Hemodialysis Access Surveillance Evaluation Study
Phase: NA
Conditions: Hemodialysis Access, Thrombosis
Sponsor: Albany Medical College

 
 
Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
 
Protocol Title: 
Transonic Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
Objectives 
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) 
recommends an organized monitoring/surveillance approach with regular assessment of 
clinical parameters of the arteriovenous access and hemodialysis (HD) adequacy. Data 
from the clinical assessment and HD adequacy measurements should be collected and 
maintained for each patient's access and made available to all staff. The data should be 
tabulated and tracked within each HD center as part of a Quality Assurance 
(QA)/continuous quality improvement (CQI) program (1). 
The evidence from observational studies has emphasized that implementation of a 
surveillance program is beneficial in regard to access thrombosis, hospitalization and cost 
burden (see below). However, small sample sizes, randomized studies with suboptimal 
design and power to detect the difference have questioned the validity of the available 
information. National debates are beginning to express the futility of the surveillance 
approach. A well-designed randomized controlled trial that is adequately powered to 
evaluate multiple variables such as access thrombosis, cumulative access patency, need 
for tunneled hemodialysis catheters and hospitalizations (all of these parameters can 
easily be extrapolated to cost) is desperately needed.   
 
Background 
Hemodialysis vascular access dysfunction contributes directly to morbidity and mortality 
and adds to the cost of medical care of dialysis patients (1, 2). While access dysfunction 
presents several predicaments (prolonged bleeding, edema, high recirculation, low 
dialysis adequacy or frequently alarming dialysis machine) access thrombosis is the most 
feared complication. In order to provide an uninterrupted, life-saving dialysis therapy, a 
clotted access requires an urgent intervention (either thrombectomy or insertion of a 
tunneled dialysis catheter). Additionally, even after a successful thrombectomy 
procedure, a thrombotic episode in and of itself can affect the longevity of the access 
even after a successful thrombectomy procedure. 
 
Vascular access stenosis develops as a result of neointimal hyperplasia and is observed in 
almost all of the patients with a clotted arteriovenous access (3, 5). It is also the most 
common cause of hemodialysis vascular access dysfunction. Indeed, a great majority of 
hemodialysis patients with an arteriovenous access will develop vascular stenosis (4). 
 
While reduction in the blood flow and its subsequent recirculation is relatively a common 
cause of low Kt/V, the presence of stenosis is the most common cause of reduced blood 
flow rates. Data have indicated that for every 0.1 decline in Kt/V there is a significant 
increase in hospitalizations, hospital days and Medicare cost (5). In this context, the 
detection of the presence of vascular stenosis and its prompt treatment with percutaneous 
transluminal angioplasty (PTA) is of paramount importance for hemodialysis patients 
receiving treatment with hemodialysis. Several centers across the Unites States are 
 
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Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
performing PTA successfully on an outpatient basis (6). There is evidence that treatment 
of vascular access stenosis might decrease vascular access thrombosis (7-9). 
There are a number of techniques that have been used to measure intra-access blood flow. 
However, most of these techniques have significant limitations. An ideal surveillance 
method is the one that can be performed during hemodialysis treatment such as 
ultrasound dilution technique (UDT) (Transonic) to enable regular periodic 
measurements and more compliance from patients (no additional appointments are 
required).  
 
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) 
recommends that access blood flow with ultrasound dilution be performed monthly 
during the first 1.5 hour of the treatment to eliminate error caused by decrease in cardiac 
output or blood pressure related to ultrafiltration or hypotension (1). The official KDOQI 
recommendation indicates that an access flow of less than 600 ml/minute in arteriovenous 
graft and less than 500 ml / minute in arteriovenous fistula or if the access flow is 1000 
ml/minute that has decreased by more than 25% over 4 months, the patient should be 
referred for hemodialysis access angiogram for further evaluation for the presence of 
stenotic lesions (1) (Table 1). 
 
