Vorapaxar Study for Maturation of AV Fistulae for Hemodialysis Access

Phase 2

Completed

Brief Summary: The Objectives of this study are:

1. To determine if vorapaxar safely improves arteriovenous (AV) fistula functional maturation when administered during the maturation process compared with placebo.

2. To determine if vorapaxar safely improves AV fistula patency, allowing for secondary procedures to aid in fistula maturation compared with placebo.

3. 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: Objectives:

1. To determine if vorapaxar safely improves arteriovenous (AV) fistula functional maturation when administered during the maturation process compared with placebo.

2. To determine if vorapaxar safely improves AV fistula patency, allowing for secondary procedures to aid in fistula maturation compared with placebo.

3. 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.

Recruitment & Eligibility

Inclusion Criteria

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.

Arm && Interventions

Group	Intervention	Description
Vorapaxar intervention	Vorapaxar sulfate	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).
Placebo intervention	Placebo	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).

Primary Outcome Measures

Name	Time	Method
Time to AV Fistula Functional Maturation	up to 238 days	Time to AV fistula functional maturation (defined as successful cannulation of the AV fistula for six hemodialysis sessions within three weeks).

Secondary Outcome Measures

Name	Time	Method
Count of All Participants With Bleeding Events	up to 238 days	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
Count of Participants With AV Fistula Use	up to 238 days	Participants able to use their AV fistula for dialysis within 180 days of surgery were considered to have met the outcome.
Count Participants With AV Fistula Patency	150-238 days	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.