Safety and efficacy of local periadventitial delivery of sirolimus for improving hemodialysis graft patency: First human experience with a sirolimus-eluting collagen membrane (Coll-R)

William D. Paulson, Nicholas Kipshidze, Konstantine Kipiani, Nutsa Beridze, Maria V. DeVita, Surendra Shenoy, Sriram S. Iyer

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Background. Neointimal hyperplasia causes a high rate of hemodialysis synthetic graft failure. Thus, therapies that inhibit neointimal hyperplasia are urgently needed. The Coll-R is a sirolimus-eluting collagen matrix designed for intra-operative perivascular implantation around the graftvenous anastomosis. Sirolimus is an anti-proliferative drug that has proven clinical utility in suppressing neointimal tissue growth in coronary artery disease when delivered locally to the vascular wall by an endovascular drug eluting stent. Methods. A cohort of 12 chronic hemodialysis patients underwent surgical placement of 13 polytetrafluoroethylene grafts 1 Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokineticsof sirolimus release, success of Coll-R implantation and primary unassisted graft patency. Results. There were no technical failures, infections, vascular anastomotic or wound-healing problems. Whole blood sirolimus levels rose to a mean peak of 4.8 ng/mL at 6 h and fell to <1 ng/mL at 1 week (n = 5). Twelve and 24-month primary unassisted patencies were 76 and 38%, respectively, and the thrombosis rate was 0.37/patient-year. Conclusions. Perivascular implantation of the Coll-R during graft surgery safely delivered sirolimus to the vascular wall. Systemic sirolimus levels were sub-therapeutic for immunosuppression. This small first-in-human study supports the concept that the Coll-R can safely deliver sirolimus to the graft-venous anastomosis. Safety and patency in this small study were sufficiently encouraging to justify randomized controlled trials to further test the efficacy of the Coll-R.

Original languageEnglish (US)
Pages (from-to)1219-1224
Number of pages6
JournalNephrology Dialysis Transplantation
Volume27
Issue number3
DOIs
StatePublished - May 1 2012

Keywords

  • Hemodialysis access
  • Neointimal hyperplasia
  • Sirolimus
  • Thrombosis
  • Vascular access

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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