THE GROWING NEED

Globally, hemodialysis represents the most common type of renal replacement therapy for End Stage Renal Disease (ESRD) patients. In the U.S., more than 400,000 patients are currently on hemodialysis.

During hemodialysis, two large bore needles are inserted into the venous limb of the vascular access, one to draw the blood out, the other to return it after passing it through a dialyzer. The ideal vascular access should (a) provide longevity of use with minimal complication rates from infection and thrombosis and (b) sustain high blood flow rates to deliver the prescribed dialysis dose. A functional vascular access, therefore, is the lifeline for these patients.

Physicians utilize one of two types of permanent, vascular accesses to support hemodialysis: An arteriovenous fistula (AVF) and an arteriovenous graft (AVG):

Arteriovenous Fistula

An artery and a vein are connected (anastomosed) directly to each other. Over the ensuing weeks (typically around 6 weeks), the diameter of the upstream vein enlarges and the wall of the vein thickens in response to the increased blood flow and wall stress – a process referred to as “fistula maturation.” Fistula maturation is a key event because it signals readiness for cannulation and the end of catheter dependence

Arteriovenous Graft

One end of a synthetic (usually PTFE) graft is anastomosed to an artery and the other end is anastomosed to a vein. Approximately 3 4 weeks post-surgery, the body of the PTFE graft can be cannulated for hemodialysis.

Current practice guidelines recommend an AV fistula as the preferred vascular access. However, today in the U.S., approximately 80% of the 104,000 incident patients begin dialysis using a central venous catheter (CVC), the least preferred option.

These patients will continue to be dialyzed using a catheter until a mature AV fistula or an AV graft is ready for insertion of needles to support dialysis (the process of needle insertion is referred to as “access cannulation”). The use of catheters is associated with serious mortality and morbidity events that include infection, thrombosis and stenosis or occlusion of the central vein.

ESRD health care providers are fully cognizant of the drawbacks of catheter use for hemodialysis and recognize the urgent need to minimize dependence on catheters.

THE PROBLEM: VASCULAR ACCESS FAILURE

A Potential Solution

Using a novel bio-resorbable collagen-based drug delivery system that is designed to self curl upon hydration, Vascular Therapies is evaluating local (perivascular) delivery of sirolimus, which is commenced intra-operatively soon after the surgical creation of the vascular access is successfully completed.

The intensely lipophilic sirolimus molecule combines with the lipid elements in the wall of the blood vessel and reduces (down regulates) cellular proliferation, a known effect of the drug when delivered to the vessel wall. Tissue pharmacokinetic studies in an animal model show persistence of drug for at least eight weeks after commencement of drug delivery.

The delivery system is designed to maintain its cylindrical shape without the need for sutures to keep the free edges approximated and to permit the expected increase in vein diameter – an integral part of fistula maturation.

Approximately 80% of patients in the United States initiate dialysis with a catheter. These patients will continue to be catheter-dependent until a fistula (or an AV graft) becomes ready for dialysis.

Reducing the time between surgery and when the fistula can be cannulated successfully for dialysis and minimizing the need for additional, supplementary interventions to help maintain fistula functionality are extremely clinically relevant outcomes. Achieving these endpoints are expected to reduce catheter dwell time and catheter dependence – a much-desired outcome with important implications for patients, dialysis providers and payors.

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