A Multicenter, Prospective, Single-Blind, Randomized, Controlled, Study of the Repair of Challenging Abdominal Wall Defects: Strattice TM in abdominal Wall Repair (StaR)

Synthetic absorbable and non-absorbable mesh materials are often used by
surgeons to assist in the closure of abdominal wall defects. However, routine
use of non-absorbable synthetic mesh in the setting of contamination can result
in chronic infection (which may require mesh removal), fistula formation,
visceral adhesion, skin or visceral erosion, and mesh extrusion, while the use
of absorbable polyglactin mesh has an expected 100% incidence of hernia
occurrence. However, it is clear that most defects of any appreciable size
should be repaired with a mesh to decrease the incidence of recurrence and
other complications.

The literature has reported that biological mesh materials are successful in
the use to repair abdominal wall defects; they are noted to be more tolerant of
contaminated environments and even in the face of infection, may be treated in
situ. In any case, in significantly contaminated or infected cases, steps
should be taken to gain control of the infection, including, but not limited
to, appropriate drainage, debridement, negative pressure therapy, and
antimicrobial therapy prior and in addition to implantation of StratticeTM TM.

For post laparotomy fascial dehiscence, the clinical published literature has
reported a variety of treatment modalities . Currently, the most common
strategy for the management of fascial dehiscence is primary closure with
suture.The literature indicates that this repair fails in 6 - 44%.

For the management of open abdomen or contaminated incisional hernia, the use
of prosthetic mesh is still contraindicated under infectious or contaminated
conditions, in which case a second stage repair should be considered, with or
without using an absorbable mesh for acute management.

The literature reports significant evidence to suggest that a mesh should be
used to repair abdominal defects of any appreciable size. Since these wounds
are considered to be bacterial contaminated, the use of permanent synthetic
mesh is contraindicated due to the high risk of local wound events and the
potential for chronic infection. The use of absorbable (polyglactin) mesh has a
higher initial success rate than primary suture closure in the management of
abdominal wall defects, but almost always necessitates additional surgeries for
repair of the abdominal wall.

The use of biological mesh in this setting where surgeons are hesitant to use
synthetic meshes, to facilitate the repair of abdominal wall defects, will be
investigated. In this post-market clinical study, the incidence of wound
complications following repair decreasing post-repair morbidity, hospital stay,
and mortality as well as the incidence of incisional hernia are being assessed.

The primary objective of this clinical study is to compare the incidence of
post-repair wound related complications, including hernia occurence/reccurence
between challenging abdominal wall defects repaired with Strattice
Reconstructive Tissue Matrix undrelay and those mananged by standard repair.

The secondary objectives of this study are to demonstrate the clinical utility
of Strattice Reconstructive Tissue Matrix in the repair of abdominal wall
defects.

This is a prospective, multicenter, single-blind, randomized, controlled study
of the repair of challenging abdominal wall defects using Strattice
Reconstructive Tissue Matrix or standard surgical repair.

One group of patients will have their abdominal wall defect repaired with
Strattice* TM, the other group of patients will have their abdominal wall
defect repaired by the standard surgical practice of the hospital.

VISIT SCHEDULE
The participant will undergo surgery to close the abdominal wall. Before the
surgery takes place, the participant's surgeon will ensure that there is no
active infection present. If an infection is present, it may take a few days to
treat the infection (for instance by antibiotic treatment, removal of dead
tissue or other wound therapies) before surgery will take place.

During this period, the participant will undergo a standard physical
examination and the medical and medication history will be reviewed and
documented. Also, a photograph of the participant's abdominal wound will be
taken. Only the participant's abdomen and wound will be in the photograph:
nobody will be able to identify the participant from the picture taken.

On the day the participant's abdominal wall is ready to be repaired and
surgically closed, he or she will be assigned randomly to one of the two
treatment groups: one group of patients will have their wound repaired with
reinforcement with Strattice* TM, the other group of patients will have their
wound repaired by the standard surgical practice of the hospital.

The participant's assignment to a treatment group will be allocated by chance,
like the flipping of a coin. He or she will have an equal chance of being
assigned to either group. Neither the participant nor the investigator will
know in advance to which group they will be assigned.

For the complete duration of the study, which is 12 months after the
participant's surgery has taken place, he or she will not know in which
treatment group they have been assigned. The reason for this is to exclude any
unfairness when the participant is asked questions during their healing time
period.

Within 24 hours after assignment to a treatment group, the participant will
undergo surgery to close her/his wound dehiscence. If the participant is
assigned to the group in which Strattice* TM is used, the surgeon will place a
piece of Strattice* TM under the the abdominal muscles during the participant's
surgery to give it extra strength.

If the participant is assigned to the group in which current standard surgical
practice will be applied, the wound will be either stitched closed with sutures
alone, or reinforced with an absorbable mesh and then stitched closed. The
surgeon will decide which of these treatments the participant will receive,
depending on the size of the wound and other criteria.

