Clinical Evaluation of a Vascular Venous Anastomotic Connector for Minimally Invasive Connection of an Arteriovenous Graft for Hemodialysis [InterGraft VIG-only Study]
Phase: NA
Conditions: End Stage Renal Disease
Sponsor: Phraxis, Inc.

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 Clinical Evaluation of a Vascular Venous Anastomotic Connector for  
Minimally Invasive Connection of an Arteriovenous Graft for Hemodialysis 
[InterGraft Study] 
 
INVESTIGATIONAL PLAN 
IDE # G140221 
 
Investigational Plan Revision History: 
 
Rev 1, October 10, 2014: Initial release, for IDE submission. 
 
Rev 2, January 30, 2015: Added details of statistical analysis, sample size, electronic data capture. 
 
Rev 3, June 2, 2015:  Added independent Medical Monitor; revised Table 1 to clarify that Transonics device or similar 
method may be used for graft flow rate evaluation, added lab tests; added note that AIG may only be used after VIG has first 
been placed; added Table 2 to summarize study enrollment; clarified that pregnancy test is required to confirm subject is not 
pregnant at time of enrollment. 
 
Rev 4, August 31, 2015: Added note to Inclusion criterion #7 that as required by an IRB, adult individuals who lack capacity 
to consent for themselves will be not be included in the study. 
 
Rev 5, July 27, 2017: Incorporated information provided in Study Operations Memos 1-8. 
 
Rev 6, November 14, 2018: Incorporated adaptive modification to the study design; added an independent DSMB, 
incorporated information in Study Operations Memos 9-13.  NOTE:  Effective with this revision, the InterGraft Arterial 
Anastomotic Connector (AIG) study device will no longer be used in the study. Reference to the AIG in this revision 6 of the 
Investigation Plan refers only to previously enrolled subjects in which an AIG was used.  
 
Rev 7, May 29, 2019:   Incorporated study design modifications, including clarification of the primary analysis population, 
sample size, planned enrollment, and statistical analysis modifications; revised 2-week follow up window in Table 1. 
 
Rev 8, July 28, 2020: Changed total roll-in subjects from 12 to 15, study sites participating from 20 to 23 and maximum total 
of enrolled subjects (including roll-ins) from 170 to 173. 
 
Sponsored by: 
 
Phraxis, Inc. 
Minneapolis, MN   USA 
 
 
Clinical Trial Registration:  
NCT02532621 
 
 

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TABLE OF CONTENTS 
 
 
 
 
 
 
 
 
 
                       Page 
ACRONYMS AND ABBREVIATIONS 
 
 
 
 
 
4 
 
 
 
 
 
1.0 GENERAL INFORMATION 
 
 
 
 
 
 
5 
 
 
2.0 INTRODUCTION and BACKGROUND 
 
 
 
 
 
6 
 
 
 
3.0 STUDY DEVICE DESCRIPTION  
 
 
 
 
 
8 
       Indication for Use  
 
 
 
 
 
 
 
8 
 
 
4.0 PRIOR STUDIES  
 
 
 
 
 
 
 
9 
       Bench Testing 
 
 
 
 
 
 
 
 
9 
       Pre-Clinical Studies  
 
              
 
 
 
 
9  
       Clinical Studies 
 
 
 
 
 
 
 
 
9 
 
 
5.0 STUDY OBJECTIVE 
 
 
 
 
 
 
 
10 
 
 
6.0 STUDY DESIGN 
 
 
 
 
 
 
 
 
11 
7.0 SUBJECT SELECTION  
 
 
 
 
 
 
 
11 
       Initial Inclusion Criteria 
 
 
 
 
 
 
 
11 
       Final Inclusion Criteria 
 
 
 
 
 
 
 
11 
       Exclusion Criteria  
 
 
 
 
 
 
 
11 
8.0 STUDY ENDPOINTS 
 
 
 
 
 
 
 
12 
Primary Endpoint  
 
 
 
 
 
 
 
12 
Secondary Endpoints 
 
 
 
 
 
 
 
12 
9.0 SUBJECT SCREENING AND INFORMED CONSENT 
 
 
 
13 
 
       Screening and Enrollment  
 
 
 
 
 
 
13 
       Baseline Imaging  
 
 
 
 
 
 
 
13 
       Informed Consent  
 
 
 
 
 
 
 
13 
10.0 STUDY PROCEDURE 
 
 
 
 
 
 
 
14 
 
       Use of Clamps 
 
 
 
 
 
 
 
 
14 
       Other Treatment Immediately after Deployment of InterGraft Connectors 
 
14 
       Vascular Grafts for Hemodialysis 
 
 
 
 
 
 
15 
       Treatment of Ipsilateral Central Venous Stenosis Prior to Enrollment  
 
15 
       Study Device Failure, Defect, or Suspected Device Problem  
 
 
15 
       Bailout Procedure  
 
 
 
 
 
 
 
16 
       Assessment of Graft Flow at the end of the Procedure  
 
 
 
16 
       Initial Use of the Graft for Hemodialysis 
 
 
 
 
 
16 
11.0 FOLLOW-UP PROCEDURES AND GRAFT INTERVENTIONS  
 
16 
       Subject Management 
 
 
 
 
 
 
 
16 
       Pharmacologic Regimen 
 
 
 
 
 
 
 
16 
       Follow-up Evaluations 
 
 
 
 
 
 
 
16 
       Telephone follow-up for subjects that miss final (6 month) visit 
 
 
17 
       Post-procedure Graft Interventions  
 
 
 
 
 
17 
       Summary of Tests and Procedures  
 
 
 
 
 
17 
       Final Events 
 
 
 
 
 
 
 
 
18 
12.0 POTENTIAL RISKS 
 
 
 
 
 
 
 
18 
       Steps to Minimize Risks 
 
 
 
 
 
 
 
19 
 

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13.0 POTENTIAL BENEFITS  
 
 
 
 
 
 
19 
14.0 SUBJECT WITHDRAWAL FROM THE STUDY  
 
 
 
