التفاصيل البيبلوغرافية
| العنوان: |
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). |
| المؤلفون: |
Paulson, William D.1,2, Kipshidze, Nicholas3, Kipiani, Konstantine4, Beridze, Nutsa4, DeVita, Maria V.5, Shenoy, Surendra6, Iyer, Sriram S.7 |
| المصدر: |
Nephrology Dialysis Transplantation. Mar2012, Vol. 27 Issue 3, p1219-1224. 6p. 1 Diagram, 2 Charts, 2 Graphs. |
| مصطلحات موضوعية: |
*DRUG efficacy, *MEDICATION safety, *RAPAMYCIN, *HEMODIALYSIS, *HYPERPLASIA, *COLLAGEN, *POLYTEF, *IMMUNOSUPPRESSION |
| مستخلص: |
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 graft-venous 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 + Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokinetics of 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. [ABSTRACT FROM PUBLISHER] |
| قاعدة البيانات: |
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