Conditions: End Stage Renal Disease Vascular Access Patency
Keywords: hemodialysis vascular access vascular access patency ticagrelor brilinta
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 54
Healthy volunteers: no

Brief summary:
This study is a randomized, placebo-controlled, single blind clinical trial. Seventy patients with ESRD on chronic HD and a functioning AVF will be recruited. The following data will be documented on each patient: 1-Age/gender/race/body weight/cause of ESRD 2-Vintage of HD 3-Time since access was placed 4-Type and place of access and blood flow rate of access 5-History of prior access problems 6-Comorbid conditions (Hypertension, coronary artery disease, Diabetes Mellitus, Bleeding problems, peripheral vascular disease). 7-Current medications (Coumadin, Erythropoiesis stimulating agents, heparin, other antiplatelets, digoxin, statins). Patients will be randomized into two groups to receive: Group 1: Ticagrelor 90 mg PO BID Group 2: Placebo drug PO BID.

Detailed description:
This study is a randomized, placebo-controlled, single blind clinical trial. Seventy patients with ESRD on chronic HD and a functioning AVF will be recruited. Consent form will be obtained. History and physical, dialysis parameters and laboratory data (CBC, CMP, PTT \& INR) will be obtained throughout the study. The following data will be documented on each patient: 1-Age/gender/race/body weight/cause of ESRD 2-Vintage of HD 3-Time since access was placed 4-Type and place of access and blood flow rate of access 5-History of prior access problems 6-Comorbid conditions (Hypertension, coronary artery disease, Diabetes Mellitus, Bleeding problems, peripheral vascular disease). 7-Current medications (Coumadin, Erythropoiesis stimulating agents, heparin, other antiplatelets, digoxin, statins). Patients will be randomized into two groups to receive: Group 1: Ticagrelor 90 mg PO BID Group 2: Placebo drug PO BID.

Subjects will have a screening visit and if they qualify for the study they will have 18 additional visits. All of these visits will occur while the subjects are at their normal dialysis treatment. Subjects will be randomized to either the Ticagrelor group or the placebo group. Subjects will be on study medication for 6 months then they will have a follow up period off drug for 6 months. Subjects will be seen twice a month while on study medication and once a month in the follow up period. While the subjects are on study medication the study team will assess any side effects of the study medication and put their relation to the study drug at each study visit. The study team will use clinical monitoring as suggested by Beathard (21). The study team will document the subject's adherence to the study, if they are hospitalized and what caused their hospitalization. A monthly intra-access flow will be obtained using ultrasound dilution by transonics as part of standard of care. Any change in the clinical assessment of the access, prolonged bleeding (\>20 minutes) after removal of needles, trend of decreasing intra-access blood flow as determined by transonic (\> 25% or original flow), or an access flow rate \< 400 ml/min, will prompt a referral for a fistulogram. If confirmed stenosis (\>50% stenosis of the access diameter) an intervention (angioplasty) will be performed. This intervention is part of the subjects standard of care.

Arms:
arm 1: 90 mg of ticagrelor to be given orally twice a day for 6 months arm 2: Placebo drug to be given twice a day for 6 months

Interventions: intervention 1: ticagrelor intervention 2: Placebo
Intervention descriptions: intervention 1: ticagrelor 90 mg twice a day for 6 months intervention 2: 1 pill twice a day for 6 months

Protocol document:
Prot_SAP_000.pdf: 
IRB-HSR# 17224: Randomized, Placebo-controlled, Single Blind, Trial to Determine the Safety and 
Efficacy of Ticagrelor for Maintaining Patency of Arterio-Venous Fistulae Created for Hemodialysis 
 
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Randomized, Placebo-controlled, Single Blind, Trial to Determine the Safety 
and Efficacy of Ticagrelor for Maintaining Patency of Arterio-Venous Fistulae 
Created for Hemodialysis. 
NCT02335099 
Version Date 19 Dec 2018 
 
IRB-HSR PROTOCOL 
Investigator Agreement 
BY SIGNING THIS DOCUMENT, THE INVESTIGATOR CONFIRMS: 
1. I am not currently debarred by the US FDA from involvement in clinical research studies. 
2. I am not involved in any regulatory or misconduct litigation or investigation by the FDA. 
3. That if this study involves any funding or resources from an outside source, or if you will be sharing data 
outside of UVA prior to publication that you will contact the Dean’s office regarding the need for a contract 
and letter of indemnification.  If it is determined that either a contract or letter of indemnification is needed, 
subjects cannot be enrolled until these documents are complete. 
4. The proposed research project will be conducted by me or under my close supervision.  It will be conducted 
in accordance with the protocol submitted to and approved by the IRB including any modifications, 
amendments or addendums submitted and approved by the IRB throughout the life of the protocol.  
5. That no personnel will be allowed to work on this protocol until they have completed the IRB-HSR On-line 
training and the IRB-HSR has been notified. 
6. That all personnel working on this protocol will follow all IRB-HSR Policies and Procedures as stated on 
the IRB-HSR Website http://www.virginia.edu/vprgs/irb/ and on the School of Medicine Clinical Trials 
Office Website:  http://knowledgelink.healthsystem.virginia.edu/intranet/hes/cto/sops/sop_index.cfm 
7. I will ensure that all those delegated tasks relating to this study, whether explicitly or implicitly, are capable 
through expertise, training, experience or credentialing to undertake those tasks.   
8. I confirm that the implications of the study have been discussed with all Departments that might be affected 
by it and have obtained their agreement for the study to take place.  
9. That no subjects will be recruited or entered under the protocol until the Investigator has received the signed 
IRB-HSR Approval form stating the protocol is open to enrollment 
10. That any materials used to recruit subjects will be approved by the IRB-HSR prior to use.  
11. That all subjects will sign a copy of the most current consent form that has a non-expired IRB-HSR 
approval stamp. 
12. That any modifications of the protocol or consent form will not be initiated without prior written approval 
from the IRB-HSR, except when necessary to eliminate immediate hazards to the subjects. 
13. Any significant findings that become known in the course of the research that might affect the willingness 
of subjects to enroll or to continue to take part, will be promptly reported to the IRB.   
14. I will report immediately to the IRB any unanticipated problems involving risk to subjects or to others 
including adverse reactions to biologics, drugs or medical devices.   
15. That any serious deviation from the protocol will be reported promptly to the Board in writing. 
16. That any data breach will be reported to the  IRB, the UVa Corporate Compliance and Privacy Office , UVa 
Police as applicable.  


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17. That the continuation status report for this protocol will be completed and returned within the time limit 
stated on the form. 
18. That the IRB-HSR office will be notified within 30 days of a change in the Principal Investigator or of the 
closure of this study. 
19. That a new PI will be assigned if the current PI will not be at UVA for an extended period of time.  If the 
current PI is leaving UVa permanently, a new PI will be assigned PRIOR to the departure of the current PI.  
20. All study team members will have access to the current protocol and other applicable documents such as the 
IRB-HSR Application, consent forms and Investigator Brochures. 
21. Signed consent forms and other research records will be retained in a confidential manner.  Records will be 
kept at least 6 years after completion of the study.  
22. No data/specimens may be taken from UVa without a signed Material Transfer Agreement between 
OSP/SOM Grants and Contracts Office and the new institution.  Original study files are considered 
institutional records and may not be transferred to another institution. I will notify my department 
administration regarding where the originals will be kept at UVa.  The material transfer agreement will 
delineate what copies of data, health information and/or specimens may be taken outside of UVa.  It will 
also approve which HIPAA identifiers may be taken outside of UVa with the health information or 
specimens. 
23. If any member of study team leaves UVa, they are STRONGLY ENCOURAGED to use Exit Checklist 
found on IRB-HSR website at http://www.virginia.edu/provost/facultyexit.pdf. 
  
The IRB reserves the right to terminate this study at any time if, in its opinion, (1) the risks of further 
experimentation are prohibitive, or (2) the above agreement is breached. 
 
Investigators Experience 
Dr. Abdel-Rahman is the director of the Acute Kidney Injury-Therapeutic Extracorporeal Unit (AKI-TECU) 
that deals with dialysis-dependent AKI patients. He has been a Nephrologist for close to 25 years. He currently 
is a professor in the division of Nephrology. He is an established researcher with more than 40 peer-reviewed 
publications. His main area of research is related to improving outcomes of patients on hemodialysis 
Signatures 
Principal Investigator 
 
____________________________ ____________________________ _______ 
Principal Investigator 
Principal Investigator 
Date 
Signature 
Name Printed 
 
Department Chair 
BY SIGNING THIS DOCUMENT THE DEPARTMENT CHAIR AGREES: 
1. To work with the investigator and with the board as needed, to maintain compliance with this agreement. 
2. That the Principal Investigator is qualified to perform this study. 
3. That the protocol is scientifically relevant and sound. 
 
___________________________ 
_______________________  
_________ 
Department Chair or Designee  
Department Chair or Designee 
Date 
Signature 
Name Printed 
 
 
 
The person signing as the Department Chair cannot be the Principal Investigator or a sub-investigator on this protocol. 
The Department Chair or Designee signature is ONLY required if this is a new protocol or a modification changing the Principal Investigator 
 
 


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Brief Summary/Abstract 
 
This study is a randomized, placebo-controlled, single blind clinical trial. Seventy patients with ESRD on 
chronic HD and a functioning AVF will be recruited. Consent form will be obtained.  History and physical, 
dialysis parameters and laboratory data (CBC, CMP, PTT & INR) will be obtained throughout the study.  The 
following data will be documented on each patient: 1-Age/gender/race/body weight/cause of ESRD 2-Vintage 
of HD 3-Time since access was placed 4-Type and place of access and blood flow rate of access 5-History of 
prior access problems 6-Comorbid conditions (Hypertension, coronary artery disease, Diabetes Mellitus, 
Bleeding problems, peripheral vascular disease). 7-Current medications (Coumadin, Erythropoiesis stimulating 
agents, heparin, other antiplatelets, digoxin, statins). Patients will be randomized into two groups to receive: 
Group 1: Ticagrelor 90 mg PO BID Group 2:  Placebo drug PO BID.   
 
Subjects will have a screening visit and if they qualify for the study they will have 18 additional visits. All of 
these visits will occur while the subjects are at their normal dialysis treatment. Subjects will be randomized to 
either the Ticagrelor group or the placebo group. Subjects will be on study medication for 6 months then they 
will have a follow up period off drug for 6 months. Subjects will be seen twice a month while on study 
medication and once a month in the follow up period.  While the subjects are on study medication we will 
assess any side effects of the study medication and put their relation to the study drug at each study visit. We 
will use clinical monitoring as suggested by Beathard (21). We will document the subject’s adherence to the 
study, if they are hospitalized and what caused their hospitalization. A monthly intra-access flow will be 
obtained using ultrasound dilution by transonics as part of standard of care. Any change in the clinical 
assessment of the access, prolonged bleeding (>20 minutes) after removal of needles, trend of decreasing intra-
access blood flow as determined by transonic (> 25% or original flow), or an access flow rate < 400 ml/min, 
will prompt a referral for a fistulogram. If confirmed stenosis (>50% stenosis of the access diameter) an 
intervention (angioplasty) will be performed. This intervention is part of the subject’s standard of care.    
 
