Anthony J Bleyer1, Vincent A Scavo2, Samuel E Wilson3, Barry J Browne4, Brian L Ferris5, C Keith Ozaki6, Timmy Lee7, Eric K Peden8, Bradley S Dixon9, Rick Mishler10, Timothy P O'Connor11, Kendrah Kidd12, Steven K Burke13. 1. Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC. Electronic address: ableyer@wakehealth.edu. 2. Cardiovascular and Thoracic Surgery, Lutheran Medical Group, Fort Wayne, Ind. 3. Vascular Surgery, University of California Irvine, Orange, Calif. 4. General Surgery, Sharp Healthcare, San Diego, Calif. 5. Lake Washington Vascular Surgeons, Bellevue, Wash. 6. Vascular Surgery, Brigham and Women's Hospital, Boston, Mass. 7. Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala. 8. Cardiovascular Surgery, The Methodist Hospital, Houston, Tex. 9. Department of Medicine, University of Iowa, Iowa City, Iowa. 10. Arizona Kidney Disease & Hypertension Centers, Phoenix, Ariz. 11. Surgery Division, RenalCare Associates, Peoria, Ill. 12. Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC. 13. Proteon Therapeutics, Waltham, Mass.
Abstract
OBJECTIVE: Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis. METHODS: PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates. RESULTS: The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use. CONCLUSIONS:Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.
RCT Entities:
OBJECTIVE:Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis. METHODS: PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates. RESULTS: The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use. CONCLUSIONS: Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.
Authors: Hualong Bai; Nirvana Sadaghianloo; Jolanta Gorecka; Shirley Liu; Shun Ono; Abhay B Ramachandra; Sophie Bonnet; Nathalie M Mazure; Serge Declemy; Jay D Humphrey; Alan Dardik Journal: Sci Transl Med Date: 2020-08-19 Impact factor: 17.956
Authors: Christoph B Olivier; Vandana Sundaram; Glenn M Chertow; Sumana Shashidhar; Lori K McDonnell; Victoria Y Ding; Manisha Desai; Kenneth W Mahaffey; Matthew Mell Journal: J Vasc Access Date: 2019-11-27 Impact factor: 2.283
Authors: Patrick Heindel; Peng Yu; Jessica D Feliz; Dirk M Hentschel; Steven K Burke; Mohammed Al-Omran; Deepak L Bhatt; Michael Belkin; C Keith Ozaki; Mohamad A Hussain Journal: Ann Surg Open Date: 2022-08-23