Abstract: TH-PO753

Vonapanitase Increases Fistula Use for Hemodialysis Using a Robust and Clinically Relevant Definition

Session Information

Category: Dialysis

  • 603 Hemodialysis: Vascular Access

Authors

  • Bleyer, Anthony J., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Dixon, Bradley S., University of Iowa Hospital and Clinics, Iowa City, Iowa, United States
  • Lee, Timmy C., Univ of Alabama at Birmingham, Birmingham, Alabama, United States
  • Burke, Steven K., Proteon Therapeutics, Inc., Waltham, Massachusetts, United States
  • Mishler, Rick E., Arizona Kidney Disease and Hypertension Center, Ltd., Phoenix, Arizona, United States
Background

Vonapanitase is an investigational recombinant human elastase applied to the external surface of the fistula at the time of surgical creation. A recently reported randomized double-blind trial (NCT02110901) showed vonapanitase increased radiocephalic fistula survival and use for hemodialysis (HD) compared with placebo in 311 pre-HD (56%) and HD (44%) patients over 1 year. In other trials, varying definitions of use have been employed that required shorter durations of use but detailed information on individual HD session blood
flow or urea clearance. The current trial employed a pragmatic definition based on continued 2-needle hemodialysis for ≧ 90 days.

Methods

Successful use was defined as (1) ≥90 days or (2) ≥30 days and in use at the final study visit for those pre-HD patients initiating HD late in the follow-up period. Non-use was defined as insufficient duration of use or fistula abandonment prior to use. Those not defined as having use or non-use were considered indeterminate (eg, a pre-HD patient who never initiated HD) and excluded from analysis. Of those with use, 82% had at least one Kt/V or URR recorded. Adequate HD was defined as Kt/V≥1.2 or URR≥65%.

Results

More vonapanitase than placebo patients successfully used the fistula for HD (n=230, 64% vs 44%, p=0.006). Use was established by the 90-day rule in 92% and the 30-day rule in 8%. Only 3 patients abandoned the fistula following successful use (2 placebo, 1 vonapanitase) the others continued use in a follow-on registry. Non-use was defined by fistula abandonment prior to use in 91% and by insufficient duration of use in 9%. Fistula abandonment was due to thrombosis (occlusion) in 64% of cases and a mix of intractable stenosis, non-maturation, inadequate HD, inability to cannulate, and steal syndrome in the remaining. The percentages of those with successful use who had adequate HD were vonapanitase 99% and placebo 97%. In those on HD at baseline, median duration from surgical creation to first use was 103 days for vonapanitase and 135 days for placebo patients.

Conclusion

Vonapanitase increased successful use of the fistula for HD employing a robust and pragmatic definition of use that is clinically relevant and associated with adequate hemodialysis. These results are being confirmed in a larger ongoing trial (NCT02414841).

Funding

  • Commercial Support