Table 1. Indications for referral for arteriovenous access angiogram 
Based on access blood flow measurement as set by KDOQI guidelines (1) 
Arteriovenous Fistula (AVF) 
Arteriovenous Graft (AVG) 
access flow rate less than 500 mL/min 
access flow rate less than 600 mL/min in 
grafts 
 
If access flow is 1000ml/min that has 
dropped 25% over 4 months 
Prospective trend analysis of the test parameter has greater power to detect dysfunction 
than isolated values alone 
Persistent abnormalities in any of the monitoring or surveillance parameters should 
prompt referral for access angiogram 
        
A number of observational studies have found a substantial decrease in the graft 
thrombosis after implementing a surveillance program (12–16). Based on these data the 
KDOQI vascular access guidelines have emphasized that hemodialysis units should 
implement graft surveillance programs and refer patients with suspected graft stenosis for 
preemptive angioplasty (1). Although there is a paucity of randomized control studies to 
evaluate hemodialysis access surveillance, the existing controlled trials have raised 
serious doubts regarding the validity of this approach (17 –25). Serious concerns are 
expressed regarding surveillance and national debates are beginning to express the futility 
of this approach. A careful analysis, however, of the available randomized trials points 
out significant limitations of these studies. Table 2 provides a summary of these trials 
(11). A brief synopsis of these studies is provided below. 
 
 
 
 
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Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
Table 2. Randomized clinical trials comparing surveillance to monitoring 
Study 
Number 
of 
patients 
Surveillance 
method 
Type of 
access 
Primary 
outcome 
Surveillance 
(Beneficial 
or 
not beneficial) 
Sands 
et 
al 
1999 (23) 
103 
• Access flow 
• Static 
venous 
pressure 
68 
AVF 
35 
AVG 
AV 
access 
thrombosis 
  
Beneficial  
Moist 
et 
al 
2003 (19) 
112 
• Access flow 
• Dynamic 
venous 
pressure 
AVG 
AV 
access 
thrombosis 
or loss 
 
Not beneficial 
Ram et al 2003 
(17) 
101 
• Access flow 
• stenosis 
AVG 
AV 
access 
thrombosis 
or 
access 
survival 
 
Not beneficial 
 
Polkinghorne 
et al 2006 (24) 
 
137 
 
• Access flow 
 
AVF 
 
Significant 
stenosis 
 
Not beneficial 
Mayer 
et 
al 
1993 (25) 
70 
• Duplex 
Scan 
(Ultrasound) 
AVG 
AVG 
Survival 
 
Beneficial 
Malik et al 
2005 (21) 
192 
• Duplex 
Scan 
(Ultrasound) 
AVG 
AVG 
Patency 
 
Beneficial 
Robbin et al 
2006 (18) 
126 
• Duplex 
Scan 
(Ultrasound) 
AVG 
AVG 
Survival 
 
Not beneficial 
Tessitore et al. 
2004 
79 
• Access flow 
AVF 
Thrombosis 
Beneficial 
 
Study Design 
Randomized, Prospective Clinical Trial.  Patients, PI, funder (Transonic) and statistician 
blinded (this will be implemented in Velos). Intervention and standard of care are 
different and cannot be blinded from attending nurses or clinic personnel. If a patient 
needs to switch schedules, they need to switch to shift that matches their protocol. 
Otherwise, they will need to switch protocols. No Transonic (funding) personnel will be 
involved in study design, protocol, analysis, or publication.  
 
Randomization:  
Patient is consented, baseline assessment taken, and evaluated for inclusion before 
randomization (baseline data will be included in analysis to determine representativeness 
of study patients to clinic patients). Randomization will occur after enrollment period 
ends. 
The intervention and control protocols are significantly different that individual patients 
in the same dialysis session would be able to identify which arm they are in. Therefore, 
blocks of patients will be randomized according to dialysis schedule within each clinic. 
 
