Note barbs that anchor VIG within the vein (arrow).  
 
 
 
          
                                             
Indication for Use (proposed) 
The InterGraft™ Venous Anastomotic Connector provides a minimally invasive, sutureless method 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 patients 
with End Stage Renal Disease. The InterGraft™ Venous Anastomotic Connector is intended to be used together 
with conventional suturing of the arterial anastomosis to facilitate creation of an arteriovenous graft in support of 
hemodialysis in patients with End Stage Renal Disease. 
 
4.0 PRIOR STUDIES 
 
The VIG, together with an arterial InterGraft Connector (AIG), were evaluated in prior studies as summarized 
below. The findings from the prior studies are also applicable to use of the VIG only.  
 
NOTE: The AIG has been discontinued and it is not studied in this investigational plan. 
 
Bench Testing   
Bench testing of the VIG confirmed the structural integrity of the device, adequacy of resistance to compressive 
forces and radial forces, adequacy of bond strengths, kink and migration resistance, and verification of critical 
dimensions.  Where applicable, testing was conducted using commercial 6mm ePTFE grafts that were selected 
due to their current widespread clinical use. 
 
Pre-Clinical Studies 
Simulated use testing was performed for verification of the VIG deployment procedure. The VIG performed 
adequately for intended use with respect to the ability to access, deploy and withdraw.  
 
Acute animal studies evaluated the deliverability of the VIG, the ability to complete an AV circuit using ePTFE 
grafts, and near-term graft patency following initial implantation of grafts using a VIG and AIG.1 Testing was 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 8 of 25 
 
performed using a canine femoral artery/vein model.  These studies provided evidence of safety and acceptable 
performance of the VIG and AIG. 
 
Clinical Studies 
 
First-in-Human Study 
A first-in-human clinical evaluation of the VIG and AIG was performed.2 The study was conducted at the Italian 
Hospital in Asuncion, Paraguay, under a protocol that was approved by the Paraguayan National Regulatory 
Authority and the institutional Ethics Committee. All subjects provided prior written consent, and the study was  
conducted in accordance with ICH Guideline for Good Clinical Practice. The InterGraft connectors were 
successfully used in 9/9 subjects for connection of an AVG in the upper arm: five subjects received both the VIG 
and the AIG, and four subjects received the VIG for the venous anastomosis and a standard sutured arterial 
anastomosis.  Delivery and deployment success was obtained in all cases. All AVGs were patent at the end of the 
procedure, with no procedural adverse events related to the VIG. Three subjects exited the study early for reasons 
unrelated to the InterGraft connectors. The remaining subjects had patent grafts at 6 months. 
VIG-only Pivotal Study (IDE G140221) 
As described in Section 2.0 above, a pivotal ‘VIG-only’ clinical study was conducted under an IDE approved by 
FDA. The study is now completed and the primary endpoint of cumulative graft patency at 6 months with 
comparison to a target Performance Goal of 75% was met (P-value < .001).  The results of the pivotal study 
provide evidence of safety and effectiveness for use of the VIG and provide justification for the continued access 
study described in this investigational plan.  
 
5.0 STUDY OBJECTIVE 
 
The objective of the VIG continued access study (VIG-CAS) is to allow study investigators and their patients 
continued access to the VIG while a marketing application is prepared by Phraxis, Inc. and reviewed by the FDA. 
The study will allow for the collection of additional safety and effectiveness data using the VIG.  
 
6.0 STUDY DESIGN 
 
The VIG-CAS is a multicenter, prospective, single-arm (non-randomized) study that will include up to 15 
subjects contributed from up to five (5) study sites/investigators who previously participated in the VIG-only 
study.  No new investigators will be included. All subjects will be assigned to treatment with the VIG and a 
standard sutured arterial anastomosis for implantation of an AVG for hemodialysis. The selection criteria (patient 
population), follow-up schedule, and study endpoints are the same as those used in the VIG-only study.  
 
Study data will be collected up to the point at which each subject has completed the final 6-month follow up or 
experienced a terminal study event.  
 
7.0 SUBJECT SELECTION 
 
The following inclusion and exclusion criteria must be met for enrollment in the study: 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 9 of 25 
 
Initial Inclusion Criteria (All must be answered YES for study eligibility.) 
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 has 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 (IRBs), where applicable, only those subjects with 
capacity to consent for themselves will be included. Thus, where required by the IRB, adult individuals 
who lack capacity to consent for themselves will be excluded from the study. 
 
Final Inclusion Criterion to be applied at the time of surgery (Must be answered YES for enrollment into 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™ Venous Connector or 
create a sutured arterial anastomosis. 
Exclusion Criteria (All must be answered NO for study eligibility.) 
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: Subjects 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.  Patients who are taking the oral anticoagulant Eliquis® (apixaban) may be included in 
the study if Eliquis is temporarily discontinued prior to the study procedure, in accordance with the 
approved prescribing instructions. 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.  
 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 10 of 25 
 
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. Subject has had >2 previous arteriovenous accesses in treatment arm. 
 
7. Subject is currently taking Aggrenox®. 
 
8. Subject needs 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. Subject is enrolled in another dialysis or vascular investigational study. 
 
8.0 STUDY ENDPOINTS 
Study endpoints include the following:  
 
Endpoint #1. Cumulative patency at 6 months, defined as the percentage of subjects free from loss of access 
of the AVG for hemodialysis, assessed at 6 months. 
 
