A Post-Market, Prospective, Multicenter, Single-Arm Trial of XenMatrix™ AB Surgical Graft in All Wound Classes Ventral or Incisional Midline Hernias
Phase: NA
Conditions: Incisional Hernia
Sponsor: C. R. Bard

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CLINICAL STUDY PROTOCOL 
Title: 
A Post-Market, Prospective, Multicenter, Single-Arm Trial 
of XenMatrix™ AB Surgical Graft in All CDC Wound 
Class Ventral or Incisional Midline Hernias 
Protocol Number: 
DVL-HE-012 
Study Type: 
Post-Market 
Date: 
August 7, 2018 
Version: 
3.0 
Study Device: 
Bard
 XenMatrix™ AB Surgical Graft 
Sponsor: 
Davol Inc. 
Subsidiary of C. R. Bard, Inc. 
100 Crossings Boulevard 
Warwick, RI 02886 
Phone: 1-800-556-6756 
Sponsor Contacts: 
Dawn Heimer, PhD 
Davol Inc. 
100 Crossings Boulevard 
Warwick, RI 02886 
Telephone: 401-825-8681 
E-mail: dawn.heimer@crbard.com
NCT number: NCT02691962
NCT number added post approval as per CT.gov requirement.

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Protocol Signature Page 
 
The Investigator agrees to conduct the clinical study which is the subject of this protocol in 
accordance with the Clinical Study Agreement, this protocol, all applicable laws and 
regulations, and the conditions of approval imposed by the reviewing Institutional Review 
Board. 
 
 
 
Agreed to by (Investigator): 
 
 
 
 
Printed Name – Investigator 
 
 
 
 
Signature – Investigator 
 
 
 
 
Date 

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Protocol Abbreviations/Acronyms 
Abbreviation/Acronym 
Definition 
ADL 
Activities of Daily Living 
AE(s) 
Adverse Event(s) 
AMP 
Antimicrobial Prophylaxis 
ASA 
American Society of Anesthesiology 
Bard 
C. R. Bard, Inc. 
BMI 
Body Mass Index 
CDC 
Centers for Disease Control 
C. difficile 
Clostridium difficile bacterium 
CFR 
Code of Federal Regulations 
cm 
Centimeter 
COPD 
Chronic Obstructive Pulmonary Disease 
CST 
Component Separation Technique 
CT 
Computed Tomography 
CV 
Curriculum Vitae 
E. aerogenes 
Enterobacter aerogenes bacterium 
E. Coli 
Escherichia coli bacterium 
eCRF(s) 
Electronic Case Report Form(s) 
e.g. 
For example 
etc. 
Et cetera, and others 
F 
Fahrenheit 
FDA 
Food and Drug Administration 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
i.e. 
Id est, that is 
IFU 
Instructions for Use 
Inc. 
Incorporated 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
kg 
Kilogram 
LTFU 
Loss/Lost to Follow-up 
m 
Meter 
mg / dL 
Milligrams per deciliter 
mITT 
Modified Intent-to-Treat 
MRI 
Magnetic Resonance Imaging 
MRSA 
Methicillin-resistant Staphylococcus aureus 
N 
Number 
POD 
Post-operative Day 
SAE(s) 
Serious Adverse Event(s) 
SAP 
Statistical Analysis Plan 
SCIP 
Surgical Care Improvement Project 
SF-12 
Short-Form-12 

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TAR 
Transversus Abdominis Release 
U.S. 
United States 
USDA 
United States Department of Agriculture 
V.A.C.® 
Vacuum-Assisted Closure 
XenMatrix™ AB 
XenMatrix™ AB Surgical Graft (device) or surgical graft 

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TABLE OF CONTENTS 
1. INTRODUCTION ........................................................................................................... 1 
1.1. 
Background  ..................................................................................................... 1 
1.2. 
Rationale  ......................................................................................................... 3 
1.3. 
Device Description  .......................................................................................... 4 
2. STUDY OBJECTIVES ................................................................................................... 4 
3. STUDY ENDPOINTS ..................................................................................................... 4 
3.1. 
Primary Endpoint  .......................................................................................... 4 
3.2. 
Secondary Endpoints  ..................................................................................... 4 
4. STUDY DESIGN ............................................................................................................. 5 
5. STUDY POPULATION ................................................................................................. 5 
5.1. 
Number Of Subjects  ....................................................................................... 5 
5.2. 
Eligibility Criteria  .......................................................................................... 5 
5.2.1. 
Inclusion Criteria  ................................................................................ 5 
5.2.2. 
Exclusion Criteria  ............................................................................... 5 
6. STUDY PROCEDURES ................................................................................................. 6 
6.1. 
Subject Screening And Baseline Evaluation  ................................................ 6 
6.1.1. 
Informed Consent  ............................................................................... 7 
6.1.2. 
Enrollment  .......................................................................................... 7 
6.1.3. 
Eligibility  ............................................................................................ 7 
6.1.4. 
Assignment of Subject Number  .......................................................... 7 
6.1.5. 
Demographics And Medical History  .................................................. 8 
6.1.6. 
Physical Examination  ......................................................................... 8 
6.1.7. 
Quality of Life Assessment  ................................................................ 8 
6.2. 
Index Procedure  ............................................................................................. 8 
6.2.1. 
Perioperative Care  .............................................................................. 8 
6.2.2. 
Abdominal Wall Reconstruction/Ventral or Incisional Hernia Surgery 
……………………………………………………………………….9 
6.2.3. 
Immediate Postoperative Care........................................................... 10 
6.2.4. 
Surgical Details  ................................................................................ 10 
6.3. 
Subject Follow-up  ......................................................................................... 10 
6.3.1. 
Assessments  ...................................................................................... 11 

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6.3.2. 
Unscheduled Visits  ........................................................................... 11 
6.4. 
Time And Events Schedule  .......................................................................... 13 
6.5. 
Subject Discontinuation  ............................................................................... 14 
6.6. 
Replacement of Subjects  .............................................................................. 14 
7. 
ADVERSE EVENTS  .................................................................................................... 14 
7.1. 
Definition of Events  ...................................................................................... 14 
7.2. 
Definition of Serious Adverse Events (SAE)  .............................................. 15 
7.3. 
Relationship Of Adverse Event To Device/Procedure  .............................. 15 
7.4. 
Severity of Adverse Events  .......................................................................... 15 
7.5. 
Reporting Of Events  ..................................................................................... 16 
8. 
MECHANICAL FAILURES, MALFUNCTIONS AND DEFECTS  ....................... 16 
9. 
RISK/BENEFIT ANALYSIS  ...................................................................................... 17 
10. CASE REPORT FORMS  ............................................................................................ 17 
11. STATISTICAL METHODS  ........................................................................................ 17 
11.1. Study Hypothesis  .......................................................................................... 17 
11.2. Sample Size Considerations  ......................................................................... 18 
11.3. Data Analysis  ................................................................................................ 18 
11.3.1. Analysis Population  .......................................................................... 18 
11.3.2. Primary Endpoint  .............................................................................. 18 
11.3.3. Secondary Endpoints  ........................................................................ 18 
11.4. Data Analysis Considerations  ...................................................................... 19 
11.4.1. Data pooling  ...................................................................................... 19 
11.4.2. Handling of missing data  .................................................................. 19 
11.5. Interim Analysis  ............................................................................................ 19 
12. ADMINISTRATIVE REQUIREMENTS  .................................................................. 19 
12.1. Investigator Selection  ................................................................................... 19 
12.2. Regulatory and Ethical Considerations  ...................................................... 20 
12.2.1. Institutional Review Board (IRB) Approval  ..................................... 20 
12.2.2. Informed Consent and HIPAA Authorization  .................................. 20 
12.3. Protocol Adherence And Deviations  ........................................................... 21 
12.4. Device Accountability  ................................................................................... 21 
12.5. Data Collection  .............................................................................................. 21 

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12.6. Subject Compensation  .................................................................................. 21 
12.7. Communications With The Sponsor  ........................................................... 21 
12.8. Required Documentation  ............................................................................. 22 
12.9. Publications  ................................................................................................... 22 
13. SITE MONITORING ................................................................................................. 22 
13.1. Study Initiation Visit  .................................................................................... 23 
13.2. Ongoing Monitoring Visits  .......................................................................... 23 
13.3. Final Monitoring Visit  .................................................................................. 23 
14. TERMINATION OF STUDY ..................................................................................... 23 
15. REPORTING REQUIREMENTS ............................................................................. 24 
16. RECORD RETENTION ............................................................................................. 24 
17. REFERENCES ............................................................................................................ 25 
18. APPENDICES .............................................................................................................. 30 
18.1. Principal Investigator Information  ............................................................. 31 
18.2. Routine Culture  ............................................................................................ 32 
18.3. Surgical Site Infection Classification  .......................................................... 34 
18.4. Clavien Dindo Classification  ........................................................................ 37 
18.5. Instructions for Use  ...................................................................................... 38 
List of Tables and Figures 
Table 1: Center for Disease Control’s Surgical Wound Classification System ....................... 2 

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1. INTRODUCTION 
 
 
1.1. Background 
 
With more than 2 million abdominal operations performed annually in the United 
States (U.S.) and with up to 20% of those patients developing ventral or incisional 
hernias, abdominal wall defects and incisional hernias represent a challenging 
surgical condition. [1, 2]  Approximately 348,000 ventral hernia repairs are 
performed on a yearly basis. [3] There are several options for repair, including 
primary repair, synthetic or biologic material placement, repair with relaxing 
incisions, and use of musculofascial flaps, utilizing both open and laparoscopic 
approaches. [2] However, there is no clear-cut consensus regarding the optimal 
hernia repair technique, particularly where patient co-morbidities exist and a high 
risk of infection is present. 
 
