Application of human type I pancreatic elastase (PRT-201) to the venous anastomosis of arteriovenous grafts in patients with chronic kidney disease

J Vasc Access. Sep-Oct 2014;15(5):376-84. doi: 10.5301/jva.5000235. Epub 2014 May 3.

Abstract

Purpose: To explore the safety and efficacy of PRT-201 applied to the outflow vein of a newly created arteriovenous graft (AVG).

Methods: Randomized, double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.01 to 9 mg) applied to the graft-vein anastomosis and adjacent outflow vein immediately after AVG placement. The primary outcome measure was safety. The efficacy measures were intraoperative increases in outflow vein diameter and blood flow rate, primary unassisted patency, and secondary patency by dose groups (placebo, low, medium, high and All PRT-201).

Results: A total of 89 patients were treated (28 placebo and 61 PRT-201). There were no significant differences in the proportion of placebo and PRT-201 patients reporting adverse events. Intraoperative outflow vein diameter increased 5% (p=0.14) in the placebo group compared with 13% (p=0.01), 15% (p=0.07) and 12% (p<0.001), in the low, medium and high groups, respectively. The comparison between the high and placebo groups was marginally statistically significant (p=0.06). The intraoperative blood flow did not change in the placebo group, and increased in the low, medium and high groups by 19% (p=0.34), 36% (p=0.09) and 46% (p=0.02), respectively. The low group had the longest primary unassisted and secondary patency and the fewest procedures to restore or maintain patency; however, the differences between groups were not statistically significant.

Conclusions: PRT-201 was well tolerated and increased AVG intraoperative outflow vein diameter and blood flow. Low dose tended to increase secondary patency and decrease the rate of procedures to restore or maintain patency. Larger studies with these doses will be necessary to confirm these results.

Trial registration: ClinicalTrials.gov NCT01001351.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arteriovenous Shunt, Surgical* / adverse effects
  • Blood Flow Velocity
  • Carrier Proteins / administration & dosage*
  • Carrier Proteins / adverse effects
  • Double-Blind Method
  • Female
  • Graft Occlusion, Vascular / diagnosis
  • Graft Occlusion, Vascular / etiology
  • Graft Occlusion, Vascular / physiopathology
  • Graft Occlusion, Vascular / prevention & control*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Elastase / administration & dosage*
  • Pancreatic Elastase / adverse effects
  • Regional Blood Flow
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / therapy*
  • Time Factors
  • Treatment Outcome
  • United States
  • Upper Extremity / blood supply*
  • Vascular Patency
  • Veins / drug effects
  • Veins / physiopathology
  • Veins / surgery

Substances

  • Carrier Proteins
  • Pancreatic Elastase
  • cholesterol-binding protein

Associated data

  • ClinicalTrials.gov/NCT01001351