19 
15.0 CRITERIA FOR STUDY TERMINATION 
 
 
 
 
19 
16.0 STUDY DURATION 
 
 
 
 
 
 
 
20 
17.0 TRAINING 
 
 
 
 
 
 
 
 
20 
 
       Roll-in Cases 
 
 
 
 
 
 
 
 
20 
18.0 STATISTICAL ANALYSIS  
 
 
 
 
 
 
20 
 
       Analysis Population 
 
 
 
 
 
 
 
20 
       Choice of Performance Goal 
 
 
 
 
 
 
21 
 
       Hypotheses  
 
 
 
 
 
 
 
 
21 
 
       Data Analysis 
 
 
 
 
 
 
 
 
21 
       Sample Size Justification and Planned Enrollment 
 
 
 
 
23 
19.0 DATA REPORTING AND PROCESSING  
 
 
 
 
24 
       Data and Collection 
 
 
 
 
 
 
 
24 
       Data Management  
 
 
 
 
 
 
 
24 
20.0 DATA MONITORING AND QUALITY ASSURANCE MEASURES 
 
24 
       Sponsor Monitoring 
 
 
 
 
 
 
 
24 
       Medical Monitor 
 
 
 
 
 
 
 
 
25 
       Unanticipated Adverse Device Effects 
 
 
 
 
 
25 
       Data and Safety Monitoring Board  
 
 
 
 
 
26 
21.0 CLINICAL EVENTS  
 
 
 
 
 
 
 
26 
       Clinical Events Committee  
 
 
 
 
 
 
28 
 
22.0 PROTOCOL VIOLATIONS 
 
 
 
 
 
 
29 
23.0 REGULATORY RESPONSIBILITIES AND CONSIDERATIONS  
 
29 
       Investigator Responsibilities 
 
 
 
 
 
 
29 
       Sponsor Responsibilities 
 
 
 
 
 
 
 
30 
       Record Retention Policy 
 
 
 
 
 
 
 
30 
24.0 MEASURES TO AVOID BIAS 
 
 
 
 
 
 
31 
 
25.0 PUBLICATION POLICY  
 
 
 
 
 
 
31 
26.0 REFERENCES 
 
 
 
 
 
 
 
 
31 
 
 
Appendix A: 
Current InterGraft™ Venous Anastomotic Connector Instructions for Use 
Appendix B:  
Summary of Literature Search- Patency Performance Goal 
Appendix C: 
Case Report Form 
Appendix D:      Sample Informed Consent Form  

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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 
DSMB  
Data and Safety Monitoring Board 
EDC 
 
Electronic Data Capture 
ESRD  
End Stage Renal Disease 
GCP 
 
Good Clinical Practice 
IFU 
 
Instructions for Use 
IRB 
 
Institutional Review Board 
KDOQI 
Kidney Disease Outcomes Quality Initiative (National Kidney Foundation) 
MM 
 
Medical Monitor 
ePTFE  
expanded Polytetrafluoroethylene 
UADE  
Unanticipated Adverse Device Effect 
VIG 
 
Venous InterGraft Connector 
 
 

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1.0 GENERAL INFORMATION 
Study Name:  
Clinical Evaluation of a Vascular Venous Anastomotic Connector for Minimally Invasive 
Connection of an Arteriovenous Graft for Hemodialysis [InterGraft Study] 
 
Study Device:  
The device evaluated in the study is the InterGraft™ Venous Anastomotic Connector (VIG).   
   
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 design 
 
Subjects:  
A total of up to 173 subjects with ESRD who have a planned arteriovenous graft implant 
procedure for hemodialysis access and who meet the study selection criteria will be included.    
Lead Principal 
Investigator: 
 
John R. Ross, MD 
 
 
 
Orangeburg, SC 
 
 
 
Phone/email: (803)533-7544/ jrrsurgery@aol.com 
 
Sponsor: 
 
Phraxis, Inc. 
Saint Paul, MN 
 
 
 
Sponsor representative: Cindy Setum, Ph.D., Director of Clinical Affairs 
 
 
 
Phone/email: (612) 801-6730/ csetum@phraxis.com 
 
Data Coordination: 
Clinical Development Associates, Inc. 
 
 
 
Richmond, VA 
 
 
 
Contact: Suzanne Cowley   Phone/email:  (804)-740-3363/ cowley1@rcn.com 
 
Statistical Analysis: 
Richard G. Holcomb, PhD 
 
 
 
Minnetonka, MN 
 
 
 
Phone/email: (952)745-0555/ rgholcomb2@cs.com  
 
 
Medical Monitor:  
Arif Asif, MD 
 
 
 
Neptune, NJ 
 
 
 
Arif.Asif@HackensackMeridian.org 
DSMB Chairman: 
Anthony Comerota, MD 
 
 
 
Alexandria, VA 
 
 
 
Anthony.comerota@Inova.org 
 

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2.0 INTRODUCTION and BACKGROUND 
End Stage Renal Disease (ESRD) is a significant and growing health problem.  In the United States (U.S.), 
571,000 ESRD subjects underwent treatment in 2009; and since 2000, a 12% increase in the incidence rate of 
ESRD has been observed in subjects ≥ 75 years of age.1  By the year 2020, the number of dialysis subjects is 
expected to reach 774,000, with an annual incidence of more than 160,000 new subjects per year. These subjects 
typically undergo three hemodialysis treatments per week, each lasting 3-4 hours.  An arteriovenous (AV) 
vascular access is needed to remove blood for dialysis filtration and return to the body. The access must provide 
high blood flow volume continuously during treatment. Due to the need for surgical healing and development, the 
access is ideally prepared several weeks or months in advance of anticipated need.  A significant challenge in 
managing ESRD subjects is providing access when needed, along with consistent and sustained access.  
 
