Format

Send to

Choose Destination
J Vasc Surg. 2014 Aug;60(2):454-461.e1. doi: 10.1016/j.jvs.2014.02.037. Epub 2014 Mar 27.

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

Author information

1
Vascular Surgery, Kaiser Permanente, San Diego, Calif.
2
Department of Cardiovascular Surgery, The Methodist Hospital, Houston, Tex.
3
Renal Care Associates, Peoria, Ill.
4
California Institute of Renal Research, San Diego, Calif.
5
Department of Medicine, University of Iowa Hospital and Clinics, Iowa City, Iowa.
6
Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, Mass.
7
Transplant Program, Rush University Medical Center, Chicago, Ill.
8
Renal-Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
9
VasCore, the Vascular Ultrasound Core Laboratory, Massachusetts General Hospital, Boston, Mass.
10
Research and Development, Proteon Therapeutics Inc, Waltham, Mass. Electronic address: sburke@proteontx.com.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01305824.

Comment in

PMID:
24684771
DOI:
10.1016/j.jvs.2014.02.037
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center