Endpoint #2. Acute device success, defined as AVG flow at the end of the procedure as determined by 
palpable graft thrill and/or audible bruit, without significant bleeding or emergent surgery. 
 
Endpoint #3. Primary Unassisted Patency at 6 months, defined as the percentage of subjects free from the first 
occurrence of either access thrombosis or an access procedure performed to maintain access patency. 
 
Endpoint #4. Time to First Cannulation, defined as the time from initial access placement to the first graft 
cannulation for hemodialysis. 
 
Endpoint #5. Number and type of interventions required to maintain secondary patency. 
 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 11 of 25 
 
Endpoint #6. Number and type of serious adverse events (SAEs) through 6 months.  SAEs include the 
following: death, emergent surgery, AVG infection requiring treatment (e.g., prolonged or intravenous 
antibiotic therapy), significant bleeding (defined as bleeding requiring treatment), and pseudoaneurysm.    
 
Expected interventions for restoration of patency will be documented and reported separately, are reflected in the 
evaluation of cumulative patency, and are not required to be reported/tabulated again as SAEs. 
 
Endpoints will be evaluated acutely (at the time of implant), at time of any AVG intervention, at two weeks, and 
monthly through 6 months for all subjects.  The study AVG patency evaluation will start immediately after the 
index procedure is completed (e.g., subject leaves the surgery suite).  This means that once the AVG is created, 
patency evaluation begins.  The occurrence of acute thrombus and treatment thereof during the index procedure 
while the vascular access is being created does not trigger the loss of primary patency.  
 
9.0 SUBJECT SCREENING AND INFORMED CONSENT 
 
Screening and Enrollment 
Patients referred for AVG implant should be screened for study eligibility.  A member of the Research Team will 
evaluate the patient for eligibility. If all initial inclusion criteria are met and no exclusion criteria are present, a 
member of the Research Team should inform the patient about the study’s purpose and should obtain written 
informed consent.  
 
Final enrollment eligibility is determined at the time of surgery, after the physician has confirmed the final 
inclusion criterion is met.  Enrolled subjects will be assigned a unique study subject identification number. Each 
study site will maintain subject screening and enrollment logs.  Reason for screen failures will be recorded.  
Screening log data will not be included in the primary database but will be reviewed during study monitoring. 
 
Baseline Imaging 
Angiographic or ultrasonic imaging of the target limb vasculature is routinely performed as part of determining 
the optimal AV access plan for a patient. As part of screening, baseline imaging should be reviewed to determine 
whether the patient meets the following criteria (as determined by the physician) for use of the VIG:   
• 
General: Flow rate must be adequate for the creation of dialysis access, as previously mapped with 
ultrasound or angiography 
 
• 
Vein inner diameter at planned anastomosis site is 4 -7 mm in luminal diameter 
 
• 
Artery inner diameter at planned anastomosis site is at least 3.5 mm in luminal diameter  
Informed Consent 
A member of the Research Team will approach the subject to obtain written informed consent. The background of 
the study and the benefits and risks of procedures and the study should be explained to the subject.  The subject 
(or their legal representative, if applicable) must sign the consent form prior to initiation of study procedures. The 
consent form used must be approved by the study site’s IRB.  Failure to provide consent renders the subject 
ineligible for the study. Subjects will be given a copy of the signed informed consent document. The signed 
informed consent will be retained with the study records at the site.  It is the responsibility of the investigator to 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 12 of 25 
 
assure that informed consent is obtained from each subject in accordance with the guidelines of the IRB and all 
applicable regulatory guidelines. A sample informed consent form is provided in Appendix B. 
 
 
10.0 STUDY PROCEDURE  
 
General Procedure 
The procedure will be performed in accordance with the VIG Instructions for Use (IFU, Appendix A).   A 
commercially available 6mm diameter ePTFE graft will be used. Conventional grafts or grafts designed for early 
cannulation (within 24-48 hours) may be used. The study procedure will be performed in an operating room that 
has fluoroscopic imaging capability for guiding placement of the VIG.  The anesthesia regimen will be 
determined at the physician’s discretion; there are no study-specific anesthesia requirements. A regional nerve 
block is typically performed for placement of an AVG.  Standard, routine hemodynamic monitoring will be 
performed to assess cardiovascular status throughout the procedure. Heparin anticoagulation may be provided at 
the physician’s discretion.  
 
Small skin incisions will be made for tunneling the graft under the skin in a standard manner.  The VIG device is 
provided pre-loaded within a customized catheter-based delivery system for over-the-wire delivery.  The VIG is 
inserted through an introducer sheath placed in the target vein so that the ‘vessel end’ of the VIG is deployed 
within the vein, and the ‘graft end’ extends out of the vein for connection to the graft.  Delivery and deployment 
will be performed under fluoroscopic guidance. The VIG will be deployed first, connected to the AVG, then the 
graft and VIG will be flushed and clamped. The arterial anastomosis will then be created using a standard suturing 
method. 
 
NOTE: Although not expected, if connection of the venous graft segment using the VIG is attempted but not able 
to be completed, the venous anastomosis should be completed using standard suturing. Such situations will be 
considered as an acute device failure. 
 