Vascular access has frequently been referred to as the “Achilles heel” of dialysis because of the high morbidity 
and mortality rates due to infection, thrombosis and ultimate access failure. Of the three types of vascular access: 
fistulas, grafts, and central venous catheters, the type used is influenced by factors such as the expected time 
course of renal failure and the condition of the subject’s vasculature. While fistulas are considered as the gold 
standard, synthetic grafts are also widely used since fistulas cannot always be successfully established.2  The 
failure rate of fistulas to mature and thus be suitable for dialysis may be as high as 60%.3 Many patients will 
require an AV graft (AVG) access at some point during the disease course.4 The creation of long term dialysis 
access remains a significant challenge, especially in patients with multiple prior failed access sites and in the 
elderly.5-7  Indeed, with continued treatment of an increasingly older ESRD population, the increased use of AVGs 
may also be required.8,9 
 
Grafts are relatively easy to place surgically using standard techniques.  Expanded polytetrafluoroethylene 
(ePTFE) is the most common graft material.4 Novel self-sealing multilayered ePTFE configurations and other 
graft materials (e.g., polyurethane) have recently been introduced, offering the potential for earlier access.10,11   
Compared with fistulas, AVGs have a greater incidence of recurrent stenosis, especially at the venous 
anastomosis,  and require more salvage interventions to maintain patency for dialysis.4  The pathogenesis of 
venous stenosis is comprised of a cascade of events resulting in endothelial and smooth muscle injury that results 
in intimal hyperplasia and ultimately flow limiting occlusion.12  With the conventional end-to-side venous 
anastomosis, the vessel wall is subjected to turbulent, nonlinear flow and low shear stress at the toe and heel of 
the anastomosis, sites that correspond to the development of intimal hyperplasia.  As hyperplasia progresses, 
increasing stenosis occurs resulting in a decrease in blood flow, leading to thrombosis. In addition to these 
hemodynamic factors, the trauma of surgical graft implantation due to relatively large (3-6cm) incision sites and 
circumferentially sutured anastomoses, contributes to increased healing time and possible complications.  These 
findings point to the need for new devices and techniques to optimize AVG flow dynamics and healing, resulting 
in the reduction of stenosis and other complications. 
Despite planning, a large percentage of patients present with an urgent need for hemodialysis and lack sufficient 
time to allow a fistula or standard surgical graft to be firmly established.  In such cases, the use of temporary 
venous catheter access is the only option currently available. More than 80% of subjects will begin dialysis with a 
catheter and approximately 28% will use a catheter for permanent access.1 Catheter use even for short periods can 
result in higher rates of infection, thrombosis, morbidity and mortality, compared to patients who do not start 
dialysis with a catheter.12 Both the Fistula First Initiative and the KDOQI guidelines have established a goal to 
limit chronic catheter use to less than 10% of dialysis patients.2,13 

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While recognizing that a native fistula is the recommended access for hemodialysis, AVGs remain a frequently 
used access type. The InterGraft™ Venous Anastomotic Connector (VIG) was developed for minimally invasive 
venous anastomosis of a standard hemodialysis graft.   This study will evaluate the safety and performance of the 
VIG for anastomosis of a commercially available, 6 mm diameter, ePTFE hemodialysis graft.  Anastomoses with 
the VIG may potentially reduce venous vessel trauma, improve the local vessel wall shear stresses and promote 
laminar flow, thereby improving patency.    
 
The original investigational InterGraft Clinical Study conducted under the approved IDE #G140221 was 
configured as a pivotal, prospective, multicenter, non-randomized, adaptive design.  The study was intended to 
enroll up to 252 subjects including roll-in subjects, subjects in whom both a VIG and AIG were used, and a small 
VIG sub-study of subjects who did not qualify for treatment with the AIG.  Subject enrollment began on 
November 12, 2015.  The study recruitment rate was slow and attributed primarily to challenges in identifying 
subjects with a suitable artery for using the AIG.  Initial investigator feedback indicated that the AIG was 
cumbersome to deploy and would not likely be adopted by clinicians in its current design.  The study was 
subsequently modified to discontinue further study of the AIG and all future enrolled subjects were to be treated 
using a VIG and sutured arterial anastomosis for AVG implantation. In accordance with the original 
investigational plan, in July 2018, an interim analysis was performed after the first 52 subjects receiving treatment 
with the VIG +AIG were enrolled and follow-up was completed.   
 
Investigator feedback, safety data and device performance data (number and type of reported device 
malfunctions) from the first 52 subjects treated with a VIG and AIG (interim analysis population) were evaluated 
and the results were used to inform the modified study design described in the previous revision 6 of the 
Investigational Plan.  
 
With this current Investigational Plan, the study primary analysis population will now include the following:  
 
• All USA subjects enrolled since June 5, 2018 and treated with the VIG + sutured arterial 
anastomosis (These subjects were not included in the interim analysis.) 
 
• All USA VIG sub-study subjects enrolled after October 17, 2017 (These subjects were not 
included in the interim analysis.) 
 
Roll-in subjects, subjects who were included in the planned interim analysis that has previously been completed, 
and other subjects that received an AIG will not be included in the primary analysis population. However, these 
subjects will continue to be followed and evaluated according to the requirements of the current protocol, which 
are identical to the previous version protocol requirements, and these results will also be included in a final study 
report. 
 
The current study will evaluate use of the VIG for placement of an AVG. The venous anastomosis will be created 
using the VIG and the arterial anastomosis will be created using standard suturing. The 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 graft implant procedural outcomes, the number and type of major adverse events, and patency throughout a 
six (6) month follow-up period will be evaluated.  The 6-month patency rate will be compared with a pre-

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specified patency performance goal that is drawn from prior surgical AVG literature and published performance 
standards.10, 14-20 
 
This study will be conducted in compliance with the Investigational Plan, Investigational Device Exemption 
(IDE) regulations, Good Clinical Practice guidelines (GCP), and other applicable regulatory requirements.  The 
study Sponsor (Phraxis, Inc.) intends that the study results will support a 510(k) marketing clearance for the 
InterGraft Venous Anastomotic Connector.   
 
3.0 STUDY DEVICE DESCRIPTION 
 
The device evaluated in the study is the InterGraft™ Venous Anastomotic Connector (VIG). The VIG 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. 
 