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Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
Because the staffing is similar across shifts, we will do block randomization where all 
patients in a shift are assigned to the same protocol at each clinic site. For each clinic, the 
blocks will be given a number based on chronological order (Monday 1st shift = 1, 
Monday 2nd shift = 2 +, Monday 3rd shift = 3, Tuesday 1st shift = 4, Tuesday 2nd shift = 5, 
Tuesday 3rd shift = 6). For each clinic site, a coin will be flipped in front of two 
witnesses: heads = first group treatment; tails = first group control. Then a die will be 
rolled. The number that is rolled will the first group assigned (based on coin toss).  The 
remaining groups will be allocated in sequence. For instance, if the coin lands on heads 
and the die lands on 3, Monday 3rd shift is intervention, Tuesday 1st shift is control, 
Tuesday 2nd shift is intervention, Tuesday 3rd shift if control, Monday 1st shift is 
intervention and Monday 2nd shift is control.  If a patient has to switch dialysis schedules, 
care must be taken to place them in the same arm.  
 
Inclusion and Exclusion Criteria 
 
Inclusion criteria:  
Chronic hemodialysis patients undergoing dialysis therapy via an upper extremity 
arteriovenous access (arteriovenous fistula or an arteriovenous graft) will be enrolled to 
have monthly surveillance flow measurement using Transonic system or physical 
examination of the arteriovenous access by qualified person at least once a month for a 
period of 2 years. 
 
Exclusion criteria:  
• Patients requiring surgical intervention on the arteriovenous access. 
• History of access thrombosis (one or more access thrombosis of the current AV 
access).  
• Patients with signs of access infection. 
• Patients with a malignancy. 
• Patients with life expectancy of less than six months. 
• Unable to understand the study. 
• Unable to sign the consent form. 
• Patients with psychiatric disorder. 
• Age less than 18 or greater than 80 years.  
• Adults unable to consent 
• Individuals who are not yet adults (infants, children, teenagers) 
• Pregnant women 
• Prisoners 
 
Procedures Involved 
Chronic hemodialysis patients receiving treatment with an upper extremity arteriovenous 
access will be enrolled in this 2 year study. End of study starts as last patient from 450 
completes follow-up.  Patients would be randomly assigned into surveillance or the 
control group. Randomization will take a cluster pattern per shift. (shift randomization). 
 
 
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Surveillance group  
a. Surveillance group would receive monthly blood flow surveillance by ultrasound 
dilution technique (using the Transonic system) plus standard care (see below). 
Patients would be referred for an intervention based on the current KDOQI 
recommendations i.e. access flow of less than 600 ml/minute for arteriovenous grafts 
and less than 500 ml/minute for patients with arteriovenous fistulas or if the access 
flow is 1000 ml/minute that has decreased by more than 25% over 4 months (1). In 
addition to the detection of access dysfunction, the time interval between the 
detection of access dysfunction by the Transonic system and the intervention will also 
be recorded. 
b. Patients will be referred for an intervention if clinical indication is met. Clinical 
indications include prolonged bleeding for more than 30 minutes (cannot be 
explained by medication), upper extremity edema, difficult cannulation, aspiration of 
clots during cannulation, aneurysmal formation. Access pressure that prevents normal 
HD machine operation (such as high venous pressure [>250 mm Hg] on three or more 
consecutive dialysis treatments, negative arterial pressure [<-250mm hg] on three or 
more consecutive dialysis treatments). Any Kt/V that cannot be explained by other 
factors and high recirculation rate of more than 10% would be checked by Transonic 
Recirculation/flow test prior to referral (rear event). 
 
Control group 
Control group will receive standard monitoring (standard care). Standard monitoring is 
physical examination by a qualified individual (nurse) at each dialysis encounter. Patients 
will be referred for an intervention if clinical indication is met. Clinical indications 
include prolonged bleeding for more than 30 minutes, low Kt/v that cannot be explained 
by other factors, high venous pressure (>250 mm hg) on three or more consecutive 
dialysis treatments, negative arterial pressure (<-250mm hg) on three or more consecutive 
dialysis treatments, upper extremity edema, difficulty cannulation, aspiration of clots 
during cannulation, aneurysmal formation and high recirculation of more than 10%. 
 