Simple suture repair has been associated with a high risk of hernia recurrence, with 
reports ranging from 10% to 55% recurrence rate. [4-7]   Primary suture repair has 
been nearly abandoned for the repair of hernias which are greater than five 
centimeters (cm) in size. [4-7] As a result, many ventral hernia repair procedures 
involve the use of a mesh material. 
 
Synthetic mesh repair procedures, either open or laparoscopic, have been reported to 
lead to fewer recurrences compared to primary repairs. [8-11] Improved outcomes 
with mesh are believed to be related to better distribution of tension on the fascial 
edges and sutures when mesh is used in hernia repair procedures. [41] However, 
complex cases and large abdominal wall defects continue to pose a challenge to 
surgeons. [32] Factors such as patient co-morbidities, defect size, location, tissue 
viability and degree of contamination are included in a surgeon’s assessment and 
decision-making process. [12, 30] These large abdominal wall defects have been 
associated with recurrence rates of up to 46%. [13] 
 
Today many surgeons prefer to close large defects primarily and then reinforce the 
primary repair with biologic or synthetic mesh.  In order to close these large defects 
surgeons rely on one of several component release techniques.  One approach to 
addressing the complexity of large abdominal wall defect (>5 cm in width) repair is 
the Component Separation Method.  The method was developed by Ramirez et al. in 
1990 and was based on the assumption that separating the muscle components of the 
abdominal wall would allow mobilization of the entire abdominal wall as a complete 
unit, allowing the surgeon to bring the midline together with less tension, thus 
allowing better repair of large abdominal wall defects. [14]  Numerous variations on 
the original component separation method have emerged and have reported 
recurrence rates from 0% to 30%.[14-19]  These variations range from procedural 
technique, selection and use of prosthetic repair material, and location of placement 
of such material.  Preliminary results suggest minimally invasive techniques may be 

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associated with fewer complications; however, there are similar recurrence rates 
between laparoscopic and open repair. [4, 20, 35] 
 
Although positive outcomes have been reported with the component separation 
technique when used with synthetic mesh, the presence of a permanent foreign body 
material may be associated with persistent wound infection, fistula formation, 
seroma development, mesh contraction and migration, visceral erosions, adhesions, 
chronic pain and foreign body reactions. [29] 
 
The reported risk of a wound infection following ventral hernia repair ranges 
between 0% and 23%. [11, 21-28]  Deep mesh infection frequently results in major 
complications including, the need for repeat surgery with or without mesh removal, 
wound dehiscence, prolonged recovery, decreased patient quality of life, and 
extended long-term hospitalization. [29] 
 
Biologic grafts provide a temporary collagen scaffold which is remodeled and 
replaced with the body’s own tissue over time to repair a hernia defect with fewer 
postoperative chronic wound complications. [33-35] These grafts aim to address 
many of the deficiencies of synthetic mesh, such as the need for additional surgery to 
remove infected permanent mesh in the event of surgical site infection while 
preserving the positive attributes of strength and the potential for durable, definitive 
hernia repair. [8, 36, 39] 
 
Risk of surgical site infection has been defined and categorized in the Centers for 
Disease Control’s (CDC) Guidelines for the prevention of surgical site infection 
published in 1999 (see Table 1). [49] This classification system has provided 
conformity in the definitions used to classify and categorize general surgical site 
infections (see Table 1). 
 
 
 
Table 1: Center for Disease Control’s Surgical Wound Classification System 
 
Class 
CDC Surgical Wound Classification49 
I 
Clean: An uninfected operative wound in which no inflammation is 
encountered and the respiratory, alimentary, genital, or uninfected urinary tract 
are not entered. In addition, clean wounds are primarily closed and, if 
necessary, drained with closed drainage. Operative incisional wounds that 
follow nonpenetrating (blunt) trauma should be included in this category if they 
meet the criteria. 
II 
Clean-Contaminated: An operative wound in which the respiratory, alimentary, 
genital, or urinary tracts are entered under controlled conditions and without 
unusual contamination. Specifically, operations involving the biliary tract, 
appendix, vagina, and oropharynx are included in this category, provided no 
evidence of infection or major break in technique is encountered. 
III 
Contaminated: Open, fresh, accidental wounds. In addition, operations with 
major breaks in sterile technique (e.g., open cardiac massage) or gross spillage 

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Class 
CDC Surgical Wound Classification49 
from the gastrointestinal tract, and incisions in which acute, nonpurulent 
inflammation is encountered including necrotic tissue without evidence of 
purulent drainage (e.g. dry gangrene) are included in this category. 
IV 
Dirty-Infected: Old traumatic wounds with retained devitalized tissue and those 
that involve existing clinical infection or perforated viscera. This definition 
suggests that the organisms causing postoperative infection were present in the 
operative field before the operation. 
 
 
The ability of biologic grafts to support revascularization and in growth of new cells 
may contribute to the clearance of bacteria. [4] Some biologic grafts have been 
shown to remain intact in the setting of active infection without requiring removal 
when exposed or infected. [31, 40, 43, 45-47]  Additionally, some clinical reports 
note patients were able to be managed non-surgically even when the patients’ 
wounds became infected. [31, 38, 45-47] 
 
In addition to selecting specific hernia repair materials, surgeons give consideration 
to the placement of repair material as there is evidence that the anatomical location 
of the graft is important.  There are three general locations for placing the graft, 
including onlay, inlay, and underlay positions, and most have found the underlay 
technique to be the better technique when complete fascial closure can be achieved 
based on the lower rate of re-herniation. [4]  It is believed that intra-abdominal 
forces are distributed more evenly across the repair material when placed in the 
underlay position as the intra-abdominal pressures push the repair material into the 
defect and against the native tissue rather than away from the defect. [4, 42] 
 
 
1.2. 
Rationale 
 
This study aims to prospectively explore the use of XenMatrix™ AB Surgical Graft for 
ventral or incisional midline hernia repair in patients across all wound classes (“All 
Comers”) through 24 months post repair. 
 
The device that will be utilized in this study (XenMatrix™ AB Surgical Graft) is 
intended for implantation to reinforce soft tissue where weakness exists and for 
surgical repair of damaged or ruptured soft tissue, including: abdominal plastic and 
reconstructive surgery; muscle flap reinforcement; hernia repair including abdominal, 
inguinal, femoral, diaphragmatic, scrotal, umbilical, and incisional hernias.  The 
Rifampin and Minocycline coating has been shown in preclinical in vitro and in vivo 
testing to reduce or inhibit microbial colonization on the device.  The claim of 
reduction of bacterial clearance of the device has not been established with human 
clinical data, nor has a clinical impact associated with this claim been demonstrated. 
 
Preclinical in vivo studies demonstrated an average of 4 log reduction of microbial 
colonization against gram-positive Methicillin-resistant Staphylococcus aureus 

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(MRSA) and an average of 4 log reduction against gram-negative Escherichia coli (E. 
coli). In vitro speed-to-kill testing demonstrated a minimum 4 log reduction against 
gram-positive MRSA and Methicillin-resistant Staphylococcus epidermidis (MRSE) 
and gram-negative Enterobacter aerogenes (E. aerogenes) and E. coli. [48] These 
preclinical efficacy results cannot be considered predictive of clinical performance. 
Clinical studies to evaluate performance and risk of infection have not been 
performed. 
 
 
 
1.3. 
Device Description 
 
XenMatrix™ AB Surgical Graft is an acellular, sterile, non-pyrogenic porcine dermal 
matrix packed dry for use in the reconstruction of soft tissue deficiencies. The device 
surfaces are coated with the antibacterial agents Rifampin and Minocycline in a 
bioresorbable L-Tyrosine succinate polymer carrier. The product has an orange surface 
and minor non-uniform color variation on the product surface (“freckles”) that is 
normal. 
 
The coating is shaded orange in color from the antimicrobial agents. In preclinical in 
vitro and in vivo testing, the antimicrobial agents reduce or inhibit microbial 
colonization of the product during the initial healing process for up to 7 days following 
surgery. Absorption of the resorbable polymer carrier for the antimicrobials is 
complete in approximately 12 months. 
 
 
2. 
STUDY OBJECTIVES 
 
The objective of this study is collect data on the performance and use of XenMatrix™ 
AB Surgical Graft for up to 24 months in subjects with ventral or incisional midline 
hernias, across all CDC wound classes in the retro-rectus or intraperitoneal location. 
 
 
3. 
STUDY ENDPOINTS 
 
 
3.1. 
Primary Endpoint 
 
1. Wound Occurrences in the first 45 days post-implantation. 
Wound Occurrences will be defined as surgical site infection, seroma, wound 
dehiscence, skin necrosis and fistulas requiring intervention 
 
 
3.2. 
Secondary Endpoints 
 
The secondary endpoints of this study are as follows: 
 
1. Wound Occurrences >45 days post-implantation 

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2. Rate of hernia recurrence 
3. Rate of reoperation due to the index hernia repair 
4. Carolinas Comfort Scale® and SF-12® 
5. Return to Work 
6. Length of Stay 
 
 
4. 
STUDY DESIGN 
 
This is a prospective, multicenter, single-arm clinical study to collect data on the 
performance and use of XenMatrix™ AB Surgical Graft for ventral or incisional 
midline hernia repair across patients in all CDC wound classes utilizing retro-rectus or 
intraperitoneal placement of mesh. The study will be conducted at approximately 10 
U.S. sites to treat approximately 75 subjects. Follow-up visits will be conducted at 1, 
3, 6, 12, 18 and 24 month(s) following surgery. See Section 6 for a detailed schedule 
of study visits and procedures. 
 