The VIG is constructed with a nitinol framework encapsulated with ePTFE in the midsection and uncoated at the 
ends (Figure 1). The VIG is delivered and deployed within the target vein using a customized transcatheter 
delivery system. The VIG is a flexible, flared, self-expanding endoprosthesis designed for coaxial placement in 
peripheral veins up to 10 mm in diameter. The distal flared end is configured as a nitinol scaffold with anchoring 
barbs that extend into the vein wall. The ‘graft end’ of the VIG is configured as a stent-like framework for 
anchoring within the ePTFE graft. The materials used in constructing the VIG are all medical-grade with well-
established biocompatibility profiles. 
 
The VIG is supplied pre-mounted within a customized transcatheter delivery system for over-the-wire delivery 
via an 11F vascular sheath. The VIG is intended as a permanent implant. The delivery system is a sterile, single 
use, disposable item.  A detailed description of the VIG and delivery system is provided in the Instructions for 
Use (Appendix A). 
Indication for Use 
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. 
 
Figure 1- InterGraft Venous Anastomotic Connector (VIG). Note barbs that anchor VIG within the vein (arrows).  
 
 
 

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4.0 PRIOR STUDIES 
 
Both the VIG and an arterial InterGraft Connector (AIG) were evaluated in the prior testing and studies described 
below. The findings from the prior testing are also applicable to use of the VIG only. The AIG will not be used in 
the current study. 
 
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 (C.R. Bard, Inc., 
Murray Hill, NJ) that were selected due to their current widespread clinical use. 
 
Computational Fluid Dynamics (CFD) modeling of the VIG used together with AIG was performed, based on a 6 
mm graft connecting artery and vein.21 This modeling demonstrated resulting graft flows of approximately 1 
L/min when the AV pressure difference was approximately 100 mm Hg.  With graft flow rates ranging from 980 -
1100 ml/min, the maximum wall shear ranged from 265Pa - 180Pa, and thus below the threshold to cause 
mechanical hemolysis (800Pa), or that thought to stimulate hyperplasia.21   These findings confirmed the 
acceptability of the InterGraft design for clinical evaluation.  
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 PTFE 
grafts, and near-term graft patency following initial placement of grafts using a VIG and AIG.22 Testing was 
performed using a femoral artery/vein canine model.  These studies provided evidence of safety and acceptable 
performance of the VIG. 
 
Clinical Studies 
First-in-Human Study 
A first-in-human clinical evaluation of the InterGraft Venous and Arterial Connectors was performed.23   The 
InterGraft Connectors were successfully used in 9/9 subjects for connection of an AVG in the upper arm: 5 
subjects received both the VIG and the AIG, and 4 subjects received the VIG for the venous anastomosis and a 
standard sutured arterial anastomosis.  InterGraft™ delivery and deployment success was obtained in all cases. 
All AVGs were patent at the end of the procedure.  
AIG Adverse events occurred during the procedure in 3 subjects: (i) In one case, a successfully deployed AIG was 
inadvertently nicked with a surgical tool during closure of the incision site. This resulted in a hole in the ePTFE 
coating on the AIG, creating a blood leak path that could not be repaired. The AIG was removed and a sutured 
arterial anastomosis was prepared at the same arteriotomy site.  There were no further sequelae. (ii) In another 
case, an acute graft occlusion occurred during the graft implant procedure.  Angiographic examination showed 
that the tunneled graft had been positioned in a manner that caused a graft kink. Aspiration thrombectomy via a 
guide catheter was performed, the graft was re-positioned to relieve the kink, and graft flow was immediately 
restored. There were no further sequelae. (iii) In another case, persistent bleeding at the AIG arteriotomy site 
occurred and was attributed to an incomplete seal around the arteriotomy site.  The cause was not determined but 

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could have been due to vessel wall damage during deployment, a coating defect on the AIG, or a mal-positioned 
AIG.  The bleeding was remedied by placement of a single suture at the leak site, and there were no further 
sequelae. 
There were no procedural adverse events related to the VIG. 
All subjects were discharged within one day after the procedure with patent grafts. Grafts were used for 
hemodialysis within 17 days, on average, and temporary venous catheters were removed.  Subjects were followed 
to six months. Three subjects exited the study early for reasons unrelated to the InterGraft devices. The remaining 
6 subjects had patent grafts. It was concluded that the InterGraft connectors can safely and successfully be used 
for AVG anastomoses.  An additional adverse event occurred in one subject after discharge: the subject had 
peritonitis and required abdominal surgery (not related to the study device). The subject developed a hospital-
acquired infection and the graft subsequently became infected and was removed. Of the 8 remaining 
subjects/grafts, 7 were confirmed to be patent at one month following the implant procedure (primary patency). In 
the remaining subject, the one month follow-up has not yet been performed. 
 
Investigator Feedback Collected During Enrollment of the First 52 Subjects in the IDE G140221 Clinical Study 
As originally designed, the IDE G140221 clinical study included both an arterial InterGraft Connector (AIG) and 
a venous InterGraft connector (VIG). Investigator feedback collected during enrollment of the first 52 subjects 
indicated the following: 
 
• 
A high level surgical/interventional skill was needed for AIG delivery and deployment; 
• 
Identifying subjects with a target artery suitable for using the AIG was a key obstacle to enrollment;  
• 
The anatomic requirements needed for proper positioning of the AIG relative to the artery orientation, to 
avoid kinks and untoward stresses to the implanted device were also obstacles to enrollment;  
• 
Investigators noted that while the AIG can work, the current design/procedure is complex and not ready 
for widespread adoption;  
• 
Several investigators appeared to have become disinterested in the study due to the above noted 
challenges, as evidenced by a very slow recruitment rate.  
 
Based on this investigator feedback, Phraxis determined that the AIG in the present configuration with a relatively 
complex delivery and deployment procedure, is excessively challenging to use, and that even if cleared-to-market, 
the AIG would likely not be readily adopted by clinicians. Thus, Phraxis concluded that the AIG is not ready for 
commercial introduction and Phraxis decided to stop further study of the AIG. On August 9, 2018, investigators 
were notified to stop further study of the AIG, and to continue follow-up to 6 months in subjects that had 
previously received an AIG, in accordance with the investigational plan. 
 