Following establishment of the AV circuit, the skin incisions will be sutured closed using standard techniques. 
The subject will be moved to a recovery area for monitoring prior to discharge. It is anticipated that most subjects 
will be discharged the same day or within 24 hours following the AVG implant procedure.  
Use of Clamps 
To avoid mechanical damage or disruption to the AVG or VIG, surgical clamps or other tools with teeth or other 
sharp features should not be used during the AVG implant procedure.  An atraumatic or guarded (e.g., rubber) 
clamp should be used for clamping the AVG, as needed.  Do not clamp or manipulate the VIG with surgical tools. 
Use only gentle pinching with the fingers to hold the VIG and to control hemostasis. 
 
Additional Treatment 
It is anticipated that no other interventional treatments will be required during the implant procedure.  At the 
venous anastomotic site, no further treatment should be provided if the luminal diameter is > 90% of the adjacent 
normal vessel, based on operator’s assessment.  If the luminal diameter is <90%, balloon angioplasty may be 
performed as follows:  
 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 13 of 25 
 
After deployment, the nitinol-reinforced VIG may be smoothed and more fully seated against the vessel wall by 
inflating an angioplasty balloon. Balloon treatment should be performed according to the manufacturer’s 
instructions, by a physician skilled in peripheral vascular interventional techniques. The balloon diameter used 
should be equal to that of the VIG diameter and should be no larger than 6mm when used to treat the VIG 
segment that is within the AVG. The balloon should be inflated within the VIG along the entire length.  Multiple 
inflations may be needed. To avoid possible displacement of the VIG, the physician should assure that the balloon 
is fully deflated prior to carefully removing the balloon. 
 
Vascular Graft for Hemodialysis  
Vascular grafts that meet the following requirements, as determined by the physician, may be used: commercially 
available, straight (not-tapered), 6 mm inner diameter ePTFE grafts.   Adequate graft length and trimming must be 
carefully determined to facilitate optimal positioning after the venous and arterial graft anastomoses have been 
completed. The graft should never be too short.  
 
Treatment of Ipsilateral Central Venous Stenosis Prior to Enrollment 
Ipsilateral central venous stenosis is a study exclusion.  However, a patient with central venous stenosis may be 
considered for the study following successful treatment of the stenosis.  Central stenosis angioplasty may be 
performed first, then immediately followed with the study procedure.  The patient may be enrolled if, as assessed 
by the investigator, the central stenosis has <30% residual stenosis, which is the KDOQI threshold for successful 
intervention.  The patient should not be enrolled if the residual stenosis is ≥ 30% or if the investigator determines 
that the treatment could impact the ability to assess the study endpoints (e.g., acute device success, graft patency, 
safety).  
Study Device Failure, Defect, or Suspected Device Problem 
Device malfunction is defined as any occurrence in which the study device does not perform as intended, when 
used or attempted to be used in a study procedure.  As described in the IFU, a visual examination of the VIG 
should be performed at the time of opening the packaging and prior to use in a subject.   Defective devices 
(obvious or suspected) should not be used.  A replacement VIG should be obtained and the study procedure 
continued.  A device accountability log will be used to account for all used and opened/unused devices in this 
study.    
 
If a VIG defect or malfunction is discovered/suspected any time prior to vascular deployment, the VIG should not 
be used.  A replacement device/component should be used and the study procedure continued.  A Device 
Malfunction CRF must be completed for all device malfunctions, failures or suspected failures, and the defective 
product identification should be recorded on the device accountability log.  Whenever possible, a 
defective/suspected defected VIG should be returned to the Sponsor for evaluation. 
The Device Malfunction CRF should be used to report and provide details of situations in which the VIG does not 
perform as intended. Failure of the VIG to perform as intended may potentially be due to a variety of reasons, 
including defect or suspected defect in the device itself or the delivery system; operator error; anatomic issues; or 
other reasons. If use of the VIG is attempted but ultimately the device is not able to be used, a Device Malfunction 
CRF should be submitted to report the surrounding details.  
 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 14 of 25 
 
NOTE: Device Malfunctions should be reported within 24 hours of discovery.  24-hour reporting of device 
malfunctions will assist with Sponsor’s efforts to assess whether any SAEs associated with a device malfunction 
may also have occurred.   
 
Bailout Procedure 
Bailout procedures are not anticipated but could potentially be required if, for example, the VIG does not deploy 
correctly,  does not seal correctly, is not deployed at an acceptable location, or if there are any major vascular 
events.  In such cases, the subject should be referred for surgical intervention.  No attempt should be made to 
remove an improperly deployed VIG using percutaneous methods.  
 
Assessment of Graft Flow at the End of the Procedure 
An AVG placed using the VIG and a sutured arterial anastomosis typically has a pulse and/or thrill which is easily 
palpable over the skin or directly on the AVG prior to closure of the surgical incisions. Thus, the AVG flow 
assessment is similar that used for standard sutured AVGs. An optimal method to confirm AVG patency at the 
end of the implant procedure is to feel a thrill near the arterial anastomosis or confirm a Doppler signal.  
Ascultation using a sterile or covered stethoscope is also acceptable.  At the physician’s discretion and as 
warranted, a final angiogram may also be performed to verify patency of the graft. 
 
Initial Use of the Graft for Hemodialysis 
Initial hemodialysis cannulation of AVGs placed with the VIG should be performed in accordance with the graft 
manufacturer’s Instructions for Use.  After needle withdrawal, use gentle, non-occlusive digital pressure to 
compress the cannulation site until hemostasis is achieved. The VIG should NOT be directly cannulated.  In 
accordance with standard practice, once placed, AVGs should be used for hemodialysis access as soon as deemed 
appropriate by the nephrologist and/or operator. For standard ePTFE AVGs, the time from placement to first 
cannulation is typically after two weeks.  Early cannulation AVGs can be used sooner, in accordance with 
approved labeling. Every effort should be made to minimize infection risk by removing central catheters as soon 
as possible.  
 
