everlinQ Endovascular Access System Enhancements (EASE) Study
Phase: NA
Conditions: Chronic Kidney Diseases
Sponsor: C. R. Bard

 
CD-0015 Rev 02 – EASE Study Clinical Protocol              CONFIDENTIAL  
 
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everlinQ Endovascular Access System Enhancements 
(EASE) Study  
 
Study Protocol: CD-0015 
 
Rev 02 
 
Date: July-5-2016 
 
 
Sponsor: TVA Medical, Inc. 
7000 Bee Cave Rd., Suite 250 
Austin, TX 78746 
 
 
 
 
 
 
 
 
     This protocol contains confidential information and is limited in its distribution to Investigational Staff 
intending to conduct the study and Ethics Committee reviewing this study 
NCT Number: 03708770 
NCT Number added post-approval per CT.gov requirement
      
NCT Number: 03708770 
NCT Number added post-approval per CT.gov requirement
     

 
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Table of Contents 
 
 1 
 
 
 
INTRODUCTION ................................................................................................................................. 3 
 1.1 
DEVICE DESCRIPTION 
...........................................................................................................................4 
 2 
 
RISKS/BENEFITS 
................................................................................................................................. 5 
 2.1 
BENEFITS 
.............................................................................................................................................5 
 2.2 
RISKS 
..................................................................................................................................................5 
 2.3 
MINIMIZATION OF RISK 
........................................................................................................................6 
 3 
 
STUDY METHODOLOGY 
................................................................................................................... 6 
 3.1 
STUDY DESIGN ....................................................................................................................................6 
 3.2 
STUDY OBJECTIVE ...............................................................................................................................6 
  3.3  
STUDY ENDPOINTS  
............................................................................................................................... 
6 
 3.4 
I
NVESTIGATIONAL SITE SELECTION ......................................................................................................7 
 3.5 
STUDY POPULATION 
.............................................................................................................................7 
 
3.5.1 
Inclusion Criteria 
............................................................................................................................. 
8 
 
3.5.2 
Exclusion Criteria 
............................................................................................................................ 
8 
4 
 
STUDY SCREENING AND FOLLOW-UP PROCEDURES 
................................................................ 
9 
 4.1 
I
NFORMED CONSENT 
............................................................................................................................9 
 4.2 
SCREENING EVALUATION 
.....................................................................................................................9 
 
4.2.1 
Duplex Ultrasound 
......................................................................................................................... 
10 
 
4.2.2 
Angiography/Venography 
............................................................................................................... 
10 
  4.3 
I
NDEX PROCEDURE ............................................................................................................................ 
10 
  4.4 
FOLLOW-UP VISITS 
............................................................................................................................ 10 
 
4.4.1 
Unscheduled Visit 
........................................................................................................................... 
10 
 
4.4.2 
Patient Disposition 
......................................................................................................................... 
10 
 4.5 
ADVERSE EVENTS 
.............................................................................................................................. 
11 
 
4.5.1 
 Relationship to Device or Procedure 
.............................................................................................. 
12 
 5 
 
DATA ANALYSIS 
............................................................................................................................... 13 
 6  
REGULATORY OBLIGATIONS 
....................................................................................................... 13 
  6.1 
RESPONSIBILITIES 
OF THE EC/EC APPROVAL ..................................................................................... 
13 
 
 
 6.2 
SPONSOR O
BLIGATIONS 
...................................................................................................................... 13 
      6.2.1          Investigator's Documents 
.............................................................................................................. 
14  
 6.3 
I
NVESTIGATOR OBLIGATIONS.............................................................................................................. 14 
 6.4 
RECORDS 
AND R
EPORTS 
..................................................................................................................... 14 
       6.4.1          Investigator's Reports ................................................................................................................... 14 
       6.4.2          Sponsor's Reports ......................................................................................................................... 15 
 6.5 
SITE TRAINING 
................................................................................................................................... 
16 
 6.6 
PROTOCOL D
EVIATIONS ..................................................................................................................... 16 
 6.7 
SITE N
ON-C
OMPLIANCE 
..................................................................................................................... 16 
 6.8 
DEVICE ACCOUNTABILITY 
.................................................................................................................. 
16 
 6.9 
CASE REPORT FORM COMPLETION...................................................................................................... 
16 
 6.10 
MONITORING PROCEDURES 
................................................................................................................. 17 
  
REFERENCES 
.................................................................................................................................... 18 

