Clinical Study of an Extended-Patency Dialysis Access Graft PROJECT SUMMARY Objective: The goals of this PAR-17-034 ?Clinical Studies Fast-Track? SBIR proposal are to move a novel hemodialysis access graft design to 510(k) submission, and upon 510(k) clearance, conduct a 25-patient clinical study to demonstrate improved performance compared to current synthetic grafts, which have high rate of clotting failure (40% patency at 1 year). Preclinical large animal studies of the novel design (ePTFE grafts treated on the venous end with a textured microporous silicone outer layer) have shown markedly superior patency and reduction of neointimal hyperplasia compared to untreated ePTFE controls. Significance: The need for frequent treatments (at least 3x per week) makes maintenance of reliable vascular access for hemodialysis patients extremely challenging. As a result of high maturation failure in autogenous arteriovenous (AV) fistulas (the preferred vascular access option) and a reluctance to use synthetic AV grafts (the safest alternative) due to poorer patency, more than half of all first-year hemodialysis patients, and more than 20% longer term, are treated via unsafe ?last-resort? infection-prone catheters. Loss of patency by AV grafts is primarily due to development of neointimal hyperplasia at the venous anastomosis, which causes progressive stenosis (narrowing) of the lumen, leading to unstable low flow followed by thrombosis failure (occlusion). Successful clinical introduction of an AV graft overcoming the neointimal hyperplasia problem would increase access options, and especially, enable a significant reduction in the use of high-risk catheters. Innovation: This approach is a new way to address the neointimal hyperplasia problem. By treating ePTFE grafts with an exterior biointerface that prevents a fibrotic encapsulation response from the surrounding tissue, the usual mechanical constriction effects from capsular contraction are eliminated. This provides freedom for the graft wall to flex in response to the pulsatile blood flow at the anastomosis, alleviating the unfavorable oscillating stresses in the neointima that ordinarily trigger neointimal thickening. The end result is prevention of the usual stenosis at the venous outflow and preservation of long-term stable flow. Design refinements on the antifibrotic biointerface, verified in our preclinical studies, allow this to be applied only to the venous end of the AV graft, using innovative coverage patterns that preserve stable high flow This removes approval risks associated with full-length coverage (e.g., kinking, cannulation concerns), allowing a clear approval path while preserving efficacy in preventing venous-end stenosis. The preclinical results suggest a high major leap in clinical use reliability. Impact: Successful commercialization of an AV graft with superior long-term patency would improve patient safety and quality of life by enabling significant reductions in the use of high-risk catheters and the number of hospitalizations related to vascular access complications. v0.04
PI Andrew Marshall, PhD NARRATIVE A significant portion of end stage renal disease (ESRD) patients on hemodialysis rely on vascular access via an implanted prosthetic arteriovenous graft. These devices suffer from progressive flow blockages and require periodic interventions to restore patency. We have discovered that these blockages can be greatly reduced by adding an outer layer of our structured porous biomaterial onto conventional grafts. This layer minimizes graft contraction and loss of flow caused by the squeezing effect of tissue fibrous capsule formation around the implants. This project is to conduct a ?first in human? clinical study with the modified grafts. 0.2
