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

39 Citations (Scopus)

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

Fingerprint

Sirolimus
Renal Dialysis
Collagen
Transplants
Safety
Membranes
Blood Vessels
Hyperplasia
Protective Devices
Drug-Eluting Stents
Polytetrafluoroethylene
Wound Healing
Immunosuppression
Coronary Artery Disease
Thrombosis
Randomized Controlled Trials
Therapeutics
Growth
Infection
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

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

In: Nephrology Dialysis Transplantation, Vol. 27, No. 3, 01.05.2012, p. 1219-1224.

Research output: Contribution to journalArticle

Paulson, William D. ; Kipshidze, Nicholas ; Kipiani, Konstantine ; Beridze, Nutsa ; DeVita, Maria V. ; Shenoy, Surendra ; Iyer, Sriram S. / 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). In: Nephrology Dialysis Transplantation. 2012 ; Vol. 27, No. 3. pp. 1219-1224.
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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.",
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T2 - First human experience with a sirolimus-eluting collagen membrane (Coll-R)

AU - Paulson, William D.

AU - Kipshidze, Nicholas

AU - Kipiani, Konstantine

AU - Beridze, Nutsa

AU - DeVita, Maria V.

AU - Shenoy, Surendra

AU - Iyer, Sriram S.

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

KW - Hemodialysis access

KW - Neointimal hyperplasia

KW - Sirolimus

KW - Thrombosis

KW - Vascular access

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