 
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1 INTRODUCTION 
End Stage Renal Disease (ESRD) currently affects over 2 million people worldwide.1 It is projected that 
the worldwide incidence of ESRD will increase dramatically over the next  10 years, due to the 
increasing incidence of an aging population, diabetes, hypertension, and obesity.2 Currently, Renal 
Replacement Therapy for patients with ESRD consists of either hemodialysis or peritoneal dialysis.  
The rates of implementation of either hemodialysis or peritoneal dialysis vary widely per country.  
According to the United States Renal Data System (USRDS), in 2006 hemodialysis accounted for 
around 60% of Renal Replacement Therapy patients in the US, while peritoneal dialysis accounted for 
6- 7% of patients in the US and the remainder is kidney transplant patients.2 
 
Vascular access is a critical component in the care of patients undergoing hemodialysis. The three 
methods of long term vascular access available to a patient requiring hemodialysis are:  an autogenous 
arteriovenous access or native arteriovenous fistula (AVF), a prosthetic arteriovenous graft (AVG) or a 
tunneled dialysis catheter.
3   The AVF has been shown to be superior to AVG and superior to catheter 
access in terms of both mortality and morbidity.4,5   In fact, the focus of numerous initiatives worldwide 
has been to increase the implementation of AVF as the preferred method of vascular access in 
patients requiring hemodialysis.  In 1997, the National Kidney Foundation Kidney Disease Outcomes 
Quality Initiative (KDOQI) guidelines were published to highlight the importance and to promote the 
increased placement of AVF.6    These guidelines and  subsequent versions have stressed the importance 
of proactive identification of patients  requiring hemodialysis, and have described procedures and 
quality initiatives to maximize access longevity.  In 2006, the updated KDOQI Guidelines 
recommended that AVF be constructed in at least 65% of prevalent hemodialysis patients.7   In 
addition, the AV Fistula First Breakthrough Initiative (FFBI), a coalition lead by the Center for 
Medicare and Medicaid Services (CMS) has set a formal goal for AVF construction of  65% in 
prevalent patients by 2009.
8   The Society for Vascular Surgery (SVS) has also approved and sponsored 
initiatives around the development and publication of reporting standards for hemodialysis access and 
the development of practice guidelines for hemodialysis access.
9 
 
An AVF is traditionally created during a surgical procedure under general anesthesia.  A  surgical 
incision is made in the forearm or upper arm
, followed by identification of target arteries and veins for 
surgical connection.  Frequently, prior to the procedure, the vessels are mapped using duplex 
ultrasound imaging, allowing for pre-operative vessel diameter measurement and vessel selection.  
Typically, the radial artery or brachial artery and the cephalic vein or basilic veins are selected.  The 
target vessels are carefully dissected and mobilized, and the vein is transected.  An arteriotomy is 
created, and an anastomosis is sewn between the vein and the artery.  After completion, the flow is 
verified using palpation and ultrasound, and the incision is closed.  Over the course of the following 1 - 
3 months, the AVF gradually matures, that is, the vein dilates and accepts increased flow sufficient for 
hemodialysis. 
 
Though there is widespread agreement that the AVF is the preferred method of vascular access, 28 – 
60% of AVFs do not successfully mature and are rendered unusable for hemodialysis.10, 12   This has 
unintended consequences for patients in immediate need of hemodialysis, since a tunneled dialysis 
catheter must often be placed.  Catheters are associated with higher morbidity, mortality, and costs 
and are therefore considered a last resort.
11 
To improve on these results, and decrease the invasiveness of the procedure, a new tool and method 
for creation of an AVF has been developed, called everlinQ system. The system uses two devices, 

 
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one inserted into an artery and the other inserted into a closely-positioned vein.  The devices contain 
magnets that bring a pair of electrodes into alignment. Radiofrequency energy is delivered to the 
electrodes, cutting and/or coagulating the tissue between the electrodes, creating an AVF.  The 
procedure is facilitated using fluoroscopy and ultrasound imaging, to assist in vessel selection and to 
verify creation of the AVF. Because the vessels are not dissected and not mobilized, leaving the 
surrounding tissues intact, the vessels do not need to be sewn together with a traditional surgical 
technique. This proposed method may facilitate the creation of AVF, while reducing the trauma to 
the patient and also potentially prevent future venous stenosis thought to arise from surgical trauma. 
In particular, the goal is to reduce the surgical manipulation of the blood vessels, particularly the 
veins in the arm, which typically exhibit intimal hyperplasia in  surgical AVF.  Intimal hyperplasia is 
believed to be a root cause of failure in surgical AVF and AVG, and this technology and method may 
help improve the patency and maturity of AVF in patients with ESRD. 
 
This clinical pilot study is being conducted to evaluate everlinQ System when utilized to create an 
AVF. 
 
1.1 Device Description 
The TVA Medical everlinQ System that will be used in this study is an investigational device, and is 
not cleared by FDA or any competent authority for sale in the US or elsewhere.  
 