 
5. 
STUDY POPULATION 
 
 
5.1. 
Number Of Subjects 
 
This study is projected to enroll up to 75 subjects at approximately 10 sites. 
 
 
5.2. 
Eligibility Criteria 
 
 
5.2.1. 
Inclusion Criteria 
 
1. Subject must be ≥18 years of age. 
2. Subject must be willing and able to give written informed consent. 
3. Subject must be diagnosed with a ventral or incisional midline hernia. 
4. Mesh must be placed in the retro-rectus or intraperitoneal plane. 
5. Subject must be willing to undergo open hernia repair and be able to undergo 
all other study procedures as outlined in this protocol. 
 
 
5.2.2. 
Exclusion Criteria 
 
1. The use of surgical graft as a bridge repair. 
2. The subject has more than 4 prior recurrences. 
3. Subject has a contraindication for the placement of surgical graft. 
4. Complete removal of existing mesh from a prior hernia repair (in the same 
affected area) is not possible. 
5. The study hernia repair requires more than a single piece mesh (including 
sufficient overlap beyond margins of the defect on all sides). 

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6. Subject has intact permanent mesh adjacent to the current hernia to be 
repaired. 
7. Subject has peritonitis at the time of surgery. 
8. The subject is an active smoker within the last 2 weeks prior to surgery. 
9. Clinically significant COPD or heart failure, defined as marked limitation in 
ability or inability to perform activities of daily living. 
10. Subject had chemotherapy within the last 12 months, is on or suspected to be 
placed on chemotherapy medications during any part of the study. 
11. Chronic steroid use (>6 months) or immunosuppression drugs. 
12. Subject’s body mass index (BMI) >45 kg/m2. 
13. Subject has cirrhosis, and/or ascites. 
14. Subject has a defined collagen disorder. 
15. Known to be infected with human immunodeficiency virus (HIV). 
16. Subject has clinically significant (not based solely on creatinine levels) 
kidney disease that limits ADL, is on hemodialysis or peritoneal dialysis. 
17. Subject is American Society of Anesthesiology (ASA) Class 4 or 5. 
18. Subject has a life expectancy < 2 years at the time of enrollment. 
19. Subject is pregnant, breastfeeding or planning on becoming pregnant during 
the course of the study. 
20. Subjects with known sensitivity to porcine products. 
21. Subjects with allergy, history of allergy or hypersensitivity to tetracyclines 
(including minocycline) or rifamycins (including rifampin). 
22. Subject has any condition in the opinion of the Investigator that would 
preclude the use of the study device, or preclude the subject from completing 
the follow-up requirements. 
 
 
6. 
STUDY PROCEDURES 
 
 
6.1. 
Subject Screening And Baseline Evaluation 
 
Subjects with a diagnosis of ventral or incisional midline hernia requiring surgical 
repair will be screened for eligibility against the study protocol inclusion and 
exclusion criteria utilizing ordinary standard of care procedures (e.g., limited physical 
examination typical for hernia patients, blood work (if necessary), medical evaluation, 
etc.) which occurred within 60 days of the date of consent. This may include a full 
anesthetic work-up, customary for hernia repair procedures. Any other standard of 
care examination or evaluation within 60 days of the date of consent may be 
considered baseline for study purposes.  Prior medical records documenting these 
tests, examinations and evaluations may be used as the source documents for the 
baseline visit. 

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During the screening and recruitment process, the Investigators will be responsible for 
describing the nature of the clinical study, verifying that the eligibility criteria have 
been met, and obtaining informed consent. Written informed consent and a Health 
Insurance Portability and Accountability Act (HIPAA) waiver must be obtained prior 
to performance of any protocol specific procedures. 
 
The following specific procedures will be conducted and documented: 
 
 
6.1.1. 
Informed Consent 
 
All subjects or legally authorized representatives will provide written informed 
consent for the study prior to collection of study data or performance of study 
procedures. A signed copy of the informed consent form (ICF) must be given to the 
subject. 
 
 
6.1.2. 
Enrollment 
 
Subjects who sign an informed consent will be considered provisionally enrolled until 
all eligibility criteria have been successfully met, at which time subjects will be 
considered formally enrolled. Subjects who do not meet all eligibility criteria will be 
considered screen failures. 
 
 
6.1.3. 
Eligibility 
 
The subject’s eligibility for study enrollment will be reviewed and documented on the 
appropriate electronic case report form (eCRF).  At the time of screening, a related 
progress note should be recorded in the medical records to indicate that all study 
eligibility criteria were reviewed with the screening results noted. 
 
Subjects who fail to meet eligibility criteria should be treated according to the 
Investigator’s standard of care practices. Study participation will end at the time of 
eligibility failure.  Data will be collected for all subjects who fail to meet eligibility 
criteria from the time the informed consent is signed until the subject is determined to 
have failed screening. At a minimum, the following information should be collected 
for all subjects who fail to meet study eligibility criteria: 
 
• 
Subject demographics 
• 
Reason for screen failure 
• 
Serious adverse events (followed until resolution or stabilization) 
 
 
6.1.4. 
Assignment of Subject Number 
 
A unique identification number will be given to each study subject at the time the 
subject provides informed consent.  Subject numbers will be assigned in a sequential 

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order.  The subject number will consist of six digits where the first three digits 
designate the study site and the last three digits designate the subject by number in 
sequential order. 
 
 
6.1.5. 
Demographics And Medical History 
 
The subject's medical history and demographic information will be documented on the 
appropriate eCRF. Demographic information will include sex, date of birth, race and 
ethnicity. 
 
Medical history information will include a review of ventral or incisional hernia 
related events and details (including previous interventions) and location of hernia, 
and previous abdominal surgery. 
 
 
 
6.1.6. 
Physical Examination 
 
A standard physical exam, appropriate to subjects about to undergo abdominal 
surgery, will be performed by the physician.  Height and weight measurements will be 
recorded to allow for the calculation of BMI.  The subject’s ability to participate and 
meet the follow-up requirements will be established. 
 
 
6.1.7. 
Quality of Life Assessment 
 
Subjects will complete the Carolinas Comfort Scale® and SF-12® to establish baseline 
measures for quality of life assessments. Occupational status will also be collected. 
 
 
6.2. 
Index Procedure 
 
The following section describes the surgical techniques that are recommended for this 
study.   Since bridging a defect with a graft is not allowed, several release techniques 
are recommended; however, other surgical techniques may be applied at the surgeon’s 
discretion.  Sponsor representatives may attend the index procedures conducted under 
this protocol. 
 
 
6.2.1. 
Perioperative Care 
 
Since the lowest incidence of post-operative infection is associated with administration 
of an antibiotic within one hour prior to incision, prophylactic antibiotics are to be 
administered within one hour prior to surgery (first skin incision) and two (2) hours 
before if the antibiotic is a fluoroquinolone or vancomycin (according to the Surgical 
Care Improvement Program [SCIP]). [51]  Prophylactic antibiotics should be 
discontinued less than 24 hours after anesthesia end time as prolonged administration 

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of antibiotics can lead to the development of antimicrobial resistant pathogens and an 
increased risk of C. difficile infection. [51] 
 
6.2.2. Abdominal Wall Reconstruction/Ventral or Incisional Hernia Surgery 
CDC Guidelines 
Intraoperative abdominal prep is to be performed according to the nationally 
recognized standard, CDC Guideline for Prevention of Surgical Site Infection. [49]  If 
not already receiving therapeutic antimicrobial agent perioperatively for an established 
infection, surgical antimicrobial prophylaxis (AMP) should be given just before the 
operation begins and timing should be based on surgeon practice but, at a minimum, 
until bactericidal concentration of the drug in serum and tissues is established by the 
time the skin is incised. Therapeutic levels should be maintained in both serum and 
tissues throughout the operation and until, at most a few hours after the incision is 
closed in the operating room.  These guidelines are as specified in the CDC Guideline 
for Prevention of Surgical Site Infection. [49] The type of AMP administered will be 
according to hospital protocol and surgeon decision and should be documented. All 
perioperative and postoperative antibiotics given to the subject should be documented. 
 
Adhesiolysis & Measurement of the Defect 
Once the adhesiolysis is performed and all of the ventral or incisional hernia has been 
exposed, the largest vertical and transverse dimensions should be recorded. 
 
Minimize Bioburden 
Every effort should be made to minimize the bacterial burden and risk of post- 
operative complications including debridement of non-viable tissue, abdominal 
washouts, careful preservation of blood supply to the skin, and complete removal of all 
prior mesh (as applicable). 
 
Ventral or Incisional Hernia Repair 
If necessary, resect/debride the edges of the rectus fascia until healthy well- 
vascularized tissue is identified to ensure proper apposition of the midline as it is 
closed. 
 
If a retro-rectus approach is preferred and the midline can be closed primarily, the 
peritoneum or posterior rectus sheath should be carefully dissected creating a retro- 
rectus pocket for the XenMatrix™ AB Surgical Graft to be placed. 
 
If further release is needed to close the midline every effort should be made to do so 
including the use of the TAR technique [50]. Care must be taken not to damage the 
blood supply and the nerves.  Once the dissection is complete the peritoneum/ 
posterior rectus sheath should be closed and the XenMatrix™ AB graft should be 
placed in the retro rectus space according to the instructions for use (IFU). 

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August 07, 2018 
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If intraperitoneal graft placement is preferred (and the midline can be closed by any 
means (including CST)), place the graft intraperitoneally and close the fascial edges of 
the defect anterior to graft. 
 
The defect will be closed and a minimum 5 cm overlap on every side should be 
factored in to determine the minimal patch size. The entire defect must be covered. 
The patch will be fixated using sutures.  If the hernia repair requires more than a single 
piece of surgical graft (with adequate overlap beyond the margins of the defect on all 
sides) the subject is excluded from the study. 
 
