Runner-up Poster Award - 2004 FDA Science Forum
B-05
Local Delivery of Estrogen Inhibits Stenosis Following Angioplasty Balloon Injury in a Swine Model: A Preliminary Report on the Safety and Effectiveness of a Trans-Vascular Needle Injection Catheter
J. W. Karanian1 , R. Virmani2 , D. Wray-Cahen1 , A. E. Ashby1 , S. L. Hilbert1 , W. F. Pritchard1 , 1Laboratory of Preclinical Studies, OST, CDRH, FDA, Laurel, MD, 2Armed Forces Institute of Pathology, Washington, DC
We have previously shown that coronary arteries in swine develop neointimal hyperplasia (NH) by 30 days after balloon angioplasty. This NH leads to stenosis, a failure mode associated with balloon angioplasty and stenting. In this earlier study, intact females had less NH than ovariectomized females, with a lesser degree of stenosis. However, chronic systemic estrogen replacement therapy (ERT) did not significantly reduce NH or stenosis in ovariectomized females. Recent reports analyzing the risks/benefits of ERT have focused on chronic systemic administration, not localized single dose delivery to the interventional site. The current study was designed to assess the safety and effectiveness of local peri-vascular administration of 17 a-Estradiol (100 µg in 350µ l vehicle) vs. vehicle alone to inhibit NH and stenosis after angioplasty. We have shown that an endoluminally delivered needle injection catheter reliably delivered 17 a-estradiol or vehicle alone (control) immediately following balloon angioplasty (peri-vascular drug delivery successful in 47 of 50 attempts). Angiographic evaluation demonstrated circumferential and longitudinal distribution in the peri-vascular space around the intervention site with no extravasation noted. Gross tissue analysis at explant (30 days post-intervention) showed no hemorrhage or petechia. Interim analysis showed little or no NH after balloon angioplasty with estrogen as compared to angioplasty with vehicle. The pharmacodynamic results combined with the pharmacokinetic analysis of drug levels will be presented. These preliminary data are consistent with the proposition that local drug delivery, via needle injection catheter, may provide a reliable, safe and efficacious therapy for the treatment of vascular disease and restenosis.
2004 FDA Science Forum | FDA Chapter, Sigma Xi | CFSAN | FDA
Last updated on 2004-JUN-24 by frf