 
The everlinQ device is  a single-use  disposable device. The everlinQ catheter system consists of two 
flexible, magnetic catheters. 
 One (venous) catheter contains an electrode to deliver radiofrequency (RF) 
energy, and has a cord that is connected for a remote hand switch.  The venous catheter and hand switch, 
along with a standard grounding pad, connect to a standard electrosurgical unit for the delivery of RF 
energy.  The second (arterial) catheter is a flexible magnetic catheter that contains a backstop for the 
RF electrode of the venous catheter to interface.  Once the catheters are properly inserted and aligned, 
the  magnets  contained  in  each  catheter  attract  to  one  another, approximating the  vessels  while 
simultaneously  aligning  the  electrode  with  the  backstop.   RF energy  is  delivered  to  the  electrode 
whereby the arterio-venous fistula (AVF) is created. 
 
For  additional  details  
regarding  device  or  
its  principal  of  operation,  please  
refer  
to the  most  current 
Instruction for Use (IFU). 
 
2 RISKS/BENEFITS 
 
2.1 
Benefits 
The everlinQ System may facilitate a less-invasive and more reproducible AVF procedure. The 
everlinQ System may allow the physician to cut and coagulate soft tissues for the creation of an AVF 
while minimizing surgical incisions. Due to the less-invasive nature of the procedure with the 
everlinQ System, the AVF may exhibit improved maturation and patency characteristics compared to 
historical maturation and patency data.  In addition, patient recovery time may be decreased, 
procedural time may be decreased, and anesthesia may be minimized compared to a conventional 
surgical AVF procedure. 
 
2.2 Risks 
 

 
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Many of the potential risks and complications associated with the everlinQ System and procedure are 
similar to the risks expected for CKD patients undergoing surgically created arteriovenous fistula (AVF) 
procedures.   The potential risks related to the everlinQ System and procedure are similar to surgical 
AVF creation and may include but not limited to: 
 
• Bruising 
• Numbness, tingling and/or coolness in the fistula extremity  
• Occlusion/stenosis (AVF clots) 
• Thrombosis (AVF completely clotted and cannot be used) 
• Failure to mature (AVF can never be used) 
• Additional procedures (interventions) 
• Venous hypertension (arm swelling) 
• Aborted or longer procedure 
• Swelling, irritation or pain 
• Bleeding, hematoma (a solid swelling of clotted blood within the tissues) or hemorrhage (an 
escape of blood from a ruptured blood vessel) 
• Wound problem 
• Fever (pyrogenic reaction) 
• Steal or ischemia (not enough blood flow to hand) 
• Embolism (blood clot or device piece) 
• Infection (local or in the blood (bacteremia)) 
• Increased risk of congestive heart failure (heart fails due to increased flow from AVF) 
• Vessel, nerve or AVF damage or rupture 
• Pseudoaneurysm (leaking hole in artery that forms blood clot on outside of it) 
• Heart problems such as arrhythmias (abnormal beats) that can be caused due to high levels of 
potassium in the blood (mostly due to CKD and not the TVA device or procedure) 
• Death (mostly due to CKD related complications not the TVA device or procedure) 
• Burns 
• Problem due to sedation or anesthesia 
• Sepsis (systemic inflammatory reaction) 
• Toxic or allergic reaction 
• Electrocution 
 
In addition, fistula infiltration injury due to needle cannulation of the fistula is also a known risk/event.  
 
Most of these potential risks also exist for creation of standard (surgical) AVFs.  There may also be 
other risks related to use of the everlinQ System and procedure that are not listed or that are not known 
at this time. This study will help characterize the adverse events associated with the everlinQ System. 
 
2.3 Minimization of Risk 
To minimize the risks, the everlinQ system has undergone pre-clinical testing. In addition, all 
Investigators participating in this clinical trial will be trained on the everlinQ procedure which will 
contribute to minimizing risks associated with the use of the device. 
 
3 STUDY METHODOLOGY 
 

 
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3.1 
Study Design 
This is a prospective, single-center study to evaluate the everlinQ System when used to create an 
endoAVF in hemodialysis patients.  A total of up to 50 subjects will be enrolled and will undergo an 
endoAVF creation procedure using the everlinQ System. All subjects will be followed for up to 12 
months post index procedure based on Investigator’s discretion. 
 
3.2 
Study Objective 
            The primary objective of this clinical study is to evaluate the safety and efficacy of using the everlinQ 
system for the creation of an endovascular AVF (endoAVF) in patients requiring hemodialysis. 
 
3.3 
Study Endpoints 
Study endpoints will be summarized using descriptive statistics. There are no formal hypothesis tests 
associated with these endpoints. 
 
