title: Application of human type I pancreatic elastase (PRT-201) to the venous anastomosis of arteriovenous grafts in patients with chronic kidney disease.
abstract: OBJECTIVE
  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.
authors.affiliation: 1 Department of Surgery, University of Louisville, Louisville, KY - USA.
authors.forename: Amit J
authors.initials: AJ
authors.lastname: Dwivedi
authors.forename: Prabir
authors.initials: P
authors.lastname: Roy-Chaudhury
authors.forename: Eric K
authors.initials: EK
authors.lastname: Peden
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Browne
authors.forename: Eric D
authors.initials: ED
authors.lastname: Ladenheim
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Scavo
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Gustafson
authors.forename: Marco D
authors.initials: MD
authors.lastname: Wong
authors.forename: Marianne
authors.initials: M
authors.lastname: Magill
authors.forename: Francesca
authors.initials: F
authors.lastname: Lindow
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Blair
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jaff
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; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D001783:Blood Flow Velocity; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006083:Graft Occlusion, Vascular / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000008:administration & dosage* / Q000009:adverse effects; D012039:Regional Blood Flow; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D034941:Upper Extremity / Q000098:blood supply*; D014654:Vascular Patency; D014680:Veins / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery
chemical_list: D002352:Carrier Proteins; D010196:Pancreatic Elastase; C017130:cholesterol-binding protein