Closure should be performed with permanent or long lasting sutures every 1-2 cm 
between sutures, for example with an interrupted Figure-8 closure or running stitch. 
 
If a previous scar of skin is present, the scar should be excised. The fascial and 
subcutaneous layers should be closed with sutures.  The skin should be closed with 
staples and/or sutures (1-2 cm between sutures preferred). 
 
 
6.2.3. 
Immediate Postoperative Care 
After surgery, study subjects will be given postoperative instructions for care of the 
ventral or incisional hernia repair site based on the Investigator’s typical protocol. 
Prescription medication should be what is normally prescribed to ventral or incisional 
midline hernia repair study subjects.  Study subjects should be asked to use 
prescription and non-prescription drugs on an as needed basis only. 
 
The Investigator will determine the extent of individual activity that is appropriate, 
including lifting and other forms of physical exertion. 
 
 
6.2.4. 
Surgical Details 
 
Surgical details will be recorded and entered in the appropriate eCRF(s).  Details may 
include but are not be limited to: ASA score, size of the defect, procedure start/stop 
time (skin to skin), perioperative antibiotics (including dose and timing), concomitant 
procedures (e.g., panniculectomy), was closure achieved (midline, fascia, skin) 
hospital length of stay, and adverse events including device or procedure related 
complications and mortality. 
 
 
6.3. 
Subject Follow-up 
 
Subjects who sign the informed consent and meet eligibility criteria but who do not 
undergo the XenMatrix™ AB Surgical Graft placement surgery per-protocol should be 
treated per hospital standard of care.  Follow-up will end at the time it is determined 
that the ventral or incisional midline hernia repair surgery utilizing XenMatrix™ AB 
Surgical Graft was not performed as planned (i.e., prior mesh could not be removed). 

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However, any study-related adverse events will be reported and followed to 
satisfactory resolution or stabilization. 
 
Failure of the study procedure must be documented and surgical details must be 
recorded on the appropriate eCRF(s). 
 
 
6.3.1. 
Assessments 
 
Subjects should report to their respective study site for follow-up visits at the post- 
operative time points below: 
 
• 
1 month: ± 2 weeks 
• 
3 month:  ± 1 month 
• 
6 month:  ± 1 month 
• 
12 month: ± 2 months 
• 
18 month: ± 2 months 
• 
24 month: ± 2 months 
 
At each study visit, the following procedures will be completed: 
 
• 
Physical exam will be performed by a study physician to check for wound 
occurrences, hernia recurrence and any other surgical complications. The 
physical exam should also include assessment of the subjects’ weight and skin 
appearance over the ventral or incisional midline hernia repair site. 
▪ A recurrent ventral or incisional midline hernia will be defined as any hernia 
identified or confirmed by the investigator, during any study follow-up visit 
(including unscheduled), within approximately 5 cm of the index hernia. 
▪ Potential recurrent hernias identified via incidental magnetic resonance 
imaging (MRI) or computed tomography (CT) scan will be evaluated by the 
operating surgeon for clinical significance. 
▪ If an infection is suspected, a routine culture shall be obtained via the 
instructions in Appendix 18.2. Classification will follow the CDC guidelines 
for superficial and deep surgical site infections in Appendix 18.3. 
▪ Return to Work 
▪ Carolinas Comfort Scale® 
▪ SF-12® 
▪ Assessment and documentation of adverse events/complications. 
 
A subject who has a re-operation at the index surgical site, or has the repair site 
surgically impacted in any way, may be withdrawn from the study upon discharge from 
hospitalization for such re-operation or other surgical intervention. Site personnel will be 
responsible for documenting, on the applicable eCRF, any adverse events or other post-
procedural complications that the subject may have encountered during the hospitalization 
and up to 30 days post-re-operation 
 
 

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August 07, 2018 
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6.3.2. 
Unscheduled Visits 
 
Unscheduled visits are visits in addition to the per protocol study schedule, at the 
request of the subject or study personnel to address intercurrent problems or 
concerns. 

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If the subject has an evaluation related to the abdomen or abdominal organs at an 
unscheduled visit at any time during the study follow-up period, the subject will be treated 
per standard of care.  Any serious adverse events and/or relevant AEs should be recorded.  If 
the subject should undergo imaging for any reason and a recurrent ventral or incisional 
midline hernia is identified, it must be recorded as well. 
 
Unscheduled Visits should only be completed in the eCRF if AEs occurred or if this 
is an Early Termination visit. 

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Davol Inc. 
XenMatrix™ AB Surgical Graft 
Protocol Version 3.0 
August 07, 2018 
 
 
 
 
6.4. Time And Events Schedule 
 
Study Procedure 
Screening and 
Baseline 
Period 
Surgery 
1 
Month 
Visit 
3 
Month 
Visit 
6 
Month 
Visit 
12 
Month 
Visit 
18 
Month 
Visit 
24 
Month 
Visit 
Unscheduled 
Visit1) 
Visit Window (days) 
Within 60 days 
of consent 
0 
16-44 60-120 150-210 305-425 485-605 670-790 
-- 
Describe study to potential subject 
X 
Obtain informed consent 
X 
Verify eligibility criteria 
X 
X 
Collect demographics and medical 
history 
X 
Conduct physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
Placement of Device 
X 
Return to Work, Carolinas Comfort 
Scale®, SF-12® 
X 
X 
X 
X 
X 
X 
X 
X 
Collect adverse events/complications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
1) Only to be completed in eCRF if subject experienced AE or if this is an Early Termination visit. 

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6.5. Subject Discontinuation 
 
Subjects may be discontinued for the following reasons: 
 
• 
Subject has device explanted. 
• 
Subject is Lost to Follow-Up (LTFU): A subject may be considered LTFU if the 
investigational site personnel are unable to locate the subject despite two documented 
attempts to notify the subject via telephone and a third attempt by certified mail. 
• 
Subject consent is withdrawn: The subject requests to terminate his/her participation in 
the study (the Investigator must attempt to identify and document the reasons for 
termination). Subjects will be informed that they have the right to withdraw from the 
study at any time, for any reason, without affecting their future care. 
• 
Study termination: The study is terminated by Sponsor. 
 
Once a subject discontinues from the study, the Investigator must complete a Study 
Completion eCRF and the reason for subject discontinuation must be fully documented. 
 
 
6.6. Replacement of Subjects 
 
A subject that discontinues from the trial will not be replaced. 
 
 
7. ADVERSE EVENTS 
 
The Investigator is responsible for the detection and documentation of events meeting the 
criteria and definition of an AE or SAE, as provided in this protocol. All AEs that occur during 
the study should be treated with established standards of care that will protect the life and 
health of the study subjects. 
 
AEs will be collected from the time of enrollment (AE onset after signing ICF) through the end 
of study participation (either study completion or early discontinuation) and will be 
documented in the medical record or source document and on study eCRFs. All events will be 
followed to satisfactory resolution or stabilization. 
 
 
7.1. Definition of Events 
 
In this study, an AE is defined as any undesirable clinical event occurring in the abdominal 
space including the lower abdominal, inguinal and pubic regions (including the skin), as well 
as any other undesirable clinical events judged to be related to the study device or surgical 
procedure regardless of anatomical region. Abnormal laboratory results are not to be 
considered AEs unless the results are accompanied by clinical signs or symptoms. The 
Investigator will assess the relationship of an AE to the study device or procedure as described 
in Section 7.3. 

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XenMatrix™ AB Surgical Graft 
Protocol Version 3.0 
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7.2. Definition of Serious Adverse Events (SAE) 
 
An event will be classified as a serious adverse event (SAE) if it meets the definition of serious 
injury or illness in the Medical Device Reporting Regulation [21 CFR 803.3] as listed below: 
 
• 
Is life-threatening, 
• 
Results in permanent impairment of a body function or permanent damage to a body 
structure, 
• 
Necessitates medical or surgical intervention to preclude permanent impairment of a 
body function or permanent damage to a body structure. Permanent means irreversible 
impairment or damage to a body structure or function, excluding trivial impairment or 
damage. 
 
NOTE:  The term serious is not synonymous with severity, which may be used to describe the 
intensity of an event experienced by the subject. 
 
 
 
7.3. Relationship Of Adverse Event To Device/Procedure 
 
Assess each AE for its relationship to the device (XenMatrix™ AB Surgical Graft) or surgical 
procedures as follows: 
• 
Device: This category should be restricted to AEs directly attributable to devices used 
as part of the study procedure. 
• 
Procedure: This category should be restricted to AEs directly attributable to the study 
device surgical procedure. 
 
Use the following categories for assigning the certainty of the relatedness: 
 
• 
Definitely Related:  An AE is definitely related if it is obvious, certain or there is little 
doubt regarding the relationship. 
 
• 
Possibly Related:  An AE is possibly related if it is capable of being related but 
relatively unlikely. 
 
• 
Not Related:  An AE is not related if it is determined that there is no plausible 
association. 
 
 
 
7.4. Severity of Adverse Events 
 
Each AE should be assessed for its severity, or the intensity of an event, experienced by the 
subject. 
 
• 
Mild:  Awareness of a sign or symptom that does not interfere with the subject’s activity 
or is transient and is resolved without treatment or sequelae. 

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• 
Moderate:  May interfere with the subject’s usual activity. 
 
• 
Severe:  Symptom(s) causing severe discomfort and significant impact of the subject’s 
usual activity and requires treatment. 
 
 
7.5. Reporting Of Events 
 
If an AE occurs, all sections of the appropriate eCRF must be completed.  In addition, 
all AEs will be classified by the investigator according to the Clavien-Dindo Grading 
System for the Classification of Surgical Complications to eliminate subjective 
interpretation of adverse events and any tendency to down-rate complications. 
 