Background 
 
1.  Provide the scientific background, rationale and relevance of this project.   
The main renal replacement therapy for End stage renal disease (ESRD) in the USA is hemodialysis (HD).  
Vascular access for hemodialysis can be provided by means of an autogenous fistula, arteriovenous graft, or 
central venous catheter. The autologous brachio-cephalic (Brescia-Cimino) fistula remains the access of choice, 
since its patency and rate of infection are superior to those made of exogenous material once early failures are 
excluded (1).   A functioning vascular access is crucial for HD. However, vascular-access failure (VAF) is 
common and is a major source of complications (1). Complications of the vascular access, particularly stenosis 
and thrombosis, continue to remain the Achilles' heel of HD therapy and lead to extensive morbidity in HD 
patients. VAF is the most common reason for hospitalization among HD patients (2-4). The economic burden of 


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VAF is estimated at greater than 1 billion dollars per year (1) and continues to grow. Recent data have 
suggested a significantly high incidence of inflow stenosis of vascular access (14–42%) in this patient 
Population (5-7).  Hence, guidelines were adopted for adequate monitoring and surveillance of the vascular 
access as well as criteria for adequate evaluation and timing intervention (8). Surveillance of an access is done 
by dynamic or static methods. Dynamic intra-access flow measures, by many methods as duplex doppler 
ultrasound, magnetic resonance angiography, and ultrasound dilution by transonics), are among the preferred 
methods of AV access surveillance (8). Patients with VAF are referred for evaluation and treatment if access 
flow rate <400-500 mL/min, in the presence of continuous persistent abnormalities in the surveillance 
parameters or a prospective trending drop of the access blood flow rate (8).  There is no consensus in the 
literature as to the use of anticoagulants or antiplatlets for arterio venous fistula prophylaxis. . Multiple studies 
aiming at thromboprophylaxis to prevent VAF were done using various antiplatelet agents (Ticlodipine (9-12), 
Dipyridamole (11, 13, 14), Aspirin (15, 16) and Clopidogrel (17-19) showing variable results. While Sreedhara 
et al (13) showed that Dipyridamole can be thromboprophylactic for new arterio-venous graft (AVG), it failed 
to show any benefit to previously stenosed grafts. Dixon et al. (14) using extended release Dipyridamole in 
addition to aspirin, showed modest, though significant, decrease in AVG stenosis. Clopidogrel decreased 
thrombotic graft episode (18) but was reported to be associated with increased bleeding (17). Ticlodipine was 
used alone (9, 10, 21) or with Dipyridamole (11) to study its role in maintaining the patency of arterio-venous 
fistula (AVF) with controversial results.  
 
Ticagrelor (Brilinta) is a new drug approved for use in patients with acute coronary syndrome to reduce the rate 
of thrombotic cardiovascular events.  Early studies (please see investigator brochure for more information) 
showed that Ticagrelor achieves a higher inhibition of platelet aggregation as compared to Clopidogrel. The 
primary route of Ticagrelor elimination is via liver metabolism, thus, does not require dose adjustment in 
patients with renal impairments. Since Ticagrelor has not been used in hemodialysis patients for the purpose of 
preventing thrombosis in dialysis vascular accesses (Arterio-Venous Fistulae and Grafts), this study is designed 
as a pilot study to evaluate the feasibility and safety of Ticagrelor in hemodialysis patients with AVF vascular 
access to see if the treatment efficacy of Ticagrelor can preserve patency of hemodialysis vascular access better 
than Placebo.                                          
Objectives: The primary objective is to evaluate the feasibility and safety of Ticagrelor in hemodialysis patients 
with AVF vascular access.  The secondary objective is to evaluate the treatment efficacy in that whether 
Ticagrelor will preserve patency of hemodialysis vascular access better than Placebo.  Hypothesis: Ticagrelor is 
safe and will preserve patency of hemodialysis vascular access (Arterio-Venous Fistulae) better than Placebo 
 
The drug Ticagrelor, approved by FDA for patients with ACS, was never tested in patients with ESRD. In 
addition, if proven safe and effective in maintaining the patency of vascular access in patients with ESRD, 
which will be a new indication for the drug and hopefully will help, patients with ESRD maintain the patency of 
their access 
Hypothesis to be Tested 
Hypothesis: Ticagrelor is safe and will preserve patency of hemodialysis Arterio-Venous Fistulae better than 
Placebo. This is a Randomized, Placebo-controlled, Single Blind clinical trial. Seventy patients with ESRD on 
chronic HD and a functioning AVF will be recruited. Consent form will be obtained.  History and physical, 
dialysis parameters and laboratory data will be obtained.  Patients will be randomized into two groups to 
receive: Group 1: Ticagrelor 90 mg PO BID Group 2:  Placebo drug PO BID Patients will be seen twice a 
month while on study treatment. We will assess any side effects and the relation to the study drug. -Clinical 
monitoring -Document adherence to the study -Document hospitalization with cause. -A monthly intra-access 


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flow will be obtained using ultrasound dilution by transonics which is a standard of care procedure. Any change 
in the clinical assessment of the access, prolonged bleeding (>20 minutes) after removal of needles, trend of 
decreasing intra-access blood flow as determined by transonic (> 25% or original flow), or an access flow rate < 
400 ml/min, will prompt a referral for a fistulogram. If confirmed stenosis (>50% stenosis of the access 
diameter) an intervention (angioplasty) will be performed. This intervention is part of the study patient’s 
standard of care. Timeline of study: -6 Months recruitment phase -6 months active study phase:  -6 months 
follow up: both groups will be monitored by complete physical examination, laboratory and dialysis data as 
well as monthly transonic assessment of intra-access blood flow rate will be done for standard of care and we 
will document if any intervention is required. -6 months statistical analysis and data documentation    
 
Objectives: The primary objective is to evaluate the feasibility and safety of Ticagrelor in hemodialysis patients 
with AVF vascular access.   
The secondary objective is to evaluate the treatment efficacy of Ticagrelor to see if it will preserve patency of 
hemodialysis vascular access better than Placebo. 
 
Study Design: Biomedical 
1.  Will controls be used? 
Yes 
 
►IF YES, explain the kind of controls to be used. 
Yes, we will have a group of study subjects that will be given a placebo in addition to what they 
would get that is the current standard of care for their medical issue.  
 
2. What is the study design?  
This is a randomized, placebo-controlled, single-blind study.  
 
3. 
Does the study involve a placebo? 
Yes 
 
►IF YES, provide a justification for the use of a placebo 
The placebo group can be used as an “add on” to standard of care in comparison to an investigational 
treatment added to standard of care. This is what will happen in this study.  
 
Human Participants 
Ages: 18 to 85  
Sex: Male and Female 
 
Race: All 
Subjects- see below 
1.  Provide target # of subjects (at all sites) needed to complete protocol. 
70 
 
2.  Describe expected rate of screen failure/ dropouts/withdrawals from all sites.   
25% 
 
3.  How many subjects will be enrolled at all sites?    
88  
 


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4.  How many subjects will sign a consent form under this UVa protocol?     
88 
 
5. Provide an estimated time line for the study. 
 
We hope to have enrollment completed within 6 months of protocol approval.  
Inclusion/Exclusion Criteria 
 
1.  List the criteria for inclusion  
• Patients on chronic hemodialysis with a functioning arterio-venous fistula 
• Subjects must agree to use adequate contraception to prevent pregnancy 
 
2.  List the criteria for exclusion 
• Hemoglobin less than 9g/dL per chart review of the last Hemoglobin level obtained for standard 
of care. 
• If the study subject can’t be washed off of anti-coagulants or antiplatelets 
• Recent history of bleeding over the last 3 months preceding enrollment  
• History of bleeding disorder (hemophilia, Von Willebrandt disease, etc….). Anemia only if it is 
chronic and thrombocytopenia if the platelet count is consistently <125,000.   
• Recent history of blood transfusion over the last 3 months preceding enrollment  
• Recent serious injury or surgery over the last 3 months preceding enrollment  
• History of gastro-intestinal ulcers  
• Moderate-severe hepatic impairment (ALT/AST greater than 3-5 times the upper limit of 
normal).   
• Uncontrolled blood pressure (SBP> 190 or DBP >110) pre or post dialysis  
• History of stroke within the last 5 years.   
• Pregnant females-self reported 
• Hypersensitivity to Aspirin /antiplatelets 
• Subjects using peroral anticoagulants 
• History of intracranial hemorrhage 
• Active pathological bleeding 
• Hypersensitivity to ticagrelor or any component of the product 
 
3.  List any restrictions on use of other drugs or treatments.    
Subjects using peroral anticoagulants will be excluded to avoid excessive bleeding risk. There will be a 4 day 
wash off for subjects who are taking anticoagulants and anti-platelets. If subjects can’t be washed off of these 
medications then they cannot be included in the study.     
Statistical Considerations 
1. 
Is stratification/randomization involved? 
Yes 
►IF YES, describe the stratification/ randomization scheme. 
 
Every other study subject will be on active study drug. Investigators and study personnel will be un-
blinded.  
 


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►IF YES, who will generate the randomization scheme?  
__X__UVa Statistician: Jennie Ma 
 
2.  What are the statistical considerations for the protocol?  
Since Ticagrelor has not been used in hemodialysis patients for the purpose of preventing thrombosis in dialysis 
vascular accesses (Arterio-Venous Fistulae and Grafts), this study is designed as a pilot study in that patients are 
randomly assigned to receive Ticagrelor or placebo drug for a six-month treatment period plus an additional 6-
month follow-up period. The primary objective is to evaluate the feasibility and safety of Ticagrelor in 
hemodialysis patients with AVF vascular access. The secondary objective is to evaluate the treatment efficacy 
in that whether Ticagrelor will preserve patency of hemodialysis vascular access better than Placebo. The study 
will follow intent-to-treat principle and all randomized patients will be included in the analyses for the primary 
and secondary objectives.  
 
