Understanding the Patient-Centered Outcomes for One-stage and Two-stage Brachial Basilic Upper Extremity Arteriovenous Fistulas: A Pilot Trial
Phase: NA
Conditions: End Stage Renal Failure, Hemodialysis Access Failure, Arterio-venous Fistula
Sponsor: Tze-Woei Tan

STUDY PROTOCOL 
Title: Understanding the Patient-Centered Outcomes for One-Stage and Two-Sage 
Brachial Basilic Arteriovenous fistulas: A Pilot Trial 
Document date: 09/17/2019 
Protocol approved by University of Arizona IRB: 01/30/2020 
Objective: 
We are proposing a randomized pilot trial, comparing the effectiveness of one stage to 
two-stage surgical approach for the creation of an upper arm brachial-basilic 
arteriovenous fistula (BBAVF). The target population are patients on renal replacement 
therapy who are receiving hemodialysis (HD) with central venous catheters (CVCs) at 
the time of the surgery and are candidates for a new BBAVF. 
Design: 
A BBAVF is a reliable autogenous hemodialysis access in patients without suitable 
cephalic vein.[1, 2] It can be created in either one or two stages.[3] The advantage of 
the one-stage approach is a shorter time between access creation and the cannulation 
for HD. The disadvantage is the potential for a longer upper arm incision if the AVF fails 
to mature. Although the two-stage approach can circumvent a more extensive 
procedure if the AVF fails, the need for two separate operations usually leads to more 
extended CVC dependency and a higher risk of CVC-related bacteremia (CRB). While 
literature confirms good results for BBAVFs, comparative studies of one-stage and two-
stage methods are limited.[1] They rest on small case series and few have reported 
relevant clinical outcomes, including functional patency, duration of CVC dependency, 
and postoperative complications. In addition, an insufficient number of studies have 
used intention-to-treat analysis to account for the risk of primary fistula failure. The 
majority of these studies have concentrated on the fistula-related outcomes rather than 
patient centric and patient-reported outcomes (PROs), including the quality of life (QOL) 
measure.[3] There is a clinical equipoise in the surgical approach for the creation of a 
BBAVF and it is unclear whether patients prefer a one-stage or two-stage procedure.[1] 
Currently, the decision to use one-stage or two-stage approach varies widely among 
access surgeons and is based on factors such as the size of basilic vein and surgeon’s 
bias or preference. A patient-centered approach, incorporating a balance between 
population-based evidence and individual patient perspectives might be preferred. This 
pilot study will allow us to understand patient-centered outcomes and QOL measures 
regarding the respective BBAVF techniques. We will use the valuable results to design a 
Patient-Centered Outcomes Research Institute (PCORI)-sponsored pragmatic clinical 
trial to determine the optimal surgical procedure for a BBAVF and to understand the 
perspective of patients receiving a complex AVF. 

The plan is to enroll 10 patients (n=5 in each group) with ESRD receiving hemodialysis 
with a CVC from the Banner University Medical Center. Within each cohort, the subjects 
will be randomized in a 1:1 ratio to one. Within each cohort, the subjects will be 
randomized in a 1:1 ratio to one stage and two-stage surgical approaches. The 
randomization scheme is as follow:  
Methods: 
The target population are patients on renal replacement therapy who are receiving 
hemodialysis (HD) with central venous catheters (CVCs) at the time of the surgery and 
are candidates for a new BBAVF. The surgery is a standard of care procedure that is 
being done whether the potential subject is enrolled in the study. Upon enrollment the 
study subject will fill out the PROMIS/CAT questionnaires. The study team will follow a 
randomized protocol so the study subject will be randomized to the one or two stage 
approach. The subjects will then be seen at the standard of care intervals for follow-up. 
At the 6 month and 12-month standard of care follow-p visits the subjects will be asked 
to fill out the PROMIS/CAT questionnaires again. The subjects medical record will be 
followed for AE and SAE study related problems during the 12 months post surgical 
procedure.  
Primary endpoint is Primary Clinical Functional Patency, defined as the successful use 
of the index fistula with two dialysis needles for at least 75% of dialysis sessions within 
a 4-week period to achieve the prescribed dialysis. The primary endpoint will be 
compared between two techniques during available follow-up up to 12-months (from the 
index procedure in the one-stage approach and the first procedure for the two-stage 
approach). Secondary endpoints will include: 1) Fistula-related outcome: stenosis and 
thrombosis, wound infection, arm swelling, hand ischemia, and surgery or intervention; 
2) CVC-related outcome: duration of catheter-dependency, infection, bacteremia, and 
additional CVC procedure (exchange, placement of new catheter); and  3) Composite 
outcomes of Primary Clinical Functional Patency or CVC-related bacteremia or death. 
We will compare the PROs using the Patient-Reported Outcome Measurement 
Information System (PROMIS) Computerized Adaptive Testing (CAT) in the randomized 
patients.  
Hypothesis: Primary Clinical Functional Patency will be superior following two-stage 
approach compared with the one-stage BBBAVF approach. Patients who underwent the 
two-stage procedure will have higher risks of infectious complications due to a more 
extended CVC dependency. The PROs will be affected by the number of procedures 
(one vs. two), postoperative fistula-related or CVC-related complications, and the 
duration of CVC dependency. 
Statistical Analysis Plan: 

The primary analysis of the primary endpoint will be a comparison of the primary clinical 
functional patency by treatment approach, where the distributions are based on 
available follow up to 12 months. A log-rank test will be used to evaluate the null. The 
secondary analytic method of the secondary endpoints will utilize a Cox regression 
model to adjust for the subject factors to adjust for baseline imbalance such as vein 
size. Based on a recent publication utilizing primary patency rate as the main outcome, 
the reported rates of primary functional patency of one-stage BBAVF was 56% at 12-
month follow-up and was 72% for the two-stage procedure.[12] Based on a two-sided 
Fisher’s exact test at significance level of 5%, a sample size of 153 per group is 
required to achieve a power of 80% to detect the percentage patency difference of 16% 
(56% vs. 72%). A sample size of 336 participants (168 per arm), with an estimated loss 
to follow-up rate of 10%, will be required to achieve a 5% significance level. With the 
restraint of the time and resources of this ASDIN research grant, the pilot trial will be 
exploratory and will be used to demonstrate the feasibility of the research plan in a high-
risk ESRD population and the recruitment target.  
The changes in the individuals’ PROMIS domain scores and overall scores from the 
baseline will be compared between the patients who underwent a one-stage procedure 
and those who had a two-stage procedure. The analysis will be performed after 
excluding those who do not complete the two-stage procedure (only first procedure for 
two-stage approach). The impact of clinical events including infection and catheter-
related complication on PROMIS domain scores will be evaluated using the student T-
test.