5.0 STUDY OBJECTIVE 
 
The objective of the current study is to demonstrate that the 6-month cumulative patency of AVGs connected with 
the InterGraft™ VIG connector is similar to that of AVGs connected using standard sutured anastomoses.   
 
 
 

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6.0 STUDY DESIGN 
 
This is a multicenter, prospective, non-randomized design study.  All enrolled subjects will receive the VIG 
device and will have a standard sutured arterial anastomosis.   The study allows for a maximum enrollment of 
173 subjects, including a provision for 12 subjects lost to follow-up and up to 15 roll-in cases.  Data from roll-in 
subjects will not be included in the primary analysis but will be analyzed separately.  
 
The study includes up to 23 participating clinical centers. Study site investigators will be physicians skilled in 
AVG placement and interventional techniques. Study data will be collected up to the point at which each subject 
has completed the 6-month endpoint or experienced a terminal study endpoint.  
 
7.0 SUBJECT SELECTION 
 
The following inclusion and exclusion criteria must be met for enrollment in the study: 
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 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 (IRB), 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. 

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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. 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 
Primary Endpoint 
The primary endpoint is cumulative patency at 6 months, defined as the percentage of subjects free from loss of 
access of the study graft for hemodialysis, assessed at 6 months.  
  
Secondary Endpoints 
Secondary endpoints for the study include: 
1. Acute device success, defined as AV graft flow at the end of the procedure as determined by palpable graft 
thrill and/or audible bruit, without significant bleeding or emergent surgery. 
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. 
2. Time to First Cannulation, defined as the time from initial access placement to the first graft cannulation. 
3. Number and type of interventions required to maintain secondary patency 
4. Number and type of serious adverse events (SAEs) through 6 months.  SAEs include the following: death, 
emergent surgery, 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 will not be tabulated again as SAEs. 
 

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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 starts 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 
All subjects referred for AVG implant should be screened for study eligibility.  A member of the Research Team 
will evaluate the subject for eligibility. If all initial inclusion criteria are met and no exclusion criteria are present, 
a member of the Research Team should inform the subject 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 screening and enrollment logs to record all subjects who were screened and all subjects 
who were enrolled.  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. 
 
No clinical site may contribute more than 25% of the total enrollment (excluding roll-in subjects).       
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 subject. As part of subject screening, baseline imaging should be reviewed to 
determine whether the subject 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 must have been previously 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 assure that informed consent is obtained from each subject in accordance with the guidelines of the 
IRB and all applicable regulatory guidelines. 
 
 

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10.0 STUDY PROCEDURE  
 
The procedure will be performed in accordance with the Instructions for Use (IFU) provided with the study device 
(Appendix A).   A commercially available 6mm diameter synthetic graft will be used. Such grafts may include 
conventional ePTFE grafts or grafts designed for early cannulation (within 24-48 hours). 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, in the event that 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 a procedure 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. 
 
Other Treatment Immediately after Deployment of the VIG 
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:  
 
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 

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Page 15 of 32 
 
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 device Instructions for Use (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 form 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 form (eCRF) 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 be 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 eCRF should be submitted to report the surrounding details.  
 
NOTE: Device Malfunctions should reported on the Device Malfunction eCRF 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.   
 
 
 

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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 Study 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 in 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 Study 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 within one week after placement. 
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 insure 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 case report form (CRF). 
 
Follow-up Evaluations 
Subjects will be followed at two weeks and monthly thereafter through six months to assess AVG patency and 
complications.  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.   
 

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Graft ultrasound evaluation should be performed at the 3 month 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 2 dialysis sessions 2 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 that miss the final (6 month) follow-up visit 
If a study 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 
at 6 months (the primary study endpoint), and to gather as much additional information as possible in order to 
complete the 6 month follow up and study completion eCRFs.  Telephone follow-up with subjects should be done 
only if the subject is unwilling or unable to come in.  If the subject cannot be reached, then the dialysis center 
should be contacted (if allowed) in order to determine AVG patency at 6 months. 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.   
Post-procedure Graft Interventions 
As per standard care following the AVG implant procedure, AVG interventions should be avoided within the first 
7 days following the index AVG implant procedure.  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 in the study, 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. 
 
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 (e.g., palpable thrill, 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, 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, 

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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  
• 
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 adverse events listed above are similar to those that can 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 

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• 
possible need for re-operation 
 
The VIG will be used together with a standard 6mm AVG for hemodialysis that is sold and packaged separately. 
Potential adverse events 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:  
• 
Rigorous technical training will be provided to physician investigators that will perform the study 
procedures. 
• 
On-site monitoring will occur during the first procedure at each site. On- site monitors will include a 
clinical representative of the sponsor. On-site monitors may also attend additional procedures throughout 
the course of the study. 
• 
The study procedure will be performed in a surgical suite with radiologic imaging capabilities. In the 
event that 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(s) for the VIG are unknown at this time.  Anastomoses with the VIG may potentially 
reduce venous vessel trauma, improve the local vessel wall shear stresses and promote laminar flow, thereby 
improving patency.  
 
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 
DSMB, or based on other considerations by the Sponsor.  Serious, device-related or possibly related adverse 
events that are unexpected in either frequency or type may prompt a review by the principal investigator, DSMB, 

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Medical Monitor 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 24-month period.  The  6-month follow-up and 2-month period of data 
analysis and regulatory submission preparation is anticipated to be completed by Q2 of 2021. 
 
17.0 TRAINING 
 
The training of appropriate clinical site personnel will be the responsibility of Phraxis Clinical Department or 
their designees [e.g. Data Coordinating Center (DCC) staff].  To assure uniform data collection and protocol 
compliance, trainers will present a formal educational session to review the Investigational Plan, techniques for 
the identification of eligible subjects, instructions on data collection, follow-up schedules and regulatory 
requirements.  Ongoing detailed email and telephone feedback regarding completion of CRFs will be provided by 
the DCC and through site monitoring to be performed by Phraxis representatives or their designee. 
 