All Investigator-judged device-related AEs that occur (whether serious or not) must be 
reported to Davol Inc. Field Assurance using the contact information provided in Section 8, 
within 24 hours of becoming aware of the event. 
 
Additionally, all SAEs (regardless of relationship) must be reported to the Sponsor within 24 
hours of becoming aware of the event by sending an email to XenAB@crbard.com. 
This email should contain the following minimal information: 
- short description of the SAE 
- device/procedure relationship 
- date SAE occurred 
 
- date of awareness 
It is the responsibility of the Investigator to inform the Institutional Review Board (IRB) of 
AEs according to IRB requirements. The Sponsor will report to the Food and Drug 
Administration (FDA) as appropriate after becoming aware of a reportable event. 
 
 
8. MECHANICAL FAILURES, MALFUNCTIONS AND DEFECTS 
 
The Investigator will record if a Sponsor device used in the study procedure failed to meet its 
performance specifications whether due to mechanical failure, malfunction or defects. This 
applies to: devices used in the subject, devices in which the package was opened but the device 
was not used for implantation in the subject, or devices with which implantation was 
attempted, but the device did not remain (was not used) in the subject. 
 
A recurrence (unless it is in a different location than the study hernia) is considered a device 
failure if the recurrence is considered to be possibly device related and not procedure related, 
or an issue of patient mismanagement (e.g., use of a Vacuum Assisted Closure (V.A.C.) system 
for too long; graft used was too small to adequately cover the defect, etc.), as determined by  
the Investigator. 

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XenMatrix™ AB Surgical Graft 
Protocol Version 3.0 
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All mechanical failures, malfunctions, missing components, or any other defect of 
XenMatrix™ AB Surgical Graft, or any components of the device kit that do not perform to 
specifications must be promptly reported to Davol: 
 
Field Assurance Department 
e-mail: Davol.FieldAssurance@crbard.com 
 
The event must also be documented on the Device Failure eCRF and the malfunctioning device 
should be retained for return and evaluation to Davol Field Assurance. 
 
 
9. 
RISK/BENEFIT ANALYSIS 
 
The device that will be utilized in this study (XenMatrix™ AB Surgical Graft) has 510(k) 
clearance from the U.S. Food and Drug Administration and is intended for implantation to 
reinforce soft tissue where weakness exists and for surgical repair of damaged or ruptured soft 
tissue, including: abdominal plastic and reconstructive surgery; muscle flap reinforcement; 
hernia repair including abdominal, inguinal, femoral, diaphragmatic, scrotal, umbilical, and 
incisional hernias. 
 
The study subjects participating in this study will require ventral or incisional midline hernia 
repair surgery as part of their standard of care. The usual risks of ventral or incisional midline 
hernia repair apply independent of the procedures required under this protocol. The known 
possible risks associated with the use of the XenMatrix™ AB Surgical Graft are outlined in the 
IFU (attached). 
 
Collection and analysis of the data generated in this study may be of benefit to future subjects 
who require ventral or incisional midline hernia repair. 
 
 
10. CASE REPORT FORMS 
 
The Investigator is responsible for ensuring the accuracy and completeness of all study 
documentation.  All clinical study data will be recorded in the eCRFs provided to the 
investigational site. 
 
 
11. STATISTICAL METHODS 
 
This section describes the planned statistical analyses for this study. A detailed Statistical 
Analysis Plan (SAP) will be completed and placed on file prior to database lock. The SAP will 
contain a comprehensive explanation of the methodology used in the statistical analyses 
described below. 
 
 
11.1. Study Hypothesis 
There is no formal statistical hypothesis for this study. The study will follow eligible 
patients across all CDC wound classes who undergo ventral or incisional midline 

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XenMatrix™ AB Surgical Graft 
Protocol Version 3.0 
August 07, 2018 
 
 
 
 
 
hernia repair with the XenMatrix™ AB Surgical Graft in order to assess wound 
occurrences. 
 
 
11.2. Sample Size Considerations 
 
This study is projected to enroll up to 75 subjects at approximately 10 sites in order to 
have 64 evaluable subjects at 24 months.  It is anticipated that there will be a 15% loss 
to follow-up rate.  The sample size of 64 evaluable subjects is based on potential 
adequacy of data to meet the study objectives. It is not based on any statistical 
consideration. 
 
 
11.3. Data Analysis 
 
11.3.1. 
Analysis Population 
The Intent-to-treat (ITT) population consists of all enrolled subjects who have signed 
the Informed Consent Form. The modified ITT (mITT) population is defined as those 
subjects in the ITT population whom underwent placement of a XenMatrix™ AB 
Surgical Graft.  Subjects who are enrolled but not treated with XenMatrix AB will be 
replaced to ensure 75 subjects are treated with the study device. All analyses will be 
primarily based on the mITT population. 
 
Demographics and baseline characteristics will be summarized using the mITT 
population. Summary statistics for categorical variables will include frequency counts 
and percentages and for continuous variables mean, standard deviation, minimum, 
median and maximum. 
 
Subjects who do not receive XenMatrix™ AB Surgical Graft will have their AEs 
summarized separately and their outcome data will not be collected or analyzed. 
 
 
11.3.2. 
Primary Endpoint 
The primary endpoint of wound occurrence rate will be assessed within the first 45 
days post-implantation.  Wound occurrences are defined as surgical site infection, 
seroma, wound dehiscence, skin necrosis and fistulas requiring intervention. 
 
 
 
11.3.3. 
Secondary Endpoints 
The following secondary endpoints will be evaluated: 
 
1. Wound occurrences > 45 days post-implantation 
2. Rate of reoperation due to the index hernia repair 
3. Carolinas Comfort Scale® and SF-12® 
4. Return to Work 
5. Length of Stay 

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For each of the above listed secondary endpoints, estimates along with their 95% 
confidence intervals of the variable of interest based on the mITT population will be 
reported. 
 
 
11.4. Data Analysis Considerations 
 
11.4.1. 
Data pooling 
Data from all investigational sites will be pooled for analysis. Sites will be tested for 
potential differences in the primary endpoint. Sites with fewer than 10 treated subjects will 
be combined for this purpose. If there is significant variation among sites, the rates of the 
primary endpoint and associated 95% confidence interval will be estimated using a logistic 
regression with sites included in the model as a random effect. 
 
 
11.4.2. 
Handling of missing data 
Study endpoints may be missing due to withdrawal of consent, investigator’s decision, lost 
to follow-up, device explanted and death. As long as the missing data is unrelated to the 
study intervention, limiting the analysis to those subjects who contribute endpoints 
produces unbiased estimates of the event rates. The reason for missing data for all subjects 
will be reported. The primary analysis will be performed without imputation for the 
missing data. As secondary analysis, the rates of the primary endpoint will be estimated 
using Kaplan Meier method that will account the time at risk prior to discontinuation of the 
study. 
 
 
11.5. Interim Analysis 
 
An interim analysis of some or all study endpoints will be performed after all active 
subjects have a 12-month visit. However, interim analyses may be performed at other time 
periods (e.g., 6-months) to assess the results. There is no statistical impact of the interim 
analysis. i.e. the study will continue as originally planned and will not be affected in any 
way by the result of the interim analysis. All study endpoints will be summarized for 12- 
month follow-up at interim analysis. 
 
 
12. ADMINISTRATIVE REQUIREMENTS 
 
This clinical study will be conducted in accordance with the Declaration of Helsinki, HIPAA 
requirements, Good Clinical Practice, and applicable FDA regulations (21 CFR Parts 50, 54, 
and 56). 
 
 
12.1. Investigator Selection 
 
The Investigator must be of good standing as an Investigator and knowledgeable in relevant 
areas of clinical research to ensure adherence to the requirements of the protocol, including 
the protection of human subjects.  Other site personnel must have appropriate research 
experience and infrastructure to ensure adherence to the protocol and enrollment of 

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sufficient numbers of evaluable subjects. The curriculum vitae (CV) of the Investigator(s) 
will be maintained in the Sponsor files as documentation of previous medical training. 
Federal databases will be searched to ensure that the Investigator(s) and/or the site are not 
prohibited from engaging in federally sponsored clinical research.  The Investigator will 
sign the signature page of this protocol, agreeing to comply with all applicable government 
regulations and the requirements of this study. 
 
 
12.2. Regulatory and Ethical Considerations 
 
 
12.2.1. 
Institutional Review Board (IRB) Approval 
 
Before commencement of the study, the Investigator must provide Sponsor with 
written documentation of IRB approval.  This approval must refer to the ICF and 
the study by both the title and the protocol number assigned by the Sponsor.  The 
Investigator, if a member of the IRB, is not to participate in the approval decision 
for this study. This non-participation should be noted in the approval letter. 
 
No device supplies, if applicable, will be shipped to the Investigator until the IRB 
approval has been supplied to Sponsor. 
 
The IRB must give written renewal of the original approval at least annually to 
continue the study.  A copy of the written renewal must be provided to Sponsor. 
 
As appropriate, amendments to the protocol must also be approved by the IRB 
before implementation at the sites, unless warranted to eliminate an immediate 
hazard. 
 
 
12.2.2. 
Informed Consent and HIPAA Authorization 
 
Prior to any study procedure, the Investigator (or designee) must explain to each 
subject in layman’s terms, the nature of the study, its purpose, expected duration, 
and the risks and benefits of study participation.  Also, subjects will be informed 
of uses and disclosures of their medical information for research purposes, and 
their rights to access information about them. The subjects must be informed of 
their right to withdraw from the study at any time and for any reason without 
sanction, penalty, or loss of benefits to which they are otherwise entitled, and that 
withdrawal from the study will not jeopardize their future medical care. After this 
explanation and before any study procedure is conducted, and before entering the 
study, the subject (or legally authorized representative) must voluntarily sign and 
date the IRB-approved ICF and HIPAA Consent Form in accordance with 21 
CFR Parts 50 and 56.  The subject will receive a copy of their ICF and HIPAA 
Consent Form. 