Independent of the treatment group the participant is in, during the surgery, a
small piece of tissue will be taken from the wound edge. That small piece of
tissue (called a biopsy) will be no more than 1x1 cm in size and will be used
to count the number and specify the type(s) of bacteria that might be present
in the tissue. These results will provide information on the status of the
wound immediately prior to closure.
The participant's tissue sample will only be used for the bacterial analysis
and will be discarded after that analysis is complete.

After the surgery has taken place, the participant's doctor will follow up with
the participant at several intervals during the course of one year:
At 7, 14 and 30 Days after the participant's wound dehiscence has been closed,
the surgeon will evaluate the wound for any type of complications the
participant may have or have had. During each of these appointments, a
photograph of the participant's wound will be taken. At 30 days after surgery
every participant will be asked to complete 2 short questionnaires on their
status of daily activities.

At 3, 6 and 12 Months after the surgery for wound closure has taken place, the
participant will be requested to visit the study surgeon again. During these
visits, the surgeon will evaluate the wound for any complications and at each
visit, a photograph will be taken. The participant will be asked to complete a
short questionnaire regarding the status of daily activities. Every participant
will also be asked when they have returned to work and whether or not they have
been hospitalized. In addition to this, the participant will be asked regarding
his or her satisfaction about the surgical repair procedure that was used.

If, at any time during the study, the surgeon suspects that the participant has
a hernia, he or she will ask the participant to have a scan, either Magnetic
Resonance Imaging (MRI) or Computed Tomography (CT), depending on standard
hospital practice. These scans can confirm if the participant indeed has a
hernia. The ordering of CT scans, when a surgeon suspects a hernia, will only
be done if according to standard procedures within the participant's hospital
and if this CT scan would also have been ordered if the participant did not
participate in this clinical study. In any other case, an MRI will be ordered.
When the scan proves that a hernia has occurred, the study participant does no
longer need to complete the remaining study visits, as the primary endpoint has
been reached.

At 12 months after the surgery has taken place, the participant will be
required to undergo an MRI scan of the abdominal wound site area. This scan
will be performed in every case, even if the surgeon does not suspect that the
participant has a hernia. This scan will allow the study surgeon to check if
the participant has a hernia or not. All scans will be sent to a central
reading facility, to have standardized, unbiased review and evaluation of all
MRI scans.

If within 12 months following the initial repair of the fascial defect, a
re-operation is deemed medically necessary (as per surgeon determination) to
address a failure of the repair or to perform a planned final repair, such need
will be identified and recorded. It is understood that multiple issues, both
from the surgeon and the patient, may influence the decision as to whether or
not a re-operation is actually undertaken. However, in the event that the
re-operation is actually performed during the 12 month follow up period, in
those patients who were randomized to and received a *standard repair*, they
will be offered the use of Strattice* TM to support the repair. If Strattice*
TM is used, these patients will be *crossed-over* into the Strattice* group and
will continue to be followed for the balance of their participation in the
study. If material(s) other than Strattice* TM is used to accomplish this new
repair, those patients will have completed their participation in the study.
For those patients who received Strattice* TM for the initial repair of their
defect and for whom a re-operation is deemed medically necessary to address the
failure of that repair (i.e. herniation), such necessity will be identified and
recorded. Patients will continue to be followed until that repair is actually
performed and will have completed their participation in the study at that time.


RISKS
The potential side-effects and risks of the surgical repair of an abdominal
wall defect with Strattice TM or the standard of care treatment include:
- Those related to the surgery and anaesthesia, such as nausea, vomiting,
headaches, bleeding, pain, abnormal clotting, infection and death;
- Those related to surgical and implantation techniques, such as seroma
(collection of fluid between the layers of tissue in your abdominal wall),
wound dehiscence (opening of the stitched wound), hematoma (a collection of
blood between the layers of tissue in your abdominal wall), skin necrosis,
(skin dying, usually at the edges of the wound) and cellulitis (a readness of
the skin around the incision);
- Those related to the mesh, such as mesh tearing, rupture or strechting, and
- Those related to long term complications, such as infection and hernia
formation.

These risks are expected and considered acceptable for the surgical repair of a
dehisced abdominal woudn with sutures or meshes.

There may be risks that are unknown at this time. Should any new developments
arise and new information is known about potential risks of using Strattice TM
in the course of this clinical study, we will inform the participant as soon as
possible.

Any candidate will be warned in the information for consent to not participate
in this trial if they are allergic to pork or sensitive ot polysorbate

Additional burdens are:
- one additional MRI exam
- Tissue biopsy from wound edge. Although this will be done during surgery and
patients are sedated and unconscious and therefore will not be considered a
real burden
- possible additional post surgery follow up visits. Although some of those
would also occur outside of the study.
- Completing questionnaires