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

Abstract

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.

• Authors: Eric K Peden, David B Leeser, Bradley S Dixon, Mahmoud T El-Khatib, Prabir Roy-Chaudhury, Jeffrey H Lawson, Matthew T Menard, Laura M Dember, Marc H Glickman, Pamela N Gustafson, Andrew T Blair, Marianne Magill, F Nicholas Franano, Steven K Burke
• Journal: The journal of vascular access (J Vasc Access) 2013 Apr-Jun Vol. 14 Issue 2 Pg. 143-51 ISSN: 1724-6032 [Electronic] United States
• PMID: 23172172 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Pancreatic Elastase
• cholesterol-binding protein

Topics

• Adult
• Aged
• Analysis of Variance
• Arteriovenous Shunt, Surgical (adverse effects)
• Carrier Proteins (administration & dosage)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Graft Occlusion, Vascular (etiology, physiopathology, prevention & control)
• Humans
• Male
• Middle Aged
• Pancreatic Elastase
• Proportional Hazards Models
• Prospective Studies
• Renal Dialysis
• Risk Factors
• Thrombosis (etiology, physiopathology, prevention & control)
• Time Factors
• Treatment Outcome
• United States
• Upper Extremity (blood supply)
• Vascular Patency (drug effects)