A Randomized Pilot Study Comparing Graft-first to Fistula-first Strategies in Older Patients With Incident End-stage Kidney Disease
Phase: NA
Conditions: Kidney Diseases
Sponsor: Wake Forest University Health Sciences

Official Title: A Randomized Pilot Study Comparing Graft-first to Fistula-first Strategies in Older Patients With 
Incident End-stage Kidney Disease 
NCT03545113
IRB-Approved Date: 3/10/2020

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Study Title:  
A randomized pilot study comparing graft-first to fistula-first strategies in older patients with 
incident end-stage kidney disease 
Principal Investigator: Mariana Murea, MD 
Co-investigator(s): Jasmin Divers, PhD (NYU Langone Health); Isai Bowline, MD; Shahriar 
Moossavi, MD, PhD; Randolph L. Geary, MD, Jennifer Gabbard, MD. 
Medical Safety Officer: Todd W. Robinson, MD 
Sponsor or funding source: National Institute on Aging GEMSSTAR, Application Number: 1 
R03 AG060178-01   
Background, Rationale and Context 
Each year, more than 600,000 people in the United States receive life-saving 
hemodialysis (HD) treatments for end-stage kidney disease (ESKD), a third of whom are older 
adults (age ≥65 years).1Timely placement of an arteriovenous (AV) vascular access (native AV 
fistula [AVF] or prosthetic AV graft [AVG]) is necessary to avoid (or limit) the use of tunneled 
central venous catheters (TCVC) for HD. Several retrospective studies presented a graded 
relationship between the type of vascular access placed or used for HD with access 
complications and patient survival. The lowest access complication rates and longest patient 
survivals were seen with native, autologous AVF, highest access complication rates and shortest 
patient survivals with TCVC, and intermediate results with prosthetic arteriovenous grafts 
(AVG).2-6These findings led national committees to promote ‘Fistula First Catheter Last’
guidelines.7 A pervasive challenge in any observational study is distinguishing whether the 
vascular access type per se directly affects clinical outcomes or whether there is a selection bias 
whereby the choice of vascular access approach and access development was a surrogate marker 
for the severity of comorbidities that themselves affected clinical outcomes. For example, the 
decision to place an AVF in a patient can reflect a healthier clinical status in ways that are not 
captured even with sophisticated statistical analyses (e.g., perceived better prognosis, less severe 

 
 
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comorbidities).8;9 These residual confounders not only can impact achievement of usable, 
developed AVF, but can also affect patient survival.  
The benefits of AVF over AVG are least certain in older adults, as age-related biological 
changes independently modulate patient outcomes.10 Nationally representative cohort studies of 
older adults with incident ESKD have shown similar patient survival between those whose first 
AV access placed or used was a fistula or a graft.11;12 Compared with grafts, fistulas fail more 
often and necessitate longer times and more subsequent procedures to aid development, exposing 
older patients to time-consuming procedures that may negatively affect upper extremity strength 
and erode their quality of life.13-16 Hitherto, the contribution of pre-operative muscle strength to 
AV access outcomes and the impact of AV access placement on upper extremity strength and 
self-sufficiency have not been evaluated. We propose a randomized pilot trial in older adults 
with pre-dialysis advanced chronic kidney disease (CKD) or incident ESKD using a TCVC for 
HD who had no prior AV access surgery and have upper extremity vasculature suitable for either 
fistula or graft placement. Participants will be randomized to receive an upper extremity AVF-
first or AVG-first access for HD.    
Objectives  
 
The primary objective of this study is to prospectively evaluate patient and vascular 
access outcomes in a randomized intervention and in a patient population in whom fistula-first 
guidelines have been applied despite the lack of proven benefit and at the detriment of more 
access failures and procedures. Our hypothesis is that there is a bidirectional relationship 
between the type of first AV access and patient outcomes as follows: a) the graft-first strategy 
will confer a more effective transition from TCVC-based to AV access-based HD and will limit 
upper extremity functional impairment from protracted access development and subsequent 
access procedures, and b) preoperative muscle strength will impact AVF development. 
Methods and Measures 
 
Design 
 
 
This randomized pilot trial will be parallel-arm in design (Appendix A). We plan to 
enroll 50 patients of age ≥65 years, with incident ESKD or advanced CKD expected to require 
HD initiation within 90 days of screening. Screening for potential participants will be performed 

 
 
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in two stages. In the first stage, all patients ≥65 years old receiving chronic HD and use a TCVC 
will be screened for eligibility. Of these patients, only those who did not have a previous AV 
access surgery and are considered for AV placement (according to goals of care established by 
the patient’s nephrologist) will be maintained as potential participants and advanced to the 
second phase of screening pending determination of surgical eligibility for placement of upper 
extremity AVF and AVG. Ultrasound vascular mapping of both upper extremities to assess 
vascular anatomy is routinely performed pre-operatively at our institution. Arterial diameter of 
≥2 mm and vein diameter of ≥2.5 mm at the site of AV anastomosis indicate suitability for AVF 
surgical creation.7 To complete the eligibility criteria, patients must have proper anatomy (in 
either upper extremity) for placement of AVF (forearm or arm) and AVG (forearm or arm). 
 