• Technical success: Verification that an endoAVF has been created and remains patent 1-7 Days 
after the index procedure.  Patency will be determined by experienced examiner as the presence 
of a bruit that is detected with stethoscope, or presence of thrill, or via Duplex Ultrasound, or via 
angiogram.   
 
• Fistula Maturation: defined as endoAVF that is free of stenosis or thrombosis, with brachial 
artery flow of at least 500 ml/min and at least 4 mm vein diameter (as measured by duplex 
ultrasound) OR patient was dialyzed using 2 needles.   
 
• The Time to Fistula Maturation: the number of days between the date of AVF creation and the 
date of endoAVF maturation (based on primary efficacy endpoint definition of maturation).  
 
• Duration of Central Venous Catheter Exposure: The rate of CVC use per enrolled subjects at 
30-45 Days and other follow-up visits. The analysis will be performed for pre-dialysis and on 
dialysis patients, as applicable. 
 
• EndoAVF-related Re-intervention Rate:  The re-intervention rate for endoAVF (defined as 
any intervention required to maintain or re-establish patency) will be calculated at each available 
follow-up visit post index procedure.  
 
• Primary Patency: The primary patency rate will be determined via Kaplan-Meier methods and 
based on the time of endoAVF creation until any intervention designed to maintain or reestablish 
patency or endoAVF abandonment.   
 
• Secondary Patency: The secondary patency rate will be determined via Kaplan-Meier methods 
and based on the time of endoAVF creation until access abandonment.  Abandonment due to 
renal transplant receipt will not be included in this endpoint assessment.  
 
• Safety: The safety endpoint is the percentage of patients who experience one or more serious 
device -related adverse events during the first 3 months following AVF creation.   
  
 

 
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Additional exploratory analysis: 
• Rate of serious procedure-related events will be reported at 3 months.  
• Rate of serious device-related event rate will be reported at 3 months.  
• Rate of device and/or procedure-related infections at 3 months. 
• Arterial and arterialized vein flow rates and diameters will be measured via DUS at 30-45 Days 
and at each available follow-up visit post index procedure.  
 
3.4 Investigational Site Selection 
Investigational site selected to participate in this clinical study will be dependent on the Investigator 
at the site having the necessary resources to fulfill the clinical research requirements outlined in the 
protocol.  These resources include adequate patient population, facilities and support staff to perform 
the clinical evaluation according to all applicable requirements. 
 
3.5 Study Population 
Candidates for this trial are patients being evaluated for placement of an arteriovenous fistula for 
chronic hemodialysis. Only patients meeting the inclusion and none of the exclusion criteria who 
signed Informed Consent Form (ICF) will be enrolled in the study.  
 
3.5.1 Inclusion Criteria 
1. Eligible for a native arteriovenous fistula. 
2. Adult (age >18 years old).  
3. Established, non-reversible kidney failure requiring hemodialysis (including pre-dialysis patients). 
4. Target vein diameter(s) ≥ 2.0 mm or large enough to accommodate device diameter. 
5. Target artery diameter ≥ 2.0 mm or large enough to accommodate device diameter. 
6. Estimated life expectancy > 1 year. 
7. Patient is free of clinically significant conditions or illness within 30 days prior to the AV fistula that 
may compromise the procedure 
 
3.5.2 Exclusion Criteria 
1. Known central venous stenosis or central vein narrowing > 50% based on imaging on the same side 
as the planned AVF creation. 
2. Upper extremity venous occlusion(s) and/or vessel abnormality(ies) on the same side as the planned 
AVF creation that precludes endovascular AVF creation by everlinQ System as deemed by the 
interventionalists’ clinical judgment. 
3. Prior surgically created access in the planned treatment location.  
4. Functioning surgical access in the planned treatment arm. 
5. Pregnant women. 
6. New York Heart Association (NYHA) class III or IV heart failure.   
7. Hypercoagulable state. 
8. Known bleeding diathesis. 
9. Immunosuppression, defined as use of immunosuppressive medications used to treat an active 
condition. 
10. Documented history of drug abuse including intravenous drugs within six months of AVF creation. 
11. “Planned” concomitant major surgical procedure within 6 months of enrollment or previous major 
surgery within 30 days of enrollment. 
12. Currently being treated with another investigational device or drug. 
13. Known allergy to contrast dye which cannot be adequately pre-medicated. 

 
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14. Known adverse effects to sedation and/or anesthesia which cannot be adequately pre-medicated. 
15. Patients who do not have an ulnar or radial artery. 
16. At the time of procedure distance between target artery and vein will not allow magnets to align 
vessels sufficiently to create the fistula. 
17. Evidence of active infections on the day of the index procedure. 
18. Written informed consent not obtained.  
 