Prior to enrollment start, technical training on use of the study devices will be provided by a Sponsor 
representative, who may also attend/observe the roll-in cases.  As part of the technical training, physician 
operators will also perform ‘test deployments’ of the study devices using a simulated-use model.   
 
Roll-in Cases 
Roll-in cases will be performed at each study site in order to confirm proper training and use of the study device 
and confirm comprehension of the study protocol.  “Roll-in” subjects will be identified as such before enrollment 
and treated according to the same protocol and 6 month follow-up duration as used in the main study. Data from 
roll-in cases will be recorded using the same CRF as the main study.  The number of roll-in cases per each site 
investigator will be determined by the Sponsor, in collaboration with the primary investigator at each site.  No 
more than 1-2 roll-in cases per investigator are anticipated. The clinical experience and procedural data from roll-
in cases will be reviewed by the Sponsor, in collaboration with each site investigator.  Upon successful 
completion of the roll-in case requirements, as determined by the Sponsor, sites will be permitted to begin 
enrollment in the main study. Clinical data from roll-in cases will not be included in the primary study analysis 
but will be analyzed and provided in a separate clinical report at the end of the study.  Data from roll-in cases will 
be included in the final safety analysis for the study.  
 
18.0 STATISTICAL ANALYSIS  
 
Analysis population 
The primary analysis population will include all subjects enrolled since June 5, 2018 and treated with the VIG + 
sutured arterial anastomosis, and also all VIG sub-study subjects enrolled after October 17, 2017.  Such subjects 
who meet the enrollment criteria and in whom use of the VIG is attempted will be included in the intention-to-
treat primary analysis population.   
 

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Data from roll-in subjects or from subjects included in the interim analysis population will not be included in the 
primary study analyses but these data will be analyzed and summarized separately.  This includes subjects who 
previously received an AIG.  
Choice of Performance Goal 
Based on a review of the literature, prior studies of AVGs cleared for commercial distribution, and on 
observations from the first 52 enrolled subjects that received an AIG+VIG (e.g., the interim analysis population), 
the observed cumulative patency rate at 6 months for standard AVG implants ranged from 65% to 98% 
(Appendix B).    Based on the proposed sample size for the current study (see below) and an expected cumulative 
patency rate of 84.6% for AVGs placed using the VIG, the exact, lower two-sided 95% confidence bound for 
cumulative patency is estimated to be 79.9%.  A comparison to a target Performance Goal (PG) of 75% has been 
chosen for the evaluation.   
 
Hypotheses 
The primary study endpoint of the cumulative patency rate at 6 months will be evaluated in the following testable 
hypotheses: 
H0:   (Cumulative Patency Rate)6 Months  ≤  PG 
H1:   (Cumulative Patency Rate)6 Months  >  PG 
where, PG = Performance Goal, here equal to 75%. 
There are no formal hypotheses associated with the evaluation of secondary endpoints. 
Data Analysis 
General Statistical Considerations 
a. Descriptive statistics will be used to summarize subject baseline and outcome data collected during the study.  
Continuous variables will be summarized using means, standard deviations, medians, interquartile ranges, 
minimums and maximums.  Categorical variables will be summarized in frequency distributions. 
b. Statistical analyses will be performed by validated software (e.g., SAS, SPSS, or Cytel Software) 
c. Copies of databases used to prepare clinical report summaries will be archived to enable any statistical 
analyses performed to be replicated. 
d. A full data listing will be prepared, including an electronic version in a standard computer-accessible format 
(e.g., SAS) at the completion of the study.  Listings of data represented on the CRF will be provided for all 
key baseline, demographic and outcome variables to facilitate further investigation of tabulated values and to 
allow for clinical review of safety variables.  
A one-sided p-value of 0.025 will be considered evidence of statistical significance for the primary study 
endpoint. 
Primary Endpoint 
Cumulative patency at 6 months will be evaluated using the estimated patency from a Kaplan Meier survival 
analysis.  The test statistic will take the following form: 
 
Z-test statistic =     (P - 0.75) / SE (P) 

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Where, (P) represents the Kaplan Meier estimate of cumulative patency at 6 months, and the standard error SE (P) 
is estimated using the method of Peto et al (1977). 24 
Subjects who withdrawn for reasons other than loss of cumulative patency will be included in the analysis up until 
the time of withdrawal, and be considered censored in the analysis, according to usual convention, after 
withdrawal. 
Secondary Endpoints 
The following secondary endpoints will be evaluated in the study, but there are no formal hypotheses that are 
tested or associated significance levels assigned to results.    Nominal confidence intervals may be calculated in 
summarizing clinical results for secondary endpoints but not for purposes of product labeling.   
1. Acute device success will be summarized by the success rate and associated 95% confidence interval. 
2. Primary Unassisted Patency at 6 Months will be summarized by the patency rate and associated 95% 
confidence interval.  
3. Time-to-First-Cannulation will be summarized by the median time and frequency distribution. 
4. Number and type of interventions required to maintain secondary patency will be summarized by the 
frequency distributions of numbers and types of interventions. 
5. Number and type of serious adverse events (SAEs) will be summarized by frequency distributions of the 
numbers and types of SAEs, the subject rates of SAEs by type, and the proportion of subjects with at least 
one SAE.  
Additional Safety Data 
In addition to summarizing and reporting SAEs (Secondary Endpoint 5), the number and type of non-serious 
adverse events (AEs) will be summarized by frequency distributions of the numbers and types of AEs and the 
subject rates of AEs by type. 
Gender Analysis 
Cumulative patency rates between genders will be compared by gender using a log rank test statistic to compare 
their respective Kaplan-Meier survival curves.   The heterogeneity of cumulative patency rates will also be 
examined using the test statistic used for the primary endpoint analysis.   Gender specific summary statistics will 
also be provided for study primary and secondary endpoints.  
 