3.  Provide a justification for the sample size used in this protocol.   
Due to the pilot nature of this study, formal power analysis and sample size estimation is not essential. 
Nevertheless, we attempted to estimate the potential treatment efficacy in this study. We considered the 
outcome measure for efficacy evaluation is the time to first stenosis event during the study period. From our 
recent clinical data, it was estimated that approximately 36% of dialysis patients experienced stenosis event at 
one-year follow-up.  We would expect that patients in the new drug arm would have 10% stenosis event rate at 
one-year follow-up, compared to the 36% stenosis event rate in the placebo group. With these considerations, 
the analysis of stenosis-free survival will require at least 21 events, which is the number of events needed for 
one-sided log-rank test at 5% significance level to have 80% power to show statistically significant difference 
when the true hazard ratio is 0.236. This estimation will result in that approximately seventy patients will be 
needed and evenly randomized into each study arm (35 patients in Ticagrelor and 35 in placebo). This is an 
open-label study. Upon completion of all the required screening assessments, eligible patients will be randomly 
assigned to the study drug or placebo at 1:1 ratio with a block size of 20 in accordance with the randomization 
schedule. The randomization schedule will be provided by the Department of Public Health, School of 
Medicine.  Patients will be identified by unique subject identifier that will remain consistent for the duration of 
the study. The active study period is 6 months followed by 6 months of monitoring, and accrual rate is 
approximately 12 patients per month. To compensate for an estimated drop-out rate of 25%, we will recruit 88 
patients to the study. 
 
4.  What is your plan for primary variable analysis? 
We have recruited/consented a total of 54 subjects into this study. We have enrolled a total of 43 patients into 
the study, 23 in the Ticagrelor treatment arm and 20 in the placebo arm. We will evaluate the safety of 
Ticagrelor in hemodialysis patients with AVF vascular access by tabulating adverse events and severe adverse 
events for the two study arms, and the difference between the two arms will be tested by chi-square test. 
 
5.  What is your plan for secondary variable analysis?  
For the secondary outcome, i.e., time to the first stenosis event, we will compare stenosis-free survival of 
Ticagrelor versus placebo using the Kaplan-Meier method. Survival probabilities and corresponding 95% 
confidence interval (CI) will be calculated at landmark time points for each arm, and survival difference 
between the two arms will be evaluated using a one-sided log-rank test stratified by the history of stenosis. 
Further, a stratified Cox proportional-hazards model will be used to derive the hazard ratio and 95% CI between 
the two regimens. 
 
6. Have you been working with a statistician in designing this protocol? 
 
Yes 


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IF YES, what is their name?   
 
Jennie Ma 
Biomedical Research 
 
1.  What will be done in this protocol?    
Subjects will be in this study for 1 year. Up to eighty eight patients with ESRD on chronic HD and a 
functioning AVF will be enrolled. For statistical purposes we will need to have seventy people complete the 
study. Consent form will be obtained. History and dialysis parameters will be taken at the screening visit. At the 
screening visit we will also be collecting a serum sample to perform a pregnancy test on female subjects of 
child bearing potential. This will be collected in a 3.5ml gold top serum separating tube. Study participants will 
be on the study medication (Ticagrelor) or placebo for six months (Visit 1 to Visit 12). Subjects will take the 
study medication twice a day. They will take it once in the morning and once in the evening. We will also 
instruct them to try and take it around the same times each day if possible. We will be collecting study 
medication to check for compliance at Visits 3, 6, 9, and 12. There will be a follow up for these subjects for six 
months (Visit 13 to Visit 18). Subjects will have a physical performed at screening, visit 12 (this is the last visit 
when subjects are on medicine), and at visit 18 which is the end of the study. We will be looking at hemoglobin 
levels that are collected as standard of care two times a month. We will be collecting the bleeding time weekly 
as well. This will be done at all visits (screening to Visit 18) which we define as the time it takes for a subjects’ 
access to stop bleeding.    
 
The following data will be documented on each subject at screening: 
1-Age/gender/race/body weight/cause of ESRD 
2-Vintage of HD 
3-Time since access was placed 
4-Type and place of access and blood flow rate of access 
5-History of prior access problems 
6-Comorbid conditions (Example: Hypertension, coronary artery disease, Diabetes Mellitus, Bleeding 
problems, peripheral vascular disease). 
7-Current medications (Example: Coumadin, Erythropoiesis stimulating agents, heparin, other antiplatelets, 
digoxin, statins) 
This data will be obtained from the dialysis computer system and will be verified with the subject. 
8-Physical Exam 
9-Vital signs (blood pressure, heart rate, and weight) will be obtained from the subject’s dialysis record.   
 
Adverse events and concomitant medications will be reviewed at each study visit. We will also note any access 
issues at each study visit.  
 
Study Medication Stopping Rules for Prolonged Bleeding:  
If post treatment bleeding time is prolonged more than 30 minutes we will stop the study drug and refer for 
fisulogram,  
If bleeding still persists after fistulogram and intervention we will continue to hold the study drug and do 
work up for bleeding. We will continue to hold study drug for 5 days if signs of increased tendency for 
bleeeding as recurrent Epistaxis > twice in one week, if any evidence of GI bleed, or if Hgb should drop > 
1gm in one week. If the bleeding is believed to be drug related or it no resolution occurs the subject will be 
withdrawn from the study.   
We will also hold study drug for 5 days if hemoglobin is consistently less than 8g/dL for 2 consecutive weeks, 
or hemoglobin dropping 1g/dL in one week.   
 


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For a prolonged bleeding event standard practice will be applied, including: (prolonged bleeding is defined as 
bleeding more than 30 minutes) 
• 
Direct pressure. Any bleeding that warrants an emergency department visit should be immediately 
controlled with the application of direct digital pressure to the puncture site for 5-10 minutes. Once the 
bleeding abates, the patient should be observed for rebleeding or early thrombosis for 1-2 hours.  
• 
Gelatin sponges. Commonly seen in the emergency department as Gelfoam®, this adjunct may aid in 
the hemostasis of bleeding AV grafts. Although studies or case reports of this material being used in this 
setting are not found in the medical literature, our clinical practice has demonstrated success by 
including it in the management of this problem. 
Life-Threatening Bleeding From Hemo Access  
A vascular surgeon should be emergently consulted if hemorrhage cannot be quickly controlled. An adjunctive 
suture may be placed if there appears to be a small laceration of the graft rather than a puncture wound. This 
suture is used only after other measures to control bleeding described above have also failed. 
Other life threatening bleeding: Subjects will be sent to the emergency department   
2. Will you be using data/specimens in this study that were collected previously, with the use of a research 
consent form, from another research study? 
No 
 
3. List the procedures, in bullet form, that will be done for research as stipulated in this protocol.  
• Physical Exams 
• Administration of Investigational Drug 
• HcG Blood Pregnancy Test 
• Collection of Bleeding Time  
 
Note:  Laboratory data will be captured and recorded for research purposes from blood collected as part of the 
subject’s clinical care-no additional blood is collected for the purpose of this study. 
 
4.  Will any of the procedures listed in item # 2 have the potential to identify an incidental finding?   
Yes 
 
►IF YES, check one of the following two options:  
__X__The examination(s) utilize(s) the same techniques, equipment, etc., that would be used if the 
subject were to have the examination(s) performed for clinical care.  There exists the potential for 
the discovery of clinically significant incidental findings.   
• The PI takes full responsibility for the identification of incidental findings:  
• The PI will inform the subjects verbally of all incidental findings that are of clinical 
significance or are of questionable significance.   
• A follow-up letter describing the finding should be provided to the subject with 
instructions to either show the letter to their PC or if the subject has no PCP, the subject 
should be instructed to make an appointment at UVa or at the Free Clinic.   
 
 


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5.  Do any of the procedures listed above, under question # 2, utilize any imaging procedures (e.g. 
ultrasound, CT scans/ x-rays etc.)? If yes, LIST PROCEDURES:  No 
 
6. Will you be using viable embryos? No 
7. Will you be using embryonic stem cells? No 
 
Specimens  
 
Specimen Information 
1.  Describe the type of specimen to be used: 
Answer/Response: At the screening visit only, we will collect a 3.5ml gold top serum separating tube from 
women in the study who are of child bearing potential.  
2.  Will the specimen be obtained BEFORE a subject has signed a consent form?  
IF YES, or if consent or documentation of consent is waived and the specimen is identifiable per HIPAA regulations, 
the research team will be required to track this disclosure with Health Information Services.  
Answer/Response: No 
 
3.  Will you be using discarded specimens? 
Answer/Response: No 
 
Answer the following two questions as it pertains to ALL blood being drawn for this study.  
►IF NO, and taking a blood sample, will blood be taken more than 2 times/week? 
Answer/Response: No 
 
►IF NO, and taking a blood sample, check the option(s) below which match the subject 
population. 
 
_____  healthy, non-pregnant adults who weigh at least 110 pounds.  
 
 
_____ Amount will NOT exceed 550 cc in an 8 week period 
_____ Amount to exceed 550 cc in an 8 week period 
 
 
__X__ Non- healthy or pregnant adults and/or children  
 
__X__ Amount will NOT exceed the lesser of 50ml or 3 ml/kg in an 8 week period 
_____ Amount will exceed the lesser of 50 ml or 3 ml/kg in an 8 week period 
 
Specimen Labeling 
1.  What information/ HIPAA identifiers will be on the specimen label when it is given to the study team 
(from clinical labs or other source outside the study team) and/or what information will you put on the 
specimen? 
Example:  name, date of collection, subject # medical record# 
Answer/Response: Name, Date/Time of Collection, Subject MRN# 
 
2.  If the specimen is given to the study team with information on the label will you delete any of the 
information on the specimen label?    
Answer/Response: No  
 
3.  Will any additional data be linked to the specimen by way of a code?   
Example:  name, date of collection, subject # medical record# , diagnosis, clinical information 
Answer/Response: No  
 


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4.  Will the analysis on the specimen be done soon (within 24 hours) after it is collected? 
INSTRUCTIONS: This question does not refer to a specimen that is collected for long term tissue banking, 
but rather analysis that is already described in the protocol. 
Answer/Response: Yes 
 
Specimen Shipping 
1.  Do you plan to ship any specimens outside of UVA? 
Answer/Response: No 
 
Data and Safety Monitoring Plan 
If you have any questions completing this section call 982-4311, 924-8660 or 243-9847 for assistance 
A Sponsor is defined as entity that will receive data prior to publication. 
1.  Definition: 
1.1 How will you define adverse events (AE)) for this study?  
__X__An adverse event will be considered any undesirable sign, symptom or medical or 
psychological condition even if the event is not considered to be related to the investigational 
drug/device/intervention. Medical condition/diseases present before starting the investigational 
drug/intervention will be considered adverse events only if they worsen after starting study 
treatment/intervention.  An adverse event is also any undesirable and unintended effect of research 
occurring in human subjects as a result of the collection of identifiable private information under the 
research.  Adverse events also include any problems associated with the use of an investigational 
device that adversely affects the rights, safety or welfare of subjects. 
1.2 How will you define serious adverse events? 
__X__A serious adverse event will be considered any undesirable sign, symptom, or medical 
condition which is fatal, is life-threatening, requires or prolongs inpatient hospitalization, results 
in persistent or significant disability/incapacity, constitutes a congenital anomaly or birth defect, 
is medically significant and which the investigator regards as serious based on appropriate 
medical judgment. An important medical event is any AE that may not result in death, be life-
threatening, or require hospitalization but may be considered an SAE when, based upon 
appropriate medical judgment, it may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in the definitions of SAEs.  
1.3 What is the definition of an unanticipated problem?  
Do not change this answer 
An unanticipated problem is any event, experience that meets ALL 3 criteria below: 
 Is unexpected in terms of nature, severity or frequency given the research procedures that are 
described in the protocol-related documents AND in the characteristics of the subject 
population being studies 
 Related or possibly related to participation in research.  This means that there is a reasonable 
possibility that the incident may have been caused by the procedures involved in the research 
study. 