4 
STUDY SCREENING AND FOLLOW-UP PROCEDURES 
 
Patients are required to undergo a thorough screening evaluation prior to the index procedure and 
return for evaluations according to the study follow-up schedule indicated in Table 1.  Study data 
will be collected on case report forms (CRFs) provided by the  Sponsor. Any site’s standard of 
care tests may be done outside of the study (e.g., prior to study participation).   
 
Table 1: Schedule of Study Procedures 
 
Assessment 
 
Screeni
ng 
Index 
Procedure 
Post Index Procedure 
1-7 Days 30-45 Days  3 Months  
6 Months 
(Optional)
1 
12 Month 
(Optional)
1 
Compliance 
window 
-30 
days 
Day 0 
1-7 days 
30-45 days 
Anniversary
 
date + 14 / -7 
days 
Anniversary
 
date  +  45 / -
15 days 
Anniversary
 
date  +  60 / -
30 days 
Informed Consent 
X 
 
 
 
 
 
 
History, Physical 
Exam, Laboratory 
Evaluation 
X 
 
 
 
 
 
 
Ultrasound 
Evaluation 
X 
X1 
X 
X 
X 
X1 
X1 
Angiography/ 
Venography  
X1 
X 
X1 
X1 
X 
X1 
X1 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
Dialysis Access 
Data 
 
 
 
X2 
X2 
X2 
X2 
1 Optional visit at the discretion of the Primary Investigator  
2 Will be obtained after dialysis is initiated using endoAVF created by the everlinQ System.  
 
4.1 Informed Consent 
Prior to enrollment, all patients will be informed in detail about the nature of the clinical investigation, 
as well as its risks, potential benefits, and any 
anticipated discomforts. All patients must provide written 
informed consent using Ethics Committee (EC) approved informed consent document.  
 
Proper informed consent should be obtained in accordance with local/country guidelines as needed. 
 
4.2 Screening Evaluation 
All patients considered for enrollment must undergo a thorough screening evaluation prior to the 
scheduled treatment with the everlinQ System.  The screening evaluation includes: 
• Collection of demographic data; 
• A medical history and physical exam; 

 
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• A laboratory evaluation (i.e. blood tests); and 
• A duplex ultrasound and optional angiography/venography assessment. 
 
There will be a final assessment of the suitability of the patient’s study eligibility due to vascular 
anatomy or other criteria made at the time of the index procedure and thus, there may be some 
consented subjects who are determined to be ineligible who will not be enrolled in the study. 
 
4.2.1 Duplex Ultrasound 
A duplex ultrasound assessment needs to be performed of the flow rates and inner diameters of the 
arteries and veins of the target vessels based on the training requirements provided for the study. 
 
4.2.2 Angiography/Venography 
An optional angiographic or venographic assessment of the suitability of the arteries or veins 
intended for the endoAVF. 
 
4.3 Index Procedure 
If a patient presents for the index procedure with an active localized infection, or other medical 
condition that precludes treatment at this time, the procedure should be delayed until the infection or 
medical condition is treated and resolved. 
 
If the Investigator is not an experienced user of the everlinQ System, a Sponsor’s representative will 
be present as needed for procedures at each site to provide technical guidance to the Investigator.   
 
4.4 Follow-Up Visits 
See Table 1 for required and optional follow-up visits. 
 
4.4.1 Unscheduled Visit 
In addition to scheduled follow-up visits, the patient should be instructed to contact the Investigator at 
any time during the follow-up period if he/she has questions or concerns relating to the procedure or 
the endoAVF.  If the patient returns to the clinic for evaluation related to his/her participation in the 
study, an Unscheduled Visit evaluation should be performed and this data should be recorded on the 
Follow-Up Visit Case Report Form.  
 
4.4.2 Patient Disposition 
The Patient Disposition Case Report Form should be completed whenever a patient exits the study.  
This includes patients enrolled in the study who: 
• complete the study protocol, 
• withdraw from the study, 
• are lost to follow-up, 
• are deceased, 
• have other reason(s) for exiting the study. 
 
 

 
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4.5 Adverse Events 
For the purpose of this protocol, an AE will be defined as any adverse medical change (i.e., de novo or 
increased severity in a preexisting condition) from the subject’s baseline condition that occurs during 
the course of the clinical study, after starting treatment, whether considered treatment-related or not.  
“Treatment” includes all investigative or commercially-approved products administered according to 
the Study Protocol. 
 