Enrollment period  
Enrollment period is expected to be 3-6 months. 
 
Transonic measurement protocol: 
Access recirculation, access flow would be determined using the ultrasound dilution 
technique (Transonic system). 
1. Within 90 min of the beginning of HD session HD03 sensors are clamped HD tubing 
lines  
2. Recirculation, access flow will be performed according to HD03 Manual. 
3. Post intervention evaluation is as per each arm follow up unless other follow up 
deemed necessary by the interventionalist. 
 
 
 
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Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
 
 
Data Management 
 
Primary Hypothesis:  
HO: Patients screened monthly with Transonic Ultrasound Dilution Technique (UDT) and 
followed up with proactive intervention (if clinically indicated) will not have a rate of 
access thrombosis that is different than patients receiving physical examination and 
reactive intervention (if clinically indicated). 
 
Secondary Hypotheses:  
HO-1: Patients screened monthly with UDT and followed up with proactive intervention 
(if clinically indicated) will not have a time to thrombosis that is different than patients 
receiving physical examination and reactive intervention (if clinically indicated) 
HO-2: Patients screened monthly with UDT and followed up with proactive intervention 
(if clinically indicated) will not have a number of angioplasty procedures that is different 
than patients receiving physical examination and reactive intervention (if clinically 
indicated) 
HO-3: Patients screened monthly with UDT and followed up with proactive intervention 
(if clinically indicated) will not have a number of thrombectomy procedures that is 
different than patients receiving physical examination and reactive intervention (if 
clinically indicated) 
HO-4: Patients screened monthly with UDT and followed up with proactive intervention 
(if clinically indicated) will not have a rate of tunneled dialysis catheter (TDC) that is 
different than patients receiving physical examination and reactive intervention (if 
clinically indicated) 
HO-5: Patients screened monthly with UDT and followed up with proactive intervention 
(if clinically indicated) will not have a rate of non-tunneled dialysis catheter (non-TDC) 
that is different than patients receiving physical examination and reactive intervention (if 
clinically indicated) 
 
Sample Size: 
α = 0.05, β = 0.80, 2-sided (testing benefit and harm)  
Main predictor: Treatment or control; Main outcome: Thrombosis or no—two-sided 
therefore chi-square for proportions of dichotomous variables was used for sample size 
calculations.   
Treatment versus control estimates of thrombosis (based on Tessitore 2004; Scaffaro 
2009, Moist 2003, Robbin 2006, Sands 1999, Ram 2003, Tessitore 2008): 34% in 
control; 24% in treatment (effect size 30%); 342 per group; loss to f/u (move, transplant, 
different clinic) 5%  = 1/(1-.5)=1.05=359 (low estimate); loss to mortality 10% a year = 
1.11 2x (per Dr. Salman) = 443 
 
Variables to be collected at baseline: 
age, sex, race (white, black, Asian/Pacific Islander, American Indian/Alaskan Native), 
ethnicity 
(Hispanic 
or 
not), 
insurance 
type 
(private, 
Medicaid, 
Medicare, 
 
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Veterans/Military, uninsured), length of time in dialysis (weeks); diabetic (y/d), CAD, 
PVD, HTN, how long access has been in place (weeks), location (Right/Left, 
arm/forearm), type of access (AVF or AVG), other clinical variables, button hole, history 
previous access (Y/N), history of previous catheter (Y/N), length of catheter 
placement/use (Days) 
 
Variables to be collected monthly:  
Monthly questionnaire. 
 
