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

• Published in: Journal of vascular surgery Vol. 60; no. 2; pp. 454 - 461.e1
• Main Authors: Hye, Robert J., MD, Peden, Eric K., MD, O'Connor, Timothy P., MD, Browne, Barry J., MD, Dixon, Bradley S., MD, Schanzer, Andres S., MD, Jensik, Stephen C., MD, Dember, Laura M., MD, Jaff, Michael R., DO, Burke, Steven K., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2014
• Subjects: Administration, Cutaneous; Adult; Aged; Arteriovenous Shunt, Surgical - adverse effects; Carrier Proteins - administration & dosage; Carrier Proteins - adverse effects; Constriction, Pathologic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Graft Occlusion, Vascular - diagnostic imaging; Graft Occlusion, Vascular - physiopathology; Graft Occlusion, Vascular - prevention & control; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pancreatic Elastase; Recombinant Proteins - administration & dosage; Renal Dialysis; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - therapy; Surgery; Time Factors; Treatment Outcome; Ultrasonography; United States; Upper Extremity - blood supply; Vascular Patency - drug effects
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2014.02.037

Objective 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.