PATENCY-2 trial of vonapanitase to promote radiocephalic fistula use for hemodialysis and secondary patency.

OBJECTIVE: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. METHODS: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula procedure rates. RESULTS: The proportions of patients with fistula use for hemodialysis was similar between groups, 70% vonapanitase and 65% placebo, (p = 0.33). The Kaplan-Meier estimates of 12-month secondary patency were 78% (95% confidence interval [CI], 73-82) for vonapanitase and 76% (95% CI, 70-82) for placebo (p = 0.93). The proportions with unassisted fistula use for hemodialysis were 46% vonapanitase and 37% placebo (p = 0.054). The Kaplan-Meier estimates of 12-month primary unassisted patency were 50% (95% CI, 44-55) for vonapanitase and 43% (95% CI, 35-50) for placebo (p = 0.18). There were no differences in the proportion of patients with fistula maturation or in fistula procedure rates. Adverse events were similar between groups. Vonapanitase was not immunogenic. CONCLUSIONS: Vonapanitase treatment did not achieve clinical or statistical significance to meaningfully improve radiocephalic fistula surgical outcomes. Outcome in the placebo group were better than in historical controls. Vonapanitase was well-tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov: NCT02414841 (https://clinicaltrials.gov/ct2/show/NCT02414841).

Comparison of postoperative ultrasound criteria to predict unassisted use of arteriovenous fistulas for hemodialysis.

INTRODUCTION: Arteriovenous fistulas (AVF) frequently fail to mature. Postoperative ultrasounds provide objective measurements to predict unassisted AVF use for hemodialysis (unassisted use) and guide interventions to salvage nonmaturing AVFs. The optimal ultrasound criteria to assess AVF maturation are uncertain. We analyzed data from a multicenter, randomized, controlled, clinical trial to compare 2 published ultrasound maturation criteria used to predict unassisted AVF use for hemodialysis. METHODS: We retrospectively analyzed prospective data on 105 patients undergoing new AVF creation, who underwent standardized postoperative ultrasounds at 6 and 12 weeks to measure AVF diameter and blood flow. Unassisted AVF use was defined as successful cannulation for ≥90 days without requiring prior surgical or percutaneous interventions. Two ultrasound criteria were assessed: (i) National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative criteria: AVF outflow vein lumen diameter ≥6 mm and blood flow ≥600 mL/min; and (ii) University of Alabama at Birmingham (UAB) criteria: AVF outflow vein lumen diameter ≥4 mm and blood flow ≥500 mL/min. Performance characteristics were calculated for both criteria. RESULTS: Compared to the NKF criteria, the UAB criteria had a higher sensitivity (89 vs.68%), but a lower specificity (42 vs. 70%) for unassisted AVF use. For radiocephalic AVFs, the UAB criteria had higher sensitivity (86 vs. 46%) and lower specificity (58 vs. 83%). For brachiocephalic AVFs, both UAB and NKF had high sensitivity (90 and 80%) but low specificity (21 and 53%), respectively. CONCLUSIONS: Using the UAB ultrasound criteria would minimize unnecessary early interventions in AVFs likely to mature without an intervention, but would delay interventions in AVFs that are unlikely to mature. The UAB criteria may be preferred in patients receiving a radiocephalic AVF.