Statistical Analysis: 
• Step 1:  Descriptive analysis to assess similarity of patients between trial arms and to 
assess 
representativeness 
of 
study 
participants 
to 
hemodialysis 
patients 
(generalizability). 
• Step 2: Descriptive analysis for primary outcome (chi-square) and secondary 
outcomes (t-test or non-parametric equivalent) 
• Step 3:   Kaplan-Meier Survival Curve (unadjusted) 
• Step 4:   Survival Time Analysis Cox proportional hazards model (adjusted)  
• Step 5:  Multilevel regression with random effects in a mixed regression model to 
adjust for potential group-level RN, center, city effects. Primary analysis is a 
dichotomous variable (y/n). Secondary analysis outcomes continuous but may be 
treated as categorical variables 
 
Covariates for evaluation in the models: individual-level predictors: age, race, sex, 
insurance, length of time in dialysis (weeks), diabetes (y/n), CVD (y/n), how long access 
has been in place (weeks), access location, type of access, location of access , length of 
time in study before thrombosis or mortality (weeks); other significant clinical variables 
group-level predictors: RN, dialysis center, city 
 
Cross-overs: intervention participants who do not get clinically indicated treatment will 
be analyzed in two ways--included in treatment arm (intention-to-treat) and excluded (per 
protocol) 
 
Statistical monitoring: analysis will be conducted 6 months; 12 months; 18 months; and 
24 months. If a clear benefit is identified early or if the intervention is unexpectedly 
harmful, the study will be stopped early. 
 
Risks to Subjects 
 
Risk from Ultrasound Dilution Technique: UDT is a non-invasive procedure that 
generates no risk to patients undergoing hemodialysis.  We do not anticipate any 
problems as a result of patients undergoing this procedure. 
 
Risk to Privacy: There may be breach of confidentiality regarding protected health 
information. To minimize the potential risk to privacy all data are de-identified with use 
of study specific ID numbers only.  To ensure that participants’ confidentiality is 
 
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maintained each participant will be assigned a unique study identification number and 
will be tracked through the study by this number.  Only the PI and authorized study 
personnel will maintain the code linking study identification numbers to specific 
participants.  When data generated from any study is shared, only de-identified 
information will be exchanged.  No protected health information will be sent to any 
collaborators or be used in any publications of the findings. 
 
Potential Benefits to Subjects 
No direct benefit can be promised to subjects from participation in this research study. 
 
Setting 
Study subjects will be recruited at four dialysis centers.  They count with the 
study populations that will make the research possible.  These centers also possess 
the resources necessary to carry out study procedures safely and effectively.  The 
centers are as follows: 
1. Dialysis Clinic Inc.  
176 Washington Avenue Extension,   
Albany, NY 12203   
2. DCI Rubin Troy 
1850 Peoples Ave,   
Troy NY 12180   
3. DCI Rubin Clifton Park 
21b the Crossings Blvd,   
Clifton Park, NY 12065   
4. DCI Rubin Saratoga Springs 
59c Myrtle St,   
            Saratoga Springs, NY 12866   
 
Resources Available 
• Loay Salman, MD MBA: 
I am an American Board of Internal Medicine (ABIM) certified in Internal 
Medicine and Nephrology. I am specialist in Hypertension. I am also certified by 
the American Society of Diagnostic and Interventional Nephrology (ASDIN) to 
do interventional Nephrology procedures. I am currently Chief: Division of 
Nephrology and Hypertension and The Thomas Ordway Distinguished Professor 
of Medicine at the Albany Medical College. I have been practicing Interventional 
Nephrology for seven years. I have published around forty articles mostly in the 
field of hemodialysis vascular access. I had established a basic research track at 
the University of Miami with focus on vascular access prior to my current 
 
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position.  In my previous position I created a very well organized data base for 
this research. University of Miami vascular lab was rewarded with RO1 grant 
from the National Institute of Health (NIH). As a principal Investigator I will 
bring my knowledge and expertise on vascular access to the research team at 
Albany Medical College.  
• Shari Meola (Senior Manager, Research Support) 
Shari Meola brings over 20 years’ experience to the current study.  She has the 
experience and skills to ensure timely completion of all the project milestones, 
organize communications among investigators, ensure regulatory and IRB 
compliance, overs study and effectively multi-task the various administrative 
duties associated with large complex studies.  She also contributes to manuscripts 
for publication and data presentations at scientific meetings.    
• Nicolle Bateman RN (AMC Study Coordinator and Dialysis Center staff)  
Nicolle Bateman has over 16 years’ experience in dialysis access and 
hemodialysis therapy.  She is CITI certified and is highly skilled at recruiting, 
enrolling and retaining participant’s in previous studies.  She has demonstrated 
that she can efficiently and effectively coordinate the flow of participants during 
their study visits to the CRC, reinforce compliance with study interventions, 
collect and retain data in a well-organized manner, and maintain updated 
regulatory documentation and case report forms.   
 
Recruitment Methods 
Study staff will identify potential subjects from dialysis centers mentioned above. 
Subjects will be approached for a brief conversation to establish if there is interest in 
hearing about the study.  If the patient is interested, the study coordinator will then 
present a detailed explanation of the study.   
 
Subjects who meet all of the inclusion criteria ascertained at the screening visit will be 
enrolled in the study.  In order to reach the goal of 450 subjects who complete the 
protocol, we will screen up to 900 subjects with CKD, allowing for a screening to 
enrollment ratio of 2:1.  Once the target enrollment is complete we will discontinue 
screening irrespective of whether we have yet to reach 900 subjects. 
 
Study team members who approach patients at centers will be very careful of explaining 
to potential subjects that research participation is completely voluntary and that their 
decision whether to participate or not, will have no impact in their medical care.  Also, 
participants will receive a full explanation of the extent of their participation in the study 
prior to signing the informed consent form. 
 
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Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
 
Number of Subjects 
450 Patients. 
  
Confidentiality 
Patients' identifying information will be stored in a password-protected, firewall enabled 
database, only available to approved study staff. The database will be kept for the 
duration of the study. 
 
All subjects will be assigned a unique study number, and a Master Key spreadsheet 
linking the subject’s name and medical record number to the study number will be kept 
by the principal investigator in a password-protected and firewall enabled file. Only 
personnel specifically involved in the conduct of the study, including the PI and research 
coordinators, will have access to the spreadsheet linking the unique study number to 
identifiable patient information. All data and questionnaires obtained from subjects will 
be labeled with their unique study numbers, and only study personnel will have access to 
the database than can link data with subject identifiable information.  All hard copies of 
data such as questionnaires will include only the subject’s unique study number to protect 
subject privacy and will be stored by the research coordinator in locked offices at the 
Dialysis Clinic Inc. located at 176 Washington Avenue Extension, Albany, NY 12203 
while the study is active.  Only the research coordinator will have access to the records.   
The offices are monitored by security personnel and require electronic keys to be 
accessed.  Once the study is completed all study documents will be archived by the PI at 
Albany Medical College. 
 
Study personnel will receive training to secure understanding of the importance of 
protecting subject privacy and the appropriate handling of subject protected health 
information.  At a minimum, this will include all mandatory training required by the 
Albany Medical College and the Subjects Human Research Office. 
 
Provisions to Protect the Privacy Interests of Subjects 
As was mentioned before, study team members who approach patients at centers will be 
very careful of explaining to potential subjects that research participation is completely 
voluntary and that their decision whether to participate or not, will have no impact in 
their medical care.  Also, participants will receive a full explanation of the extent of their 
participation in the study prior to signing the informed consent form.  They will be 
explained that if they want to stop participation at any time, they may do so without any 
consequences. 
 
Patients will be given ample opportunity to voice any particular limitations or objections 
they have to participation previous to signing the informed consent form and their 
requests will be taken into consideration at the moment of decision to include them in the 
study. 
 
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Hemodialysis Access Surveillance Evaluation (HASE) Study 
 
 
Consent Process 
Written, informed consent to participate in the study will be obtained by a qualified, 
authorized member of the study team as determined by the IRB and the Principal 
Investigator; a process that will take place prior to carrying out any study procedures.   
 
 
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