VASCular no-REact® Graft Against INfection (VASC-REGAIN) Trial

BioIntegral Surgical is a manufacturer of medical devices for cardiovascular
surgery and produeces products which are all-biological and have a long and
demonstrated history in fighting infection in cardiac, vascular and general
surgery settings.

The No-React® Non-Valved Conduit (NRVC) is composed of a bovine pericardium
sutured into a singleconduit or bifurcated conduit of variable diameters.

Like all BioIntegral products, the glutaraldehyde cross-linked conduit has been
detoxified with a unique process. In contrast to conventional glutaraldehyde
treatment, No-React® detoxified tissue does not leach detectable glutaraldehyde
molecules and has been clinically proven to invite
endothelial cells to its surfaces which are in contact with blood. What*s more,
the process also pacifies the tissue and creates a more permanent bond among
the glutaraldehyde and collagen, ensuring improved long-term durability of the
grafts. The No-React® process makes the xenograft
vessel tissue biocompatible, anti-infective, avoids coagulation and biological
degeneration, all while retaining all the positive physical attributes of
glutaraldehyde-treated tissues.

The No-React® Non-Valved Conduit (NRVC) is intended for use when there is a
need for a biocompatible and infection resistant graft to replace infected
prostheses or to treat patients at high risk of (re)infection in the following
locations: descending aorta, aorto-iliac, aorto-femoral and above-knee
peripheral vasculature. There is no restriction on the age indication for this
product.

This study seeks to demonstrate the effectiveness and safety of the Non-Valved
Conduit on the basis of infection. The rationale for infection resistance with
the conduit is that Biointegral Surgical No-React® treated products have a
well-documented history of infection resistance in hybrid
vascular settings.

- Primary objective: Determine (re)-infection rate of the vascular conduit at 3
months following implantation in high infection risk patients or as a
replacement for infected prosthetic graft.

- Secondary objective: Determine the patency rate of the vascular conduit at 12
months following implantation.

- Other objectives: Any adverse event * morbidity or mortality * is to be
reported regardless if it is device or non-device related. In each case, the
distinction between device and non-device related adverse event must be made.

This is a multicenter prospective intervention study which will require the
inclusion of 60 patients from 10 vascular centers in the Netherlands.

Included patients will have an operation for the implantation of the No-React®
Non-Valved Conduit (NRVC) as vascular conduit.

Subjects can expect to have a lower risk of (re)infection, amputation and
mortality.

There are no anticipated adverse device effects.

Residual risks related to the device are due to the nature of the product or
the manufacturing process and have been classified as residual risks due to the
serious, critical or catastrophic consequence. However, all of these residual
risks are acceptable as per the risk analysis; no further
risk control is possible without sacrificing the integrity of the device.

The risks associated with participation in the clinical investigation include
are infection, thrombosis/thromboembolism, haemolysis, bleeding, stenosis, BSE
and/or other possible contaminants and surgical risks. These risks can result
in graft explantation, amputation, sepsis and/or death. However, the likelihood
of these occurring is improbable or remote at worst. As per the risk analysis,
the clinical benefits far outweigh the risks associated with participation,
considering the expected urgent state of the subjects. The inherent design of
the device and the implantation of
all possible controls minimize the probability of any of these events but they
must be included due to their serious, critical or catastrophic consequences to
the subject. The manufacturer does not expect any of these to occur in relation
to the device.