Setting 
Participant recruitment will occur at Wake Forest Baptist Medical Center (WFBMC) 
Outpatient Nephrology Clinics, WFBMC Inpatient Nephrology Service, Wake Forest Outpatient 
Dialysis (WFOPD) units or any other Wake Forest affiliated institution (i.e., High Point Regional 
Medical Center).. After the screening process identifies a potential study candidate, the patient 
will be approached for study participation. The study coordinator and/or the PI and/or other 
study member will contact the patient and present an overview of the study. This will be done 
either in person, by phone, or electronically (e.g., Skype or Facetime). When the patient presents 
interest in the study after the initial overview, the study coordinator and/or the PI or other study 
team member will meet in person with the potential study participant to further review the study 
and the informed consent to patient’s and/or patient’s family member/representative full 
understanding, and finalize the enrollment. 
 
 
 
 
Subjects selection criteria  
The overall eligibility will be reached as a consensus between the PI and the vascular 
surgeon. 
 
Inclusion Criteria 
1. Age ≥ 65 years 

 
 
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2. Incident ESKD on chronic HD and recovery of kidney function is unlikely or advanced 
CKD expected to require HD initiation within 90 days of screening and deemed 
medically necessary by the treating nephrologist to proceed with AV access placement 
(either AVF or AVG) in preparation for HD initiation 
3. TCVC is the sole vascular access used for HD 
4. Did not undergo AV access placement in the past 
5. Medically eligible to receive AVF or AVG placement as deemed by the treating 
nephrologist  
6. Surgically eligible to receive either an AVF or an AVG 
7. HD is the intended long-term modality of treatment for ESKD 
8. Planning to remain within Wake Forest provided health care for at least 12 months 
 
Exclusion Criteria 
1. Presence of an AVF or AVG 
2. Previous attempt(s) for AV vascular access placement 
3. Native vasculature not suitable for placement of AV access  
4. Imminent transplant planned (within 6 months) 
5. Anticipated life expectancy <9 months 
 
This study targets elderly population with advanced CKD and ESKD; therefore, the 
clinical scenario of when an elderly individual is not able to consent for himself or herself will 
not be uncommon. Because the study objectives will not be met without including these subjects, 
this study plans to enroll elderly subjects who are not able to consent for themselves. The 
foreseeable risks to these subjects in this study are low as is the negative impact. For elderly with 
impaired mental capacity, permission for study participation will be obtained from the subject’s 
Legally Authorized Representative (LAR).  
 
 
 
Sample Size 
 
 
This pilot trial has the principal aim of testing the feasibility of randomizing initial AV 
access placement to an upper extremity AVG-first (intervention) or AVF-first (comparator) 
strategy in patients ≥65 years of age. For this goal, we plan to enroll 50 participants (25 per arm).  

 
 
