AV Fistula
Conditions
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.
Interventions
DRUGVorapaxar sulfate
The study drug (12-week supply of study drug) will be dispensed to enrolled patients on the first day following surgery.
DRUGPlacebo
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.
Sponsors
Merck Sharp & Dohme LLC
Ken Mahaffey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>18 2. Receiving or planning to receive maintenance hemodialysis 3. Ability to sign informed consent 4. 3 mm venous diameter within recipient vein
Exclusion criteria
1. History of stroke, transient ischemic attack or intracranial hemorrhage 2. History of or high level of suspicion for, severe arterial insufficiency of the hand 3. Indication or ongoing therapy with other antiplatelet agents, other than aspirin 81 mg daily 4. Indication or ongoing therapy with anticoagulants, including warfarin, low molecular weight heparin, factor Xa inhibitors or direct thrombin and other inhibitors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
United States
Participant flow
Pre-assignment details
17 participants were enrolled, 13 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Vorapaxar Intervention Participants were randomized to receive vorapaxar sulfate for 12 weeks (2.5 mg orally once daily). | 6 |
| Placebo Intervention Participants were randomized to receive placebo to match vorapaxar sulfate for 12 weeks. | 7 |
| Total | 13 |
Baseline characteristics
| Characteristic | Vorapaxar Intervention | Total | Placebo Intervention |
|---|---|---|---|
| Age, Continuous | 50.0 years | 56.0 years | 62.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 8 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 0 / 6 | 0 / 7 |
| serious Total, serious adverse events | 3 / 6 | 3 / 7 |
Outcome results
Primary
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).
Time frame: up to 238 days
Population: Pre-specified time for assessment of this Outcome Measure was up to 180 days, but data collected is out of window due to delayed and rescheduled visits.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vorapaxar Intervention | Time to AV Fistula Functional Maturation | 169 Days to functional maturation |
| Placebo Intervention | Time to AV Fistula Functional Maturation | 145 Days to functional maturation |
Secondary
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
Time frame: up to 238 days
Population: Pre-specified time for assessment of this Outcome Measure was up to 180 days, but data collected is out of window due to delayed and rescheduled visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorapaxar Intervention | Count of All Participants With Bleeding Events | 0 Participants |
| Placebo Intervention | Count of All Participants With Bleeding Events | 1 Participants |
Secondary
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.
Time frame: up to 238 days
Population: Pre-specified time for assessment of this Outcome Measure was up to 180 days, but data collected is out of window due to delayed and rescheduled visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorapaxar Intervention | Count of Participants With AV Fistula Use | 2 Participants |
| Placebo Intervention | Count of Participants With AV Fistula Use | 4 Participants |
Secondary
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.
Time frame: 150-238 days
Population: Pre-specified time for assessment of this Outcome Measure was up to 180 days, but data collected is out of window due to delayed and rescheduled visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorapaxar Intervention | Count Participants With AV Fistula Patency | 1 Participants |
| Placebo Intervention | Count Participants With AV Fistula Patency | 5 Participants |