Determine the Safety/Efficacy of Ticagrelor for Maintaining Patency of Arterio-Venous Fistulae Created for Hemodialysis

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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End Stage Renal Disease, Vascular Access Patency

Intervention / Treatment
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* Drug: ticagrelor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients on chronic hemodialysis with a functioning arterio-venous fistula Exclusion Criteria: Recent history of bleeding over the last 3 months preceding enrollment History of bleeding disorder (hemophilia, Von Willebrandt disease, etc….) 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 Uncontrolled blood pressure (SBP> 200 or DBP >110) post dialysis History of stroke Pregnant females-self reported Hypersensitivity to Aspirin /antiplatelets Subjects using peroral anticoagulants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ticagrelor<br>90 mg of ticagrelor to be given orally twice a day for 6 months | Drug: ticagrelor<br>* ticagrelor 90 mg twice a day for 6 months<br>* Other names: Brilinta;|
| Placebo Comparator: Placebo<br>Placebo drug to be given twice a day for 6 months | Drug: Placebo<br>* 1 pill twice a day for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility and Safety of Ticagrelor in Hemodialysis Patients | Number of Participants with prolonged bleeding (>30 minutes) after removal of needles | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Efficacy of Ticagrelor to Preserve Patency of Hemodialysis Vascular Access | Percentage of participants with stenosis free survival | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemodialysis, vascular access, vascular access patency, ticagrelor, brilinta