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Interventions and Interactions 
Screening for potential participants will be performed in two stages. In the first stage, all 
patients ≥65 years old who have pre-dialysis CKD or have ESKD receiving chronic HD will be 
screened for eligibility. Of these patients, only those who did not have a previous AV access 
surgery and are considered for AV placement (according to goals of care established by the 
patient’s nephrologist) will be maintained as potential participants and advanced to the second 
phase of screening pending determination of surgical eligibility for placement of upper extremity 
AVF and AVG. Ultrasound vascular mapping of both upper extremities to assess vascular 
anatomy is routinely performed pre-operatively at our institution. Arterial diameter of ≥2 mm 
and vein diameter of ≥2.5 mm at the site of AV anastomosis indicate suitability for AVF surgical 
creation.7 To complete the eligibility criteria, patients must have proper anatomy (in either upper 
extremity) for placement of AVF (forearm or arm) and AVG (forearm or arm). After written 
informed consent is obtained, participants will be allocated with equal probability to either a 
graft-first (intervention) or fistula-first (comparator) strategy. Allocation to AVG or AVF will be 
done using randomly permuted blocks of varying sizes to maintain balance between the groups. 
Demographic and medical data will be collected from all participants, using direct patient 
interview and electronic medical records. Following randomization, collected data is derived 
from standard of care and from assessments specifically conducted as part of this study.  
Study-specific assessments will include muscle strength (assessed with upper arm grip-
strength test in each arm using a hand-held dynamometer)17, four-meter gait speed (4MGS) 
18(HealthMeasures. NIH Toolbox training manualdEnglish version. 
Available at: http://www.healthmeasures.net/images/nihtoolbox/ 
Training-Admin-Scoring_Manuals/NIH_Toolbox_Training_ManualEnglish_9-25-12.pdf. 
Accessed November 16, 2018), satisfaction with the vascular access (using the short-
form vascular access questionnaire [SF-VAQ])19, pain at the AV access site (using the Verbal 
Descriptor Scale [VDS] or the modified Abbey Pain Scale [mAPS] for people who cannot 
verbalise)20;21, level of independence (using activities of daily living [ADL] and independent 
ADL [IADL] instruments)22;23,  and health-related quality of life (using the Kidney Disease 
Quality of Life instrument short form [KDQOL-SF] version 1.3. which consists of a generic core 
(Short Form-36 [SF-36]) and an 11-item kidney disease-specific scale).24 , participant’s 

 
 
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individual study experience (study conduct, intervention outcomes, and intervention decisions) 
(using the Qualitative Study Interview designed by the PI and safety monitor).   The assessment 
instruments (SF-VAQ, mAPS, ADL, IADL, KDQOL-SF) are summarized in Appendix B. The 
schedule of assessments is summarized in Appendix C.  
 
 
 
 
 
Data Collection and Outcome Measure(s)  
 
Data collection at enrollment: sociodemographic characteristics (age, sex, race, marital status, 
educational level, living arrangement); health behaviors (smoking and alcohol consumption [no, 
formerly, or yes]); ESKD etiology; date of HD commencement; and pre-dialysis care (first 
nephrology clinic visit and number of clinic visits prior to the first HD date); Charlson 
comorbidity index (CCI); medications (lipid lowering drugs, anticoagulants, antiplatelets); upper 
limb muscle strength assessed with grip-strength test in each arm using an isometric 
dynamometer; gait speed. The grip-strength test will be performed twice on each hand for each 
assessment and the mean of the two results will be used for statistical analyses; a cut-off point 
<16 kg in women and <26 kg in men will define muscle weakness. The four meter gait speed 
(4MGS) will be assessed on a flat, unobstructed four meter delineated course by trained research 
staff following a standard operating procedure. 
Data regarding arterial and venous diameters on pre-operative ultrasound mapping, AV access 
date of placement, and location of AV anastomosis will be recorded for each participant. Results 
of blood work obtained on a monthly basis (per standard care) at the outpatient dialysis units. 
This includes measurements of dialysis adequacy, anemia management, and bone-mineral 
metabolism.  
Vascular access outcomes.  
• The study participants will undergo evaluation of the index vascular access placed as part 
of the study (AVF or AVG) within 6-8 hours post-operatively; we will document the 
nature of the vascular access thrill, bruit, pulse, and/or if any signs of ischemia to the 
upper arm. For participants that have surgery at any other Wake Forest affiliated 
institution (i.e., High Point Regional Medical Center), we will attempt to obtain the post-
operative assessment data from the operation note. 

 
 
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• Three weeks after the index AVG is placed or four weeks after the index AVF is placed, 
the patients will have the vascular access evaluated at the Dialysis Access Group (DAG) 
of Wake Forest University; at this evaluation, the development of the vascular access will 
be assessed, as well as the feasibility of vascular access cannulation for HD (Appendix C, 
Schedule of Assessments).  For participants that have surgery at any other Wake Forest 
affiliated institution (i.e., High Point Regional Medical Center), we will attempt to obtain 
the evaluation data from the standard of care one month post-surgery follow up vein 
duplex performed at their respective institution. 
• The outcomes of AVF and AVG that will be continuously monitored during the study are 
listed in the (AppendixD;) these will include: vascular access procedures (e.g., 
angioplasty, stent placement, surgical revision, ligation of accessory veins, 
superficialization of vein), date of successful AV access cannulation, AV access 
infectious (cellulitis, abscess, bacteremia) and non-infectious (bleeding, stenosis, 
thrombosis, arterial steal syndrome, nerve injury, seroma, aneurysm, pseudoaneurysm, 
infiltration) complications, and patency outcomes.25  
 
Patient-reported views on AV access outcomes (Appendix B). Pain at the AV access site during 
access cannulation will be assessed using the VDS or mAPS. Using VDS, pain will be 
categorized into four intensity levels: absent/no pain, mild pain, moderate pain, and severe 
pain/pain as bad as could be/extreme pain. Patients' satisfaction with the vascular access will be 
assessed with the SF-VAQ. Pain at the AV access site will be assessed as acute pain and chronic 
pain. Acute AV access pain (evaluated with VDS or mAPS) will be assessed as pain experienced 
during AV access cannulation; the average score obtained at 3 consecutive access cannulation 
sessions (initial assessment being done with the first cannulation) will be used for analysis. 
Chronic AV access pain will be assessed as part of the physical symptom domain with SF-VAQ. 
 
TCVC-related outcomes: infectious (e.g., catheter exit site infection, tunnel infection, catheter-
related bacteremia) and non-infectious (e.g., catheter malposition, mechanical dysfunction, 
catheter migration, venous thrombosis, pneumothorax, arterial puncture, hemothorax).  
 

 
 
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Clinical outcomes related to hospital admissions observed during the study period will be 
recorded and will include the main admission diagnosis and length of hospitalization. 
 
All deaths that occur during the study period will be recorded and classified into six categories 
(Appendix E), and sub-classified as to whether death was access-related. The cause of death will 
be determined by the patient’s primary nephrologist and/or primary doctor according to usual 
practice. 
 
Analytical Plan 
 
 
 
We will begin by examining descriptive statistics (means, standard deviations, minima, 
quartiles, maxima) and plots of the data (histograms and boxplots) to become familiar with the 
data and check for outliers. The proportion of people meeting each of the feasibility and protocol 
adherence endpoints with accompanying 95% confidence intervals (CI) will be calculated using 
skew-corrected score tests with a continuity correction. The maximum uncorrected error margin 
associated with the estimation of consent and surgery rates is 0.138, obtained at p=0.5. This 
suggests that CI around these estimates will tight enough to provide meaningful guideline in the 
design of the larger trial. We will describe participant characteristics and evaluate reasons for 
protocol violations. We will calculate rates of dropout and other events, although we expect low 
numbers. Robust regression and non-parametric methods will be used for comparisons between 
randomized arms. The associations between pre-operative muscle strength (continuous or binary 
variable) with AV access primary outcome will be tested using logistic regression. The 
participants will be followed for a minimum of 12 months following index AV access placement. 
Participants who undergo AV access placement >90 days after randomization or who experience 
primary or secondary AV access failure will be analyzed as randomized in the intention-to-treat 
(ITT) analysis. Missing data will be handled under the missing at random (MAR) assumptions in 
compliance with an ITT protocol.26 We will pay close attention to variables with higher rates of 
missingness, relative to others or display missingness patterns that deviate from the MAR 
assumptions since they could inform and guide the development of the larger trial. Results from 
the pilot analyses are likely to have high variability, but will provide valuable insight that will be 
considered in the design of a larger trial. 

 
 
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Recruitment will be determined as the proportion of people meeting inclusion criteria 
who ultimately consent to randomization. We aim to consent ≥70% of those eligible. Protocol 
adherence is based on the ability to undergo a graft or fistula surgery within 90 days of 
randomization, which we aim to attain in ≥70% of participants. Outcomes of quality of life 
stratified by the type of first AV-access strategy. Changes in grip strength, pain related to the 
access (acute and chronic pain), patient’s satisfaction with the access, changes in the level of 
independence (ADLs and IADLs) and HRQoL—will be compared between the two arms, with 
baseline (preoperative) assessments used as reference. 
 
 
 
 
 
Subject Recruitment Methods 
 
Clinical records of Wake Forest Nephrology practice, including WFOPD facilities, 
WFBMC nephrology outpatient clinics, and WFBMC nephrology inpatient service will be 
reviewed for eligibility. Study participants will be older adults of age ≥65 years with a diagnosis 
of incident ESKD or have advanced CKD expected to require HD initiation within 90 days of 
screening who meet the following additional inclusion criteria: (1) use a TCVC for HD, (2) did 
not undergo surgical creation of an AV access in the past, (3) are medically eligible to undergo 
surgery for AV access placement, and (4) are surgically eligible to undergo surgical placement of 
AVF and AVG. Medical eligibility for surgical placement of AV access will be determined as 
part of standard of care for patients with ESKD. In clinical practice, this aspect takes in 
consideration patient’s clinical prognosis (e.g., unlikely to recover kidney function, medically 
stable to undergo surgical placement of AV access, anticipated life expectancy ≥9 months) and 
goals of care (HD is the intended long-term modality of treatment). Surgical suitability for 
placement of AV access, AVF and AVG, will be determined as part of standard of care by the 
vascular surgeon. To make this determination, the vascular surgeon will use the results of the 
ultrasound vascular mapping of both upper extremities. Patients who meet all the eligibility 
criteria will be approached by the vascular access coordinator, study coordinator, and/or PI for 
explanation of study participation. 
 