Any pre-planned procedures, interventions, etc. or expected progression of pre-existing conditions 
(e.g., cancer progression) will not be considered AEs for this study. In addition, normally expected 
symptoms caused by the treatment are not considered an AE for this study.  These may include but are 
not limited to: 
• Transient arterial spasm resolving spontaneously OR with medication only. 
• Minor discomfort or bruise at the arterial access place. 
• Small amount of bleeding at point of arterial access. 
• Transient numbness, tingling or coolness that resolved within 4 weeks post index procedure. 
• Bruising at the AVF creation site.  
• Side effects of standard-of-care medications.    
• Hematoma at the arterial and/or venous access site(s) managed prior to patient discharge and did 
not adversely affect patient discharge.  
 
Only AEs that are relevant to index procedure, study device, access site or AVF will be collected in 
the study. For example, if the patient has knee replacement or undergo hysterectomy, these events will 
be considered as non-study related and will not be required to be recorded via Adverse Event form.  
AE Type 
Definition 
Serious Adverse 
Event (SAE) 
AE that 
a) led to death, 
b) led to serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function, 
c) led to foetal distress, foetal death or a congenital abnormality or birth defect 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by 
the Study Protocol, without serious deterioration in health, is not considered a SAE.
13 
Adverse Device 
Effect (ADE) 
AE related to the use of study device.  
NOTE:  
This definition includes adverse events resulting from insufficient or inadequate IFU, 
deployment, installation, or operation, or any malfunction of the study device. 
This definition includes any event resulting from use error or from intentional misuse 
of the study device. 
Serious ADE 
(SADE) 
ADE that has resulted in any of the consequences characteristic of a SAE 
Unanticipated 
SADE (USADE) 
USADE which by its nature, incidence, severity or outcome has not been identified in 
the current version of the study protocol, IFU, or other study documentation.  
SUSAR 
A SUSAR is suspected unexpected serious adverse reaction 
Anticipated 
SADE (ASADE) 
An effect which by its nature, incidence, severity or outcome has been identified in the 
study documentation.  
 

 
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To classify the event, you may follow the steps below (please refer to additional local requirements as 
needed). 
 
Is this event: 
1. Serious 
Yes 
No 
2. Study device or 
procedure related 
Yes 
No 
Yes 
No 
3. Unanticipated? 
Yes 
No 
 
 
 
Event type is  
USADE 
or 
SUSAR 
 
ASADE 
 
SAE 
 
ADE 
AE (i.e., 
non-
SAE) 
 
4.5.1 Relationship to Device or Procedure 
The investigator will also evaluate the relationship of the adverse event to the everlinQ device or 
procedure according to the following definitions: 
 
Definite (YES): 
The AE follows a reasonable timing from treatment (or attempted 
treatment) with the device and the possibilities of factors other than the 
device or the index procedure, such as underlying disease, concomitant 
drugs, or concurrent treatment can be excluded.  This includes an AE that 
occurs during the index (AVF creation) procedure. 
       Probable (YES): 
The AE follows a reasonable timing from treatment (or attempted 
treatment) with the device and the probability of device or procedure 
involvement cannot be excluded.  However, other factors such as 
underlying disease, concomitant medications, or concurrent treatment may 
be possible. 
 
Unlikely (NO): 
The AE follows an unlikely timing relationship from treatment (or 
attempted treatment) or is more likely due to other factors and there is no 
definitive information suggesting that it was related to the device or 
procedure.    
 
 Not Related (NO):  
The AE has no timing relationship from treatment (or attempted treatment) 
or it can be explained by other factors, including underlying disease, 
concomitant medication, or concurrent treatment. 
 
The investigator will also evaluate the relationship to the everlinQ portion of the procedure using the 
yes/no definitions above.  The everlinQ portion of the procedure only includes insertion, deployment 
and removal of the everlinQ catheters.  
 
5 DATA ANALYSIS 
 
Data analysis will be primarily descriptive in nature.  Continuous variables, such as age, height, weight, 
will be summarized by the mean, standard deviation, median, minimum and maximum values.  Nominal 

 
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variables, such as gender, ethnicity, presence of co-morbid conditions, will be summarized by the number 
and percentage of subjects within each category defined by the variable.  Summary statistics for discrete 
variables will consist of the number and percent of responses in each category.   
 
6 REGULATORY OBLIGATIONS 
 
6.1 Responsibilities of the EC/EC Approval 
The EC has the main responsibility to oversee the welfare of the subjects entered into this study.  The 
EC, by its approval of the informed consent form, also ensures that the potential subjects are aware of 
the benefits and risk of participation in the study. 
 
Each site must obtain EC approval and any other Regulatory agency’s approval as required by 
local or country guidelines prior to study initiation.  A copy of the approval notification and 
the approved study specific patient informed consent must also be kept on file at the site and a 
copy provided to Sponsor prior to the enrollment of patients. If applicable, written EC 
approval of any subject’s information materials or any advertisement must also be attained 
prior to their use. 
 
