A double-blind, randomized, placebo-controlled pilot trial to evaluate safety and efficacy of vorapaxar on arteriovenous fistula maturation

Abstract

Background: Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk.

Objective: The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease.

Methods: VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5 mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing.

Results: A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56 years and seven participants (54%) were female. The median (minimum-maximum) days to functional maturation were 169 (77-287) days in the vorapaxar group and 145 (48-198) days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180 days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group.

Conclusion: Fewer than half of participants had functional maturation within 180 days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.

Keywords: Arteriovenous fistula; VorapAccess; clinical trial; dialysis; thrombin; vorapaxar.

Figure 1.. Study flow chart.

Thirteen participants were assigned to receive the vorapaxar 2.5 mg daily or a look-alike placebo with a 1:1 randomization in blocks of four. Participants were stratified based on fistula location (lower arm or upper arm) and instructed to take the study medication for twelve weeks starting on day two after surgery.

Figure 2.. Primary end point: time to functional maturation.

The median (minimum–maximum) days to functional maturation were 169 (77–287) days in the vorapaxar group and 145 (48–198) days in the placebo group. Six of the 13 participants (46%) had AVF functional maturation within 180 days after surgery; two of six (33%; at 77 and 96 days after randomization, respectively) in the vorapaxar group and four of seven (57%; at 48, 76, 84, and 145 days after randomization, respectively) in the placebo group.