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medical community endorses radiocephalic AVFs as the optimal form of vascular access and the recommended first choice for new hemodialysis patients. Creating the vascular access site
at the wrist preserves the potential future use of other access further up in the arm, is simpler to create, and is less likely to create heart failure or steal syndrome, where the diversion of flow
through the AVF reduces blood to the hand. Radiocephalic AVFs are also less likely to suffer from central stenoses in the shoulder and chest, remote from the site of the AVF. The Kidney Disease
Outcome Quality Initiative Guidelines, or KDOQI Guidelines, authored by the National Kidney Foundation, or NKF, specifically recommend starting with a radiocephalic AVF if possible, stating that
"starting [closer to the hand] and moving [further up the arm] provides for the possibility of preserving as many potential sites as possible for future
access creation." If a radiocephalic AVF must be abandoned, a surgeon can create a new vascular access higher up the arm, most likely a brachiocephalic AVF. However, if a brachiocephalic AVF is placed
first, the surgeon cannot later move down that same arm to create a radiocephalic AVF because the cephalic vein has already been transected for use in the brachiocephalic AVF.
(wrist) AVFs suffer from high rates of patency loss and maturation failure, with up to 70% being subject to primary unassisted patency loss and up to 35% being abandoned
within twelve months after their surgical placement. Patency loss in radiocephalic AVFs occurs due to stenosis formation at or near the AVF 75% - 95% of the time. Some patients never receive a
radiocephalic AVF because the surgeon believes the risk of failure is too high for those patients. These patients will typically undergo placement of an AVF higher up on the arm and permanently lose
at least one of their access sites. We believe that the number of radiocephalic AVFs created annually may rise significantly if PRT-201 improves outcomes and allows vascular surgeons to create
radiocephalic AVFs in sites that they previously considered to pose an unacceptably high risk of failure.
second choice for vascular access after AVF is an AVG in which a surgeon connects an artery and vein using a synthetic tube. Based on reported data, approximately 20% of hemodialysis
patients in the United States dialyze with an AVG, compared to approximately 5-12% of patients in the major European countries and approximately 7% of patients in Japan.
least desirable type of vascular access is a catheter, a plastic tube that is placed directly through the skin into a vein, typically via an incision in the neck enabling placement
of the catheter into a large vein that leads directly to the heart. The catheter connects the patient's vasculature to the hemodialysis machine. Because the catheter penetrates the skin continuously,
it is subject to a high risk of infection
and increased mortality. One of the primary goals of hemodialysis care is to keep patients off catheters. However, patients most often initiate hemodialysis through a catheter until an AVG or AVF is
ready to be used, and are dialyzed temporarily through a catheter when the AVF or AVG they have been using fails and a new one has to be created. Approximately 20% of hemodialysis patients in the
United States dialyze with a catheter, compared to 10-28% of patients in the major European countries and 2% of patients in Japan, based on published data.
Established Medical Need
The need to improve vascular access outcomes is well established in the hemodialysis community. The health-related and economic cost of
creating and maintaining vascular access for hemodialysis has led to a global effort to address the problem. Over the last ten years, the NKF has established guidelines in an effort to increase the
use of AVFs while reducing the rate of complications, mostly through the identification and promulgation of best practices. The National Institutes of Health joined the effort in 2000 with the
creation of a multi-center consortium of medical centers, the Dialysis Access Clinical Trials Consortium to coordinate the testing of new treatments designed to improve AVF and AVG outcomes. The
intensity of these efforts increased markedly in 2004, when the Centers for Medicare and Medicaid Services, or CMS, reacting to health and economic data, announced the "Fistula First" initiative to
increase the use of AVFs while reducing complications. According to Fistula First, AVFs should be considered for every patient needing hemodialysis because AVFs last longer than AVGs, require fewer
surgical and endovascular interventions, are associated with lower rates of infection, hospitalization and