Pooling of Sites 
Cumulative patency rates will be compared between study sites using a Chi-square test to evaluate the association 
between rates and sites.   A p-value of 0.15 or less will be considered evidence of a possible site interaction, 
requiring a further evaluation of subject baseline factors to determine if site differences can be explained by these 
factors.   
 
 
 
 

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Sample Size Justification and Planned Enrollment 
Sample size adjustment recommendations from the planned interim analysis subject data have been considered in 
determining the sample size for the current study. The required sample size for the study was estimated using the 
following assumptions: 
• 
Test basis:   Kaplan-Meier estimate of cumulative patency rate at 6 months, with exact binomial estimation 
for purposes of sample size 
• 
Type I error (alpha):   0.025 (one-sided) 
• 
Statistical power:  80% 
• 
Performance Goal (PG):  75% 
• 
Expected cumulative patency for InterGraft at 6 months:   84.6%. 
 
Based on the above assumptions, a total of 146 evaluable subjects will be required to compare observed 
cumulative patency to a PG of 75%.   With an expected loss-to-follow-up rate of 8% over 6 months (e.g., 12 
subjects), a total of 158 evaluable subjects will be enrolled into the main study, defined as primary analysis 
population of 146 subjects plus allowance for 12 subjects lost-to-follow up.   Planned minimum and maximum 
enrollment under the current investigational plan is summarized in Table 2.  
Table 2: Planned Enrollment in the Current Investigational Plan 
Study Group 
Minimum enrollment 
Maximum enrollment 
Roll-in 
0 
15 
Primary analysis   
146 
146 
Allowance for subjects lost-to- follow up 
12 
12 
TOTAL 
158 
173 
 
Planned enrollment under the entire study conducted under IDE G140221 is summarized in Table 3. This 
includes all subjects previously enrolled under the approved IDE G140221. 
 
Table 3: Summary of Planned Enrollment under IDE G140221, as of May 22, 2019 
Study Group 
Maximum enrollment                     
(or actual enrollment if known) 
 Roll-in subjects enrolled prior to May 22, 2019 (includes USA + 
Mexico Sites) 
25 (actual enrollment) 
Current Investigational Plan: Roll-in subjects 
up to 15 
Current Investigational Plan: subjects previous enrolled and to be 
included under the current investigational plan 
30 (actual enrollment) 
Current investigational plan:  new subjects remaining to be 
enrolled after May 22, 2019 (Primary analysis + allowance for 
lost-to-follow up 
128 
Previously enrolled subjects that received VIG+ AIG (includes 
USA + Mexico sites, does not include roll-in cases) 
68 (actual enrollment) 
Previously enrolled subjects in VIG sub-study that are not 
included under the current Investigational Plan, but were included 
in the interim analysis) 
7 (actual enrollment) 
TOTAL 
273 
 
 

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19.0 DATA REPORTING AND PROCESSING 
 
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. Electronic data capture (EDC) will be used.  The EDC system(s) 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 following guidance is provided regarding entry of CRF data into the EDC: 
• 
Pre-procedure (baseline) Imaging, Inclusion/Exclusion, Index Procedure, and Discharge information 
should be submitted within 2 days of enrollment.  
• 
Follow-up Forms should be submitted within 2 days of the follow-up visit.  
 
A complete copy of eCRF data to be collected is provided in Appendix C. 
 
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.  Once the study is completed, 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.  After database lock, the DCC will export the data into SAS 
datasets and provide them to the project statistician. 
 
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 (e.g. contract monitors). On-
site monitoring will be performed to ensure that the study is conducted in compliance with applicable regulations 

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and with the study protocol. A pre-investigation visit will be made to each new study site to orient the staff to the 
study device and procedures, the study protocol, applicable regulations and requirements, study administration 
expectations. The prospective site will be evaluated to ensure that it has an adequate patient base and can provide 
sufficient staff and documentation 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. 
 
Medical Monitor 
An independent study medical monitor (MM) will be designated. The MM will be a qualified physician that is not 
a study investigator. The MM has the responsibility to review and evaluate information relevant to the study 
device safety throughout the development and implementation of the protocol. This oversight includes reviewing 
safety information and providing applicable recommendations to the sponsor. More specifically, the MM will: 
• Evaluate all SAEs and review safety reports. SAEs will be evaluated immediately upon report of 
occurrence. 
• Evaluate all UADEs at the time of occurrence. 
• Advise the Sponsor (IDE holder) 
Unanticipated Adverse Device Effects (UADE) 
Federal law requires that the FDA be notified immediately of all Unanticipated Adverse Device Effects (UADE).  
Investigational device exemption (IDE) regulations define an UADE 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).” 
 
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.  

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(ii) 
The Sponsor will immediately conduct an evaluation and prepare a UADE report.  The Sponsor 
will consult with the Medical Monitor (MM) as part of the UADE evaluation process, and the 
MM will review the UADE report and applicable information for clarity and completeness. The 
sponsor and MM may contact the site, as needed, for additional information and clarification.  
(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).  
NOTE:  Not all SAEs may bear a relation to the study device or procedure, and it is partly the responsibility of the 
MM to confirm that any claims of connectivity are reasonable and that all serious events are properly reported, 
regardless of causation.  
In summary, the MM will collaborate with the Sponsor on safety oversight to meet human subjects’ safety 
standards as defined by applicable Federal regulations, International Conference on Harmonization (ICH) Good 
Clinical Practice Guidelines (GCP). 
Data and Safety Monitoring Board 
An independent DSMB is established and has responsibility for safeguarding the interests of study 
participants, assessing the safety and efficacy of study procedures, and for monitoring the overall 
conduct of the study. The DSMB is an independent group advisory to the Sponsor, and is required to 
provide recommendations about starting, continuing, and stopping the study. In addition, the DSMB is 
asked to make recommendations, as appropriate, to the Sponsor about: 
• 
Efficacy of the study intervention 
• 
Benefit/risk ratio of procedures and participant burden 
• 
Selection, recruitment, and retention of participants 
• 
Adherence to protocol requirements 
• 
Completeness, quality, and analysis of measurements 
• 
Amendments to the study protocol and consent forms 
• 
Performance of individual centers and core labs 
• 
Participant safety, and 
• 
Notification of and referral for abnormal findings 
Details of DSMB operations are defined in the DSMB Charter document. 
21.0 CLINICAL EVENTS  
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 
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 

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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 
 
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, assessed and classified by the principal 
investigator as serious/not serious. The investigator will also determine the relatedness of the AE to the study 
device and study procedure according to the following definitions:  
 
o Related (AE is clearly related to the device/procedure);  
o Possibly related (AE may be related to the device/procedure); 
o 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.  
Device-related events that occur during the study procedure are also procedure-related events.  
 
