MARS study- Mesh Augmented Reinforcement of Abdominal Wall Suture Line in Patients Undergoing Midline Laparotomy to limit the Rate of Incisional Hernia ( IH) Occurrence

Pls see section 4.1 of the CIP version 2.0, 10Jul2023

The purpose of this prospective, pivotal, multi-center, single-arm cohort,
pre-market, investigational clinical study is to assess the safety and
performance of Deternia* Self-Gripping Resorbable Mesh when used for suture
line reinforcement after midline laparotomy in clean and clean-contaminated
fields (CDC Classification I and II). Data from this study will be used to
support market applications.

This study is a prospective, pivotal, multi-center, single-arm, pre-market,
investigational clinical study evaluating the use of the Deternia*
Self-Gripping Resorbable Mesh in patients undergoing midline laparotomy in
clean and clean-contaminated fields (CDC Classification I and II) in order to
limit the rate of IH occurrence.
All subjects will receive midline abdominal wall closure with small bites
technique reinforced by Deternia* Self-Gripping Resorbable Mesh placed in the
retrorectus space. The purpose of the investigation is to limit the IH
occurrence and demonstrate expected performance of the study device against a
Performance Goal based on historical data on primary laparotomy incision suture
closure with small bites only.

Study duration is estimated to be 27 months of recruitment and 36 months of
follow-up post-surgery.
Participating centers and investigators are qualified surgeons experienced in
the surgical management of patients with mesh augmented reinforcement for
abdominal laparotomies or experienced with mesh placement for hernia repair.

Subjects will be evaluated at baseline/screening, during surgery, at discharge,
and at 3-, 6-, 12-, 24-, and 36-months post-surgery. Assessments to be
conducted/data collected include:

Pre-operative data:
* Subject eligibility (pre-operative criteria)
* Subject informed consent (Subject should be re-consented if date of original
consent is greater than 30 days before the procedure)
* Subject demographics
* BMI
* Medical and abdominal surgical histories and relevant risk factors
* American Society of Anesthesiologists (ASA) grade
* EQ-5D-5L Quality of life questionnaire - pre-operative assessment
* Pain (Numeric Rating Scale (NRS) score from 0 to 10) of the abdominal wall
Note: Preoperative (screening) day and operative day can be combined

Operative data (Day 0):
* Eligibility criteria (Intra-operative criteria)
* Pregnancy status
* BMI
* Date of surgery, operative start and stop times (from skin incision to skin
closure)
* General anesthesia information (type)
* Intraoperative wound contamination class
* Antibiotic prophylaxis
* Anticoagulation use
* Indication for midline laparotomy, surgical technique approach, and type of
surgery
* Abdomen description and fascial closure details (length of fascial incision,
suturing closure technique, suture type, suture length, drains left)
* Study device data (mesh size, location of mesh placement, mesh overlap,
location of grip placement, lot number)
* Number/type of fixation, if applicable
* Adverse events and device deficiencies, if applicable,
* Surgeon satisfaction questionnaire
* Amount of time to create the retrorectus space and insert, position, and
fixate the mesh, if applicable
Note: Preoperative (Screening) Day and Operative Day can be combined

Discharge data:
* Pain (Numeric Rating Scale (NRS) score from 0 to 10) at site of surgery
* Adverse events and device deficiencies, if applicable
* Anticoagulation use, if applicable
* Length of hospital stay

3-month (± 14 days) and 6-month (± 14 days) Follow-up:
* Pain (NRS score from 0 to 10) at site of surgery
* EQ-5D-5L Quality of Life questionnaire - Post-operative assessment
* Adverse events and device deficiencies, if applicable
* Anticoagulation use, if applicable
* Clinical physical examination for incisional hernia
* Details of incisional hernia, if applicable (EHS classification, mesh
placement location, defect size, etc.)
* Mesh removal, if applicable

12-month (± 30 Days), 24-month (± 45 Days), and 36-month (± 45 Days) Follow-up:
* Pain (NRS score from 0 to 10) at site of surgery
* EQ-5D-5L Quality of Life questionnaire - Post-operative assessment
* Adverse events and device deficiencies, if applicable
* Anticoagulation use, if applicable
* Clinical physical examination for incisional hernia
* Details of incisional hernia if applicable (EHS classification, mesh
placement location, defect size, etc.)
* Imagery (ultrasound required and CT scan as desired/needed per SOC) for
incisional hernia
* Mesh removal, if applicable

Additional visits
* Clinical physical examination for incisional hernia if applicable
* Details of incisional hernia, if applicable (EHS classification, mesh
placement location, defect size, etc.)
* Imagery (ultrasound required and CT scan as desired/needed per SOC/) for
incisional hernia if applicable
* Mesh removal, if applicable
* Adverse events and device deficiencies, if applicable
* Anticoagulation use, if applicable

Based on the literature, there are 3 type of prosthetic materials mostly used
for the prevention of incisional hernia including:

•Synthetic nonabsorbable or partially absorbable material: will remain in the
body indefinitely and is considered a permanent implantation; used to provide
permanent reinforcement to the abdominal wall
•Biological material: "transforms" itself into the tissue with which it comes
in contact and disappears completely after having exercised its containment
effect for the necessary time
•Biosynthetic or synthetic fully and slow absorbable material: constitutes a
class of materials that are completely absorbed by the surrounding tissue over
time

According to the available clinical data, there is quantity of evidence on the
use of permanent synthetic mesh as prophylactic mesh for prevention of
incisional hernia. However, some surgeons might be mostly reluctant to implant
a permanent synthetic mesh leaving permanent foreign body material in a patient
because of the long-term postoperative complications such as infection and
chronic pain. Biologic mesh are also used in this indication but their high
costs limit their use and do not have always optimal properties for this
purpose (references: Soderback, Pizza, Faulkner ).

Deternia* Self Gripping Resorbable mesh is a synthetic slowly resorbable mesh
that will reinforce the abdominal wall during the critical healing period and
progressively resorbs while fascia will retrieve its original strength over the
time. There is therefore medical-scientific interest in examining if such mesh
will result in the same outcomes as synthetic permanent mesh with fewer
long-term side effects.
Regarding the risk/benefit assessment of a slowly resorbable type of mesh used
in this study, Medtronic has performed a literature review of the available
clinical data. The 3 on-market products considered to be competitive to
Deternia* Self-Gripping Resorbable mesh are: Phasix* (Bard), Gore* Bio A*
(Gore), and Tiger* Matrix (Novus Scientific). Please refer to Section 4.1.
Previous Clinical Experience in chapter 4. Existing Clinical Data in the MARS
Investigator*s Brochure v.1.0-21Apr2022 for more information.
This literature review concluded that based on clinical data from published
scientific literature and post market surveillance, synthetic absorbable
meshes, which are part of the state of the art for suture-line reinforcement,
appear to present a favorable benefit/risk profile in such an indication. The
benefit/risk assessment performed for the study mesh is also described in
Section 5.1. Benefit-Risk Analysis and Results under chapter 5. Risk Management
of the Investigational Device in the MARS Investigator*s Brochure v.1.0 -
21Apr2022 and in the Risk Management Report RMR070 Rev. B .