title: A multi-center, dose-escalation study of human type I pancreatic elastase (PRT-201) administered after arteriovenous fistula creation.
abstract: OBJECTIVE
  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.affiliation: Department of Cardiovascular Surgery, The Methodist Hospital, Houston, TX, USA.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Peden
authors.forename: David B
authors.initials: DB
authors.lastname: Leeser
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Dixon
authors.forename: Mahmoud T
authors.initials: MT
authors.lastname: El-Khatib
authors.forename: Prabir
authors.initials: P
authors.lastname: Roy-Chaudhury
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lawson
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Menard
authors.forename: Laura M
authors.initials: LM
authors.lastname: Dember
authors.forename: Marc H
authors.initials: MH
authors.lastname: Glickman
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Gustafson
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Blair
authors.forename: Marianne
authors.initials: M
authors.lastname: Magill
authors.forename: F Nicholas
authors.initials: FN
authors.lastname: Franano
authors.forename: Steven K
authors.initials: SK
authors.lastname: Burke
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D002352:Carrier Proteins / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D034941:Upper Extremity / Q000098:blood supply*; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D010196:Pancreatic Elastase; C017130:cholesterol-binding protein