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 has a serious adverse event (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 
is done in order to collect general information about the subject’s health status after the AVG is abandoned.   

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After that visit, the subject can then be formally withdrawn 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 unanticipated adverse device effects (UADE) 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 study medical monitor and/or Sponsor. 
 
Reporting Deaths. 
Data regarding a subject death should be recorded on the AE/SAE eCRF 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 eCRF either by selecting from the checklist of specified AEs OR by selecting 
"Other" and then specifying the AE causing the death. 
 
If a death is discovered during follow-up and there is no information available regarding the AE(s) leading to the 
death outcome, please complete the AE/SAE eCRF, 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 this eCRF.   
 
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 study Clinical Events Committee or 
DSMB, should be provided as soon as it becomes available.  
 
Clinical Events Committee 
A Clinical Events Committee (CEC) will provide medical review of SAEs, UAEs, and any deaths that may occur 
throughout the study.  The CEC will be comprised of the Medical Monitor, and the Sponsor’s Chief Science 
Officer, Chief Technology Officer and Director of Clinical Affairs.  Details of CEC operations are defined in a 
CEC Charter document. 
 
The principal investigator/institution will permit study-related monitoring, audits of IRB/Ethics committee 
reviews, and regulatory inspections by providing direct access to source data and documents. On-site data 
monitoring will be performed by Sponsor’s study monitors.  Any data discrepancies will be resolved and 
documented by a standardized data query process.  
 
 
 
 

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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 1 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). 
 
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.  A sample Informed 

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Consent form is included in Appendix D. This may be modified to suit the requirements of the individual 
site. 
• 
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.  
 
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 

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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 medical monitor and DSMB 
• Use of independent statistician 
• 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, in order to allow for preparation and publication of the multicenter results. 
 
26.0 REFERENCES 
 
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in the United States. Bethesda, MD, National Institutes of Health, National Institutes of Diabetes, and 
Digestive and Kidney Diseases; 2011 
 
2. www.fistulafirst.org/AboutAVFistulaFirst  
 
3. Dember LM, Beck GJ, Allon M, et al. Effect of Clopidogrel on early failure of arteriovenous fistulas for 
hemodialysis: A randomized controlled trial. JAMA 2008; 299:2164-2171 
 
4. Akoh JA. Prosthetic arteriovenous grafts for hemodialysis. J Vasc Access 2009; 10:137-147  
 
5. Roy-Chaudhury P, Kelly BS, Zhang, et al. Hemodialysis vascular access dysfunction: From 
pathophysiology to novel therapies. Blood Purif 2003; 21:91-110 
 
6. Lee T, Roy-Chaudhury P. Advances and new frontiers in the pathophysiology of venous neointimal 
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7. Lok CE, Allon M, Moist L, et al. Risk equation determining unsuccessful cannulation events and failure 
to maturation in arteriovenous fistulas (REDUCE FTM 1). J Am Soc Nephrol 2006; 17:3204-3212 
 
8. Lee HW, Allon M. When should a subject receive an arteriovenous graft rather than a fistula? Semin Dial 
2013; 26:6-10 
 
9. Shingarev R, Maya ID, Barker-Finkel J, Allon M. Arteriovenous graft placement in predialysis subjects: 
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graft as compared with the expanded polytetrafluoroethylene vascular access graft in hemodialysis 
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11. Hudson P. Early cannulation of vascular access sites for dialysis. Dialysis and Transpl 1996; 8:523-526  
 
12. Roy-Chaudhury P, Sukhatme VP, Cheung AK. Hemodialysis vascular access dysfunction: A cellular and 
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13. NKF-KDOQI Clinical Practice Guidelines for Vascular Access: Update 2000. Part VI. Potential Quality 
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14. Dixon BS, Beck GJ, Vasquez MA et al. Effect of dipyridamole plus aspirin on hemodialysis graft 
patency. NEJM 2009; 360:2191-2201 
 
15. Miller PE, Carlton D, Deierhoi MH et al.  Natural history of arteriovenous grafts in hemodialysis 
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17. Hurlbert SN, Mattos MA, Henretta JP et al. Long-term patency rates, complications and cost effectiveness 
of polytetrafluoroethylene (PTFE) grafts for hemodialysis access: a prospective study that compares 
Impra versus Gore-tex grafts. Cardiovas Surg 1998; 6:652-656 
 
18. Bartlett ST, Schweitzer EJ, Roberts JE et al.  Early experience with a new ePTFE vascular prosthesis for 
hemodialysis. Am J Surg 1995; 170:118-122 
 
19. Hodges TC, Fillinger MF, Zwollak RM et al. Longitudinal analysis of dialysis access methods. J Vasc 
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20. Evaluation of the GORE® ACUSEAL Vascular Graft for Hemodialysis Access. ClinicalTrials.gov 
identifier: NCT01173718  Results provided at: http://clinicaltrials.gov/show/NCT01173718   
 
21. Data on file with Phraxis, Inc. 
 
22. 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. 
 
23. 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. 
 
24. Peto R, Pike MC, Armitage P et al. Design and Analysis of Randomized Clinical Trials Requiring 
Prolonged Observation of each Patient. British J of Cancer 1977; 35:1-39 
 
25. Cui, L, Hung, HM, and Wang, SJ.  Modification of Sample Size in Group Sequential Clinical Trials.  
Biometrics 1999; 55: 853-857