 
11.0 FOLLOW-UP PROCEDURES AND GRAFT INTERVENTIONS 
 
Subject Management 
Prior to discharge, the study investigator or their designee should confirm that the subject understands the 
postoperative care requirements, as determined by the physician, and the required follow-up schedule.  The two-
week visit should be scheduled. 
 
It is recommended that investigators follow the Fistula First Guidelines for vascular access monitoring  
(http://esrdnetwork18.org/pdfs/QI%20-%20FF%20Tools/FFTool_VAMPFlowChrt.pdf  or current). 
 
Pharmacologic Regimen 
There are no study-specific pharmacologic requirements.  The need for intraoperative and postoperative 
anticoagulation therapy should be based on subject history and maintained as deemed appropriate by the 
physician.  Anticoagulation/anti-platelet therapy will be recorded on the eCRF. 
 
 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 15 of 25 
 
Follow-up Evaluations 
Subjects will be followed at two weeks and monthly thereafter through six months to assess AVG patency and 
any complications, if applicable.  Measurement of access flow rate is part of standard care. Data from routine AV 
access flow monitoring performed as part of usual care, as available, will also be collected.   
 
Graft ultrasound evaluation should be performed at the 3- and 6- month follow-up visits and the results recorded 
on the CRF.  
 
NOTE: For reference and in accordance with standard care, baseline flow measurements are typically assessed 
during two dialysis sessions two weeks apart; and monthly measurements will be performed thereafter.   An 
access flow rate < 500 mL/min or a drop in access flow rate of 25% from baseline should trigger an angiographic 
evaluation of the AVG and possible intervention.  
 
Telephone Follow-up for Subjects Who Miss Final Visit 
If a subject misses or is unavailable/unwilling to return for the final 6-month follow-up visit, telephone follow-up 
with the subject or their dialysis center should be attempted to determine the patency status of the AVG and to 
gather as much additional information as possible to complete the 6 month follow up and study completion CRFs.  
Telephone follow-up should be done only if the subject is unwilling or unable to return for an in-person visit.  If 
the subject cannot be reached, then their dialysis center should be contacted (if allowed) to collect information 
about the most recent hemodialysis using the AVG. If it is not possible to reach the subject by phone or to contact 
the dialysis center, then the subject will be considered as lost-to-follow up.   
 
Follow-up Considerations Related to the COVID-19 Pandemic 
To reduce the likelihood of community exposure to COVID-19, investigators will be allowed to implement non-
contact monthly study follow-up visits, in accordance with institutional and IRB requirements and approval to do 
so, and as deemed appropriate based on the COVID-19 pandemic situation at each site.  Non-contact follow-up 
visits may include communications via telephone, FaceTime, email, Virtual Care or similar. In lieu of an in-
person AVG patency assessment, investigators should obtain a copy of the most recent hemodialysis record as 
verification of AVG patency.  
If non-contact follow-up is implemented due to the local pandemic situation, AVG ultrasound examinations will 
not be expected (at the 3- and 6-month follow-ups) and failure to perform the ultrasound examination will not be 
considered as a protocol deviation.  
Investigators will be required to report the reason for performing non-contact follow up (due to pandemic, or 
other reason).  
Graft Interventions 
As per standard care following the AVG implant procedure, AVG interventions should be avoided within the first 
7 post-operative days.  As warranted and determined by the physician, standard balloon angioplasty and 
thrombectomy procedures may be performed within the AVG, VIG, and adjacent native artery and vein. 
Mechanical thrombectomy devices that use spinning, rotating or other movable parts should NOT be used within 
the VIG, as this may result in entanglement or other damage to the VIG. The balloon diameter used should be 
equal to that of the VIG diameter and should be no larger than 6mm when used to treat the VIG segment that is 
within the AVG. 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 16 of 25 
 
Summary of Tests and Procedures 
The required schedule for subject treatment and follow-up evaluation is shown in Table 1.   
 
Table 1: Schedule of Subject Treatment and Evaluation 
Timeframe (window) 
Test/Procedure 
Pre-procedure (within 30 days) 
Baseline imaging of target AVG site (performed as part of 
standard care) 
Baseline labs: Hgb, Hct, WBC, platelets 
Pre-procedure (within 24 hours) 
Urine pregnancy test for female subjects with reproductive 
potential 
Immediately following end of AVG implant procedure 
(before leaving surgery suite) 
Confirmation of AVG flow (palpable thrill/pulse, audible bruit) 
At the physician’s discretion and if warranted, an angiogram 
may also be performed to confirm patency. 
Post- procedure (within 48 hours) 
Post procedure labs: Hgb, Hct 
At discharge  
Confirmation of AVG flow (palpable thrill/pulse, audible bruit) 
2 weeks following the procedure (14 +4/-7 days) 
Clinical follow- up with AVG evaluation (includes collection of 
information regarding any subsequent hospitalization, AEs, 
AVG interventions) 
30, 60, 90, 120, 150,180 days following the procedure (± 
14 days) 
Clinical follow- up with AVG evaluation (includes collection of 
information regarding any subsequent hospitalization, AEs, 
AVG interventions) 
 
AVG flow rate evaluation (ultrasound or similar) is performed 
at the 90-day and 180-day follow-up visits.  
 