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12.3. Protocol Adherence And Deviations 
 
The study will be conducted as described in this protocol. Any deviations from this 
protocol must be documented by the Investigator.  If an emergency situation arises in 
which the safety and welfare of a subject may require immediate alternative intervention, 
the Investigator should act in the best interests of the subject.  The Sponsor and the site’s 
IRB must be notified immediately if this occurs.  All notifications should be followed 
with written confirmation that describes the emergency action and outcomes.  Written 
confirmations should be sent to Sponsor and the IRB within 10 business days from the 
date of the emergency action. 
 
 
12.4. Device Accountability 
 
The Investigator will ensure that the device components are stored under the conditions 
outlined in the IFU and maintained under secure storage. Device accountability records 
will be maintained and monitored.  Study devices may not be re-sterilized or reused. 
 
 
12.5. Data Collection 
 
The Investigator is responsible for completely and accurately recording study data in the 
appropriate sections of the eCRFs provided by Sponsor.  The eCRFs must be signed by 
the Investigator or by his/her documented designee. 
 
The investigator is also responsible for making source documents and forms readily 
available for a thorough review by the study monitor at each monitoring visit.  The 
monitor will ensure the accuracy of data recording at each investigational site by 
comparison to supporting source documents during periodic site visits. Adherence to 
proper recording of information as well as assuring that corrections are being made will 
also be addressed during these periodic visits. 
 
 
12.6. Subject Compensation 
 
To compensate subjects for their time and participation, they may receive stipends upon 
completion of each of the protocol specified study visits.  If the subject does not complete 
a visit, compensation will not be provided for that visit. 
 
 
12.7. Communications With The Sponsor 
 
Although the Investigator and his/her staff may have contact with key individuals at the 
Sponsor throughout the course of the study, all communications regarding conduct of the 
study must be channeled through the Sponsor’s clinical affairs personnel or their 
designees.  The Sponsor contact listed on the title page of this protocol should be 
contacted first with any matters regarding the conduct of this study. 

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12.8. Required Documentation 
 
An Investigator may not screen or enroll subjects until authorized to do so by the 
Sponsor.  At a minimum, the following documentation must be received by the Sponsor 
prior to study commencement: 
 
• 
CVs and medical licenses for the principal Investigator and Sub-Investigator(s); 
• 
signed Clinical Study Agreement; 
• 
signed Nondisclosure Agreement; 
• 
signed Protocol Signature Page; 
• 
written approval from the IRB of both the protocol and informed consent form; 
• 
signed Financial Disclosure Statement; and, 
• 
IRB Assurance of Compliance Form or equivalent. 
 
 
12.9. Publications 
 
At the conclusion of the Study, a multi-center journal article may be prepared for 
publication in a reputable scientific journal. The publication of the principal results 
from any single-center experience within the study is not allowed until the preparation 
and publication of the multi-center results. Exceptions to this rule require the prior 
approval of Bard. The analysis of other pre-specified and ad hoc endpoints will be 
performed by Bard or its designee. Such analyses, as well as other proposed 
investigations will require the approval of Bard. Bard anticipates many secondary 
manuscripts with principal authorship. For purposes of timely abstract presentation and 
publication, such secondary publications will be delegated to the appropriate principal 
authors, and final analyses and manuscript review for all multi-center data will require 
the approval of the Bard. 
 
 
 
13. SITE MONITORING 
 
The study monitors are designated as agents of the Sponsor and are assigned to oversee the 
conduct and progress of the study and to be the principal communication link between 
Sponsor and Investigator. The study monitors will be involved in Investigator selection and 
training, assurance of IRB approvals, and periodic on-site inspection and monitoring of sites 
and records, to ensure continued compliance with the protocol and adequacy of the 
Investigator and the facility to carry out the study.  In addition, the monitor will verify that 
the device is being used in accordance with the protocol instructions. The monitor will 
perform several types of site visits during the course of the study. 
 
The investigational sites may also be subject to quality assurance audit by the Sponsor (and 
its affiliates) and the Sponsor’s study contractor personnel, as well as by FDA 
representatives.  It is important that the Principal Investigator and the relevant investigational 

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site personnel are available during the monitoring visits and possible audits and that 
sufficient time is devoted to the process. 
 
 
13.1. Study Initiation Visit 
 
Before the study begins, the study monitor will visit the site. The purpose of this visit 
is to review with the Investigator and staff the provisions and proper conduct of the 
clinical evaluation. This includes a detailed review of the protocol and eCRFs with 
instructions as to their completion, as well as reviewing regulations pertaining to the 
conduct of the clinical study.  Arrangements for timely and accurate reporting of 
clinical data and relevant medical events will be established as well as ensuring safe 
and secure storage for the study devices. 
 
The study monitor will: 
• 
confirm that the ICF to be used is the one approved by the IRB; 
• 
verify that all necessary documents are on file at the site; and 
• 
confirm that there are provisions to continue and maintain all documents and 
records throughout the study as required by good clinical practice regulations. 
 
 
13.2. Ongoing Monitoring Visits 
 
The study monitor will maintain personal contact with the Investigator and staff 
throughout the study by telephone, e-mail, fax, mail, and on-site visits. On-site 
monitoring will begin after the first subjects are enrolled and continue until the study is 
completed.  This monitoring will assure continued protocol compliance, adequate 
subject enrollment, accurate data reporting (including the comparison of eCRFs with 
subject records), device accountability, and continued IRB acceptance of the study. 
The study monitor will evaluate and summarize the results of each visit in written 
reports, identifying any ongoing data problems with any study site and specifying 
recommendations for resolution of noted deficiencies. 
 
 
13.3. Final Monitoring Visit 
 
At the completion of the study, the study monitor will conduct a final on-site visit. The 
purpose of this visit is to collect all outstanding study data documents, confirm that the 
Investigator’s files are accurate and complete, review the record retention requirements 
with the Investigator, provide for the return of unused devices to Sponsor, review 
records which account for device shipments, and assure that all applicable requirements 
for closure of the study are met. The actions and observations made at this visit will be 
recorded and filed. 
 
 
14. TERMINATION OF STUDY 

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Sponsor reserves the right to suspend enrollment or terminate the study at any time as set 
forth in the Clinical Study Agreement. Written notice will be submitted to the Investigator in 
advance of such termination. 
 
Sponsor may suspend enrollment or terminate the study at a specific site for reasons 
including, but not limited to, inadequate data collection, low subject enrollment rate, 
achievement of the total enrollment, administrative reasons, or non-compliance with the 
protocol or other clinical research requirements. 
 
 
15. REPORTING REQUIREMENTS 
 
This study protocol is exempt from 21 CFR 812 as the device is cleared for 
commercialization in the U.S. and the usage in this protocol in on-label.  In addition to the 
AE reporting described above, all sites are also required to submit annual study progress 
reports to the Sponsor. 
 
 
 
16. RECORD RETENTION 
 
The investigator shall retain all study records for a period of two years after the latter of the 
following two dates: the date on which the study is terminated or completed, or the date a 
marketing application is approved for the indication for which it is being investigated.  The 
investigator may withdraw from the responsibility to maintain records for the period required 
and transfer custody of the records to any other person who will accept responsibility for 
retaining them.  Notice of a transfer shall be given to the Sponsor not later than 10 working 
days after transfer occurs. 

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17. REFERENCES 
 
1. Cobb WS, Kercher KW, Heniford BT. Laparoscopic repair of incisional hernias. Surg 
Clin North Am 2005 Feb;85(1):91-103. 
 
2. Schuster R, Singh J, Safadi BY, Wren SM.  The use of acellular dermal matrix for 
contaminated abdominal wall defects: wound status predicts success. Am J Surg 
2006;192(5):594-597. 
 
3. Poulose BK, Shelton J, Phillips S, Moore D, Nealon W, Penson D, Beck W, Holzman 
MD.  Epidemiology and cost of ventral hernia repair: making the case for hernia research. 
Hernia 2012; 16:179-183. Epub 2011 Sept 9. 
 
4. Breuing K, Butler CE, Ferzoco S, Franz M, Hultman CS, Kilbridge JF, Rosen M, 
Silverman RP, Vargo D (The Ventral Hernia Working Group).  Incisional ventral hernias: 
review of the literature and recommendations regarding the grading and technique of 
repair.  Surgery 2010;148(3):544-558. Epub 2010 Mar 20. 
 
5. Geisler DJ, Reilly JC, Vaughan SG, Glennon EJ, Kondylis PD. Safety and outcome of 
use of nonabsorbable mesh for repair of fascial defects in the presence of open bowel. 
Dis Colon Rectum 2003;46(8):1118-1123. 
 
6. Neff M, Cantor B, Geis WP. Laparoscopic-assisted primary repair of a complicated 
ventral incisional hernia.  JSLS 2005;9(2):241-244. 
 
7. Cavallaro A, Lo Menzo E, Di Vita M, Zanghì A, Cavallaro V, Veroux PF, Cappellani A. 
Use of biological meshes for abdominal wall reconstruction in highly contaminated 
fields.  World J Gastroenterol 2010;16(15):1928-1933. 
 
8. Byrnes MC, Irwin E, Carlson D, Campeau A, Gipson JC, Beal A, Croston JK.  Repair of 
high-risk incisional hernias and traumatic abdominal wall defects with porcine mesh. 
Am Surg 2011;77(2):144-150. 
 