6.2 Sponsor Obligations 
The Sponsor must assume responsibilities that are not limited to the following: 
• Provide the Investigator with the necessary information (protocol and IFU) and training 
required to conduct the investigational study. 
• Inform study Investigators of all new information. 
• Conduct an evaluation of any 
USADE and report the result of such evaluation to all reviewing ECs 
and all participating Investigators within 10 working days of first receiving notice of the event. 
 
6.2.1 Investigator’s Documents 
The following documents will be provided to the study Sponsor by the Investigator prior to initiation 
of the study. 
• A signed and dated Study Agreement. 
• Current (within one year) curriculum vitae of the Principal Investigator and all Co-
Investigators.  
• A copy of the approval letter by the EC for the study protocol and the informed consent. 
 
6.3 Investigator Obligations 
Upon signing the Study Agreement, the Investigator agrees to assume the following responsibilities, to 
keep the required records, and to file the required reports in a timely  manner. 
 
The Investigator agrees to: 
• Conduct the investigation in compliance with the signed agreement, study protocol, and applicable 
regulations.  Changes to the protocol will only be made after approval by the sponsor and the 
reviewing EC, or when necessary to protect the safety, rights or welfare of a subject. 
• Conduct the investigation in compliance with the EC and other applicable Regulatory agencies. 
• Personally conduct or supervise the investigation. 
• Ensure that all associates, colleagues and employees assisting in the conduct of the  study are 

 
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informed about their obligations. 
• Protect the rights, safety and welfare of research subjects.  All subjects must be informed 
that the device is being used for investigational purposes. 
• Assure initial and continuing review of the investigation by an EC. 
 
6.4 Records and Reports 
All records and reports pertaining to this protocol are subject to inspection by regulatory 
agencies and must be retained for at least two years after the date on which the investigation is 
terminated or completed or for two years after the date that the records are no longer required for 
the purpose of supporting an application to regulatory agencies for commercial approval of the 
therapy/claims, or per local regulations, whichever is later. 
 
6.4.1 Investigator’s Reports 
 
The investigator is responsible for the preparation and submission of the reports listed below: 
 
Report 
Submitted to 
Description 
Unanticipated 
Serious Adverse 
Device Events and 
Serious Adverse 
Device Effects 
Sponsor & 
EC 
The investigator’s report on any unanticipated serious 
adverse device event (USADE) or serious adverse 
device effect (SADE) must be submitted within 10 
working days after the investigator first learns of the 
event. 
Withdrawal of  
EC approval 
Sponsor 
The investigator must report a withdrawal of reviewing EC 
approval within 5 working days. 
 
Deviations from 
Study Protocol  
Sponsor & 
EC 
Notification must be made within 5 working days of the 
occurrence of an emergency deviation (made to protect the 
life or physical well-being of a subject). 
 
If the deviation affects the rights, safety, or welfare of the 
subjects (and is not an emergency), or the scientific 
soundness of the investigation, prior approval must be 
obtained from Sponsor, the reviewing EC and applicable 
Regulatory Authorities (when required).  For all other 
deviations, prior approval must be obtained from Sponsor. 
All deviations must be documented on a Protocol 
Deviation Form. 
Failure to obtain 
Informed Consent 
Form 
Sponsor & 
EC 
Notification must be made within 5 working days of use of 
the device. 
 
 
 

 
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6.4.2 Sponsor’s Reports 
Sponsor is responsible for the preparation and submission of the reports listed below: 
 
Report 
Submitted to 
Description 
Unanticipated 
Serious Adverse 
Device Effects 
EC & 
Investigators 
Sponsor will report on any unanticipated serious adverse 
device effect evaluation within 10 working days after 
receiving notice of the effect. 
Recall and Device 
Disposition 
EC & 
Investigators 
Notification will be made within 30 working days of 
Sponsor’s request that an investigator return, repair or 
otherwise dispose of any devices.  Such notification will state 
why the request was made. 
Notification of 
Termination or 
Completion 
EC & 
Investigators 
Notification will be made within 30 working days of 
completion or termination of the investigation. 
Final Report 
EC & 
Investigators 
A final report will be submitted within six months after study 
completion or termination. 
Emergency 
Deviations from 
Study Protocol 
EC 
Notification will be made within 5 working days after 
Sponsor learns of an emergency deviation from the 
Investigational Plan where the deviation was made to 
protect the life or physical well-being of a subject. 
 
 
6.5 Site Training 
Sponsor representative(s) will be responsible for site personnel training to ensure that all site 
personnel have a thorough understanding of the protocol, case report forms and associated 
study requirements. 
 
A Sponsor’s representative(s) will meet with the Investigator at each study site prior to the 
enrollment of patients for the purpose of reviewing and discussing the protocol and  supporting 
documentation to assure total understanding of the requirements involved in performing the 
clinical evaluation. 
 