 
Final Events 
The following final events will justify cessation of study follow-up: death, AVG abandonment, lost to follow up 
(at least 3 attempts to contact the subject should be made and documented), or completion of study follow-up.   
 
 
12.0 POTENTIAL RISKS 
 
 
Potential adverse events that may occur and/or require treatment with use of the VIG include but are not limited 
to: 
• 
allergic reaction to device materials or procedure medications 
• 
anastomotic disruption or tearing 
• 
aneurysm 
• 
artery tear or rupture 
• 
bleeding  
• 
bruising 
• 
contrast dye reaction 
• 
death 
• 
device breakage 
• 
dissection or ‘tissue flap’ in blood vessels in which the VIG has been inserted  

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 17 of 25 
 
• 
embolism 
• 
hematoma 
• 
infection  
• 
inflammation 
• 
kinking/compression of the AVG and/or VIG device 
• 
migration or misplacement of VIG device 
• 
occlusion 
• 
pseudoaneurysm in the AVG, VIG device, or adjacent native blood vessels 
• 
seroma 
• 
stenosis of the AVG 
• 
swelling of implanted arm 
• 
thrombosis of the AVG 
• 
vessel spasm 
 
Many of the potential AEs listed above are similar AEs that may occur during and after AVG placement using 
standard surgical techniques. Potential risks of a standard surgical procedure to implant an AVG for hemodialysis 
include but are not limited to the following: 
• 
failure of sutures 
• 
bleeding immediately after the procedure 
• 
infection 
• 
possible need for re-operation 
 
The VIG will be used with a standard 6 mm AVG for hemodialysis that is sold and packaged separately. Potential 
AEs that may occur with use of the AVG are described in the Instructions for Use packaged with the AVG. 
Pregnant subjects are excluded from the study. In females of reproductive capacity, a pregnancy test must be 
performed prior to the procedure.  This is to ensure that a fetus is not irradiated.  Other potential risks to a fetus 
related to the study procedure are unknown.  
There are no unique blood tests required for the study; however, results of standard blood tests performed to 
evaluate general health status at baseline, during the study procedure and during study follow-up will be included 
with the study data.  Risks of having blood drawn include infection (rare) and bleeding (rare). 
Steps to Minimize Risk 
The following steps will be taken to minimize potential risks:  
• 
The study will include only investigators who have prior training and clinical experience using the VIG. 
• 
The study procedure will be performed in a surgical suite with radiologic imaging capabilities. If the 
study procedure is unable to be performed (not expected), the patient will be able to receive traditional 
surgical graft implantation. 
 
 
 
 
 
 
 
 
 
13.0 POTENTIAL BENEFITS 
Potential clinical benefit for the VIG is unknown.  Anastomoses with the VIG may potentially reduce venous 
vessel trauma, improve the local vessel wall shear stresses, and promote laminar flow, thereby improving patency.  

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 18 of 25 
 
14.0 SUBJECT WITHDRAWAL FROM THE STUDY 
 
Subjects may withdraw consent from the study at any time.   Study data collected prior to withdrawal will be 
analyzed and included with the final study results.  The investigator may withdraw the subject from the study at 
any time if assessed to be in the best interest of the subject.  
 
15.0 CRITERIA FOR STUDY TERMINATION 
 
The study may be terminated at any time for reasons of safety, based on a recommendation by the IRB, the study 
Clinical Events Committee (CEC), or other considerations of the Sponsor.  Serious, device-related or possibly 
related AEs that are unexpected in either frequency or type may prompt a review by the principal investigator, 
CEC, and/or Sponsor, and may lead to consideration of stopping the study. Such a review and discussion will be 
documented and included with the study records.  
 
 
16.0 STUDY DURATION 
 
Enrollment is expected to occur over a 6-month period. Thus, completion of enrollment and 6-month follow up is 
anticipated within a 12-month duration. 
 
 
17.0 TRAINING 
 
Training of appropriate clinical site personnel will be the responsibility of the Sponsor or their designees.  To 
assure uniform data collection and protocol compliance, trainers will provide an educational session to review the 
VIG-CAS Investigational Plan, techniques for the identification of eligible subjects, instructions on data 
collection, follow-up schedules and regulatory requirements.  Ongoing email and telephone feedback regarding 
completion of eCRFs will be provided by the DCC and study monitors.  
 
Prior to enrollment start, refresher technical training for set-up and use of the VIG will be provided. Only prior 
investigators with experience using the VIG will participate in the study; thus, roll-in cases will not be required.  
 
 
18.0 STATISTICAL ANALYSIS  
 
All subjects who meet the enrollment criteria and in whom use of the VIG is attempted will be included in the 
intention-to-treat analysis population.   
 
Descriptive statistics will be used to summarize subject baseline and outcome data.  Continuous variables will be 
summarized using means, standard deviations, medians, interquartile ranges, minimum and maximum values.  
Categorical variables will be summarized in frequency distributions. A copy of the database used to prepare 
clinical report summaries will be archived to enable any statistical analyses performed to be replicated. A full data 
listing will be prepared at the completion of the study.  Listings of data represented on the CRF will include key 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 19 of 25 
 
baseline, demographic, and outcome variables to facilitate further investigation of tabulated values and to allow 
for clinical review of safety variables.  
 