9. Luijendijk R, Hop W, van den Tol M et al. Comparison of suture repair with mesh repair 
for incisional hernia. New Engl J Med 2000;343(6):392-398. 
 
10. Anthony T, Bergen PC, Kim L et al. Factors affecting recurrence following incisional 
herniorrhaphy. World J of Surg 2000;24(1):95-101. 
 
11. Burger J, Luijendijk R, Hop W et al. Long-term follow-up of a randomized controlled 
trial of suture versus mesh repair incisional hernia.  Ann Surg 2004;240(4):578-583. 
 
12. van Geffen H, Simmermacher R, van Vroonhoven T, van der Werken C. Surgical 
treatment of large contaminated abdominal wall defects. J Am Coll Surg 2005;201:206- 
212. 

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13. George C, Ellis H. The results of incisional hernia: a twelve year review.  Ann R Coll 
Surg Engl 1986;68:185-187. 
 
14. Ramirez O, Ruas E, Dellon A. “Components separation” method for closure of 
abdominal-wall defects: An anatomic and clinical study. Plast Reconstr Surg 
1990;86(3):519-526. 
 
15. DiBello J, Moore J. Sliding myofascial flap of the rectus abdominis muscle for the 
closure of recurrent ventral hernias. Plast Reconstr Surg 1996;98(3):464-469. 
 
16. Girotto J, Ko M, Redett R et al. Closure of chronic abdominal wall defects: a long-term 
evaluation of the component separation method. Ann Plast Surg 1999;42(4):385-395. 
 
17. Shestak K, Edington H, Johnson R. The separation of anatomic components technique for 
the reconstruction of massive midline abdominal wall defects: anatomy, surgical 
technique, application and limitations revisited. Plast Reconstr Surg 2000;105(2):731- 
738. 
 
18. Lowe J, Garza J, Bowman J et al. Endoscopically assisted “components separation” for 
closure of abdominal wall defects. Plast Reconstr Surg 2000;105(2):720-729. 
 
19. de Vries Reilingh T, Goor H, Rosman C et al. “Components separation technique” for the 
repair of large abdominal wall hernias. J Am Coll Surg 2003;196(1):32-37. 
 
20. Giurgius M, Bendure L, Davenport DL, Roth JS. The endoscopic component separation 
technique for hernia repair results in reduced morbidity compared to the open component 
separation technique.  Hernia. 2011 Aug 11. [Epub ahead of print] 
 
21. Korenkov M, Sauerland S, Arndt M, et al. Randomized clinical trial of suture repair, 
polypropylene mesh or autodermal hernioplasty for incisional hernia. Br J Surg 2002; 
89(1):50-56. 
 
22. Petersen S, Henke G, Zimmermann L, et al. Ventral rectus fascia closure on top of mesh 
hernia repair in the sublay technique. Plast Reconstr Surg 2004;114(7):1754-1160. 
 
23. den Hartog D, Dur AHM, Tuinebreijer WE, Kreis RW. Open surgical procedures for 
incisional hernias. Cochrane Database of Systematic Reviews 2008;(3):No.: CD006438. 
DOI: 10.1002/14651858.CD006438.pub2. 
 
24. Dur AH, den Hartog D, Tuinebreijer WE, et al. Low recurrence rate of a two-layered 
closure repair for primary and recurrent midline incisional hernia without mesh. Hernia 
2009;13(4):421-426. 
 
25. Pierce RA, Spitler JA, Frisella MM, et al. Pooled data analysis of laparoscopic vs. open 
ventral hernia repair: 14 years of patient data accrual. Surg Endosc 2007; 21(3):378-386. 

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26. Carlson MA, Frantzides CT, Shostrom VK, Laguna LE. Minimally invasive ventral 
herniorrhaphy: an analysis of 6,266 published cases. Hernia 2008;12(1):9-22. 
 
27. Itani KM, Hur K, Kim LT, et al. Comparison of laparoscopic and open repair with mesh 
for the treatment of ventral incisional hernia: a randomized trial. Arch Surg 
2010;145(4):322-328. 
 
28. Forbes SS, Eskicioglu C, McLeod RS, Okrainec A. Meta-analysis of randomized 
controlled trials comparing open and laparoscopic ventral and incisional hernia repair 
with mesh. Br J Surg 2009;96(8):851-858. 
 
29. Jezupovs A, Mihelsons M. The analysis of infection after polypropylene mesh repair of 
abdominal wall hernia.  World J Surg. 2006 Dec;30(12):2270-8; discussion 2279-2280. 
 
30. Szczerba SR, Dumanian GA. Definitive surgical treatment of infected or exposed ventral 
hernia mesh.  Ann Surg 2003;237:437-441. 
 
31. Kim H, Bruen K, Vargo D. Acellular dermal matrix in the management of high-risk 
abdominal wall defects. Am J Surg 2006;192:705-709. 
 
32. de Vries Reilingh TS, van Geldere D, Langenhorst B, de Jong D, van der Wilt GJ, van 
Goor H, Bleichrodt RP. Repair of large midline incisional hernias with polypropylene 
mesh: comparison of three operative techniques. Hernia 2004;8(1):56-59. 
 
33. Gupta A, Zahriya K, Mullens PL, Salmassi S, Keshishian A. Ventral herniorrhaphy: 
experience with two different biosynthetic mesh materials, Surgisis and Alloderm. 
Hernia. 2006;10(5):419-425. Epub 2006 Aug 22. 
 
34. Franklin M, Russek K.  Use of porcine small intestine submucosa as a prosthetic material 
for laparoscopic hernia repair in infected and potentially contaminated fields: long-term 
follow-up assessment. Surg Endosc 2011;25(5):1693-1694. 
 
35. Holton LH 3rd, Kim D, Silverman RP, Rodriguez ED, Singh N, Goldberg NH. Human 
acellular dermal matrix for repair of abdominal wall defects: review of clinical 
experience and experimental data. J Long Term Eff Med Implants 2005;15(5):547-558. 
 
36. Shah BC, Tiwari MM, Goede MR, Eichler MJ, Hollins RR, McBride CL, Thompson JS, 
Oleynikov D. Not all biologics are equal! Hernia 2011;15(2):165-171. Epub 2010 Dec 
28. 
37. Franklin ME Jr, Gonzalez JJ Jr, Glass JL, Manjarrez A. Laparoscopic ventral and 
incisional hernia repair: an 11-year experience. Hernia 2004;8(1):23-27. Epub 2003 Sep 
20. 
 
38. Diaz JJ Jr, Guy J, Berkes MB, Guillamondegui O, Miller RS. Acellular dermal allograft 
for ventral hernia repair in the compromised surgical field. Am Surg 2006;72:1181-1187. 

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39. Diaz JJ Jr, Conquest AM, Ferzoco SJ, Vargo D, Miller P, Wu YC, Donahue R. Multi- 
institutional experience using human acellular dermal matrix for ventral hernia repair in a 
compromised surgical field.  Arch Surg 2009;144(3):209-215. 
 
40. Pomahac B, Aflaki P. Use of a non-cross-linked porcine dermal scaffold in abdominal 
wall reconstruction. Am J Surg. 2010 Jan;199(1):22-27. Epub 2009 May 9. 
 
41. Jin J, Rosen MJ, Blatnik J, McGee MF, Williams CP, Marks J, Ponsky J. Use of acellular 
dermal matrix for complicated ventral hernia repair: does technique affect outcomes? J 
Am Coll Surg 2007;205(5):654-660. Epub 2007 Sep 14. 
 
42. Kolker AR, Brown DJ, Redstone JS, Scarpinato VM, Wallack MK. Multilayer 
reconstruction of abdominal wall defects with acellular dermal allograft (AlloDerm) and 
component separation. Ann Plast Surg 2005;55(1):36-41; discussion 41-2. 
 
43. Candage R, Jones K, Luchette FA, Sinacore JM, Vandevender D, Reed RL 2nd. Use of 
human acellular dermal matrix for hernia repair: friend or foe? Surgery 2008;144(4):703- 
9; discussion 709-711. Epub 2008 Aug 29. 
 
44. CDC Surgical Site Infection (SSI) Event Protocol 
http://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf 
 
45. Patton JH Jr, Berry S, Kralovich KA. Use of human acellular dermal matrix in complex 
and contaminated abdominal wall reconstructions. Am J Surg 2007;193:360-363. 
 
46. Helton WS, Fisichella PM, Berger R, Horgan S, Espat NJ, Abcarian H. Short-term 
outcomes with small intestinal submucosa for ventral abdominal hernia. Arch Surg 
2005;140:549-560. 
 
47. Maurice SM, Skeete DA.  Use of human acellular dermal matrix for abdominal wall 
reconstructions.  Am J Surg 2009;197(1):35-42. 
 
48. Data on file at Davol Inc. 
 
49. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR.  Guideline for Prevention 
of Surgical Site Infection.  Infection Control and Hospital Epidemiology. 1999;20(4). 
 
50. Novitsky YW, Elliott HL, Orenstein SB, Rosen MJ.  Transversus abdominis muscle 
release: a novel approach to posterior component separation during complex abdominal 
wall reconstruction. Am J Surg. 2012;204(5):709-16. 
 
51. Specifications Manual for National Hospital Inpatient Quality Measures.  Version 4.4a. 
Surgical Care Improvement Project (SCIP). 

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52. Routine Culture Guidelines Adapted From: SPECIMEN COLLECTION:  GUIDELINES 
FOR BEST PRACTICES. Center for Health Hazards Preparedness. University of 
Louisville. School of Public Health and Information Sciences. June 2007. 
 
 
53. Dindo D, Demartines N, Clavien PA. Classification of Surgical Complications: A New 
Proposal with Evaluation in a Cohort of 6336 Patients and Results of a Survey. Annals of 
Surgery. 2004 Aug; 240(2):205-13. 