 
 
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Human Subjects Protection 
 
 
      This study poses moderate risks to the study participants. The potential participants for 
this study have already been determined to need an AV access for chronic HD. This study plans 
to randomize the participants into two groups; each group will undergo surgical placement of one 
of the two types of AV access, fistula (forearm or arm) or AVG (forearm or arm), respectively. 
All interventions, procedures and complications will be treated and followed by their 
nephrologist as standard of care. Postoperative evaluation of AV access development will follow 
according to usual clinical practice for each individual. The patients are examined at the 
outpatient dialysis unit on a regular basis by the nephrologist, physician assistant, and nurses 
with experience in vascular access assessment. Timing of AV access cannulation and TCVC 
removal/reinsertion will be determined by patient’s nephrologist. Any abnormalities that relate to 
the AV access including changes on physical examination (such as extremity edema; collateral 
veins; alterations in the pulse, thrill, or bruit of the fistula or graft; signs and symptoms indicative 
of limb ischemia) or problems noted during the dialysis session (such as inability to maintain 
prescribed blood flow rates, abnormal venous and/or arterial access pressures, prolonged 
bleeding at the end of dialysis, unexplained decrease in dialysis clearance) will be addressed as 
directed by patient’s nephrologist according to standard practice. Vascular access procedures that 
may be performed on the AV access following surgical placement (such as fistulogram, 
thrombectomy, angioplasty, stent placement, ligation of collateral veins, access ligation, fistula 
superficialization) will also be directed by the patient’s nephrologist and vascular surgeon 
according to standard practice.  
 
      All the assessments of upper arm muscle strength, AV access pain, level of 
independence, and patient reported views on vascular access and quality of life will be gathered 
either at participant’s dialysis session or at regular physician office visit. Evaluation of acute AV 
access pain will be performed at the beginning of dialysis session. There will be no medical 
visits and no blood collections done exclusively for this study. 
 
Informed Consent 
 
 
Signed informed consent will be obtained from each subject by the study coordinator, a 
study team member, the vascular access coordinator, or the PI. The participant will have 

 
 
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sufficient time to read the Informed Consent and to have all questions answered. The vascular 
access coordinator and study coordinator involved in this study have good knowledge on the 
medical aspects of both types of AV accesses: fistulas and grafts. Patients will be informed on 
both types of AV access and the expected course of each type of AV access. The assessments 
involved in the study and the chances of being assigned randomly to one of two groups will be 
explained to each potential participant. We will provide adequate opportunity for the subject to 
consider all options, and respond to the patient’s questions to ensure the information was 
comprehended. Informed consent will be obtained in the dialysis centers, outpatient nephrology 
clinics, or inpatient service. Patients will be made aware of their right to withdraw from the study 
at any time without adverse effects on their clinical care. 
 
 
Confidentiality and Privacy 
 
 
Taking part in this research study may involve collection of information that is 
considered confidential or private. Confidentiality will be protected by collecting only 
information needed to assess study outcomes, minimizing to the fullest extent possible the 
collection of any information that could directly identify subjects, and maintaining all study 
information in a secure manner.  To help ensure subject privacy and confidentiality, only a 
unique study identifier will appear on the data collection form.  Any collected patient identifying 
information corresponding to the unique study identifier will be maintained on a linkage file, 
store separately from the data.  The linkage file will be kept secure, with access limited to 
designated study personnel.  Following data collection subject identifying information will be 
destroyed three years after closure of the study consistent with data validation and study design, 
producing an anonymous analytical data set.  Data access will be limited to study staff.  Data and 
records will be kept locked and secured, with any computer data password protected.  No 
reference to any individual participant will appear in reports, presentations, or publications that 
may arise from the study. 
 