No formal hypotheses will be tested or associated significance levels assigned to study results.    Nominal 
confidence intervals may be calculated in summarizing clinical results for study endpoints but not for purposes of 
product labeling.   
In addition to summarizing and reporting SAEs that are part of Study Endpoint #6, listings of other AEs (serious 
and non-serious) will be prepared and evaluated. 
 
19.0 DATA COLLECTION AND MANAGEMENT 
 
Data Collection 
Primary data collection based on source documented medical records will be performed by study coordinators or 
other designated research staff at each site. A copy of the CRF (data to be collected) is provided in Appendix C. 
Electronic data capture (EDC) will be used.  The EDC system used will be compliant with FDA requirements.  
Site training on EDC data recording will be provided by the Data Coordinating Center (DCC).  All EDC training 
will be documented in the Investigator site file. Throughout the study, a help desk at the DCC will be available for 
any questions that arise from the sites concerning EDC. 
 
Notification of subject enrollment must be provided to the Sponsor within 24 hours. The enrollment notification 
may be made by email to the Sponsor or by entry of an enrollment form into the EDC within 24 hours of 
enrollment.  
 
The timeline for entry of CRF data into the EDC is as follows: 
 
• 
Pre-procedure (baseline) Imaging, Inclusion/Exclusion, Index Procedure, and Discharge information 
should be entered within 7 days of enrollment.  
 
• 
Follow-up Forms should be entered within 7 days of the follow-up visit.  
 
For any deaths that may occur throughout the study duration, efforts should be made to obtain a copy of the death 
certificate and autopsy report, as applicable. 
 
Data Management 
The DCC will use a validated clinical data management system consisting of a relational database and a web 
application to capture the study data through single-pass data entry.  Automated edit checks for missing, 
discrepant, and out of range data will be programmed into the data entry forms, and manual edits will be 
conducted by the DCC Managers on an ongoing basis. The Sponsor will provide a list of edit checks to the DCC.   
 
Any data discrepancies identified during data monitoring will be communicated to study sites for resolution or 
justification. Once all discrepancies and queries have been resolved, the site principal investigator will confirm 
the data accuracy with his/her signature on a Verification CRF, or similar method.  Once the study is completed, 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 20 of 25 
 
all data have been entered into the clinical database, and all discrepancies have been resolved, an audit will be 
conducted to verify that all requirements for database lock have been met.  The database will then be locked and 
final analyses performed.  
 
CRF submission status will be tracked by the Sponsor and DCC.   
 
 
20.0 DATA MONITORING AND QUALITY ASSURANCE MEASURES 
 
Sponsor Monitoring 
Study site monitoring will be performed by Sponsor personnel or Sponsor designees (contract monitors) to ensure 
that the study is conducted in compliance with applicable regulations and with the study protocol. A pre-
investigation visit will be made to orient the staff to the study protocol and procedures, applicable regulations and 
requirements, and study administration expectations. Study sites will be evaluated to ensure an adequate patient 
base and sufficient staff support for proper study conduct.   
 
No sites may receive shipment of study devices until the following documents are received by the sponsor: 
 
• Written IRB approval for conduct of the study 
• IRB approval of a consent form 
• Signed Investigator Letter of Agreement 
• Executed Study Agreement 
• Copies of Investigator’s CV and medical license 
• Financial Disclosure 
 
Clinical sites will be regularly monitored for timeliness and accuracy of data submitted to the DCC.  Any evident 
patterns of noncompliance with respect to the protocol, data accuracy, maintenance of source documentation, or 
timeliness will be cause for the site to be put on probation. If correction actions are not made, the site will be 
asked to withdraw from the study. 
Clinical Events Committee 
An independent Clinical Events Committee (CEC) will provide medical review of SAEs, UADEs, and any deaths 
that may occur throughout the study.  The CEC will be comprised of independent physicians with expertise in the 
care and management patients that comprise the potential study population.  Details of CEC operations will be 
defined in a CEC Charter. 
 
21.0 ADVERSE EVENTS  
Definitions 
Adverse Event (AE) is defined as any undesirable sign, symptom or medical or psychological condition 
even if the event is not considered to be related or possibly related to the study device or study 
procedure/intervention.  Medical condition/diseases present before starting the study will be considered 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 21 of 25 
 
adverse events only if they worsen after starting study treatment. An adverse event is also any undesirable and 
unintended effect of research occurring in human subjects as a result of the collection of identifiable private 
information under the research. Adverse events also include any problems associated with the use of a study 
device that adversely affects the rights, safety or welfare of subjects. 
 
Serious Adverse Event (SAE) is defined as any undesirable sign, symptom, or medical condition which 
is fatal, is life-threatening, requires or prolongs in-patient hospitalization, results in persistent or significant 
disability/incapacity, constitutes a congenital anomaly or birth defect, is medically significant and which the 
investigator regards as serious based on appropriate medical judgment. An important medical event is any AE that 
may not result in death, be life-threatening, or require hospitalization but may be considered an SAE when, based 
upon appropriate medical judgment, it may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in the definitions of SAEs. 
 
Unanticipated Adverse Event (UAE) is defined as any event or experience that meets all three criteria below: 
 
• 
Is unexpected in terms of nature, severity or frequency, given the research procedures that are described 
in the protocol-related documents AND in the characteristics of the subject population being studied 
• 
Related or possibly related to participation in research. This means that there is a reasonable possibility 
that the incident may have been caused by the procedures involved in the research study. 
• 
The incident suggests that the research placed the patient or others at greater risk of harm than was 
previously known or recognized OR results in actual harm to the patient or others 
 
Unanticipated Adverse Device Effects (UADE) is defined as any serious adverse effect on health or safety or any 
life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects” (21 CFR 812.3(s). 
 
Review and Notification of UADEs 
Federal law requires that the FDA be notified immediately of all UADEs.  The UADE review and notification 
process will be as follows:  
 
(i) 
The study site will submit an Adverse Event (AE) report, indicating that the AE is serious and 
related or possibly related to the study device.  Study sites must report all SAEs (including 
UADEs) to the Sponsor within 24 hours of discovery.  If additional supporting information 
regarding the SAE is requested after the initial 24-hour report, the information will be promptly 
sent to the Sponsor, when available, via email.  
 
(ii) 
The Sponsor will immediately conduct an evaluation and prepare a UADE report.  The Sponsor 
will consult with the CEC as part of the UADE evaluation process.  
 
(iii) 
The Sponsor will report the results of the UADE evaluation to FDA, all reviewing IRBs, and 
participating investigators within 10 working days after the Sponsor first receives notice of the 
UADE (§§ 812.46(b), 812.150(b)(1).  

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 22 of 25 
 
Investigator Evaluation of Adverse Events 
The occurrence of AEs, including SAEs and UAEs, will be monitored throughout the study duration.  Adverse 
event information will be collected and reported on designated AE forms and classified by the principal 
investigator as serious/not serious. The investigator will determine the relatedness of the AE to the study device 
and study procedure according to the following definitions:  
 
• 
Related (AE is clearly related to the device/procedure) 
• 
Possibly related (AE may be related to the device/procedure) 
• 
Unrelated (AE is clearly not related to the device/procedure) 
 
Procedure-related AEs are AEs that occur during the time interval from when the subject enters and leaves the 
surgical treatment suite for the index procedure (e.g., AVG implant procedure).  Thus, the procedure includes use 
of the study device, as well as any treatments or procedures that are applied before or after the study device (eg, 
anesthesia, suturing of incision sites after AVG is completed), while the subject is in the surgical suite. 
Device-related AEs are AEs related or possibly related to the study device or to the study device procedure which 
includes delivery, deployment, and attachment of the study device to the AVG.  
Procedure-related events may not necessarily be related to the study device; for example, a procedure event such 
as an anesthesia reaction would not be related to the study device.   
 
Device-related events may also occur after the study procedure, for example, fracture of metal strut in the VIG. 
 
For situations in which a study subject experiences a SAE that results in abandonment of the study AV access 
site, the subject should be followed to the next follow-up visit after the study AVG is abandoned. This allows for 
collection of information about the subject’s health status after the AVG is abandoned.  After that visit, the 
subject can then be formally exited from the study. This means that the date that AVG patency is lost and the date 
of study withdrawal are not necessarily the same date. 
 
Reporting and Review of Serious Adverse Events 
SAEs must be reported to the Sponsor within 24 hours of discovery, and to national and local regulatory 
authorities, in accordance with national and local policies and procedures.  In addition, all UADEs will be 
evaluated at the time of discovery and reported to the Sponsor within 24 hours.  SAEs are reported by email or 
telephone call, using a designated SAE reporting form provided by the Sponsor. 
 
A final determination as to whether an SAE meets the requirements for expedited reporting to the FDA and 
participating IRBs will be made by the Sponsor. 
 
Reporting Deaths 
Data regarding a subject death should be recorded on the AE/SAE CRF as follows: 
 
If the outcome of an AE is reported as FATAL, then the STOP DATE of the AE should be date of the death.  
The AE with the fatal outcome will generally be the ‘cause of death’ as stated in source documents. The AE 
causing the death should be recorded on the CRF either by selecting from the checklist of specified AEs OR 
by selecting "Other" and then specifying the AE causing the death. 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 23 of 25 
 
 
If a death is discovered during follow-up and there is no information available regarding the AE(s) leading to 
the death outcome, and mark as “other” for AE type.  Record ‘fatal’ for the outcome. The START DATE and 
STOP DATE recorded should be the same date, eg the date of death.  In the “Event Summary” section, 
provide the date of death.  Complete as much information as possible on the CRF.   
 
For all deaths, a copy of source document information (e.g., death record, hospital admission and discharge 
summary, etc) should be provided, if available.  Deaths should be reported to the Sponsor within 24 hours of 
discovery, along with any available source documents describing the death, as available. Additional Source 
document information regarding the death, as may be requested by the CEC, should be provided as soon as it 
becomes available.  
 
22.0 PROTOCOL VIOLATIONS 
 
Protocol Violation is defined as any change, deviation, or departure from the study design or procedures of the 
research project that is not approved by the IRB and study sponsor prior to its initiation or implementation, OR 
deviation from standard operating procedures, Good Clinical Practices (GCPs), national or local regulations. 
Protocol violations may or may not be under the control of the research team or hospital staff.  
 
Major Protocol Violations 
All major protocol violations must be reported to the IRB, as applicable and in accordance with local IRB policy, 
AND to the study sponsor, immediately upon discovering them, and no later than seven (7) calendar days from 
the time the study team receives knowledge of the event. 
 
A major violation is a protocol violation that meets the following criteria: 
• 
Represent a serious or continuing failure on the part of the study team to comply with the protocol, 
standard operating procedures, GCPs, federal, state or local regulations 
• 
Impacts subject safety or substantially alter risks to subjects. May or may not result in actual harm 
(clinical, emotional, social, financial, etc) 
• 
Significantly damages the completeness, accuracy and reliability of the data collected for the study 
• 
Is under control of the investigator/research team/hospital staff. 
 
Any evident patterns of noncompliance with the protocol requirements will be cause for the site to be put on 
probation for a period of one month. If corrective actions are not made, the site will be asked to withdraw from 
the study. 
 
A log of all protocol deviations should be maintained in the study regulatory binder.  
 
 
23.0 REGULATORY RESPONSIBILITIES AND CONSIDERATIONS 
 
The responsibilities described in this section are required by Federal law and regulation (21 CFR 812, 
Investigation Device Exemptions; 21CFR 50, Protection of Human Subjects; 21 CFR 56, Institutional Review 
Boards). 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 24 of 25 
 
Investigator Responsibilities 
The study site investigator is responsible for ensuring that the study is conducted according to all signed 
agreements, the study protocol, and applicable FDA regulations.  These responsibilities are listed below.  In 
addition, each investigator must complete and sign the Investigator’s Letter of Agreement provided by the 
Sponsor. 
• 
IRB approval. The investigator must submit the study protocol to his/her IRB and obtain their written 
approval before being allowed to participate in the study. The investigator is also responsible for fulfilling 
any conditions of approval imposed by the IRB. 
• 
Informed consent. Part of the IRB approval will include approval of Informed Consent text specific to the 
study.  The investigator must administer the approved informed consent text to each prospective study 
subject, and obtain the subject’s signature on the text, prior to study enrollment.   
• 
Study coordinator.  To assure proper execution of the protocol, site investigators must identify a study 
coordinator for the site. Working under the authority of the investigator, the coordinator will assure that 
study requirements are fulfilled, and will be the key contact person at the site for all aspects of study 
administration.  
• 
Records.  Site investigators must maintain accurate, complete, and current records relating to the conduct 
of the study.  Such records include key study related correspondence (e.g., correspondence with IRB, 
DCC, sponsor, study monitors); study device accountability records; subject case history information 
(CRFs, consent form, AE records). 
• 
The study site principal investigator has overall responsibility for supervision of the use of the study 
device. The study investigator shall permit the device to be used only with subjects under his/her 
supervision.   
• 
Reporting requirements. The investigator is responsible for reporting any unanticipated adverse device 
effects, SAEs, protocol violations, withdrawal of IRB approval, and other required reports (progress 
report and final report) according to the FDA guidelines and ICH GCP guidelines. 
 
Sponsor Responsibilities 
Phraxis, Inc. is the manufacturer of the VIG study device, the Sponsor of the study, and the IDE holder.  The 
Sponsor’s responsibilities include: 
• 
Ensure that the study is conducted according to the signed study site clinical agreement, investigational 
plan and protocol, ICH GCP guidelines, and all applicable regulatory regulations. 
• 
Provide study devices to participating study sites 
• 
Provide study device training to investigators and study site staff 
• 
Select the Principal investigator, site investigators, study sites and other study consultants (e.g. DCC) who 
participate in the study 
• 
Provide financial support to study sites and consultants per individual Agreements 
• 
Establish regulatory standards per federal regulations for clinical study sites and other study participants 
and perform regular site monitoring to assure compliance with them. 
• 
Perform site monitoring of clinical data at study sites 
 
The Sponsor (Phraxis) retains ownership of all clinical data generated in the study and controls the use of the data 
for purposes of regulatory submission to the US and other governments.  
 

VIG-CAS/Investigational Plan 
CONFIDENTIAL 
Phraxis, Inc. 
 
 
Page 25 of 25 
 
Supply of Study Devices 
VIG devices will be provided to each study site per the terms of a Study Agreement between Phraxis, Inc. and the 
site. At the cessation of the study, all unused study devices will be dispositioned per the agreements between the 
site and Phraxis, Inc. 
 
Record Retention Policy 
Study documents should be retained for at least two years after the last approval of a marketing application, and 
until there are no pending or contemplated marketing applications; OR at least two years have elapsed since the 
formal discontinuation of clinical development of the investigational product.  The Sponsor will inform in writing 
when study documents are no longer needed.  Study sites should not destroy any study records without first 
confirming with the sponsor.  
 
 
 
24.0 MEASURES TO AVOID BIAS 
 
Measures that will be used to avoid bias include: 
• Use of independent CEC 
• Objective criteria for endpoint determination 
•  Intention-to-treat primary analysis 
 
 
25.0 PUBLICATION POLICY 
 
The publication of results from any single center experience within the study is strongly discouraged until one 
year following the study’s termination to allow for preparation and publication of the multicenter results. 
 
 
26.0 REFERENCES 
 
1. Yevzlin AS, Setum CM, Kallok MJ, Valliant A. Percutaneous AVG creation in a canine model. 
Presented at the 2013 American Society of Diagnostic and Interventional Nephrology 9th Annual 
Scientific Meeting. 
 
2. Ebner, A, Ross JR, Setum CM, Kallok, MJ, Yevzlin AS. Transcatheter Anastomosis Connector System 
for Vascular Access Graft Placement: Results from a First-in-Human Pilot Study. J Vasc Access 2016; 
17:111-117.