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

• Sponsor: University of Virginia (Other)
• Overall Status: Completed
• CT.gov ID: NCT02335099
• Collaborator: AstraZeneca (Industry)
• Enrollment: 54
• Location: 1
• Arms: 2
• Actual Duration (Months): 54
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease; Vascular Access Patency	Drug: ticagrelor; Drug: Placebo	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Randomized, Placebo-controlled, Single Blind, Trial to Determine the Safety and Efficacy of Ticagrelor for Maintaining Patency of Arterio-Venous Fistulae Created for Hemodialysis
• Actual Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Feasibility and Safety of Ticagrelor in Hemodialysis Patients [6 months]

   Number of Participants with prolonged bleeding (>30 minutes) after removal of needles

Secondary Outcome Measures

1. Treatment Efficacy of Ticagrelor to Preserve Patency of Hemodialysis Vascular Access [1 year]

   Percentage of participants with stenosis free survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Virginia - Hospital West Kidney Center Dialysis	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• University of Virginia
• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 19, 2018
• Informed Consent Form - Jun 26, 2018

More Information

Publications

None provided.

• Responsible Party: Emaad Abdel-Rahman, MD, Principal Investigator, University of Virginia
• ClinicalTrials.gov Identifier: NCT02335099
• Other Study ID Numbers: 17224
• First Posted: Jan 9, 2015
• Last Update Posted: Jun 8, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Emaad Abdel-Rahman, MD, Principal Investigator, University of Virginia: hemodialysis; vascular access; vascular access patency; ticagrelor; brilinta
• Additional relevant MeSH terms: Kidney Failure, Chronic; Arteriovenous Fistula; Fistula; Ticagrelor

Study Results

Participant Flow

Pre-assignment Detail	10 of 54 consented subjects failed screening and were not assigned to the study arms.

Arm/Group Title	Treatment	Placebo
Arm/Group Description	90 mg of Ticagrelor to be given orally twice a day for 6 months	Placebo drug to be given twice a day for 6 months
Period Title: Treatment
STARTED	22	22
COMPLETED	17	17
NOT COMPLETED	5	5
Period Title: Treatment
STARTED	17	17
COMPLETED	17	16
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Treatment	Placebo	Total
Arm/Group Description	90 mg of Ticagrelor to be given orally twice a day for 6 months	Placebo drug to be given twice a day for 6 months	Total of all reporting groups
Overall Participants	17	17	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (12.4)	60.8 (10.4)	58.2 (11.6)
Sex: Female, Male (Count of Participants)
Female	3 17.6%	5 29.4%	8 23.5%
Male	14 82.4%	12 70.6%	26 76.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 64.7%	13 76.5%	24 70.6%
White	6 35.3%	4 23.5%	10 29.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	90 mg of Ticagrelor to be given orally twice a day for 6 months	Placebo drug to be given twice a day for 6 months
Measure Participants	17	17
Count of Participants [Participants]	1 5.9%	3 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.77
	Confidence Interval	(2-Sided) 95%; 0.27 to 217.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	90 mg of Ticagrelor to be given orally twice a day for 6 months	Placebo drug to be given twice a day for 6 months
Measure Participants	17	17
Number (95% Confidence Interval) [percentage of participants]	72.2 424.7%	75.0 441.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.23 to 3.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	1 year
Arm/Group Title	Treatment		Placebo
Arm/Group Description	90 mg of Ticagrelor to be given orally twice a day for 6 months		Placebo drug to be given twice a day for 6 months
All Cause Mortality
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		1/17 (5.9%)
Serious Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		1/17 (5.9%)
Cardiac disorders
cardiac arrest	1/17 (5.9%)	1	0/17 (0%)	0
myocardial infarction	0/17 (0%)	0	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/17 (17.6%)		2/17 (11.8%)
Blood and lymphatic system disorders
transient ischemic attack - stroke	1/17 (5.9%)	1	0/17 (0%)	0
bloody drops on penis	1/17 (5.9%)	1	0/17 (0%)	0
Gastrointestinal disorders
increased diarrhea	1/17 (5.9%)	1	0/17 (0%)	0
General disorders
tickling feeling in head	1/17 (5.9%)	1	0/17 (0%)	0
bruise on hand	1/17 (5.9%)	1	0/17 (0%)	0
Infections and infestations
cold	0/17 (0%)	0	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
worsening pulmonary hypertension	0/17 (0%)	0	1/17 (5.9%)	1

Limitations/Caveats

The results may be affected by the enrollment that did not reach a goal of 70 subjects with only 34 subject or 48.5% of the projected number completing the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.