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Human type I pancreatic elastase treatment of arteriovenous fistulas in patients with chronic kidney disease.

AbstractOBJECTIVE:
This study explored the safety and efficacy of recombinant type I pancreatic elastase (PRT-201) topically applied once to the external surface of an arteriovenous fistula.
METHODS:
This was a randomized, double-blind, placebo-controlled trial. Adults with kidney disease undergoing creation of a radiocephalic fistula (RCF) or brachiocephalic fistula were randomized to treatment with placebo (n = 51), PRT-201 at 10 μg (n = 51), or PRT-201 at 30 μg (n = 49). The primary efficacy measure was unassisted primary patency (PP) over 1 year. Secondary efficacy measures were secondary patency (SP), unassisted maturation by ultrasound interrogation, use for hemodialysis, and hemodynamically significant lumen stenosis.
RESULTS:
Median PP was 224 days for placebo and >365 days for the PRT-201 groups. At 1 year, 45%, 54%, and 53% of placebo, 10-μg, and 30-μg patients retained PP. The risk of PP loss was nonsignificantly reduced for 10 μg (hazard ratio [HR], 0.69; P = .19) and 30 μg (HR, 0.67; P = .17) vs placebo. In the subset (44% of patients) with a RCF, the median PP was 125 days for placebo and >365 days for the PRT-201 groups. At 1 year, 31%, 50%, and 63% of placebo, 10-μg, and 30-μg RCFs retained PP. The risk of RCF PP loss was nonsignificantly reduced by 10 μg (HR, 0.59; P = .18) and significantly reduced by 30 μg (HR, 0.37; P = .02) vs placebo. At 1 year, 77%, 81%, and 83% of placebo, 10-μg, and 30-μg patients retained SP. The risk of SP loss was nonsignificantly reduced for 10 μg (HR, 0.79; P = .61) and 30 μg (HR, 0.76; P = .55) vs placebo. In the subset with RCFs, 65%, 82%, and 90% of placebo, 10-μg, and 30-μg patients retained SP at 1 year. The risk of RCF SP loss was nonsignificantly reduced for 10 μg (HR, 0.45; P = .19) and 30 μg (HR, 0.27; P = .08) vs placebo. At month 3, 67%, 87% (P = .03), and 92% (P < .01) of the placebo, 10-μg, and 30-μg group fistulas had unassisted maturation by ultrasound interrogation. At month 3 in the subset with an RCF, 47%, 74% (P = .17), and 93% (P < .01) of placebo, 10-μg, and 30-μg group fistulas had unassisted maturation by ultrasound interrogation. Adverse event reports were not meaningfully different between groups.
CONCLUSIONS:
PRT-201 appeared safe. The primary efficacy end point was not met. However, both PRT-201 doses were associated with improved unassisted maturation. The 30-μg dose was associated with increased PP in the subset with RCF.
AuthorsRobert J Hye, Eric K Peden, Timothy P O'Connor, Barry J Browne, Bradley S Dixon, Andres S Schanzer, Stephen C Jensik, Laura M Dember, Michael R Jaff, Steven K Burke
JournalJournal of vascular surgery (J Vasc Surg) Vol. 60 Issue 2 Pg. 454-461.e1 (Aug 2014) ISSN: 1097-6809 [Electronic] United States
PMID24684771 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Chemical References
  • Carrier Proteins
  • Recombinant Proteins
  • Pancreatic Elastase
  • cholesterol-binding protein
Topics
  • Administration, Cutaneous
  • Adult
  • Aged
  • Arteriovenous Shunt, Surgical (adverse effects)
  • Carrier Proteins (administration & dosage, adverse effects)
  • Constriction, Pathologic
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Graft Occlusion, Vascular (diagnostic imaging, physiopathology, prevention & control)
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Elastase
  • Recombinant Proteins (administration & dosage)
  • Renal Dialysis
  • Renal Insufficiency, Chronic (diagnosis, therapy)
  • Time Factors
  • Treatment Outcome
  • Ultrasonography
  • United States
  • Upper Extremity (blood supply)
  • Vascular Patency (drug effects)

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