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

Randomized, Placebo-controlled, Single Blind, Trial to Determine the Safety and Efficacy of Ticagrelor for Maintaining Patency of Arterio-Venous Fistulae Created for Hemodialysis

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.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; Vascular Access Patency
• Intervention / Treatment: Drug: ticagrelor; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia - Hospital West Kidney Center Dialysis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ticagrelor; 90 mg of ticagrelor to be given orally twice a day for 6 months	Drug: ticagrelor; ticagrelor 90 mg twice a day for 6 months; Other Names: Brilinta
Placebo Comparator: Placebo; Placebo drug to be given twice a day for 6 months	Drug: Placebo; 1 pill twice a day for 6 months

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: January 8, 2015
• First Posted (Estimate): January 9, 2015

Study Record Updates

• Last Update Posted (Actual): June 8, 2022
• Last Update Submitted That Met QC Criteria: May 13, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: ticagrelor; hemodialysis; vascular access; vascular access patency; brilinta
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Renal Insufficiency; Pathological Conditions, Anatomical; Renal Insufficiency, Chronic; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Kidney Failure, Chronic; Fistula; Arteriovenous Fistula; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor
• Other Study ID Numbers: 17224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO