Vorapaxar Study for Maturation of AV Fistulae for Hemodialysis Access

Study Overview
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Brief Summary
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The Objectives of this study are: To determine if vorapaxar safely improves arteriovenous (AV) fistula functional maturation when administered during the maturation process compared with placebo. To determine if vorapaxar safely improves AV fistula patency, allowing for secondary procedures to aid in fistula maturation compared with placebo. To determine if vorapaxar safely facilitates successful cannulation of AV fistulas for hemodialysis compared with placebo. This is a randomized placebo-controlled double-blind pilot trial. Study procedures will be conducted at Stanford University Medical Center, and standard-of-care (SOC) procedures will be conducted at Stanford and it's affiliated hospitals (Veteran's Affairs Palo Alto Health Care System and the Stanford Vascular Surgery Clinic at Valley Medical Center). The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm).

Detailed Description
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Objectives: To determine if vorapaxar safely improves arteriovenous (AV) fistula functional maturation when administered during the maturation process compared with placebo. To determine if vorapaxar safely improves AV fistula patency, allowing for secondary procedures to aid in fistula maturation compared with placebo. To determine if vorapaxar safely facilitates successful cannulation of AV fistulas for hemodialysis compared with placebo. This is a randomized placebo-controlled double-blind pilot trial. Study procedures will be conducted at Stanford University Medical Center, and standard-of-care (SOC) procedures will be conducted at Stanford and it's affiliated hospitals (Veteran's Affairs Palo Alto Health Care System and the Stanford Vascular Surgery Clinic at Valley Medical Center). The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm). Participation in this study will not affect standard care of patients with AV fistulae receiving hemodialysis. The only additional treatment is administration of the study drug or placebo and additional monitoring, including one additional ultrasound, for 6 months.

Official Title
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A Double-blind, Randomized, Placebo Controlled Pilot Trial to Evaluate the Safety and Efficacy of Vorapaxar in Maturation of Arteriovenous Fistulae for Hemodialysis Access

Conditions
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AV Fistula

Intervention / Treatment
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* Drug: Vorapaxar sulfate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 Receiving or planning to receive maintenance hemodialysis Ability to sign informed consent 3 mm venous diameter within recipient vein Exclusion Criteria: History of stroke, transient ischemic attack or intracranial hemorrhage History of or high level of suspicion for, severe arterial insufficiency of the hand Indication or ongoing therapy with other antiplatelet agents, other than aspirin 81 mg daily Indication or ongoing therapy with anticoagulants, including warfarin, low molecular weight heparin, factor Xa inhibitors or direct thrombin and other inhibitors.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vorapaxar intervention<br>This arm will receive the study drug: Vorapaxar sulfate. The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm). | Drug: Vorapaxar sulfate<br>* The study drug (12-week supply of study drug) will be dispensed to enrolled patients on the first day following surgery.<br>* Other names: Zontivity;|
| Placebo Comparator: Placebo intervention<br>This arm will receive the matching placebo. The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm). | Drug: Placebo<br>* The placebo will match the study drug, vorapaxar sulfate, in appearance. A 12-week supply will be dispensed to enrolled patients on the first day following surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to AV Fistula Functional Maturation | Time to AV fistula functional maturation (defined as successful cannulation of the AV fistula for six hemodialysis sessions within three weeks). | up to 238 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants With AV Fistula Use | Participants able to use their AV fistula for dialysis within 180 days of surgery were considered to have met the outcome. | up to 238 days | 
| Count Participants With AV Fistula Patency | Criteria for outcome: AV fistula patency at 150-180 days, with at least 50% increase in vein diameter by ultrasound compared with preoperative vein diameter measurement. | 150-238 days | 
| Count of All Participants With Bleeding Events | Bleeding events according to GUSTO (criteria for bleeding: Severe, Moderate or Mild) and BARC (bleeding criteria Type 0-5, with 0 being no bleeding and 5 referring to probable or definite fatal bleeding) Criteria | up to 238 days |