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 The incident suggests that the research placed the subject or others at greater risk of harm 
than was previously known or recognized OR results in actual harm to the subject or others 
 
1.4 What is the definition of a protocol violation?  
Do not change this answer 
A protocol violation is defined as any change, deviation, or departure from the study design or 
procedures of a research project that is NOT approved by the IRB-HSR prior to its initiation or 
implementation, OR deviation from  standard operating procedures, Good Clinical Practices 
(GCPs), federal, state or local regulations. Protocol violations may or may not be under the control 
of the study team or UVa staff. These protocol violations may be major or minor violations. 
 
Additional Information: see the IRB-HSR website at  
http://www.virginia.edu/vpr/irb/HSR_docs/Forms/Protocol_Violations_%20Enrollment_Exceptions
_Instructions.doc 
 
1.5 If pregnancy occurs how will this information be managed? 
_____  Adverse Event- will follow adverse event recording and reporting procedures outlined in 
section 3.  
 
__X__  Unanticipated Problems- will follow Unanticipated Problem recording and reporting 
procedures outlined in section 3.  
 
1.6 What is the definition of a Protocol Enrollment Exception?   
__X__NA- No outside sponsor 
 
1.7 What is the definition of a data breach? 
Do not change this answer 
A data breach is defined in the HITECH Act (43 USC 17932) as an unauthorized acquisition, 
access, or use of protected health information (PHI) that compromises the security or privacy of 
such information. 
 
Additional Information may be found on the IRB-HSR Website: Data Breach 
2.  Identified risks and plans to minimize risk 
 
2.1 What are identified risks and plans to minimize risk 
**Please Also Refer to the Investigator Brochure and the Package Insert for Brilinta/ Ticagrelor 
Adverse Events with Brilinta/Ticagrelor 
Frequent complaints (seen in at least 3% of study participants) that have been reported during studies: 
• Bleeding 
• Dyspnea (Shortness of Breath) 
• Cough 
• Dizziness 
• Nausea 
• Atrial Fibrillation (Heart Rhythm Disorder) 
• Hypertension (High Blood Pressure) 
• Non-Cardiac Chest Pain 


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• Diarrhea 
• Back Pain 
• Hypotension (Low Blood Pressure) 
• Fatigue 
• Chest Pain 
• Headache 
 
More Frequent complaints (seen in at least 6 to 7% of study participants) that have been reported during studies: 
• Bradycardia (Slow Heart Rate)  
• Elevated Serum Creatinine  
There have also been cases of increased uric acid levels for subjects taking ticagrelor. A high uric acid level, or 
hyperuricemia, is an excess of uric acid in your blood. Uric acid is produced during the breakdown of purine, a 
substance found in many foods. Once produced, uric acid is carried in your blood and passes through your 
kidneys, where most of it leaves your body when you urinate. A high uric acid level may result in attacks of 
gout, but not everyone who has high uric acid gets gout, and not everyone with gout has high uric acid. 
Increased uric acid may also increase the chances of kidney stones. There is also an increased risk of severe 
bleeding for subjects taking ticagrelor. Due to the increase risk of severe bleeding there may be a risk of delay 
in any surgery that you may need while taking this study medication.  
Expected Risks related to study 
participation.  
Frequency 
 
Reproductive Risks 
These are unknown at this time.  
Minimized due to the requirements of this protocol.   
Violation of subject’s privacy and 
confidentiality 
Minimized due to the requirements of the privacy 
plan in this protocol 
 
2.2   List by bullet format a summary of safety tests/procedures/observations to be performed that will 
minimize risks to participants:   
• Study personnel will be checking on patients twice a month for six months while subjects are on study 
treatment and once a month while subjects are in the follow up visits.   
• We will be monitoring the time it takes for the subject’s access to clot. 
• AE monitoring at each visit 
• Weekly Hemoglobin Tests 
 
2.3 Under what criteria would an INDIVIDUAL SUBJECT’S study treatment or study participation be 
stopped or modified 
__X__At subject, PI or sponsor’s request 
 
__X__Treatment would be stopped if the subject had a serious adverse event deemed related to 
study 
__X__ Subjects will be stopped if they meet one or more of the study stopping rules 
 
2.4 Under what criteria would THE ENTIRE STUDY need to be stopped.   


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These are called stopping rules for early termination of the entire study. 
List criteria regardless of whether the study is sponsored or not.  
Be sure to include any criteria for which the UVa PI would halt the study at UVa. 
__X__Per IRB, PI, DSMB, or sponsor discretion 
 
2.5 What are the criteria for breaking the blind/mask? 
__X___NA – Not blinded/masked 
 
 
2.6 How will subject withdrawals/dropouts be reported to the IRB prior to study completion? 
__X__IRB-HSR continuation status form  
 
3.  Adverse Event / Unanticipated Problem Recording and Reporting 
 
3.1 Will all adverse events, as defined in section 1.1, be collected/recorded? 
No 
►IF NO, what criteria will be used?   
 
__X__Only adverse events that are deemed related AND serious  
 
3.2 How will adverse event data be collected/recorded?  
__X__Paper AE forms/source documents  
 
3.3. How will AEs be classified/graded?  
_____World Health Organization Criteria (WHO) 
_____NCI Common Toxicity Criteria, Version 2.0/ NCI Common Terminology Criteria, Version 3.0 
_____NCI CTCAE Version 4.0 
__X__Mild/Moderate/Severe 
__X__Serious/Not serious  
 
3.4 What scale will the PI use when evaluating the relatedness of adverse events to the study 
participation?   
 
__X__The PI will determine the relationship of adverse events to the study 
 using the following scale: 
 
Related:      
 
AE is clearly related to the intervention 
Possibly related: 
AE may be related to the intervention 
Unrelated:  
 
AE is clearly not related to intervention 
 
3.5 When will recording/reporting of adverse events/unanticipated problems begin? 
 
__X__After subject begins study drug/ device placement/intervention /study-related procedure/specimen 
collection 
 
3.6 When will the recording/reporting of adverse events/unanticipated problems end? 


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_____End of study drug/device/intervention/participation  
_____30 days post study drug/device/intervention 
__X__Subject completes intervention and follow up period of protocol 
 
3.7 How will Adverse Events, Unanticipated Problems, Protocol Violations and Data Breaches be 
reported?  Complete the table below to answer this question 
 
Type of Event 
To whom will it 
be reported: 
Time Frame for 
Reporting 
How reported? 
Any internal event resulting in 
death that is deemed 
DEFINITELY related to 
(caused by) study participation 
An internal event is one that 
occurs in a subject enrolled in a
UVa protocol 
IRB-HSR 
Within 24 hours 
IRB Online and phone call 
 
www.irb.virginia.edu/ 
 
Internal, Serious, related and 
Unexpected adverse event  
 
  
IRB-HSR 
Within 7 calendar days 
from the time the 
study team received 
knowledge of the 
event. 
 
Timeline includes 
submission of signed 
hardcopy of AE form. 
IRB Online 
 
www.irb.virginia.edu/ 
 
Unanticipated Problems that are
not adverse events or protocol 
violations  
This would include a Data 
Breach.   
IRB-HSR 
 
 
Within 7 calendar days 
from the time the 
study team received 
knowledge of the 
event.  
Unanticipated Problem report 
form.  
 
http://www.virginia.edu/vp
rgs/irb/HSR_docs/Forms/R
eporting_Requirements-
Unanticipated_Problems.d
oc ) 
Protocol Violations 
 (The IRB-HSR only requires 
that MAJOR violation be 
reported, unless otherwise 
required by your sponsor, if 
applicable.) 
 
Or  
 
Enrollment Exceptions 
See definition- only allowed if 
there is a commercial sponsor 
or a DSMB that has granted the
enrollment exception.  
IRB-HSR 
 
 
Within 7 calendar days 
from the time the 
study team received 
knowledge of the 
event.  
 
Protocol Violation and 
Enrollment Exception Reporting 
Form 
 
 
http://www.virginia.edu/vp
rgs/irb/hsr_forms.html 
 
Go to 3rd bullet from the 
bottom. 
  


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Data Breach  
The UVa 
Corporate 
Compliance and 
Privacy Office, a 
 
 
ITC:  if breach 
involves  electronic 
data-  
 
 
 
UVa Police if 
breach includes 
such things as 
stolen computers.  
As soon as possible 
and no later than 24 
hours from the time 
the incident is 
identified. 
 
As soon as possible 
and no later than 24 
hours from the time 
the incident is 
identified. 
IMMEDIATELY.  
 
 
UVa Corporate Compliance and 
Privacy Office- Phone 924-9741 
 
 
 
 
ITC:  Information Security 
Incident Reporting procedure,  
http://www.itc.virginia.edu/secur
ity/reporting.html 
 
 
Phone- (434) 924-7166 
  
UVa PI HELD IND 
Type of Event 
To whom will it 
be reported: 
Time Frame for Reporting 
How reported? 
Life-threatening and/or fatal 
unexpected events related or 
possibly related to the use of 
the investigational agent. 
FDA 
Within 7 calendar days of 
the study team learning of 
the event 
Form FDA 3500A (MedWatch) 
or narrative 
Serious, unexpected and 
related or possibly related 
adverse events 
FDA 
Within 15 calendar days 
after the study team 
receives knowledge of the 
event 
Form FDA 3500A (MedWatch) 
or narrative 
All adverse events 
FDA 
Annually 
IND annual report 
 
 
Reporting of serious adverse events  
Investigators and other site personnel must inform the FDA, via a MedWatch/AdEERs form, of any serious or 
unexpected adverse events that occur in accordance with the reporting obligations of 21 CFR 312.32, and will 
concurrently forward all such reports to AZ.  A copy of the MedWatch/AdEERs report must be faxed to 
AstraZeneca at the time the event is reported to the FDA.  It is the responsibility of the investigator to compile 
all necessary information and ensure that the FDA receives a report according to the FDA reporting requirement 
timelines and to ensure that these reports are also submitted to AstraZeneca at the same time. 
When reporting to AstraZeneca, a cover page should accompany the MedWatch/AdEERs form indicating the 
following: 
• 
Investigator Sponsored Study (ISS) 
• 
The investigator IND number assigned by the FDA 
• 
The investigator’s name and address 
• 
The trial name/title and AstraZeneca ISS reference number 
Investigative site must also indicate, either in the SAE report or the cover page, the causality of events in 
relation to all study medications and if the SAE is related to disease progression, as determined by the principal 


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investigator. Send SAE report and accompanying cover page by way of fax to AstraZeneca’s designated fax 
line: 1-866-984-7229.Serious adverse events that do not require expedited reporting to the FDA need to be 
reported to AstraZeneca preferably using the MedDRA coding language for serious adverse events.   
In the case of blinded trials, AstraZeneca will request that the Sponsor either provide a copy of the 
randomization code/ code break information or unblind those SAEs which require expedited reporting. 
All SAEs have to be reported to AstraZeneca, whether or not considered causally related to the investigational 
product.  All SAEs will be documented.  The investigator is responsible for informing the IRB and/or the 
Regulatory Authority of the SAE as per local requirements. 
 