 
 
 
 

 
 
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Data and Safety Monitoring 
 
 
The principal investigator will be responsible for the overall monitoring of the data and 
safety of study participants.  The principal investigator will be assisted by other members of the 
study staff. Complications related to placement of an arteriovenous graft for hemodialysis, such 
as graft thrombosis and graft infection with/without systemic infection, will be closely tracked. 
All vascular access-related clinical events will be adjudicated (based on standards of care) by the 
patient’s nephrologist and treating physicians. Events will be recorded electronically and 
reported to the principal investigator monthly. An independent Safety Officer, unblinded to 
treatment assignments, will review the following vascular access-related events on a quarterly 
basis: primary access failure, access infection (local and systemic), access thrombosis, and 
arterial steal syndrome. All concerns regarding the frequency of arteriovenous graft-related 
complications will be reported to the Wake Forest IRB. In addition, the principal investigator, 
Safety Officer, and members of the research group will carefully consider amendments 
(including halting the trial if necessary).  
 
Reporting of Unanticipated Problems, Adverse Events or Deviations (Appendix E) 
 
 
The principal investigator along with the research staff will be responsible for periodic 
evaluation of clinical trial data to ensure continued participant safety, protocol compliance, data 
collection as well as scientific validity. Adverse events are not anticipated, but any occurring will 
be documented and reported according to WFSM IRB policies and procedures. Cumulative 
adverse events and study progress summary will be communicated to the IRB at the time of 
continuing review. Protocol violations and expected procedure-related events (i.e., having a 
potentially causal relationship to the strategy) occurring within 7 days of an access intervention 
will be collected.  
 
 
All deaths occurring during the trial period will be collected. The cause of death will be 
determined by the patient’s nephrologist and/or primary team according to standard practice. 
Deaths will be classified into one of six categories: cardiovascular, infectious, malignancy-
related, elective withdrawal from dialysis, sudden death at home, or other). After deaths are 
classified into these categories, they will be further classified as to whether the death was access-

 
 
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related. Deaths will be considered access-related if resulted from a direct complication of the 
access or an access-related procedure (e.g. complications of catheter-related bacteremia leading 
to death). Access-related deaths will be further sub-classified as index fistula-related, index graft-
related or catheter-related deaths. All vascular access-related clinical events will be adjudicated 
(based on standards of care) by the patient’s nephrologist and treating physicians. Events will be 
recorded electronically and reported to the PI monthly. An independent Medical Safety Officer 
(Dr. Todd W. Robinson), unblinded to treatment assignments, will review the following vascular 
access-related events on a quarterly basis: primary access failure (i.e., permanent access failure 
before hemodialysis suitability), access infection (local and systemic), secondary access failure 
(i.e., permanent access failure after was used for hemodialysis), and arterial steal syndrome. Any 
unanticipated problems, serious and unexpected adverse events, deviations or protocol changes 
will be promptly reported by the PI or designated member of the research team to the IRB and 
the NIA government agency as appropriate. 
 
 
 
 
 
 
Appendices 
 
Appendix A:  Study Flow Diagram 
Appendix B :   Assessment Instruments 
Appendix C :   Schedule of Assessments 
Appendix D:  Vascular access outcomes 
Appendix E:  Protocol Violation, Expected Events, Cause of Death 
 
 
 
 
 
 

 
 
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Appendix A:  Study Flow Diagram 
 
Enrollment 
Randomize 
 Upper Extremity AV Access Placement 
GRAFT-FIRST (intervention) 
Received allocated intervention 
Did not receive allocated intervention*  
FISTULA-FIRST (comparator) 
Received allocated intervention 
Did not receive allocated intervention*  
Follow-up 
Patient outcomes 
Access related events 
Dropouts* 
Per-Protocol Analysis 
Intention-to-Treat Analysis* 
Patient outcomes 
Access related events 
Dropouts* 
Study flow diagram 
Screening  
Stage 1 
Excluded 
Previous AV access  
Not meeting inclusion criteria 
(other than vascular anatomy) 
Age≥65 years, Incident HD, Using TCVC 
Screening  
Stage 2 
Excluded 
Vascular anatomy not suitable 
for AVF & AVG placement 
Declined to participate 
Other reasons 
Ultrasound Vascular 
Mapping, both Upper Extremities 
 
 
 
 

 
 
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Appendix B:   Assessment Instruments 
 
