A randomized trial of vonapanitase (PATENCY-1) to promote radiocephalic fistula patency and use for hemodialysis

Abstract

Objective: Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis. Methods: PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n ¼ 210) or placebo (n ¼ 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates. Results: The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P ¼ .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P ¼ .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P ¼ .035) with unassisted use for hemodialysis and 64% and 44% (P ¼ .006) with unassisted plus assisted use. Conclusions: Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.

Small GTPases and Their Role in Vascular Disease

“…Therapeutic manipulation of the small GTPases is particularly attractive for the treatment of surgical diseases. We have the ability to directly treat blood vessels through pressurized perfusion, as in the PREVENT trial [3], or with topical treatment of the target vessel, as in the PATENCY trial [88]. Our group has extensive experience delivering siRNA to isolated vessels and in vivo [14,89,90].…”

Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study

“…3 Increasing AVF use-a priority of national vascular access recommendations for the past two decades-has been limited by the unexpectedly high rate of AVF maturation failure, ranging from 30% to 60%. [4][5][6][7] Approximately half of new AVFs require one or more interventions to promote their maturation before successful use for dialysis ("assisted maturation"). Two small studies from one to two medical centers reported that AVFs with assisted maturation were associated with more frequent interventions to maintain patency after maturation and had greater AVF abandonment compared with AVFs with unassisted maturation.…”

A Randomized Trial of Liposomal Prednisolone (LIPMAT) to Enhance Radiocephalic Fistula Maturation: A Pilot Study

“…The 62% successful cannulation rate observed in the LIPMAT study was comparable to previous studies on functional AVF maturation. 1,7 Although the nonsignificant result may be a mere result of a lack of power due to the small sample size, also no trend toward any difference between the treatment and control group was observed. Apart from a lack of statistical power, several factors might explain the lack of therapeutic efficacy of liposomal prednisolone to improve AVF maturation.…”