Serious adverse events that do not require expedited reporting to the FDA need to be reported to AstraZeneca 
on a quarterly basis preferably using the MedDRA coding language for serious adverse events.  
 
4.    How will the endpoint data be collected/recorded.  
_____Protocol specific case report forms  
__X__Source documents 
5. Data and Safety Oversight Responsibility 
 
5.1. Who is responsible for overseeing safety data for this study ?  
 
__X__No additional oversight body other than PI at UVa Skip question 5.2 
 
5.2. What is the composition of the reviewing body and how is it affiliated with the sponsor? N/A   
 
5.3. What items will be included in the aggregate review conducted by the PI?  
 
__X___All adverse events 
_X____Unanticipated Problems 
_X____Protocol violations 
_X____Audit results 
_____Application of dose finding escalation/de-escalation rules  
These should be outlined under 2.4. 
_____Application of study designed stopping/decision rules 
_____Early withdrawals 
_X___Whether the study accrual pattern warrants continuation/action 
_____Endpoint data 
 
5.4 How often will aggregate review occur? 
For additional information on aggregate review see: 
www.virginia.edu/vpr/irb/hsr/continuations.html#aggreview 
__X__Annually 
 
5.5. How often will a report, regarding the outcome of the review by the DSMB/DSMC, be sent to 
the UVa PI? 


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A copy of these reports must be sent to the IRB if applicable as soon as they are received by the PI.  
Do not wait until the next continuation to submit them to the IRB.   
__X__NA- PI is the overall person overseeing the safety data for this study.     
 
5.6. How will a report of the information discussed in question 5.4 OR 5.5 be submitted to the 
IRB?   
 
__X__Part of IRB-HSR continuation status form 
Payment 
What is the difference between compensation and reimbursement? 
A reimbursement is used when the subject is paid back for travel expenses such as mileage, lodging, food while 
traveling. Receipts or mileage must be submitted for a reimbursement.  
Compensation is "payment" for things such as time, discomfort, inconvenience. 
Total possible compensation should reflect the true value of the total possible dollar amount per participant for 
one year involvement in the study whether it be cash, check, gift card, goods, etc. or a combination of these 
items. 
 
Retention “Gifts”- gifts may be given to a subject periodically during the study to remind them they are in the 
study.  Sponsors may provide such items as water bottles, birthday cards etc. to the subject.  NOTE:  Cash or 
gift cards are NOT allowed as retention items.  
 
1.  Are subjects being reimbursed for travel expenses (receipts /mileage required)?No 
 
2.  Are subjects compensated for being in this study? 
 
Yes 
2a. What is the maximum TOTAL compensation to be given over the duration of the protocol? 
$415.00 
 
2b. Explain compensation to be given. 
• For the screening visit subjects will be compensated $25.00 due to length of time necessary to 
complete this visit.  
• For the first 6 months of study participation, when subjects are on ticagrelor or placebo (visit 1 to 
visit 12) subjects will be compensated $25.00 for their time in completing these visits. 
• For the last 6 months of study participation, when study subjects will not be taking ticagrelor or 
placebo subjects will be compensated $15.00 for their time in completing these visits. 
  
2c. Is payment pro-rated (e.g. some compensation is given even if subjects do not complete the 
entire study)? 
Subjects will be compensated for all visits that they complete.  
If No, explain why payment cannot be pro-rated.   
 
2d.  Is money paid from UVa or State funds (including grant funds) or will items such as gift cards 
be distributed through UVa? 


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Yes 
 
2d(i).  How will the researcher compensate the subjects? 
__X___Check issued to participant via UVA Oracle or State system  
 
2d(ii).  Which category/ categories best describes the process of compensation?  
 
__X___ All compensation will be made via check issued to participant via UVA Oracle 
or State system  
Risk/ Benefit Analysis 
 
1.  What are the potential benefits for the participant as well as benefits which may accrue to society in 
general, as a result of this study? 
The main renal replacement therapy for End stage renal disease (ESRD) in USA is hemodialysis (HD).  A 
functioning vascular access is crucial for HD. However, vascular-access failure (VAF) is common and is a 
major source of complications. Complications of the vascular access, particularly stenosis and thrombosis, 
continue to remain the Achilles' heel of HD therapy and lead to extensive morbidity in HD patients. VAF is the 
most common reason for hospitalization among HD patients. The economic burden of VAF is estimated at 
greater than 1 billion dollars per year and continues to grow. 
Ticagrelor (Brilinta) is a new drug approved for use in patients with acute coronary syndrome to reduce the rate 
of thrombotic cardiovascular events.  If Ticagrelor is shown to be safe and is efficacious in preserving patency 
of hemodialysis vascular access (Arterio-Venous Fistulae) better than Placebo, it will be an addition to our 
armamentarium that and will improve patients' lives, quality of lives as well as a potential big impact on 
lowering the cost burden of HD patients, by avoiding frequent interventions to restore patency to a stenosed 
AVF. 
 
2.  Do the anticipated benefits justify asking subjects to undertake the risks?   
The drug, Ticagrelor (Brilinta), is FDA approved for patients with acute coronary syndrome and thus has an 
acceptable safety profile. The potential benefit of the drug such as minimizing the interventions for stenosed 
AVF, decreasing hospitalization for fistulae-related admissions, outweigh the potential risk. Safety precautions 
such as frequent monitoring of the patients by the Principal Investigator and obtaining periodic laboratory data 
will minimize any potential risks 
Bibliography 
1- Feldman HI, Kobrin S, Wasserstein A: Hemodialysis vascular access morbidity. J Am Soc Nephrol 7:523–
535, 1996 
2-US Renal Data System: Excerpts from the USRDS 1999 annual data report. Am J Kidney Dis 34:s40–s62, 
1999 
3- Woods JD, Port FK: The impact of vascular access for haemodialysis on patient morbidity and mortality. 
Nephrol Dial Transplant 12:657– 659, 1997 
4- Winsett OE, Wolma FJ: Complications of vascular access for hemodialysis. South Med J 78:513—517, 1985  
5-Beathard GA, Arnold P, Jackson J, et al., Physician Operators Forum of RMS Lifeline. Aggressive treatment 
of early fistula failure, Kidney Int, 2003;64:1487–94. 
6-Khan FA, Vesely TM, Arterial problems associated with dysfunctional hemodialysis grafts: Evaluation of 
patients at high risk for arterial disease, J Vasc Interv Radiol, 
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7-Asif A, Gadalean FN, Merrill D, et al., Inflow stenosis in arteriovenous fistulas and grafts:A multicenter, 
prospective study, Kidney Int, 2005;67:1986–92. 
8-http://www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_uptoc.html 
Accessed 9/1/13 
9- Gro¨ntoft KC, Mulec H, Gutierrez A, Olander R. Thromboprophylactic effect of ticlopidine in arteriovenous 
fistulas for haemodialysis. Scand J Urol Nephrol 1985; 19:55-7 
10- Gro¨ntoft KC, Larsson R, Mulec H, Weiss LG, Dickinson JP. Effects of ticlopidine in AV-fistula surgery in 
uremia. Scand J Urol Nephrol 1998; 32: 276–83. 
11-Yevzlin AS, Conley EL, Sanchez RJ, Young HN, Backer BN. Vascular access outcomes and medications 
use: a USRDS study. Semin Dial 2006; 19: 535 
12- Fickerstrand CE, Thompson IW, Burnet ME, Williams P, Anderton JL. Double-blind randomized trial of 
the effect of ticlopidine in 
arteriovenous fistulas for hemodialysis. Artif Organs 1985; 9: 61–3.  
13-Sreedhara R, Himmilfarb J, Lasarus JM, Hakim RM. Anti-platelet therapy in graft thombosis: results of a 
prospective, randomized, double-blind study. Kindey Int 1994; 45: 1477–83. 
14-Dixon BS, Beck GJ, Vazquez MA et al. Effect of dipyridamole plus aspirin on hemodialysis graft patency. 
N Engl J Med 2009; 360: 2191–201.  
15-Kooistra MP, Van Es A, Marx JJM, Hertsig MLA, Struyvenberg A. Low-dose aspririn does not prevent 
thrombovascular accidents in low-risk haemodialysis patients during treatment with recombinant human 
erythropoietin. Nephrol Dial Transplant 1994; 9: 
1115–20. 
16 Andrassy K, Malluche H, Bornefeld H et al. Prevention of p.o. clotting of av. Cimino fistulae with 
acetylsalicyl acid. Results of a prospective double blind study. Klin Wochenschr 1974; 52: 348–9. 
17-Kaufman JS, O’Connor TZ, Zhang JH et al. Randomized controlled trial of clopidogrel plus aspirin to 
prevent hemodialysis access graft thrombosis. J Am Soc Nephrol 2003; 14: 2313–21. 
18- Trimarchi J, Young P, Forrester M, Schropp J, Pereyra H, Freixas E. Clopidogrel diminishes hemodialysis 
access graft thrombosis. Nephron Clin Pract 2006; 102: c128–32. 
19-Dember LM, Beck GJ, Allon M et al. Effect of clopidogrel on early failure of arteriovenous fistulas for 
hemodialysis. A randomized controlled trial. JAMA 2008; 299: 2164–71. 
     20-Coleman CI, Tuttle LA, Teevan C, Baker WL, White CM, Reinhart KM.    Antiplatelet   
      agents for the prevention of arteriovenous fistula and graft thrombosis:   a meta analysis.  
       CI Int J Clin Pract 2010; 64 (9):1239-1244, 
    21-An algorithm for the physical examination of early fistula failure Semin Dial 2005 18(4):   
         331-335 
APPENDIX:  Legal/Regulatory 
Recruitment 
The following procedures will be followed: 
• Finders fees will not be paid to an individual as they are not allowed by UVa Policy 
• All recruitment materials will be approved by the IRB-HSR prior to use.  They will be submitted to 
the IRB after the IRB-HSR has assigned an IRB-HSR # to the protocol. 
• Only those individuals listed as personnel on this protocol will recruit and or conduct the consenting 
process with potential subjects.  
 