1) Grip Strength Test:  a muscle strength test that uses a hand-held dynameter to assess the 
upper arm grip-strength in each arm.  Study participant will squeeze the dynameter as hard 
as possible two separate times for each arm.  
2) The four meter gait speed (4MGS) will be assessed on a flat, unobstructed four meter 
delineated course by trained research staff following a standard operating procedure. 
Participants will be asked to walk at their usual pace from a standing start. Two trials will 
be completed.  The arithmetic mean of the two trials will be used for analysis. Participants 
will be allowed to use their usual walking aids and ambulatory oxygen, with the cylinder 
carried by an assistant and these factors will be kept constant within person measurements 
on repeated walk tests. To express gait speed in ms-1, distance walked (i.e. 4 meters) will 
be divided by time expressed in seconds. 
3) Short Form Vascular Access Questionnaire (SF-VAQ):  a questionnaire that the study 
participant will complete that measures the participant’s satisfaction with their vascular 
access.  Participant will circle a number on the scale that indicates their level of agreement 
with each statement regarding physical symptoms, social functioning, complications and 
overall satisfaction. 
4)  Verbal Descriptor Scale (VDS):  a scale the study participant will complete that 
measures their pain at the AV access site.  The participant will rate their pain as either 
absent/no pain, mild pain, moderate pain, or severe pain/pain as bad as could be/extreme 
pain. 
5) modified Abbey Pain Scale (mAPS) :  a scale used for people who cannot verbalize that 
measures their pain at the AV access site.  The study staff will score the scale by 
observing the participant’s vocalization, facial expression, and body language. 
6) Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL): 
these two scales measure the level of independence of the study participant.  For the ADL 
scale, study staff will ask participants how well they can perform various daily activities 
such as bathing, grooming, dressing, eating, etc. 

 
 
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For the IADL scale, study staff will ask participants how well they can perform various 
daily activities such as housekeeping, food preparation, shopping, etc. 
7) Kidney Disease Quality of Life instrument short form (KDQOL-SF) version 1.3:  this 
survey consists of a generic core (Short Form-36 [SF-36]) and an 11-item kidney disease-
specific scale.  This survey will be completed by the study participant and asks a wide 
variety of questions about their health and quality of life. 
8) Qualitative Study Interview:  this interview will consists of questions regarding the 
participant’s study experience (study conduct, intervention outcomes, and intervention 
decisions). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Appendix C:   Schedule of Assessments 
 
 
 
Schedule of assessments 
Assessment 
Enrollment 
Week 1 or 2 
after AV 
access 
placement 
Week 3 after 
AVG placed 
or Week 4 
after AVF 
placed 
Week 5 or 6 
after first 
AV access 
cannulation 
Week 24 or 25 
of AV access 
use 
Week 24 or 25 
after AV access 
placement if 
primary AV 
access failure 
Grip strength 
√ 
√ 
Evaluation at 
DAG to 
assess AV 
access 
development 
and 
suitability 
for 
cannulation 
√ 
√ 
√ 
4MGS 
√ 
 
√ 
√ 
√ 
VDS or mAPS 
 
√ 
√ 
√ 
√ 
SF-VAQ 
 
√ 
√ 
√ 
√ 
ADLs and 
IADLs 
√ 
 
 
√ 
√ 
KDQOL-SF 1.3. 
√ 
 
 
√ 
√ 
Qualitative Study 
Interview 
 
 
 
 
 
 
AV, arteriovenous; 4MGS,  four meter gait speed; VDS, Verbal Descriptor Scale; mAPS, Modified Abbey Pain 
Scale; SF-VAQ, Short-form vascular access questionnaire; ADLs, Activities of daily living; IADLs, Instrumental 
ADLs; KDQOL-SF, Kidney Disease Quality of Life Short-form. The Qualitative Study Interview will be performed 
on a maximum number of 10 subjects who have been enrolled in study >6 months and have had AV access surgery  
and are still currently enrolled in study either during a study visit or before the subject’s dialysis treatment at their 
respective dialysis center. 

 
 
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Appendix D. Vascular access outcomes 
Vascular access outcomes (according to the recommendations of the Committee on Reporting Standards for 
Arteriovenous Accesses, Society for Vascular Surgery and American Association for Vascular Surgery 
AV access outcome 
Definition  
Primary access failure 
Permanent failure of the fistula or graft before hemodialysis suitability. 
This includes inadequate maturation, thrombosis, failure of first and 
subsequent cannulations, and other complications leading to 
nonfunctional fistula or graft. 
Successful cannulation 
The arteriovenous access became the primary vascular access for 
hemodialysis (the fistula or graft access has been cannulated with two 16- 
or 15-gauge needles for ≥3 consecutive dialysis sessions and the TCVC 
was removed).  
Suitability for hemodialysis 
Fistula or graft use with two needles and maintenance of blood flow 
≥300ml/min for ≥75% of dialysis sessions over a continuous 4-week. The 
maturation criteria can be satisfied at any time within 6 months of fistula 
or graft creation surgery. 
Unassisted access maturation 
Criteria for fistula or graft suitable for hemodialysis (based on the above 
criteria) are met before any endovascular or secondary surgical procedure 
to facilitate maturation. 
Assisted access maturation  
 
