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 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.