Retention Incentives 


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Any item used by the sponsor/ study team to provide incentive to a subject to remain in the study, other than 
compensation identified in the Payment section, will be submitted to the IRB for review prior to use.  The IRB-
HSR will provide the study team with a Receipt Acknowledgement for their records.  Retention incentive items 
are such things as water bottles, small tote bags, birthday cards etc.  Cash and gift cards are not allowed as 
retention incentives.  
 
Clinical Privileges 
The following procedures will be followed:  
• Investigators who are members of the clinical staff at the University of Virginia Medical Center must 
have the appropriate credentials and been granted clinical privileges to perform specific clinical 
procedures whether those procedures are experimental or standard.  
• The IRB cannot grant clinical privileges.   
• Performing procedures which are outside the scope of the clinical privileges that have been granted 
may result in denial of insurance coverage should claims of negligence or malpractice arise. 
• Personnel on this protocol will have the appropriate credentials and clinical privileges in place before 
performing any procedures required by this protocol.  
• Contact the Clinical Staff Office- 924-9055 or 924-8778 for further information. 
 
Sharing of Data/Specimens 
Data and specimens collected under an IRB approved protocol are the property of the University of Virginia.  
You must have “permission” to share data/ specimens outside of UVa other than for a grant application and or 
publication.  This “permission” may come in the form of a contract with the sponsor or a material transfer 
agreement (MTA) with others.  A contract/ MTA is needed to share the data outside of UVa even if the data 
includes no HIPAA identifiers and no code that could link the data back to a HIPAA identifier.   
• No data will be shared outside of UVa, beyond using data for a grant application and or publication, 
without a signed contract/MTA approved by the SOM Grants and Contracts office/ OSP or written 
confirmation that one is not needed. 
• No specimens will be shared outside of UVa without a signed contract/MTA approved by the SOM 
Grants and Contracts office/ OSP or written confirmation that one is not needed. 
 
Prisoners 
If the original protocol/ IRB application stated that no prisoners would be enrolled in this study and 
subsequently a subject becomes a prisoner, the study team must notify the IRB immediately.  The study team 
and IRB will need to determine if the subject will remain in the study.  If the subject will remain in the study, 
the protocol will have to be re-reviewed with the input of a prisoner advocate.  The prisoner advocate will also 
have to be involved in the review of future continuations, modifications or any other reporting such as protocol 
violations or adverse events.   
 
Prisoner- Individuals are prisoners if they are in any kind of penal institution, such as a prison, jail, or juvenile 
offender facility, and their ability to leave the institution is restricted. Prisoners may be convicted felons, or may 
be untried persons who are detained pending judicial action, for example, arraignment or trial. 
For additional information see the OHRP website at  http://www.hhs.gov/ohrp/policy/populations/index.html 
APPENDIX:  Recruitment 
Recruitment includes identifying, review of records to determine eligibility or any contact to determine a 
potential subjects interest in the study. 
 


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*The UVa HIPAA covered entity is composed of the  UVa VP Office of Research, the Health System, School 
of Medicine, School of Nursing, the Sheila C. Johnson Center, the Exercise and Sports Injury Laboratory 
and the Exercise Physiology Laboratory.   
 
1. How do you plan to identify potential subjects? 
To "identify" a potential subject refers to steps you plan to take to determine which individuals 
would qualify to participate in your study. This does NOT include steps to actually contact those 
individuals. 
If your study involves more than one group of subjects (e.g. controls and cases or subjects and 
caregivers) note below which groups are being identified by the given method.  
 
a. _X___ Chart Review/ Clinic Schedule Review/ Database Review from a database 
established for health care operations (departmental clinical database) or quality 
improvement. 
 
DHHS: Study team requests Waiver of Consent to identify potential subjects.  
 
HIPAA- Allowed under Preparatory to Research if PHI to be accessed.  
IMPORTANT 
Keep in mind that PHI in the medical record may only be accessed by individuals 
who work under the UVa HIPAA covered entity; which means they meet one of 
the following criteria: 
 a UVa student working in the UVa HIPAA Covered Entity*   
 a faculty  or staff member in a PAID appointment in  the UVA HIPAA 
Covered Entity* 
b. ____ Review of a database that was established to keep data to be used for future 
research such as the CDR, departmental research database or use of data from a separate 
current active research protocol.     
DHHS: Study team requests Waiver of Consent to identify potential subjects. 
HIPAA- Allowed under Preparatory to Research if PHI to be accessed.  
IMPORTANT 
Keep in mind that PHI in the medical record may only be accessed by 
individuals who work under the UVa HIPAA covered entity; which means 
they who meet one of the following criteria: 
 a UVa student working in the UVa HIPAA Covered Entity*   
 a faculty  or staff member in a PAID appointment in  the UVA HIPAA 
Covered Entity* 
NOTE:  The information from which you are obtaining potential subjects must 
also have an IRB protocol approval.  
IRB# ________________ 
If obtaining information from the Clinical Data Repository (CDR) insert IRB # 10797. 
c. ____ Patients UVa health care provider supplies the UVa study team with the patients 
contact information without patients knowledge.  
DHHS: Study team requests Waiver of Consent to identify potential subjects.  


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HIPAA- Allowed under Preparatory to Research if PHI will be shared by the health care 
provider.  
IMPORTANT 
Keep in mind that PHI may only be given to individuals who work under the UVa 
HIPAA covered entity; which means they meet one of the following criteria: 
 a UVa student working in the UVa HIPAA Covered Entity*   
 a faculty  or staff member in a PAID appointment in  the UVA HIPAA 
Covered Entity* 
d. ____ Patient obtains information about the study from their health care provider.  The 
patient contacts the study team if interested in participating.  
DHHS:  NA 
HIPAA:  Allowed under Health Care Operations 
If this choice is checked, check 3d-INDIRECT CONTACT below.  
e. ____ Potential subjects will not be directly identified. They will respond to an 
advertisement such as a flyer, brochure etc.   
If this choice is checked, check 3d- INDIRECT CONTACT below.  
DHHS & HIPAA:  NA 
f. _____  Potential subjects have previously  signed a consent to have their name in a 
registry/database to be contacted for future studies of this type.   
IRB#  of registry/ database:  ________________ 
DHHS & HIPAA:  NA 
 
If item # a, b or c is checked above and if this protocol involves the use of protected health 
information you confirm the following to be true: 
• The use or disclosure is sought solely to review protected health information as necessary 
to prepare the research protocol or other similar preparatory purposes. 
• No PHI will be removed from the UVa covered entity. 
• The PHI that the researcher seeks to use or access is necessary for the research purposes. 
Yes 
 
2. How will potential subjects be contacted? 
To "contact" a potential subjects refers to the initial contact you plan to take to reach a potential 
subject to determine if they would be interested in participating in your study.  This may include 
direct contact by such methods as by letter, phone, email or in-person or indirect contact such as 
the use of flyers, radio ads etc.  
If your study involves more than one group of subjects (e.g. controls and cases or subjects and 
caregivers) note below which groups are being contacted by the given method.    
 
a.____Direct contact of potential subjects by the study team via letter, phone, direct e-
mail. Members of study team ARE NOT health care providers of patients.  Information 
will not be collected from psychotherapy notes.  
Note:  Letter, phone, direct email scripts must be approved by IRB prior to use.  
See IRB-HSR Website for templates. 
 


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DHHS/HIPAA: Study team requests a Waiver of Consent and Waiver of 
HIPAA Authorization to contact potential subjects.  
IMPORTANT:   
Keep in mind that if PHI was collected during the identification phase that 
contact with potential subjects may only be performed by individuals who work 
under the UVa HIPAA covered entity; which means they meet one of the following 
criteria: 
 a UVa student working in the UVa HIPAA Covered Entity*   
 a faculty  or staff member in a PAID appointment in  the UVA HIPAA 
Covered Entity* 
b._X___Potential subjects will be approached while at UVa Hospital or Health Clinic by 
a person who is NOT a member of their health care team.  Information will not be 
collected from psychotherapy notes.  
 
DHHS & HIPAA: Study team requests a Waiver of Consent and a Waiver of 
HIPAA Authorization to contact potential subjects.  
 
IMPORTANT:   
Keep in mind that contacting individuals in a clinical setting may only be 
performed by individuals who work under the UVa HIPAA covered entity; which 
means they  meet one of the following criteria: 
 a UVa student working in the UVa HIPAA Covered Entity*   
 a faculty  or staff member in a PAID appointment in  the UVA HIPAA 
Covered Entity* 
You should share the following information with the potential subject:  
1. Your name 
2. Who you are:  physician, nurse etc. at the University of Virginia.    
3. Why you want to speak with them 
4. Ask if you have their permission to explain the study to them 
5. If asked about how you obtained their information use one of the following 
as an option for response.     
• DO NOT USE THIS RESPONSE UNLESS YOU HAVE OBTAINED 
PERMISSION FROM THEIR UVa PHYSICIAN:   
Your doctor, Dr. insert name wanted you to be aware of this research 
study and gave us permission to contact you.    
• We obtained your information from your medical records at UVa.   
Federal regulations allow the UVa Health System to release your 
information to researchers at UVa, so that we may contact you regarding 
studies you may be interested in participating.  We want to assure you that 
we will keep your information confidential.  
IF THE PERSON SEEMS ANGRY, HESITANT OR UPSET, THANK THEM 
FOR THEIR TIME AND DO NOT ENROLL THEM IN THE STUDY.  YOU 
MAY ALSO REFER THEM TO THE IRB-HSR AT 924-9634. 


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c._X___Direct contact of potential subjects by the study team by approaching in person 
at UVa or via letter, phone, direct e-mail. Members of study team contacting potential 
subjects ARE health care providers of patients.  
If you are not approaching them in person but using a letter, phone call or direct 
email please note that the letter, phone, direct email scripts must be approved by 
IRB prior to use.  See IRB-HSR Website for templates. 
DHHS:  Study team requests a Waiver of Consent to contact potential subjects 
HIPAA:  Allowed under Health Care Operations.  
 
d.____ Indirect contact (flyer, brochure, TV, broadcast emails, patient provided info 
about the study from their health care provider and either the patient contacts study team 
or gives their healthcare provider permission for the study team to contact them.) 
The indirect method used (flyer, brochure, TV, broadcast emails) must be approved by 
the IRB prior to use.    The IRB does not need to review any type of script to use when the 
potential subject responds to the indirect method.   
 