Satisfaction of the criteria for fistula or graft suitability for hemodialysis 
after a procedure to facilitate maturation (e.g., angioplasty, stent 
placement, surgical revision, ligation of accessory veins). 
Primary access patency  
Intervention-free access survival defined as the time from fistula or graft 
creation to any intervention to maintain patency. 
Secondary access failure 
Permanent failure after the fistula or graft met dialysis suitability criteria 
with subsequent abandonment. 
Noninfectious complications 
Stenosis, thrombosis, hand ischemia, aneurysm, pseudoaneurysm, 
infiltration.  
Infectious complications 
Fistula or graft cellulitis, abscess, bacteremia.  
Access procedures 
Angioplasty, stent placement, surgical revision, ligation of accessory 
veins, superficialization of vein. 
Other clinical outcomes 
TCVC placement, new AV access surgical creation, AV access–related 
hospitalization or death. 
Limb ischemia following AV access placement 
Symptoms  
Paresthesia, pain, hand stiffness, ulceration and tissue loss in the limb 
with arteriovenous access. 
Physical examination 
Diminished or absent radial pulse, pallor, diminished sensation, and, in 
advanced stages or severe cases, ulceration and gangrene. 
Grade 1, mild 
Cool extremity with few symptoms but steal demonstrable by flow 
augmentation with access occlusion. 
Grade 2, moderate 
Intermittent ischemia only during dialysis/claudication. 
Grade 3, severe 
Ischemic pain at rest/tissue loss. 
TCVC access outcome 
Examples 

 
 
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Infectious complications 
Catheter exit site infection, tunnel infection, bacteremia. 
Non-infectious complications 
Catheter malposition, mechanical dysfunction, catheter migration, venous 
thrombosis, pneumothorax, heamothorax, arterial puncture. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Appendix E. Protocol Violation, Expected Events, Cause of Death 
 
A. Protocol violations 
Dropouts and their causes (e.g., withdrawal of consent, transfer to another center, refusal to undergo 
study-specific assessments) 
B. Expected procedure-related events 
Local events 
Systemic events 
Bleeding from access site requiring intervention Allergic reaction to local anesthetic 
Nerve injury 
Allergic reaction to generalized anesthetic 
Ischemia (to nerves or distal extremity) 
Heart failure (high output congestive heart failure) 
Arterial steal syndrome requiring intervention 
Myocardial infarct 
Seroma 
Pulmonary embolism  
 
Aspiration pneumonia 
 
Nosocomial infection 
 
Sudden death 
C. Classification of causes of death 
1. Cardiovascular  
Acute coronary syndromes and related complications 
Heart failure 
Cardiac dysrhythmias 
Valvular disorders 
Myocardial disorders 
Pericardial disorders 
Complications of cardiac or vascular surgery 
Complications of cardiac or vascular procedures 
Cardiac perforation following hemodialysis catheter insertion 
Cardiac arrest during placement of a dialysis catheter in radiology suite 
Acute stroke syndromes and complications (ischemic and hemorrhagic) 
Complications of peripheral vascular disease (examples: ischemic gut, ischemia of the extremities) 
Complications of aortic dissection and aortic aneurysm 
Complications of congenital heart disease 
2. Sudden death at home   
without antecedent illness or procedure that could have contributed to the death. 
3. Infectious 
Bacteremia/sepsis from any source, including complications of vascular access. 
Examples of sources of sepsis: pneumonia, urinary tract, infective endocarditis, intra-abdominal 
abscess, colitis, septic joint, soft tissue ulcer, dialysis vascular access related bacteremia,   dialysis 
vascular access related sepsis and infective endocarditis,   dialysis vascular access related sepsis and 
osteomyelitis, dialysis vascular access related sepsis and ectopic abscess,  infective endocarditis of 
mechanical valve from infectious complication of  dialysis vascular access, etc. 
4.  Malignancy-related 
Complications of any malignancy leading to death. This includes metastatic disease leading to 
withdrawal of care or palliation. 
5.  Elective withdrawal from dialysis 
Elective discontinuation of dialysis therapy, in the absence of an acute, antecedent precipitant such as 

 
 
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an acute medical illness. 
6. Other:   
Any other condition that did not fall into one of the 5 preceding categories. 
Examples: admission for failure to thrive with sudden death in the hospital and no clear precipitant, 
admission for bowel perforation and died in hospital from complications,  air embolism related to 
placement of hemodialysis catheter,  intravascular clot and embolism from dialysis catheter, etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Reference List 
 
 
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