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18. APPENDICES 

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18.1. 
Principal Investigator Information 
 
Robert Martindale, MD 
Oregon Health and Science University 
3303 SW Bond Ave 6th FL 
Portland, OR 97239 
(503) 494-4373 
martindr@ohsu.edu 

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18.2. 
Routine Culture [56] 
 
 
BASIC GUIDELINES FOR COLLECTION 
 
 
 
1. Collect the material from the site in which the etiologic agent will most likely be found. 
 
 
2. Obtain cultures prior to administration of antibiotics whenever possible. 
 
 
3. Collect adequate volume of material. Inadequate amounts of specimen may yield false 
negative results. 
 
 
4. Collect specimen in a manner that minimizes or eliminates contamination from indigenous 
flora as possible to ensure that the sample will be representative of the infected site. 
 
 
5. Use appropriate collection devices, transport media, and sterile, leak proof containers. 
 
 
6. Use sterile equipment and aseptic technique to collect specimen to prevent introduction of 
microorganisms during invasive procedures. 
 
 
7. Clearly label the specimen including specific information regarding site of collection (e.g., 
blood obtained via blue lumen of right subclavia central catheter) and complete the 
ordering process. 
 
 
8. Identify  the  specimen  source  and/or  specific  site  correctly  so  that  proper  processing 
methods and culture media will be selected by the laboratory personnel. 
 
 
9. Deliver the specimen promptly to the laboratory.  Delay in transport may compromise the 
specimen. 
 
 
SUBCUTANEOUS AND SKIN SPECIMEN: 
 
 
 
A. Superficial Wound (bacterial) 
1. Syringe aspiration is preferable to swab collection. 
 
 
2. Disinfect the surface of the wound with 70% alcohol followed by povidone-iodine or 
povidone-iodine alone.  Allow the skin disinfectant to dry prior to collection the 
specimen.  Remove iodine with alcohol after procedure to prevent irritation. 

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3. Using a 3 – 5 ml syringe with a small gauge needle, a physician will aspirate the deepest 
portion of the lesion. If a vesicle is present, collect both fluid and cells from the base of 
the lesion. 
 
 
4. If the initial aspiration fails to obtain material, inject sterile, preservative-free saline 
subcutaneously then repeat aspiration if necessary. 
 
 
5. If no material is obtained, rinse needle and syringe with broth by drawing the culture 
medium through the needle into the syringe. 
 
 
WOUNDS, ASPIRATES, AND TISSUE SPECIMEN: 
 
 
 
A. Deep Wounds or Abscesses: 
 
 
1. Disinfect the surface with 70% alcohol and a povidone-iodine solution.  Remove iodine 
with alcohol after procedure to prevent irritation. 
 
2. Aspirate the deepest part of the lesion, avoiding contamination by the wound surface.  If 
collection is done at surgery, a portion of the abscess wall should also be sent for culture. 
 
 
B. Punch Biopsy: 
 
 
1. Disinfect the skin surface with 70% alcohol and then with a povidone-iodine solution. 
Remove iodine with alcohol to prevent irritation. 
 
2. Collect 3 – 4 mm sample with a dermal punch. 
 
3. Submit for culture in a sterile container without formalin. 
 
4. Place specimen onto a sterile gauze pad moistened with preservative-free saline in order 
to keep the specimen from drying. 
 
 
 
C. Soft Tissue Aspirate 
 
 
1. Disinfect the skin surface with 70% alcohol and then with a povidone-iodine solution. 
Remove tincture of iodine with alcohol to prevent irritation. 
 
 
2. Aspirate the deepest portion of the lesion or sinus tract. Be careful to avoid 
contamination by the wound surface. 

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18.3. 
Surgical Site Infection Classification [44] 
 
Surgical Site Infection Criteria 
 
Superficial Incisional Surgical Site Infections (SSI) 
 
Infection occurs within 30 days after the operative procedure (where day 1 = procedure day) 
AND 
involves only the skin or subcutaneous tissue of the incision 
AND 
at least one of the following: 
A. Purulent drainage from the superficial incision or subcutaneous tissue. 
B. Organisms isolated from an aseptically obtained culture of fluid or tissue from the 
superficial incision. 
C. Superficial incision that is deliberately opened by a surgeon, attending physician or other 
designee and is culture positive or not cultured 
AND 
Patient has at least one of the following signs or symptoms: pain or tenderness; localized 
swelling; erythema; or heat. A culture negative finding does not meet this criterion. 
D. Diagnosis of a superficial incisional SSI by the surgeon or attending physician or other 
designee. 
 
COMMENT: There are two specific types of superficial incisional SSIs: 
1. Superficial Incisional Primary (SIP) –a superficial incisional SSI that is identified in the 
primary incision in a patient that has had an operation with one or more incisions (e.g., C - 
section incision or chest incision for CBGB) 
2. Superficial Incisional Secondary (SIS) – a superficial incisional SSI that is identified in the 
secondary incision in a patient that has had an operation with more than one incision (e.g., 
donor site incision for CBGB) 
 
The following do not qualify as criteria for meeting the definition of superficial SSI: 
• 
Diagnosis/treatment of cellulitis (redness/warmth/swelling), by itself, does not meet 
criterion d for superficial incisional SSI.  An incision that is draining or culture (+) is not 
considered a cellulitis. 
• 
A stitch abscess alone (minimal inflammation and discharge confined to the points of 
suture penetration). 
 
Deep Incisional SSI 
Infection occurs within 90 days after the operative procedure (for herniorrhaphy)(where day 1 
= procedure day) 
AND 
involves deep soft tissues of the incision (e.g., fascia and muscle layers) 
AND 
patient has at least one of the following: 
a. Purulent drainage from the deep incision. 

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b. A deep incision spontaneously dehisces or is deliberately opened or aspirated by a 
surgeon, attending physician or other designee and is culture positive or not cultured 
AND 
patient has at least one of the following signs or symptoms: fever (>38°C), localized 
pain or tenderness.  A culture negative finding does not meet this criterion. 
c. An abscess or other evidence of infection involving the deep incision that is detected 
on gross anatomical or histopathologic exam, or imaging test. 
 
COMMENTS: There are two specific types of deep incisional SSIs: 
 
1. Deep Incisional Primary (DIP) –a deep incisional SSI that is identified in a primary incision 
in a patient that has had an operation with one or more incisions (e.g., C-section incision or 
chest incision for CBGB) 
2. Deep Incisional Secondary (DIS) – a deep incisional SSI that is identified in the secondary 
incision in a patient that has had an operation with more than one incision (e.g., donor site 
incision for CBGB) 
 
Organ/Space SSI 
Must meet the following criteria: 
Infection occurs within 90 days after the operative procedure (for herniorrhaphy)(where day 1 
= procedure day) 
AND 
infection involves any part of the body deeper than the fascial/muscle layers, that is opened or 
manipulated during the operative procedure 
AND 
patient has at least one of the following: 
a. purulent drainage from a drain that is placed into the organ/space (e.g., closed suction 
drainage system, open drain, T-tube drain, CT guided drainage) 
b. organisms isolated from an aseptically-obtained culture of fluid or tissue in the 
organ/space 
c. an abscess or other evidence of infection involving the organ/space that is detected on 
gross anatomical or histopathologic exam, or imaging test 
AND 
meets at least one of the organ/space infection site “intraabdominal” criteria: 
1. Patient has organisms cultured from abscess and/or purulent material from 
intraabdominal space. 
2. Patient has abscess or other evidence of intraabdominal infection on gross anatomic or 
histopathologic exam. 
3. Patient has at least two of the following signs or symptoms: fever (>38.0°C±), nausea*, 
vomiting*, abdominal pain*, or jaundice* 
And at least one of the following: 
a. organisms seen on culture or Gram stain of drainage or tissue obtained during 
invasive procedure or from an aseptically-placed drain (e.g., closed suction 
drainage system, open drain, T-tube drain, CT guided drainage) 

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b. organisms cultured from blood and imaging test evidence suggestive of infection 
(e.g., ultrasound, CT scan, MRI, radiolabel scans [gallium, technetium, etc.] or on 
abdominal x-ray), which if equivocal is supported by clinical correlation. 
* With no other recognized cause 
± As documented in the medical record 

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18.4. 
Clavien Dindo Classification [57] 
 
Grades 
Definition 
Grade I 
Any deviation from the normal postoperative course without the need for 
pharmacological treatment or surgical, endoscopic and radiological 
interventions 
Allowed therapeutic regimens are: drugs as anti-emetics, antipyretics, 
analgetics, diuretics and electrolytes and physiotherapy. This grade also 
includes wound infections opened at the bedside. 
Grade II 
Requiring pharmacological treatment with drugs other than such allowed for 
grade I complications. 
Blood transfusions and total parenteral nutrition are also included. 
Grade III 
Requiring surgical, endoscopic or radiological intervention 
- IIIa 
Intervention not under general anesthesia 
- IIIb 
Intervention under general anesthesia 
Grade IV 
Life-threatening complication (including CNS complications)* requiring 
IC/ICU-management 
- IVa 
single organ dysfunction (including dialysis) 
- IVb 
Multi-organ dysfunction 
Greade V 
Death of a patient 
Suffix "d" 
If the patients suffers from a complication at the time of discharge, the 
suffix  "d" (for 'disability') is added to the respective grade of complication. 
This label indicates the need for a follow-up to fully evaluate the 
complication. 
 
 
 
 
*brain hemorrhage, ischemic stroke, sub-arrachnoidal bleeding, but excluding transient ischemic 
attacks (TIA);IC: Intermediate care; ICU: Intensive care unit. 

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18.5. 
Instructions for Use 

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