6.6 Protocol Deviations 
            A Protocol Deviation CRF must be completed for each deviation from the Study Protocol that occurred 
at the site  (e.g., failure to obtain informed consent, enrolling a patient who does not meet 
inclusion/exclusion criteria, not performing required testing, missed follow-up visits, etc.). 
 
6.7 Site Non-Compliance 
            Repeated serious protocol deviations will be closely monitored.  If excessive deviations or a failure to 
reduce deviations is noted, the Sponsor reserves the right to suspend study enrollment or terminate the 
site from the study until a sufficient system is in place at the site to reduce further deviations.  
 
6.8 Device Accountability 
            A Device Accountability Log (DAL) will be maintained at the study site.  Devices allocated for 
investigational site use will be recorded in the DAL upon delivery to the study site and will be stored in 
a secured area until use.  No devices will be shipped until EC approvals to begin the study are received 
by the Sponsor.  Site personnel will be responsible for tracking the receipt and disposition of all study 
devices. All unused study devices must be returned to the Sponsor.  

 
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            The DAL will be updated as each device is used, opened, or returned.  The DAL will contain delivery 
dates of devices to the site, dates used, returned-to-Sponsor dates and the reason for the return, lot 
numbers of devices delivered to the site, and the patient ID for all used devices. 
 
6.9 Case Report Form Completion 
Complete and accurate Case Report Forms (CRFs) must be kept for all patients enrolled in the study.  
All entries in the CRFs should be made with black or blue ink.  There must be an entry for every data 
point in the CRFs.  Corrections to the CRFs should be made by striking out the initial entry with a 
single horizontal line, with placement of the new entry just above the old.  All corrections must be 
initialed and dated by the person making the correction. 
 
All data collected in the study must be supported by source documentation.  Source documentation 
may include, but not necessarily be limited to: patient medical record notes, patient history 
questionnaires, physical examination forms, duplex ultrasound data, radiology reports, operative 
summaries or other documentation that is pertinent to the patient’s participation in the study.  In 
addition to existing patient records, a copy of the CRF for the study may be used to directly record 
study data.  If the CRF copy is the only documentation of the collection of study data, the copy should 
be signed and dated by the Investigator and kept in the patient’s record as source documentation. 
 
6.10 Monitoring Procedures 
The Sponsor or a Sponsor representative will monitor the progress of the study as required by GCP.  
The study data will also be monitored (by utilizing remote risk-based monitoring, if feasible). The 
Sponsor will request the source documents to be submitted to them in de-identified manner (subject’s 
name and other personal identifiers must be removed and replaced with the study subject identification 
(ID) number). These source documents may include but not limited to: 
• Admission, procedural and discharge reports/notes 
• Any documentation relevant to SAE and procedure and device-related AEs 
Monitoring will be performed by qualified and appropriately trained monitors onsite and/or remote. 
They may be Sponsor’s employees or Sponsor’s representatives.  
On-site visits may be performed as needed based upon enrollment, data integrity and site compliance 
(e.g. repeated and serious non-compliance by the site (significant number of DCFs at the site, etc.). 
Each remote or on-site monitoring visit will be documented.  
 
 
 

 
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th International Congress of 
the Vascular Access Society, Berlin, Germany, 2005. www.vascularaccesssociety.com 
 
2. United States Renal Data System (USRDS) 2008 Annual Report. 
 
3. Sidway, A.N. et al
. Recommended standards for reports dealing with arteriovenous 
hemodialysis access. J. Vasc. Surgery Vol 35(3): 603-610 March 2002. 
 
4. Xue, J.L. et al
. The association of initial hemodialysis type with mortality outcomes in elderly 
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5. Dhingra, R.K. Type of vascular access and mortality in U.S. hemodialysis patients 
Kid Int Vol 60: 1443-1451, 2001. 
 
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8. Fistula First National Vascular Access Improvements Initiative. Available at: 
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9. Sidway A.N. et al
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10. Asif, Roy-Chaudhury, Beathard, G.  Early Arteriovenous Fistula Failure: A Logical Perspective of 
How and Why to Intervene.  Clin J Am Soc Nephrol 1: 332–339, 2006. 
 
11. Schwab, J., Beathard, G. The hemodialysis catheter conundrum: Hate living with them, but 
can’t live without them. Kidney International Vol 56:1-17, 1999. 
 
12. Dember, L., Beck, G., Allon, M., et al
. Effect of Clopidogrel on Early Failure of Arteriovenous 
Fistulas for Hemodialysis: A Randomized Controlled Trial.  JAMA  299(18):2164-2171, 2008.