Human type I pancreatic elastase treatment of arteriovenous fistulas in patients with chronic kidney disease
AuthorsHye, Robert J.
Peden, Eric K.
O'Connor, Timothy P.
Browne, Barry J.
Dixon, Bradley S.
Jensik, Stephen C.
Dember, Laura M.
Jaff, Michael R.
Burke, Steven K.
UMass Chan AffiliationsDepartment of Surgery, Division of Vascular and Endovascular Surgery
Document TypeJournal Article
*Arteriovenous Shunt, Surgical
Dose-Response Relationship, Drug
Graft Occlusion, Vascular
Renal Insufficiency, Chronic
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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 mug (n = 51), or PRT-201 at 30 mug (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-mug, and 30-mug patients retained PP. The risk of PP loss was nonsignificantly reduced for 10 mug (hazard ratio [HR], 0.69; P = .19) and 30 mug (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-mug, and 30-mug RCFs retained PP. The risk of RCF PP loss was nonsignificantly reduced by 10 mug (HR, 0.59; P = .18) and significantly reduced by 30 mug (HR, 0.37; P = .02) vs placebo. At 1 year, 77%, 81%, and 83% of placebo, 10-mug, and 30-mug patients retained SP. The risk of SP loss was nonsignificantly reduced for 10 mug (HR, 0.79; P = .61) and 30 mug (HR, 0.76; P = .55) vs placebo. In the subset with RCFs, 65%, 82%, and 90% of placebo, 10-mug, and 30-mug patients retained SP at 1 year. The risk of RCF SP loss was nonsignificantly reduced for 10 mug (HR, 0.45; P = .19) and 30 mug (HR, 0.27; P = .08) vs placebo. At month 3, 67%, 87% (P = .03), and 92% (P < .01) of the placebo, 10-mug, and 30-mug 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-mug, and 30-mug 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-mug dose was associated with increased PP in the subset with RCF.
SourceJ Vasc Surg. 2014 Aug;60(2):454-461.e1. doi: 10.1016/j.jvs.2014.02.037. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/49720
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