A multi-center, dose-escalation study of human type I pancreatic elastase (PRT-201) administered after arteriovenous fistula creation.

Published

Journal Article

PURPOSE: To explore the safety and efficacy of PRT-201. METHODS: Randomized, double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.0033 to 9 mg) applied after arteriovenous fistula (AVF) creation. Participants were followed for one year. The primary outcome measure was safety. Efficacy measures were the proportion with intra-operative increases in AVF outflow vein diameter or blood flow ≥25% (primary), changes in outflow vein diameter and blood flow, AVF maturation and lumen stenosis by ultrasound criteria and AVF patency. RESULTS: The adverse events in the PRT-201 group (n=45) were similar to those in the placebo group (n=21). There were no differences in the proportion with ≥25% increase in vein diameter or blood flow, successful maturation or lumen stenosis. There was no statistically significant difference in primary patency between the dose groups (placebo n=21, Low Dose n=16, Medium Dose n=17 and High Dose n=12). In a subgroup analysis that excluded three participants with early surgical failures, the hazard ratio (HR) for primary patency loss of Low Dose compared with placebo was 0.38 (95% CI 0.10-1.41, P=0.15). In a Cox model, Low Dose (HR 0.27, 95% CI 0.04-0.79, P=0.09), white race (HR 0.17, 95% CI 0.03-0.79, P=0.02), and age <65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P<0.10) with a decreased risk of primary patency loss. CONCLUSIONS: PRT-201 was not different from placebo for safety or efficacy measures. There was a suggestion for improved AVF primary patency with Low Dose PRT-201 that is now being studied in a larger clinical trial.

Full Text

Duke Authors

Cited Authors

  • Peden, EK; Leeser, DB; Dixon, BS; El-Khatib, MT; Roy-Chaudhury, P; Lawson, JH; Menard, MT; Dember, LM; Glickman, MH; Gustafson, PN; Blair, AT; Magill, M; Franano, FN; Burke, SK

Published Date

  • April 2013

Published In

Volume / Issue

  • 14 / 2

Start / End Page

  • 143 - 151

PubMed ID

  • 23172172

Pubmed Central ID

  • 23172172

Electronic International Standard Serial Number (EISSN)

  • 1724-6032

Digital Object Identifier (DOI)

  • 10.5301/jva.5000125

Language

  • eng

Conference Location

  • United States