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

作者：Peden Eric K; Leeser David B; Dixon Bradley S; El Khatib Mahmoud T; Roy Chaudhury Prabir; Lawson Jeffrey H; Menard Matthew T; Dember Laura M; Glickman Marc H; Gustafson Pamela N; Blair Andrew T; Magill Marianne; Franano F Nicholas; Burke Steven K^*

来源：Journal of Vascular Access, 2013, 14(2): 143-151.

DOI：10.5301/jva.5000125

• Arteriovenous fistula
• Clinical trial
• Pancreatic elastase
• PRT-201
• Renal dialysis

Purpose: To explore the safety and efficacy of PRT-201. %26lt;br%26gt;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 %26gt;= 25% (primary), changes in outflow vein diameter and blood flow, AVF maturation and lumen stenosis by ultrasound criteria and AVF patency. %26lt;br%26gt;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 %26gt;= 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 %26lt;65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P%26lt;0.10) with a decreased risk of primary patency loss. %26lt;br%26gt;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.

• 出版日期2013-6