HEALIONICS CORPORATION — Department of Health and Human Services SBIR Phase II: 400

Description

DESCRIPTION provided by applicant Objective The goals of this Phase II SBIR proposal are to evaluate longer term patency and safety of a novel hemodialysis access graft design ePTFE treated with textured microporous silicone exterior layer and complete the necessary development steps to prepare the device for clinical evaluation The Phase I feasibility study demonstrated markedly superior patency and reduction of neointimal hyperplasia compared to untreated ePTFE controls through weeks in a sheep model Significance The need for frequent treatments at least x 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 AV grafts the safest alternative due to longer term patency concerns more than half of all first year hemodialysis patients and more than longer term are treated via unsafe andquot last resortandquot infection prone catheters Loss of patency by AV grafts is primarily due to development of neointimal hyperplasia at the venous anastomosis which causes progressive narrowing of the lumen leading to unstable low flow followed by thrombosis failure Successful clinical introduction of an AV graft overcoming the hyperplasia problem would increase access options and especially enable a significant reduction in the use of high risk catheters Innovation A number of factors including surgical trauma at time of implant graft vein compliance mismatch and unfavorable hemodynamic shear stress patterns are known to contribute to neointimal hyperplasia But the underlying root cause of the problem that causes synthetic AV grafts to fail is the self reinforcing andquot death spiralandquot feedback loop hyperplasia causes low flow which upregulates the advance of hyperplasia By treating ePTFE grafts with an exterior biointerface that prevents the formation of a fibrous perigraft tissue capsule the usual mechanical constriction effects are eliminated The retained natural dynamic compliance of the perigraft tissue permits greater freedom for elastic and vibratory motion of the graft wall This reduces compliance mismatch and provides more favorable stress conditions at the ePTFE neointima interface It also changes the usual flow effect of hyperplasia An increase in stenotic resistance is compensated via a mechanism that widens the upstream hydraulic diameter This appears to replace the pathologic feedback loop with a more favorable self stabilizing feedback loop The promising Phase I results suggest that this approach can lead to a major leap in AV graft clinical performance and reliability Approach Specific aims are evaluating long term patency demonstrating cannulation safety and completing requisite function and reliability testing The proposed Randamp D steps will support a subsequent IDE application for a First In Human Early Feasibility Study for this Class II device Project success would offer a safer and more reliable treatment option for a large fraction of the dialysis patient population PUBLIC HEALTH RELEVANCE 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 verify the initial observations demonstrate the improved graft function over an extended time period and qualify the design towards human use