DHHS & HIPAA:  NA 
 
e. ____  Potential subjects are not patients.  The study does not include obtaining 
subjects health information.   Subjects will be contacted directly via email, phone, 
letter or presentation in group setting with consent then obtained individually in a 
private setting.  
If you are not approaching them in person but using a letter, phone call or direct 
email please note that the letter, phone, direct email scripts must be approved by IRB 
prior to use.   
See IRB-HSR Website for templates. 
DHHS: Study team requests a Waiver of Consent to contact potential subjects.  
HIPPA:  NA 
 
3. Will any additional information be obtained from a potential subject during "prescreening"?   
No  
 
4. Do you plan to ask the subjects to do anything, other than answering questions, for the study 
prior to signing a consent? No 
 
5. How will the consenting process take place with either the prospective subject, the subject’s 
legally authorized representative or parent/legal guardian of a minor ( if applicable)?    
Patients who appear to meet inclusion/exclusion criteria (chart pre-review), and also, express interest 
in participation, will be approached by an investigator or study coordinator to discuss the informed 
consent process.  Unless the patient states preference to review the document the day of initial 
contact, then a copy of the informed consent document will be provided to the patient, and 
arrangements made for the coordinator or investigator to meet the patient at a future date/time to 
review the document.  Patients will be encouraged to take the consent home to share with family 
members, and also instructed to write down any questions they wish to have addressed.  The meeting 
to review the document will take place at a time designated as convenient by the patient.  Each 
section of the informed consent document will be reviewed with the patient, and the consent 
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participate, then he/she will sign the informed consent.  The research team member obtaining 
consent will sign the document, too.  Patients who consent will be given a copy of their signed 
informed consent. The consent process will be documented.  
 
6. Will subjects sign a consent form for any part of the study?  
Yes 
 
7.  Will the study procedures be started the same day the subject is recruited for the study?  
No 
 
8.  Is there the potential to recruit economically or educationally disadvantaged subjects, or other 
vulnerable subjects such as students or employees?Yes 
 If yes, what protections are in place to protect the rights and welfare of these subjects so 
that any possible coercion or undue influence is eliminated?   
Study staff will inform the subject that participation is voluntary and choosing not to participate 
will not affect their care, their status as a student or employee at UVA. 
 
9. Do you need to perform a “dry run” of any procedure outlined in this protocol?    
No 
APPENDIX:  Drug Information 
 
1   What is the drug name, manufacturer and IND# if available?    
Drug Name: Ticagrelor (Brilinta) and Placebo, Manufacturer: Astra Zeneca 
IND exempt notification from FDA on file 
2.   If IND application has been submitted to the FDA, who is the Principal Investigator on the IND?     
Emaad Abdel-Rahman, MD 
 
3.  What is the phase or stage of this study?    
Pilot 
APPENDIX:  Pharmacy-Investigational Drugs/Biologics  
 
1.   What is the name of the investigational drug/biologic?    
Brilinta® (ticagrelor)  
 
2. Where will the subjects be seen for the administration/dispensing of the drug?     
__X___  Outpatient Unit:  specify: The study drug will be given to dialysis patients at their regularly 
scheduled dialysis treatment on the 5th floor of the West Complex in the Dialysis Unit 
 
3.  What dose will be utilized in this study?    
Brilinta® (ticagrelor) - 90mg  
 
4. What will be the frequency of dosing in this study?    
Twice a day 
 
5.  What will be the duration of dosing in this study?    
6 months 
 
6.  What route of administration will be utilized?    


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Oral 
 
7.  Will drug need to be prepared by the UVa Investigational Drug Service (IDS)?     
_____  YES 
__X__  NO- Drug will be prepared and/or administered per package insert 
 
8.  Are there any special handling instructions mandated by the study (e.g. weighing hazardous 
materials)?    
No 
 
9.  Does the protocol provide provisions for dose titration, dose reductions, and or re-challenged (if drug 
is stopped), etc.?    
No 
 
10.  How will missed doses be handled?     
If a subject misses a dose we will document the missed dose and the subject will not replace the dose 
that was missed.  
 
11.  Will a comparator (active or placebo) be utilized in the protocol?    
Yes 
 
►IF YES, comparator is: 
__X___  Placebo: The placebo medication will be identical in appearance to the active study 
medication.   
 
12.  Does this study involve research on a drug, biologic, supplement or food additive?     
Yes 
 
►IF YES, is this study investigator initiated?    
 
If yes, answer questions # 13 and 14 
 
If no, answer question # 13 only. 
Yes 
 
13    Are you using a drug/supplement/food additive in a manner not approved by the FDA?     
Yes 
 
IF YES, answer questions 13a-13f 
You may reference the non-IRB protocol to answer these questions. 
 
13a.  Describe pertinent animal data that is available regarding the toxicity/safety of this drug.    
See section 1 and section 4 of the investigator brochure 
 
13b. Describe pertinent human data that is available regarding the toxicity/safety of this drug.    
See section 1 and section 14 of the investigator brochure 
 
13c. Have there been any human deaths associated with this drug?    
No 
 
13d. In how many humans has this drug been used previously?    


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This is an approved drug for use in patients with acute coronary syndrome (ACS) (unstable 
angina, non-ST elevation myocardial infarction, or ST elevation myocardial infarction) 
 
13e. If this protocol will be used in children describe any previous use of this drug with children of 
a similar age range.    
N/A 
 
14.  Do the following criteria apply? Check all that apply 
 
_____  The investigation is intended to be reported to FDA as a well-controlled study in support of a 
new indication for use or intended to be used to support any other significant change in the labeling for 
the drug; 
 
_____  If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, 
the investigation is intended to support a significant change in the advertising for the product; 
 
__X__  The investigation does involve a route of administration or dosage level or use in a patient 
population or other factor that significantly increases the risks (or decreases the acceptability of the 
risks) associated with the use of the drug product.  
 
__X__  The investigation will be conducted in compliance with the requirements for institutional review 
set part in part 21CFR56 and with the requirements for informed consent set forth in part 21CFR50 ; and   
This item must be checked. 
 
__X__ The investigation will be conducted in compliance with the requirements of 21CFR312.7 
(Promotion and charging for investigational drugs) 
 This item must be checked. 
 
15.  Is this a post-marketing study?       
 
No 
APPENDIX:  Privacy Plan for Studies With Consent 
1.  Answer the questions below (1a-1e) to describe your/central registry’s plan to protect the 
identifiable data from improper use and disclosure.   
 
1a.  How will data be stored? 
__X___  Data, which may include health information, or other highly sensitive data will 
be stored with HIPAA identifiers.   
 
1b. Will specimens be stored by the UVa study team? No 
 
1c.  Will any of the data be stored electronically by the UVa study team? 
 
Yes 
►IF YES, will it include any HIPAA identifiers with health information or other 
highly sensitive data? 
 
►IF YES, where will it be stored?  
__X___  a Health Systems Computing Services (HS/CS) managed server that is 
configured to store data regulated by HIPAA. 
 


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1d. Will any of the data be collected or stored in hard copy format by the UVa study team 
(e.g.- on paper) ?  Yes 
►IF YES, where will it be stored?  
 
__X___ case report forms will be stored in a secure area with limited access.  
 
1e.  The following procedures will also be followed.  
• Only investigators for this study and clinicians caring for the patient will have access 
to the data.  They will each use a unique log-in ID and password that will keep 
confidential.  
• Each investigator will sign the University’s Electronic Access Agreement forward the 
signed agreement to the appropriate department as instructed on the form. 
If you currently have access to clinical data it is likely that you have already signed 
this form.  You are not required to sign it again.  
• UVa Institutional Data Protection Standards will be followed 
http://itc.virginia.edu/security/dataprotection.  Identifiable data is considered to be   
“Highly Sensitive”.  A Limited Data Set is usually considered to be “Moderately 
Sensitive” and de-identified data is usually considered to be “Not Sensitive”.   
• If identifiable data (data with health information and HIPAA identifiers) is transferred 
to any other location such as a desktop, laptop, memory stick, CD etc. the researcher 
must follow the University’s  “Electronic Storage of Highly Sensitive Data Policy”. 
Additional requirements may be found in the Universities Requirements for Securing 
Electronic Devices.  
• If identifiable health information is taken away from the UVa Health System, Medical 
Center Policy # 0218 will be followed.  
• The data will be securely removed from the server, additional computer(s), and 
electronic media according to the University's Electronic Data Removal Policy.  
• The data will be encrypted or removed if the electronic device is sent outside of UVa 
for repair according to the University's Electronic Data Removal Policy. 
• If PHI will be faxed, researchers will follow the Health System Policy # 0194.     
• If PHI will be emailed, researchers will follow the Health System Policy # 0193 and 
UVa Institutional Data Protection Standards . 
• The data may not be analyzed for any other study without additional IRB approval.  
• If you are using patient information you must follow Health System Policy  # 0021. 
 
Summary of Requirements to Comply with UVa Health System, Medical Center and 
University Policies and Guidance as noted above: 
 
Highly Sensitive Data is: 
-personal information that can lead to identify theft if exposed or 
-health information that reveals an individual’s health condition and/or history of health services 
use.  
 
PHI- a type of Highly Sensitive Data, is health information combined with a HIPAA identifier 
 


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• LIMIT- Limit the HIPAA identifiers to the minimal amount needed- e.g. use initials 
instead of name, use a code instead of initials, limit amount/type of health information 
collected, and collect and share only those items you state you will in this protocol.  
• SECURE- Secure Highly Sensitive Data 
o Because single-use electronic devices and media, such as desktops, laptops, memory 
sticks, CDs, smartphones etc., can be easily lost or stolen, the University strictly 
limits the circumstances under which Highly Sensitive Data may be stored on them. 
In accordance with the University’s Electronic Storage of Highly Sensitive Data 
Policy, you must obtain written approval from your Department AND VP or Dean 
prior to moving data to single use devices or media by using the Highly Sensitive 
Data Storage Request Form. 
  You additionally are responsible for applying all security safeguards covered 
in that policy, including but not limited to password protecting and encrypting 
any document on a single access electronic device.  
 If you use your smartphone to send email and your phone is not managed was 
not purchased and/or set up for you by the Health System, you cannot send 
Highly Sensitive Data via email.   
 In addition, do not use Outlook Web to send your email if it contains 
sensitive data.   
 Also, you are not allowed to auto forward your email to outside email 
systems like Gmail or Yahoo.   
 Do not save any email attachment containing Highly Sensitive Data to 
a single use device.   
 You are allowed to access Highly Sensitive Data stored on the University or 
Health Systems network via a VPN, however you cannot download any of the 
information onto your desktop or laptop. 
 Store files containing Highly Sensitive Data on a network drive specifically 
designated for storing this type of data, e.g. high-level security servers 
managed by Information Technology Services or the “F” and “O” managed 
by Heath Systems Computing Services.  You may access it via a shortcut icon 
on your desktop, but you are not allowed to take it off line to a local drive.  
 If data will be collected and/or viewed via a website, it is critical that the 
website and associated data file are set up in a highly secured manner. Do not 
attempt without assistance from:  
University Side:    ITCmicrosystems@virginia.edu 
Health System:   Web Development Center:   (434-243-6702) 
o Encrypt any electronic file containing Highly Sensitive Data that is not on a network 
drive specifically designated for this purpose.  . See encryption solutions guidance.  
o Password protect any electronic device containing Highly Sensitive Data. 
o Lock up hard copies of Highly Sensitive Data. 
• PROTECT- Protect Highly Sensitive Data 
o Do not leave a hard copy file open on your desk when not using it and secure your 
computer when not attended. 
o Have discussions in private. 
o If you lose Highly Sensitive Data, you must report it in accordance with the 
Information Security Incident Reporting Policy. 


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o Do not share Highly Sensitive Data with those not on the study team or those who 
do not have a need to know. 
o Do not share with sponsor unless subject has already signed a consent form or 
IRB has approved waiver of consent.  
o If faxing Highly Sensitive Data within UVa 
 Verify fax numbers before faxing, and use fax cover sheets with a 
confidentiality statement.  
 If printing to a central printer, ensure that names and identifiers on the 
documents are given to the correct patient. 
o If faxing Highly Sensitive Data outside of UVa to the sponsor or CRO after the 
subject has signed consent:  
 the receiving fax machine is in a restricted-access location,  
 the intended recipient is clearly indicated,  
 the recipient has been alerted to the pending transmission and is available 
to pick it up immediately.  
 Verify fax numbers before faxing, and use fax cover sheets with a 
confidentiality statement.  
 If printing to a central printer, ensure that names and identifiers on the 
documents are given to the correct patient. 
o Highly Sensitive Data may not be stored in a Drop Box. 
o If you plan to store data in the Cloud, you must consult with UVa Information 
Technology Services (ITS) to verify all essential security measures are in place.  
If you have a contract to use the cloud, the contract must include required security 
measures as outlined by ITS.   
o DO NOT email health information with name, medical record number or Social 
Security number to or from an email address that does not have an *HS in the 
address.  May use subject initials if within the UVa HIPAA covered entity:  The 
"UVA HIPAA covered entity" includes the hospital, health system, School of 
Medicine School of Nursing and the VP for Research Office.   
o Be aware:  PHI collected without consent/ HIPAA authorization will NOT be 
allowed to leave UVa in an identifiable form unless the disclosure is tracked with 
Health Information Services.   
o Any Highly/Moderately Sensitive Data sent outside of UVa (e.g. to sponsor) that 
was obtained under a consent must be encrypted and password protected.   
o If your electronic device is sent outside of UVa for repair, all institutional data, 
whether Highly Sensitive or not, must be either encrypted or removed.  
o If transporting Highly/Moderately Sensitive Data in paper format from one UVa 
building to another, take the following steps to protect it: 
1. Put paper inside a closed container such as a briefcase, or sealed 
envelope to limit the chance of a losing a piece. 
2. Do not leave Highly Sensitive Data unattended in a public area if it is 
not locked up.  


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o When the study is complete, all electronic files containing Highly/Moderately 
Sensitive Data must be stored on a network drive specifically designated for that 
purpose.  They may not be stored on a single use device such as a CD. 
• STOP, THINK and BE CAREFUL- 
o If this was your Highly Sensitive Data how would you want it protected?  
o There are significant monetary fines to the individual and the institution for loss 
or misuse of sensitive data. 
o Your job may also be on the line. 
 
 
2.  Describe your/central registry’s plan to destroy the HIPAA identifiers at the earliest opportunity 
consistent with the conduct of the research and in accordance with any stipulations in the research 
sponsor contract and UVa records management guidelines. 
 
__X__The HIPAA identifiers (except full dates and or address information if needed) will be destroyed 
as soon as all publications are complete.  
This wording would allow the researcher to keep HIPAA identifiers until all queries/ request for 
additional information from publisher are addressed 
 
3.  Do you confirm that you will not reuse the identifiable data (HIPAA identifiers or health information) 
or disclose any of this information to any other person or entity except as outlined in this protocol, except 
as required by law, for authorized oversight of the research study, or use it for other research unless 
approved by the IRB-HSR? Yes 
 
This means that after the study is closed at UVa: 
 
• You cannot contact the subject by any method (you cannot call them, send a letter, talk to them in 
person about the study, etc) without additional IRB approval 
• You cannot use the data for any research that is not already described in your IRB protocol 
without additional IRB approval (if you change your hypothesis you must modify your protocol)  
• You cannot share your research data with another researcher outside of your study team without 
additional IRB approval 
• Any health information with HIPAA identifiers will be shredded or discarded by using recycling 
bins for confidential material found in clinic settings.  For large item disposal of confidential 
material contact Environmental Services at 2-4976 or University Recycling at 2-5050.  
TABLE A:  HIPAA Identifiers (Limited Data Set)  
1.  Name 
2.  Postal address information, other than town or city, state, and zip code 
3.  Telephone numbers 
4  Fax numbers 
5.  Electronic mail addresses 
6.  Social Security number 
7.  Medical Record number 
8.  Health plan beneficiary numbers 
9.  Account numbers 
10.  Certificate/license numbers 
11.  Vehicle identifiers and serial numbers, including license plate numbers 
12.  Device identifiers and serial numbers 
13.  Web Universal Resource Locators (URLs) 
14.  Internet Protocol (IP) address numbers 
15.  Biometric identifiers, including finger and voice prints 
16.  Full face photographic images and any comparable images  
17.  Any other unique identifying number, characteristic, code that is derived from or related to information 


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about the individual (e.g. initials, last 4 digits of Social Security #, mother’s maiden name, first 3 letters of last 
name.) 
 
APPENDIX:  Sponsor 
Sponsor Information 
1. Explain the sponsorship for this study.  
INSTRUCTIONS:  
• List names of companies, institutes, foundations with which you have a grant or a contract from an 
entity that is not a support source.   
• Example:  This study is funded via a contract with the University of New York, which has a grant from 
the NIH to conduct this study.  We will be receiving free drug from Glaxo.  Glaxo will receive data 
prior to publication. 
• If the outside entity will be monitoring the study or receiving data prior to publication enter them as a 
sponsor.   
• If you are receiving things such as free supplies/ drug/ devices from a company   who WILL NOT be 
monitoring the study or be receiving data prior to publication do NOT enter them here- enter this 
information under Support Source below.   
Answer/Response: University of Virginia Department of Nephrology – Nephrology Clinical Research Center 
 
2. Do you confirm that you will obtain a contract/ material transfer agreement with the sponsor via the 
School of Medicine Grants and Contracts Office or the Office of Sponsored Programs (OSP) 
ospnoa@virginia.edu? 
INSTRUCTIONS: 
You should have answered YES to the following question in Protocol Builder:  
--“Do you/will you have a contract with an outside entity to support this protocol?” 
Answer/Response: N/A - departmental sponsor 
 
 
APPENDIX:  Support Source 
The support source is any source outside of UVA providing support such as supplies/drug/device’s.  Do not 
enter a company/ organization as a supply source unless the support has been secured.  The IRB-HSR must be 
notified and the consent form revised if a support source changes.  (Example-the NIH or an investigator-
initiated study in which the pharmaceutical company is providing drug free of charge.) 
 
1. Describe what will be provided and by whom.   
This study is an investigator initiated study that will be funded by Astra Zeneca. They will also be 
supplying study medication and placebo. Astra Zeneca will not be monitoring this study.  
 
2. Do you confirm that you will obtain a contract/ material transfer agreement with the provider via 
the 
Medical 
Center 
Procurement 
office 
or 
Office 
of 
Sponsored 
Programs 
(OSP) 
ospnoa@virginia.edu? yes 
You should have answered YES to the following question in Protocol Builder:  
Do you/will you have a contract with an outside entity to support this protocol? 


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Go through Medical Center Procurement if the item will be used on a patient in the Medical Center.   
Go through OSP is the item will be used outside of the Medical Center.  
 
3. Will the Support Source be obtaining data prior to publication or performing monitoring of the 
study?  
 
Astra Zeneca will not see the data prior to publication 
APPENDIX:  Transfer of Data Outside of UVa 
 
1.  What identifiers will be sent with the data?-NONE 
 
 
YES 
NO 
1.  Name 
YES 
NO 
2.  All geographic subdivisions smaller than a state, including street address, city, county, precinct, 
zip code, and their equivalent geocodes, except for the initial three digits of the zip code if, 
according to the current publicly available data from the Bureau of the Census: (1) The geographic 
unit formed by combining all zip codes with the same 3 initial digits contains more than 20,000 
people and (2) The initial 3 digits of a zip code for all such geographic units containing 20,000 is 
changed to 000.  
YES 
NO 
3.  All elements of dates (except year) for dates directly related to an individual, including birth date, 
admission date, discharge date, date of death; and all ages over 89 and all elements of dates 
(including year) indicative of such age, except that such ages and elements may be aggregated into a 
single category of age 90 or older. 
 [This means you may record the year but not record the month or day of any date related to the 
subject if the subject is under the age of 89.  In addition if the subject is over the age of 89 you may 
not record their age and  you may not record the month, day or year of any  date related to the 
subject ]  
YES 
NO 
4.  Telephone numbers 
YES 
NO 
5.  Fax numbers 
YES 
NO 
6.  Electronic mail addresses 
YES 
NO 
7.  Social Security number 
YES 
NO 
8.  Medical Record number 
YES 
NO 
9.  Health plan beneficiary numbers 
YES 
NO 
10.  Account numbers 
YES 
NO 
11.  Certificate/license numbers 
YES 
NO 
12.  Vehicle identifiers and serial numbers, including license plate numbers 
YES 
NO 
13.  Device identifiers and serial numbers 
YES 
NO 
14.  Web Universal Resource Locators (URLs) 
YES 
NO 
15.  Internet Protocol (IP) address numbers 
YES 
NO 
16.  Biometric identifiers, including finger and voice prints 
YES 
NO 
17.  Full face photographic images and any comparable images  
YES 
NO 
18.  Any other unique identifying number, characteristic, code that is derived from or related to 
information about the individual (e.g. initials, last 4 digits of Social Security #, mother’s maiden 
name, first 3 letters of last name.) 
YES 
NO 
19.  Any other information that could be used alone or in combination with other information to 
identify an individual. (e.g. rare disease, study team or company has access to the health 
information and a HIPAA identifier or the key to the code . ) 
 
2.  How will data be sent? 
 
____ Paper forms via mail/ FedEx, UPS etc.  
 
__X_ Email:  Not allowed if you have answered YES to any item above. 
                ______FAX: Not allowed unless receiving fax machine is in a restricted-access location, the intended 
recipient is clearly indicated, and that recipient has been alerted to the pending transmission and 
is available to pick it up immediately.  Also verify FAX numbers before faxing and use FAX cover 
sheet with a confidentiality statement.  


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   ____ Devices such as flashdrive/ CD etc.: 
Not allowed if you have answered YES to any item above.  
____ Web Based Data Entry (e.g website, database, registry): Not Encrypted and Password 
Protected; Not allowed if you have answered YES to any item above.  
____ Web Based Data Entry (e.g website, database, registry): Encrypted and Password Protected; 
If checked, do you confirm that you have verified with host site that data will be sent and stored 
in an encrypted fashion (e.g. via Secure FX, Secure FTP, HTTPS, PGP)?   YES 
NO 

ICF_001.pdf: