A Prospective Randomized Trial of Biologic Mesh Versus Synthetic Mesh for the Repair of Complex Ventral Hernias
Phase: NA
Conditions: Ventral Hernia
Sponsor: Michael Rosen

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A Prospective Randomized Trial of Biologic Mesh versus Synthetic Mesh 
for the Repair of Complex Ventral Hernias. 
P.I.  Michael Rosen MD 
 
 
 
 
 
 
 
 
 

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SPECIFIC AIMS 
Ventral hernia (VH) is a frequent sequela of abdominal surgery, occurring after 
up to 10-20% of laparotomy incisions.[1, 2] This results in almost 250,000 annual 
ventral hernia repairs in the United States, making it one of the most common 
procedures performed by general surgeons.[3] The annual health care 
expenditures associated with hernia repairs now exceeds $5 billion US dollars. 
[4] Since prosthetic mesh has been shown to reduce recurrence rates by over 
50%, most surgeons agree that some form of prosthetic reinforcement should be 
added to all but the smallest ventral hernia repairs.[5]  Traditionally, this has 
involved a permanent prosthetic material in clean cases (without bacterial 
contamination) at relatively low cost (approximately $150 for a 900cm2 mesh).  
The management of more complex hernias where infection or contamination is 
present is not well defined.  These patients are often severely disabled by the 
chronic infectious nidus and suffer a very poor quality of life until reconstruction 
of their abdominal wall anatomy and resolution of the infection.  Historically, this 
has involved a two-stage approach for hernias where simultaneous 
gastrointestinal, biliary, and/or genitourinary procedures were performed or if 
there was an active infection of a prosthetic material.  The first stage involved 
removing the infectious or contaminated source, and performing a temporary 
closure of the abdominal wall with an absorbable material. This approach of so-
called “planned hernia” would almost uniformly require another major operation.   
 
 

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Approximately 6 months to one year later, the abdominal wall is repaired with a 
permanent synthetic material in a clean setting.  This approach avoids placing 
the synthetic mesh in the field of contamination, but is associated with significant 
morbidity as it requires two operations and potential long-term disability during 
the recovery period.  Recognizing the limitations of this two-stage approach, new 
biologic materials have been designed to offer a single-stage approach for 
infected and contaminated abdominal wall reconstruction.  These materials are 
derived from various sources including human or porcine dermis, bovine 
pericardium, or intestinal submucosa.  They are processed in such a way as to 
render an acelluar collagen-rich graft that reportedly acts as a cellular scaffold to 
allow native tissue in-growth and regeneration of tissue.  They are marketed as 
resistant to infection and therefore as a suitable hernia repair material for clean-
contaminated and contaminated abdominal wall defects.  However, these 
products are very expensive with a 400cm2 porcine dermal graft costing over 
$10,000, and currently represent the most rapidly growing market in hernia 
repair, with estimates of almost $500 million dollars in annual revenue by the 
year 2013.[6]  Despite the rapid acceptance of these materials, there is little 
preclinical or clinical evidence to support their claims of regeneration, or that they 
provide a durable repair to the abdominal wall in the setting of a clean-
contaminated (Class 2) or a contaminated (Class 3) surgical procedure.   
In our experience, the single-stage repair of contaminated abdominal wall 
defects with these biologic grafts has resulted in a 40%-80% recurrence rate with 
long term follow up.[7, 8]  Given these disappointing results, other investigators 

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have evaluated the role of synthetic mesh in the repair of contaminated 
abdominal wall defects in small, retrospective non-randomized trials.[9-11]  
Importantly, several recent modifications to polypropylene mesh have yielded 
potential options for repairing contaminated defects.  These modifications include 
reducing mesh weight, increasing mesh porosity, and utilizing monofilament 
unwoven material that resists bacterial colonization in animal studies.[12, 13]  In 
fact, our lab has recently evaluated 9 commercially-available prosthetic materials 
and has found that certain meshes can clear bacterial contamination similar to 
biologic grafts in a rat hernia model. These materials have been used for years in 
clean repairs of large complex abdominal wall defects with significantly lower 
recurrence rates (<5%) than a biologic mesh.[14]  Beyond doubt, a non-biased 
prospective randomized trial is long overdue to compare the safety and efficacy 
of a biologic graft versus a macroporous light-weight polypropylene synthetic 
material for the repair of complex ventral hernias. This study will compare the 
safety, efficacy, and cost-effectiveness of a permanent synthetic mesh versus a 
biologic prosthesis for the open repair of ventral hernias in the setting of clean-
contaminated (Class 2) or contaminated (Class 3) surgical procedures.   
This study will have a major impact on the field of hernia surgery, as the 
study findings will provide an objective guide to mesh selection, optimize surgical 
approaches for complex ventral hernia repair, and ultimately significantly improve 
patient outcomes.  The lack of data as to the ideal mesh selection for complex 
ventral hernia repair has resulted in physicians relying on anecdotal experience, 
industry marketing, and personal bias.  Presently, hundreds of thousands of 

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patients are affected by this condition and would significantly benefit from clear 
practice guidelines regarding the best approach and the most appropriate 
prosthetic selection for repairing these complex ventral hernias.  In order to 
address this important need, the overall safety, efficacy, and cost-effectiveness 
of a biologic prosthetic as compared to a synthetic material for the open repair of 
complex defects should be subjected to a prospective randomized clinical trial.   
We hypothesize that reinforcement of single-stage open repairs of 
complex abdominal wall defects with a macroporous light-weight polypropylene 
synthetic mesh will result in significantly lower rates of hernia recurrence (HR) 
and surgical site occurrences requiring procedural intervention (SSOPI) at 24 
postoperative months, and greater cost-effectiveness compared to reinforcement 
with a biologic mesh.  We further hypothesize that reinforcement with 
macroporous light-weight polypropylene synthetic mesh will be associated with a 
significantly greater change in preoperative to postoperative patient-reported 
quality of life (QOL) compared to reinforcement with biologic mesh for clean-
contaminated or contaminated ventral hernias.  
The specific aims of the proposal are: 
1. To demonstrate that a single-stage repair of clean-contaminated (Class 2) 
or contaminated (Class 3) ventral hernias using a macroporous light-
weight polypropylene synthetic mesh will result in superior clinical 
outcomes compared to a biologic mesh.  
a. Task 1- Demonstrate that repairs of clean-contaminated and 
contaminated ventral hernias performed with macroporous light-

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weight polypropylene mesh will result in fewer recurrent hernias 
and fewer surgical site occurrences requiring procedural 
intervention at 24 postoperative months compared to repairs of 
clean-contaminated and contaminated ventral hernias performed 
with biologic mesh. 
b. Task 2- Compare postoperative pain, and demonstrate greater 
change in preoperative to postoperative quality of life (QOL) at 1 
month, 6 months, 12 months, and 24 months following clean-
contaminated or contaminated ventral hernia repair with a 
macroporous light-weight polypropylene mesh versus a biologic 
prosthesis.   
2. To demonstrate that a macroporous light-weight polypropylene mesh is 
the more cost-effective strategy than a biologic prosthetic in clean-
contaminated and contaminated abdominal wall reconstruction.   
a. Task 1-Estimate direct and indirect economic costs associated with 
clean-contaminated or contaminated ventral hernia repair using 
either polypropylene mesh or biologic mesh from a limited societal 
perspective. 
b. Task 2 – Perform health utility valuation in patients undergoing 
repair of clean-contaminated or contaminated ventral hernias using 
either polypropylene mesh or biologic mesh. 
c. Task 3 – Calculate and compare incremental cost-effectiveness 
ratios for patients undergoing repair of clean-contaminated or 

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contaminated ventral hernias using polypropylene mesh versus 
biologic mesh. 
 
                         Research Strategy 
SIGNIFICANCE 
 
The repair of ventral hernias in the presence of active infection or 
contamination is an extremely challenging problem for the reconstructive  
surgeon. Very little data exists as to the ideal surgical approach or the 
appropriate class of reconstructive material to affect a long-term durable repair 
without promoting chronic mesh contamination or infection.  This lack of scientific 
evaluation of this very common clinical scenario has resulted in the development 
of one of the fastest growing markets in abdominal wall reconstruction: biologic 
mesh.  Healthcare expenditures associated with hernia repair have topped $5 
billion dollars, and a substantial and growing amount can be attributed to biologic 
prosthetics.   
 
Based on well-designed prospective randomized trials, typical hernia 
repairs in a “clean” (Class 1 wound) field are almost always performed with a 
synthetic mesh, as long term results have demonstrated reduction in recurrence 
rates of up to 50%. [5, 15]  Despite almost no strong clinical evidence, it has 
generally been accepted by the US surgical community that synthetic mesh 
should be avoided in the presence of contamination.[10, 12, 16-19]  The exact 
basis of these concerns is not entirely clear.  Based on historic data and 
evaluating microporous or heavy weight materials, several authors have reported 

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high rates of mesh sepsis requiring explanation.[16]  This has created an 
overwhelming fear amongst surgeons that synthetic mesh will almost always 
become infected and will always require surgical excision.  However, a closer 
inspection of the literature would suggest that some synthetic materials are in 
fact quite resistant to bacterial contamination. Furthermore, both in vitro and in 
vivo analyses have demonstrated that various prosthetic meshes can be 
salvaged if exposed to bacterial contamination.[11-13, 19-22]  
 
The fear of placing a synthetic mesh in a clean-contaminated or 
contaminated field has resulted in two common approaches to this clinical 
problem.  Historically, the standard of care for repairing these hernias occurring 
in compromised fields has involved two staged procedures.  Initially, the 
contaminated portion of the procedure (takedown of fistula, bowel resection, 
removal of infected prosthetic, or clearance of abdominal wall infection) is 
performed and the abdominal wall is temporarily closed with sutures or an 
absorbable mesh.  After 6 to 12 months and complete healing of the wound, the 
patient undergoes a definitive abdominal wall reconstruction, often with synthetic 
mesh.  While this approach has resulted in acceptable long-term outcomes, the 
patients have a prolonged period of convalescence, extended hospitalizations, 
restricted activity, and poor quality of life.  Recognizing these limitations, the 
potential alternative of a definitive single-stage reconstruction for clean-
contaminated and contaminated abdominal wall defects is particularly appealing.  
[23]  These single-stage repairs have routinely been performed with biologic 
prosthetics with variable results.  If biologic mesh could result in healed wounds 

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and durable single-stage repairs with low recurrence rates, it could reduce 
patient recovery times and improve return to a normal functional status while 
eliminating a second procedure.  Since these repairs are often occurring in clean-
contaminated, contaminated, and dirty fields, the reported incidence of surgical 
site infections are as high as 8%, 15%, and 27%, respectively.[24]   
 
Over the past decade, a multitude of biologic prosthetics have been 
released to improve the results of single-stage repairs for these challenging 
cases.  These materials are derived from various sources including human or 
porcine dermis, bovine pericardium, or intestinal submucosa.  They are 
processed to render an acellular collagen-rich graft designed to act as a cellular 
scaffold to allow native tissue in-growth and regeneration of tissue.  They are 
marketed as resistant to infection and therefore as a suitable alternative to 
repairing clean-contaminated and contaminated abdominal wall defects. [8, 25-
28] However, these products are very expensive, with a 400cm2 porcine dermal 
graft costing over $10,000 dollars, and currently represent the most rapidly 
growing market in hernia repair, with estimates of almost $500 million dollars in 
annual revenue by the year 2013.[6] Despite the rapid acceptance of these 
materials, there is little preclinical or clinical evidence to support their claims of 
regeneration, or that they provide a durable repair to the abdominal wall in the 
setting of clean-contaminated (Class 2) or contaminated (Class 3) surgical 
procedures. In our experience, the single-stage repair of contaminated 
abdominal wall defects with these biologic grafts has resulted in a 40%-80% 
recurrence rate with long-term follow-up.[7]  Given these disappointing results, 

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other investigators have evaluated the role of synthetic mesh in the repair of 
clean-contaminated and contaminated abdominal wall defects in small, 
retrospective non-randomized trials.[9-11]  Importantly, several recent 
modifications to polypropylene mesh have yielded potential options for repairing 
contaminated defects.  These modifications include reducing mesh weight, 
increasing mesh porosity, and using monofilament unwoven materials that resist 
bacterial colonization in animal studies.[12, 13]  In fact, our lab has recently 
evaluated 9 commercially-available prosthetic materials and has found that 
certain meshes can clear bacterial contamination similar to biologic grafts in a 
rodent chronic infection model.[29] (Figure 1) These synthetic materials have 
been used for years in repairing large complex abdominal wall defects in clean 
settings with significantly lower recurrence rates (<5%) than biologic meshes.[14]  
A non-biased prospective randomized trial is long overdue to compare the safety 
and efficacy of a biologic graft versus a macroporous light weight polypropylene 
synthetic material for the open repair of complex ventral hernias to appropriately 
guide mesh selection and optimize patient outcomes.  This study will compare 
the safety, efficacy, and cost-effectiveness of a permanent synthetic mesh versus 
a biologic prosthesis for the open repair of ventral hernias in the setting of clean-
contaminated (Class 2) or contaminated (Class 3) surgical procedures..   
 
APPROACH 
We hypothesize that reinforcement of single-stage open repairs of 
complex abdominal wall defects with a macroporous light-weight polypropylene 

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synthetic mesh will result in significantly lower rates of hernia recurrence (HR) 
and surgical site occurrences requiring procedural intervention (SSOPI) at 24 
postoperative months, and greater cost-effectiveness compared to reinforcement 
with a biologic mesh.  We further hypothesize that reinforcement with 
macroporous light-weight polypropylene synthetic mesh will be associated with a 
significantly greater change in preoperative to postoperative patient-reported 
quality of life (QOL) compared to reinforcement with biologic mesh for clean-
contaminated or contaminated ventral hernias.  
The specific aims of the proposal are: 
1. To demonstrate that a single-stage repair of clean-contaminated (Class 2) 
or contaminated (Class 3) ventral hernias using a macroporous light-
weight polypropylene synthetic mesh will result in superior clinical 
outcomes compared to a biologic mesh.  
a. Task 1- Demonstrate that repairs of clean-contaminated and 
contaminated ventral hernias performed with macroporous light-
weight polypropylene mesh will result in fewer recurrent hernias 
and fewer surgical site occurrences requiring procedural 
intervention at 24 postoperative months compared to repairs of 
clean-contaminated and contaminated ventral hernias performed 
with biologic mesh. 
b. Task 2- Compare postoperative pain, and demonstrate greater 
change in preoperative to postoperative quality of life (QOL) at 1 
month, 6 months, 12 months, and 24 months following clean-

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contaminated or contaminated ventral hernia repair with a 
macroporous light-weight polypropylene mesh versus a biologic 
prosthesis.   
2. To demonstrate that a macroporous light-weight polypropylene mesh is 
the more cost- effective strategy than a biologic prosthetic in clean-
contaminated and contaminated abdominal wall reconstruction.   
a. Task 1-Estimate direct and indirect economic costs associated with 
clean-contaminated or contaminated ventral hernia repair using 
either polypropylene mesh or biologic mesh from a limited societal 
perspective. 
b. Task 2 – Perform health utility valuation in patients undergoing 
repair of clean-contaminated or contaminated ventral hernias using 
either polypropylene mesh or biologic mesh. 
c. Task 3 – Calculate and compare incremental cost-effectiveness 
ratios for patients undergoing repair of clean-contaminated or 
contaminated ventral hernias using polypropylene mesh versus 
biologic mesh. 
 
STUDY DESIGN 
 
We propose a multi-center prospective double-blinded randomized 
controlled trial comparing 253 patients with clean-contaminated (Class 2) or 
contaminated (Class 3) abdominal wall ventral hernias undergoing single-stage 
open repair. Soft Mesh™ by CR Bard™, a macroporous monofilament 

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polypropylene permanent mesh, will be compared to Strattice™ mesh by 
LifeCell™, a non-crosslinked porcine dermal biologic graft, for the single-stage 
open reconstruction of clean-contaminated and contaminated abdominal wall 
defects.  The primary outcome variables will be the absence of surgical site 
occurrence requiring procedural intervention and the absence of a hernia 
recurrence from the time of surgery up to 24 months of postoperative follow-up.  
 
 
Study Procedures 
 
Patients undergoing open ventral hernia repair for clean-contaminated and 
contaminated abdominal wall hernias meeting inclusion criteria will be 
randomized to receive a synthetic mesh or a biologic mesh.  Randomization will 
be carried out using computer-generated randomization blocks at the time of 
enrollment.  Stratified randomized will be used with the strata formulated by 
medical center then by clean-contaminated or contaminated surgical site class.  
The Investigator will be blinded to patient randomization assignment until the 
point of intra-operative device use following final CDC wound classification, 
whereas patients and co-investigators responsible for data analysis will remain 
blinded to patient randomization until the conclusion of the study period.  As 
such, a double-blinded study protocol will be maintained.  Patients randomized to 
synthetic mesh will receive Soft Mesh™ (CR Bard™, Murray Hill, NJ), and those 
patients randomized to biologic mesh will receive Strattice™ (LifeCell™, 
Branchburg NJ).  The use of biologic and synthetic meshes in clean-
contaminated and contaminated fields is considered experimental; however, the 

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selection of these prosthetics was based on a careful review of the multiple 
animal models, preclinical data, and our own clinical experience with each of 
these materials placed in both clean and contaminated abdominal wall 
reconstructions.[26, 30-35]   
 
Soft Mesh™ is a light-weight (44 g/m2) monofilament macroporous 
polypropylene synthetic mesh.  It does not have an anti-adhesive barrier and 
must be place in an extraperitoneal position.  Our lab has evaluated this material  
in a chronic rat infection model and has shown clearance rates of bacterial 
contamination comparable to biologic grafts (Figure 1). This prosthetic has 
become our material of choice for routine abdominal wall reconstruction and 
ventral hernia repairs, given its chemical and structural properties. In addition, we 
have also utilized Soft Mesh™ in the retrorectus position in several cases of 
elective bowel surgery, parastomal hernia repair, and inadvertent enterotomies 
with excellent results including no mesh infections and no long-term hernia 
recurrences.  Other authors have reported excellent outcomes with 
polypropylene-based synthetic material placed in the extraperitoneal position.[14] 
Interestingly, reports of placing several forms of polypropylene-based meshes 
with anti-adhesive barrier coatings into the peritoneal cavity for elective hernia 
repair with concomitant bowel surgery has shown very high rates of mesh sepsis 
and subsequent mesh excision.[36]  Mesh placed in the intraperitoneal position 
comes in contact with the viscera and therefore requires some form of an anti-
adhesive barrier.  We noted that these anti-adhesive barriers prevent bacterial 
clearance in an experimental study (Figure 1).  Based on our findings, it is likely 

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that both the specific type of synthetic mesh and the compartment of the 
abdominal wall in which it is placed will have significant effects on bacterial 
clearance and success when placed in a clean-contaminated or contaminated 
field.  Potential extraperitoneal compartments for mesh deployment include the 
onlay (placed above the fascia in the subcutaneous space) or a retro-rectus 
(below the muscles but above the peritoneum) position.  The onlay position can 
result in early mesh exposure if wound infection or breakdown occurs and has 
been shown in other prospective randomized trials to result in a high rate of 
mesh infections.[37]  Alternatively, the retro-rectus repair with synthetic mesh 
reinforcement has been demonstrated by multiple authors as a durable repair 
with very low rates of mesh infection and hernia recurrence.[14, 38]  For these 
reasons, we feel it is particularly important to design this experiment to use an 
unprotected macroporous light-weight polypropylene mesh placed in the retro-
rectus position.   
 
The Strattice™ biologic mesh is derived from porcine dermis and 
processed to remove the cells but maximally preserve the dermal matrix. The 
processing avoids the use of collagen cross linking agents in a reported effort to 
minimize immunogenic response, improve biocompatibility, and ultimately 
promote rapid revascularization and tissue regeneration.[39]  Multiple biologic 
grafts have been developed to repair contaminated abdominal wall defects, 
however little comparative data exists to definitively guide selection of these 
grafts.  Our lab has performed several preclinical evaluations of these materials 
and has chosen Strattice™ based on our findings.  Strattice™ mesh showed 

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excellent biocompatibility from an immunologic perspective when compared to 
other human and porcine derived biologic products.[40]  This selection should 
limit the potential for immunologic responses to the biologic material confounding 
our results.  We also evaluated the ability of various biologic grafts to clear 
bacterial contamination in a chronic infection rodent model.[29]  Strattice™ mesh 
had the highest rates of bacterial clearance when compared to other porcine 
derived materials.  Interestingly, it appears that based on our findings, Soft 
Mesh™ and Strattice™ result in similar rates of bacterial clearance, which is the 
primary driving force of our renewed interest in evaluating the usage of these 
inexpensive synthetic meshes in clean-contaminated and contaminated fields.   
 
Patients will be evaluated at initial preoperative visit for meeting inclusion 
and exclusion criteria.  Patients will be included in this study if they are 21 years 
of age or older (including women of childbearing age), undergoing a planned 
single-stage open reconstruction of a contaminated (CDC wound class 2 or 3) 
abdominal wall defect (including concomitant procedures: creation of a stoma, 
bowel resection, panniculectomy, removing uninfected mesh, and 
gastrointestinal, genitourinary, or gynecologic procedure) under general 
anesthesia, can achieve midline fascial closure, and have a parastomal hernia or 
midline defect at least 9 cm2.   Patients will be excluded from the study if they 
meet any of the following criteria: are undergoing a laparoscopic or robotic repair 
of the abdominal wall defect, have a CDC class 1 or 4 wound (see CDC 
guidelines below),have a defect that the surgeon cannot achieve primary fascial 
apposition and requires a bridge of mesh, body mass index (BMI) >45 kg/m2, 

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chronic immunosuppression including medically-induced with >10 mg of 
prednisone/day, collagen vascular disorder, severe malnourishment (albumin 
<2.0 g/dl), ascites refractory to medical management, end stage renal disease 
(indwelling hemodialysis or peritoneal dialysis), pre-existing liver disease 
(hepatitis B or C or total bilirubin >3.0 mg/dl), smoking history within 1 month of 
surgery, current pregnancy, require removal of a prior surgical mesh during a 
planned ventral hernia repair due to active mesh infection (as defined by a 
synthetic mesh that is not incorporated into the tissue, is extracorporeally 
exposed, or has a chronic draining sinus with clear fluid around the material; but 
not including synthetic mesh that is incorporated into the abdominal wall and not 
infected), are unable to undergo successful retro-rectus preperitoneal mesh 
placement, if they object to the implantation of porcine products, or if they are 
participating in other clinical trials. 
 
Upon enrollment into the study, patients will be randomized to either 
synthetic or biologic mesh for their repair.  All patients will undergo our standard 
pre-operative evaluation. Briefly, it will include a complete set of laboratory 
studies including complete blood count, comprehensive metabolic panel, 
albumin, prealbumin, HbA1C (for diabetic patients), and urinalysis.  Pregnancy 
test will be performed for those patients of child bearing potential.  Photos may 
be taken of the anterior abdominal wall.  An abdominal pelvic CT scan will be 
obtained preoperatively in all patients based on our standard approach, 
(abdominal pelvic CT scan within the past twelve months is sufficient) and any 
issues postoperatively (including suspected recurrence) will be evaluated with a 

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CT scan as clinically indicated.  Preoperative demographics and clinical data 
including sex, race, age, body mass index (BMI), location of the hernia, length 
and width of the hernia defect, wound classification(per CDC guidelines, table 1), 
smoking status (active within 3 month of surgery), medical history, surgical 
history of  prior abdominal surgical procedures and prior ventral/incisional hernia 
repairs will be documented. Intraoperative details will include patient ASA score, 
patient temperature, use of epidural catheters, size of fascial defect (measured 
as maximal width and length), fascial layers released (external oblique, posterior 
rectus sheath, or transversus abdominis muscle), adhesions, concomitant 
procedures, wound characterization, mesh type, mesh placement, operative 
time, estimated blood loss, blood transfusion requirement, perioperative antibiotic 
administration (including type, dose, frequency, and times of initiation and 
discontinuation), and intraoperative fluid administration.  Postoperatively, patients 
will be evaluated for signs and symptoms of complications along with presence 
or absence of surgical site infections (SSIs) per CDC definitions as categorized 
below (Appendix 4), presence or absence of surgical site occurrences (SSOs) 
and any procedural interventions required to treat these SSOs, presence or 
absence of hernia recurrence and any reoperations, length of hospital stay, 
discharge date, time to return of bowel function and any readmission. Wound 
erythema treated with antibiotics will be considered a wound cellulitis. Wounds 
that are opened and cultured will be appropriately categorized as postoperative 
SSIs based on CDC definitions. Type, dose, frequency, and duration of 
antibiotics will be recorded. Patients will also fill out HerQLes (Appendix 1) and 

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EQ-5D (Appendix 2) quality of life tools preoperatively and during each post-
operative visit, at 4 weeks (± 2 weeks), 6 months (±,2month), 12 months (± 3 
months), and 24 months (± 4 months). See Appendix 7 for Plan for Continuation 
of Study Follow-up Visits for Patients Previously Enrolled at University Hospital 
There is substantial evidence that the majority of hernia recurrences occur within 
the first 24 months after repair.[5, 15, 41]   
 
Preoperative antibiotic usage will be standardized (as per SCIP protocol) 
as follows.  All patients will receive a second generation cephalosporin within 60 
minutes prior to the surgical incisions.  Patients with a prior history of penicillin 
allergy or MRSA wound/mesh infections will instead receive a preoperative dose 
of intravenous vancomycin.  The exact drug, along with the dose, frequency, and 
time administered will be recorded.  All antibiotics will be discontinued after 24 
hours of surgery unless otherwise indicated.  Prolonged antibiotic usage will be 
clearly documented as to indication, type, dose, frequency, and duration.  
 
The surgical approach to repairing these defects will be standardized, as 
previously described.   All patients will receive a chlorhexidine skin preparation, 
an iodine-impregnated skin barrier, and all stoma sites will be over sewn at the 
muco-cutaneous junction to limit bacterial contamination prior to skin preparation. 
If patients have an allergy to chlorhexidine, then Duraprep™ will be utilized.  For 
any patient who has an allergy to iodine, then a Steri-Drape may be used as a 
skin barrier.  Hair will be removed at the time of surgery with electric clippers. 
The midline fascia will be opened and complete adhesiolysis performed to free 
up the entire abdominal wall.  All concomitant procedures will be performed prior 

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to beginning the abdominal wall reconstructive phase, and documented.  
Intraoperative concomitant procedures will be allowed unless they change the 
wound classification to a class 4. Acceptable concomitant procedures include: 
the creation of a stoma, bowel resection, gastrointestinal surgery, genitourinary 
surgery, gynecological surgery, panniculectomy, and removing uninfected mesh. 
The abdominal wall is reconstructed by initially incising the posterior rectus 
sheath just lateral to the linea alba.  The release is performed at least 5 
centimeters above and below the fascial defect.  The posterior rectus sheath is 
then separated off the rectus muscle to the linea semilunaris.  If additional 
release is necessary to achieve fascial closure, the transversus abdominis 
muscle or the external oblique muscle may be released at the discretion of the 
surgeon and documented.  The posterior components are then reapproximated 
to exclude the abdominal viscera from the mesh.  If the mesh cannot be placed in 
the retro-rectus or preperitoneal position, then the patient will be excluded from 
the study.  Unless contraindicated due to drug allergies, a pulse lavage antibiotic 
irrigation using a 3 liter bag with Gentamycin (240 mg), Ancef (3gm), and 
Bacitracin (50,000 units) will be applied to the posterior rectus sheath and 
subcutaneous tissues after the components are reapproximated and prior to 
mesh placement.  If there is a drug allergy, then pulse lavage irrigation with 
sterile saline only will be applied.  Final wound classification will occur just prior 
to mesh placement per CDC criteria. Surgical wounds will be classified based on 
CDC criteria and only Class 2 and 3 wounds will be included in this study (see 
Appendix 3): 

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Class 2:  Clean-Contaminated 
 
Operative wounds in which the respiratory, alimentary, genital*, or urinary 
tract 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.  
*Includes female and male reproductive tracts 
 
Class 3- Contaminated 
 
A surgical field with any of the following: open, fresh, accidental wounds; 
operations with major breaks in sterile technique or gross spillage from the 
gastrointestinal tract; and incisions in which acute, nonpurulent inflammation is 
encountered. 
 
Following wound classification, the allocation of the patient to either the biologic 
mesh cohort or the permanent synthetic mesh cohort will be revealed to the 
operating surgeon, according to the previously-described computer-generated 
block randomization scheme stratified by wound classification and medical 
center.  The corresponding prosthetic material will then be placed with at least 5 

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cm of fascial coverage on all sides of the defect.  The mesh will be fixated with 
trans-abdominal #1 Maxon or PDS sutures at 5-10 cm intervals.  Number of 
sutures to secure the mesh will be documented.  All patients will have closed 
suction drains placed above the mesh and below the fascial closure.  These 
drains will be removed postoperatively when the collected fluid is < 30 cc/day for 
48 hours and documented.  The fascia will be closed with a running or 
interrupted Maxon or PDS #1 suture.  The skin will be closed loosely with 
staples.  Dry sterile dressings will be placed at the conclusion of the procedure 
and will be removed on postoperative day 2.  No further dressings will be applied 
to the wound.   
 
Postoperative complications will be defined and recorded on the CRF’s based on 
CDC standardized terms and definitions for Surgical Site Infections as follow: [42, 
43]-See appendix 4.  
 
Superficial Incisional Surgical Site infection (SSI) 
 
A superficial incisional SSI must meet the following criteria:  
Infection occurs within 30 days after the operative procedure AND involves only 
skin and subcutaneous tissue of the incision AND patient has at least ONE of the 
following:  
           a. purulent drainage from the superficial incision.  
           b. organisms isolated from an aseptically-obtained culture of fluid or tissue 
from the superficial incision.  

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           c. superficial incision that is deliberately opened by a surgeon and is 
culture-positive or not cultured AND the patient has at least one of the following 
signs or symptoms: pain or tenderness, localized swelling, redness, or heat.  A 
culture-negative finding does not meet this criterion.  
           d. diagnosis of superficial incisional SSI by the surgeon or attending 
physician.  
 
NOTE: 
 
a. Do NOT report stitch abscess (minimal inflammation and discharge 
confined to suture penetration site) as an infection. 
 
b. Do NOT report a localized stab wound or pin site infection.  Instead, 
report these as skin or soft tissue infections, depending on their depth. 
 
c. “Cellulitis" by itself does NOT meet criteria for superficial incisional SSI 
           d. If infection involves or extends into the fascial and muscle layers report 
as a deep incisional SSI. 
 
 
Deep Incisional SSI 
 
A deep incisional SSI must meet the following criteria:  
Infection occurs within 30 or 90 days after the operative procedure AND the 
infection involves deep soft tissues (e.g., fascial and muscle layers) of the 
incision AND patient has at least ONE of the following:  

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          a. purulent drainage from the deep incision but not from the organ/space 
component of the surgical site  
          b. a deep incision spontaneously dehisces or is deliberately opened by a 
surgeon AND is culture-positive or not cultured AND the patient has at least one 
of the following signs or symptoms: fever (>38°C), or 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 is 
found on direct examination, during invasive procedure, or by histopathologic 
examination or imaging test.  
         d. diagnosis of a deep incisional SSI by a surgeon or attending physician.  
 
NOTE:   
a. Classify an infection that involves both superficial and deep incision sites 
as a deep incisional SSI.  
b. Classify infection that involves superficial incisional, deep incisional, and 
organ/space sites as deep incisional SSI. This is considered a 
complication of the incision. 
 
 
Organ/Space SSI 
An organ/space SSI must meet the following criteria:  
Infection occurs within 30 or 90 days after the operative procedure AND infection 
involves any part of the body, excluding the skin incision, fascia, or muscle layers 

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that is opened or manipulated during the operative procedure AND the patient 
has at least ONE of the following:  
          a. purulent drainage from a drain that is placed into the organ/space  
          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 found on direct examination, during invasive procedure,, or by histopathologic 
examination or imaging test.  
         d. diagnosis of an organ/space SSI by a surgeon or attending physician 
and meets at least one criterion for a specific organ/space infection site listed in 
NHSN. 
All study co-investigators agree to follow these CDC definitions of SSIs for study 
subjects enrolled in this trial to maximize objectivity of this study measure. 
 
Surgical Site Occurrence 
 
A surgical site occurrence (SSO) will be defined as a complication or 
adverse event occurring at the surgical site, including but not limited to, 
superficial, deep incisional, and organ/space surgical site infections.  Consensus 
definitions and treatment plans for common SSOs following open complex 
ventral hernia repair were developed a priori by the co-investigators for the 
purposes of this study protocol (Appendix 6).  All study co-investigators agree to 
follow these consensus definitions and treatment plans for study subjects 
enrolled in this trial to maximize objectivity of this outcome measure.          

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Surgical Site Occurrences Requiring Procedural Intervention 
 
A surgical site occurrence requiring procedural intervention (SSOPI) will 
be defined as a complication or adverse event occurring at a surgical site that is 
managed or treated with an invasive procedure.  Consensus definitions and 
treatment plans for common SSOs following open complex ventral hernia repair 
were developed a priori by the co-investigators for the purposes of this study 
protocol (Appendix 6).  All study co-investigators agree to follow these consensus 
definitions and treatment plans for study subjects enrolled in this trial to maximize 
objectivity of this study measure.          
 
Ventral Hernia Recurrence 
 
A ventral hernia recurrence (HR) will be defined as any fascial defect of 
the anterior abdominal wall located within 7 cm of the index ventral hernia repair 
site detected by physical exam or abdominal computed tomography (CT) 
examination. These defects will be categorized as to whether they occur at the 
midline or parastomal hernia site, or both. Alternatively, for patients that are not 
amenable to come to the hospital for an in-person visit, recurrence will be 
assessed using a validated patient-reported outcome tool denominated the 
Ventral Hernia Recurrence Inventory (VHRI).[32] The VHRI is a short 3-question 
survey that can be applied in person or through a telephone contact, and was 
shown to have higher sensitivity and specificity to diagnose hernia recurrence 
than physical examination. Also, it was shown to have the ability to rule out 

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hernia recurrence when patients answer “no” to its questions.  All study co-
investigators agree to follow this consensus definition of ventral hernia 
recurrence for study subjects enrolled in this trial to maximize objectivity of this 
study measure.     
 
RISKS AND DISCOMFORTS  
As with any surgical procedure, there are some risks that are associated and  
they will be discussed in a separate surgical consent form. The subjects may 
experience some pain, bleeding and discomfort; however this is with any surgical 
operation.  Common occurrences following hernia repair include seroma or 
hematoma around the hernia repair, inflammation, opening of the wound, or 
infection. Subjects may also experience additional therapies or treatments, 
including the removal of the mesh to treat any of these events.  
 
 
 
BENEFITS 
There are no direct benefits to subjects for participating in this study.  Subject 
participation will help us better understand the comparative safety and 
effectiveness of synthetic versus biologic meshes in clean-contaminated and 
contaminated open ventral hernia repair. 
 
COSTS TO THE SUBJECTS 

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There are no extra costs to the subjects associated with the research.  
Procedures related to the hernia surgery are considered standard of care and will 
be the responsibility of the subject and the subject’s insurance company.   
 
ALTERNATIVES TO PARTICIPATION 
The subjects are under no obligation to participate in this study.  The subjects may 
decide not to have mesh used for their hernia repairs.  The PI or surgeon co-
investigator at each site will discuss all available options.  Those subjects not 
willing to participate in this study may be considered for the alternative treatment 
of primary defect closure/hernia repair with or without a similar biologic or synthetic 
product. 
 
PAYMENTS TO THE SUBJECTS 
Patients will not be paid for participation in this study.    
 
PLAN FOR OBTAINING INFORMED CONSENT 
For each subject, written informed consent will be obtained prior to any protocol-
related activities. As part of this procedure, the principal investigator, surgeon co-
investigator, or one of the approved study coordinators must explain orally and in 
writing the nature, duration, and purpose of the study in such a manner that the 
subject is aware of the potential risks, inconveniences, or adverse effects that may 
occur. The subjects will be informed that they may withdraw from the study at any 
time.  Subjects will receive all information that is required by federal regulations. 

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After a potential study patient is identified, the investigator or the study coordinator 
listed in this protocol as a person who will obtain consent will be responsible for 
instituting the informed consent process in a face-to-face manner. Before starting 
any study procedures, the investigator will discuss the proposed research study in 
detail with the potential subject during the office visit to discuss treatment options.  
The subject will be allowed ample time to read and review the informed consent 
document, and ask questions.  The informed consent document will be reviewed 
with the subject in depth by the participating investigator or designated member of 
the research team to ensure that the potential participant has a good 
understanding of the study protocol; what is required of the study participants; the 
potential risks and benefits of study participation; and his or her rights as a study 
participant.  The investigators will be available by phone or office visit to answer 
any questions that the participant may have.  After consideration, the subject may 
return if necessary for another visit with the investigator to discuss the study, ask 
questions, and sign the informed consent document to participate in this study.  
 
After the subject has read and reviewed the informed consent document and has 
agreed to participate, he/she will be asked to sign and date the document. The 
study member obtaining consent will also sign and date the form, and 
documentation of the informed consent process will be included in the research 
file (i.e., the person who obtained consent, where and when consent was 

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obtained, and who was present during the process). A copy of the consent form 
will be given to the subject.  
 
PROVISIONS FOR SUBJECTS FROM VULNERABLE POPULATIONS 
The population to be studied includes adults 21 years of age or over, so children 
are therefore excluded.  Decisionally-impaired and cognitively-impaired persons 
will not be approached to participate in this study as we are seeking subjects who 
have the capacity to understand and actively consent to the procedure 
independently.  Pregnant women will be excluded from participating in this study.  
 
Staff and employees of the participating sites (Cleveland Clinic,  Greenville 
Health Systems Vanderbilt University Medical Center,  and Washington 
University ) are considered vulnerable populations.  Staff and employees of any 
of the participating sites may be eligible to participate in this study. Since 
subjects may or may not benefit from this study, we do not want to exclude this 
population.  If an employee is a potential candidate for this study, the subject will 
be informed during the consent process that his/her participation or refusal to will 
in no way influence grades, employment, or subsequent recommendations.  
Every effort will be made to prevent coercion during this initial process and 
throughout study participation.  According to IRB policy, students and house staff 
cannot be asked to participate in research conducted while under the direct 
supervision of the investigator, so those subjects will not be enrolled.  
 

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In those instances where potential participants cannot read the consent form 
because they do not speak English, we will work with the IRB to develop a 
language-appropriate consent form.  In addition, a qualified translator will be 
present to assist with obtaining the informed consent of the participant. 
 
In addition, in the unusual situation where a subject cannot read a consent form  
due to illiteracy or blindness, a member of the research study staff will read and 
explain the consent form to the participant or to the participant’s legally-
authorized representative.  A witness, who will sign and date the consent form, 
must also be present during this oral presentation. 
 
SUBJECT PRIVACY AND DATA CONFIDENTIALITY 
Anonymity and confidentiality of subjects participating in this study will be 
maintained. The only potential identifiers on any study documents submitted to 
the sponsor or designee will be subject study numbers, dates of birth, and dates 
of procedures.  Every effort will be made to maintain the confidentiality of 
documents that identify the subject by name (e.g., signed informed consent 
documents, clinic charts), except to the extent necessary to allow monitoring by 
the Center for Clinical Research  at Cleveland Clinic, internal monitoring by any 
of the participating sites,  or auditing by the FDA or other regulatory authorities.  
Should the name and/or address of a subject participating in this trial be on a 
document submitted to the FDA or other regulatory authority (e.g., laboratory 

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report), the name and/or address will be completely blocked out and replaced 
with the subject study number. 
 
Additionally, patient charts and clinical records will be requested and reviewed so 
that protocol adherence and source documentation can be verified. There is a 
possibility that the Institutional Review Boards of any of the participating sites, 
the Food and Drug Administration, and possibly foreign regulatory agencies may 
review the de-identified study records.  
All information collected, such as name or medical record number, will be stored 
utilizing a customized Research Electronic Data Capture (REDCap®) database 
program for multi-institutional data collection. This is in a secure network/firewall 
protected electronic database to which only the investigator and the designated 
members of the study team will have access using an individual assigned login 
and password. Only approved study members listed on the IRB protocol will have 
access to the separately-stored master list.  User rights will be assigned such 
that the designated research coordinator at each site may only enter and review 
data from that site.  Only the Principal Investigator, Lead Research Coordinators, 
and Biostatisticians will be granted access to retrieve patient data from all sites 
for routine data quality assessments and data analyses. All electronic records 
pertaining to the clinical study will be password-protected, and only approved 
study members listed on the IRB protocol will have password access. 

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Any information about the subject collected on paper, as well as the subject 
enrollment log linking the subjects to their identifiers, will be kept under lock and 
key in the Department of Surgery at the corresponding participating site.   
 
Anticipated results and limitations  
 
We expect that the synthetic mesh may be associated with an initial higher 
rate of mesh infections than a biologic mesh.   However, we also believe that 
these infections will be treatable with local measures and not require surgical 
excision of the mesh.  We believe that light-weight macroporous materials will 
granulate and heal without long-term adverse outcomes.  This should result in a 
significant reduction in long-term hernia recurrences with the synthetic material.  
Another concern with this trial is the ability to recruit enough patients meeting 
inclusion criteria.  The multi-center nature of this study with well-established 
expert hernia surgeons with extensive experience in complex abdominal wall 
reconstruction should significantly reduce the risk of poor enrollment.  Each 
program is a high-volume referral center for complex abdominal reconstructions 
performing on average of 4 cases per week.  Finally, the ability to generalize our 
results to all available biologic mesh and synthetic mesh will not be possible.  
However, if the synthetic mesh is proven safe and effective in the single-stage 
repair of clean-contaminated and contaminated defects, it is likely that no 
surgeon will utilize any biologic graft costing over 100 times the price.    
 
Power Calculation 

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We are investigating two primary outcomes: surgical site occurrences requiring 
procedural intervention (SSOPI) and hernia recurrence (HR).  Surgical site occurrences 
requiring procedural intervention (SSOPI) is a repeated binary outcome measurement.  
Hernia recurrence (HR) is a single binary outcome measurement.  In a multi-institutional 
retrospective review of clean-contaminated and contaminated ventral hernia repair, 
hernia recurrence rates were 29.21% versus 9.01%, and surgical site occurrences 
requiring procedural intervention were 39.02% versus 9.01% for the biological mesh and 
permanent synthetic mesh cohorts, respectively.[44]  Based on review of these multi-
institutional data, an estimated 253 patients will be enrolled in the proposed trial.  
Assuming a maximum 20% loss to follow-up, 202 patients will remain in the study sample 
for a 1:1 randomized allocation to each treatment arm (101 subjects per cohort).  At the 
two-tailed overall (two hypotheses) type I error rate of 0.05, the study will have 92% 
power to detect a significant difference in the rates of hernia recurrence (29.21% vs. 
9.01%, and a 100% power to detect a significant difference in surgical site occurrences 
requiring surgical intervention for the primary hypothesis (39.02% vs. 9.01%; with four 
repeated measurements and autoregressive correlation of rho=0.5) With 4 centers each 
performing approximately 1 eligible procedures per week, there will be 192 total 
procedures performed per year, from which it would be feasible to achieve the total 
enrollment goal of 253 subjects within 2 years.   
 
Analysis 
Specific Aim 1 - To demonstrate that a single-stage repair of clean-
contaminated (Class 2) or contaminated (Class 3) ventral hernias using a 

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macroporous light-weight polypropylene synthetic mesh will result in superior 
clinical outcomes compared to a biologic mesh.  
 
Primary Analyses of Primary Outcomes: 
The primary outcomes are rates of surgical site occurrences requiring procedural 
intervention (SSOPI) and hernia recurrence (HR) assessed postoperatively at 1 
month, 6 months, 12 months, and 24 months.  For SSOPI with 4 repeated binary 
measurements, a generalized mixed model analysis with repeated measures will 
be performed to determine if a significant difference exists between the biologic 
mesh and the permanent synthetic mesh cohorts in the rate of SSOPI.  For HR, 
which is a single binary outcome, simple chi-square tests will be used for 
unadjusted analyses and a logistic regression model will be used for adjusted 
analyses. As this is a randomized trial, differences in baseline demographic and 
clinical characteristics between the biologic mesh cohort and the permanent 
synthetic mesh cohort are expected to occur at random.  Any significant 
differences found among the demographic or preoperative clinical characteristics 
between the two treatment groups will be controlled for in the final analysis to 
limit potential confounding of results.   
      
Secondary Analyses of Primary Outcomes: 
These primary outcomes will also be assessed as time-to-event analyses (time-
to-a-healed-wound and time-to-hernia-recurrence, respectively.  In these 
analyses, the time-to-recurrence in the synthetic mesh group will be compared to 

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the time-to-recurrence in the biologic mesh group using a two-sided log-rank test.  
The null hypothesis is that the time-to-recurrence is the same between the two 
groups (H0: Hazard Ratio = 1), and the alternative hypothesis is that the time-to-
recurrence is significantly greater for the permanent synthetic mesh cohort 
compared to the biologic mesh cohort (H1: Hazard Ratio not= 1).  Since this is a 
randomized clinical trial, observed differences in other covariates between the 
two study groups are assumed to arise by chance.  Therefore, the simple 
unadjusted analysis is sufficient to answer the research question, assuming 
adequate power (see above).  However, since the association between other 
covariates and time-to-recurrence may be of interest and because group 
imbalances may occur due to chance, it is of interest to consider further analyses 
that adjust for covariates in the relationship of time-to-recurrence and mesh type.  
To that end, the following multivariable models are pre-specified:  1) 
Demographics:  age, race, gender, and mesh type; and 2) Known linkages to 
hernia recurrence:  BMI, history of smoking, size of defect, number of previous 
hernia repairs, and mesh type.  These models will be fit with Cox proportional 
hazards models.  If other covariates are found to be highly imbalanced between 
groups or found to be associated with time-to-recurrence, they can also be 
included in multivariable models; however, this type of post-hoc model selection 
is to be considered inferior to the pre-specified models and is speculative in 
nature.  A similar analysis will ensue for the time-to-a-healed-wound outcome.  
The null hypothesis is that the time-to-a-healed-wound is the same between the 
two groups (H0: Hazard Ratio = 1), and the alternative hypothesis is that the 

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time-to-a-healed-wound is significantly greater for the permanent synthetic mesh 
cohort compared to the biologic mesh cohort (H1: Hazard Ratio not= 1).     
 
Analyses of Secondary Outcomes: 
The secondary outcomes are pain and quality of life (QOL).  The assessment of 
the association between these outcomes and mesh type will parallel what was 
described above for the primary outcome.  The differences are as follows.  First, 
the primary analysis will utilize an ANCOVA model adjusting for baseline pain 
(QOL) and correlations among repeated measurements.  The null hypothesis is 
that the pain (QOL) is the same, on average, between the synthetic and biologic 
mesh groups (H0: Beta-mesh-type = 0).  The alternative hypothesis is that the 
pain (QOL) is different, on average, between the two groups (H1: Beta-mesh-
type not= 0).  Second, the multivariable modeling will utilize multiple linear 
regressions.  A mixed model analysis with repeated measures will be performed 
to determine if a significant difference exists between the biologic mesh and the 
permanent synthetic mesh cohorts in the mean change in score from the 
preoperative assessment to the postoperative assessments at 1 month, 6 
months, 12 months, and 24 months for the EQ-5D and HerQLes quality of life 
instruments.  The null hypothesis is that there is no significant difference between 
the biologic mesh and the permanent synthetic mesh cohorts in the mean 
change in score from the preoperative to the postoperative assessments at any 
of the time points for either the EQ-5D or the HerQLes quality of life instruments.  
The alternate hypothesis is that there is a significantly greater change in EQ-5D 

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and HerQLes scores from the preoperative assessment to the postoperative 
assessment at each of the time points for the permanent synthetic mesh cohort 
compared to the biologic mesh cohort 
 
 
In these data analyses, we will explore the possibility of medical center effect and 
treatment by medical center interaction.  In particular, in the regression analyses, 
we will use indicator variables for medical center effect and indicator 
variable*treatment for possible treatment by medical center interaction.  If 
treatment by medical center interaction is significant, then it is more appropriate 
that the treatment effects are summarized by medical center.  
 
Specific Aim 2 - Demonstrate that a macroporous light-weight polypropylene 
mesh is the more cost-effective strategy than a biologic prosthetic in clean-
contaminated and contaminated abdominal wall reconstruction.   
 
The first task to address this specific aim will be to estimate direct and indirect 
economic costs associated with clean-contaminated and contaminated open 
ventral hernia repair.  A micro-costing approach will be used assuming a limited 
societal perspective.  Costs associated with the preoperative, operative, and 
postoperative phases of care will be considered as it pertains to the management 
of the ventral hernia.  In most cases, one to two preoperative clinic visits will be 
necessary.  Final operative costs will be based on each patient’s actual inpatient 
encounter cost obtained from the participating institutions.  Postoperative costs 

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will account for routine outpatient visits, costs incurred for complications, and 
time lost from work due to ventral hernia management.  All costs will be reported 
in U.S. dollars, adjusted for the years in which the data were obtained.  Should 
institutional data not be available for a particular cost, the best available evidence 
from currently published analyses will be used.  The second task for this specific 
aim is to perform health utility valuation in patients undergoing open repairs of 
clean-contaminated and contaminated ventral hernias.  Patients will be 
administered the EQ-5D and the HerQLes instruments at one preoperative visit 
and postoperatively at scheduled visits at 4 weeks (± 2 weeks), 6 months (± 2 
month), and 12 months (± 3 months), and 24 months (± 4 months).  HerQLes 
and EQ-5D valuations will be converted to health utility estimates based on 
published norms from the Agency for Healthcare Research and Quality (AHRQ).  
Quality-adjusted life years (QALYs) will be calculated based on these health 
utilities obtained in the postoperative phase.  For a given strategy (light-weight 
macroporous polypropylene mesh or biologic mesh), it is anticipated that health 
utility variation will be affected more than survival.  As such, calculations of 
QALYs will assume that all patients survive during the 24 month follow-up period, 
but differ in their health utility valuation.   
 
Cost-Effectiveness Evaluation 
Once costs and QALYs have been calculated for each strategy, a decision 
analysis model will be constructed incorporating these values and the associated 
outcomes and complications that are thought to have an impact on which 

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strategy is the better choice for patients.  One-way and two-way sensitivity 
analyses will be performed to help determine the degree to which each variable 
impacts the decision to choose either a light-weight macroporous polypropylene 
mesh or biologic mesh for repair of clean-contaminated or contaminated ventral 
hernias.  If appropriate, a multi-way probabilistic sensitivity analysis will be 
performed incorporating the uncertainty associated with known values for certain 
variables.  Costs, effectiveness (as measured by QALYs), cost-effectiveness 
ratios, and incremental cost-effectiveness ratios will be calculated to help 
determine the best strategy for mesh selection based on the results from this 
study and published data. 
 
INNOVATION 
 
This study would represent the first prospective randomized trial 
comparing synthetic and biologic meshes in the single-stage open repair of 
complex ventral hernias.  Currently, there is no level 1 clinical evidence to guide 
surgeons to the most appropriate prosthetic choice for these challenging cases.  
Given the lack of FDA regulations for clinical evidence to support the usage of 
these materials or provide comparative evaluations of these materials, it is 
unlikely that any company will perform this trial and potentially risk a negative 
outcome.  These materials have been available for almost 20 years, and some 
products still have no published data supporting their usage, even in an animal 
model.  This vacuum of evidence has left the surgeon to make decisions based 
largely on anecdotal experiences that are heavily influenced by strategic industry 

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marketing campaigns.  These marketing campaigns have included generalized 
claims of synthetic mesh being easily infected, and requiring major surgical 
resection for removal leaving the patient with a very morbid operation and high 
re-herniation rate.  In practice, newer lighter-weight meshes have actually been 
shown to be quite resistant to infection and often tolerate exposure and/or direct 
bacterial contamination.  It is paramount to the thousands of patients that are 
affected by this condition, and the hundreds of millions of dollars spent on these 
expensive products by hospitals and insurance companies that their indications 
and contraindications are clearly defined in appropriately-designed and 
conducted clinical trials.  Proving the potential advantages of utilizing a 
permanent synthetic mesh material in clean-contaminated and contaminated 
abdominal wall reconstruction could not only reduce healthcare expenditure by 
hundreds of millions of dollars, but also result in improved long-term patient 
outcomes with healed wounds and reduced recurrence rates. Our results will 
establish the standard of care for complex ventral hernia repair and guide the 
reconstructive surgeon on appropriate mesh selection.   
 
References:  
 
1. 
Mudge, M. and L.E. Hughes, Incisional hernia: a 10 year prospective study of 
incidence and attitudes. Br J Surg, 1985. 72(1): p. 70-1. 
2. 
Regnard, J.F., et al., Ventral incisional hernias: incidence, date of recurrence, 
localization and risk factors. Ital J Surg Sci, 1988. 18(3): p. 259-65. 
3. 
DeFrances, C.J., et al., 2006 National Hospital Discharge Survey. Natl Health 
Stat Report, 2008(5): p. 1-20. 

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4. 
Poulose, B.K., et al., Epidemiology and cost of ventral hernia repair: making the 
case for hernia research. Hernia, 2011. 
5. 
Luijendijk, R.W., et al., A comparison of suture repair with mesh repair for 
incisional hernia. N Engl J Med, 2000. 343(6): p. 392-8. 
6. 
Harth, K.C. and M.J. Rosen, Major complications associated with xenograft 
biologic mesh implantation in abdominal wall reconstruction. Surg Innov, 2009. 
16(4): p. 324-9. 
7. 
Blatnik, J., J. Jin, and M. Rosen, Abdominal hernia repair with bridging acellular 
dermal matrix--an expensive hernia sac. Am J Surg, 2008. 196(1): p. 47-50. 
8. 
Jin, J., et al., Use of acellular dermal matrix for complicated ventral hernia 
repair: does technique affect outcomes? J Am Coll Surg, 2007. 205(5): p. 654-60. 
9. 
Kelly, M.E. and S.W. Behrman, The safety and efficacy of prosthetic hernia 
repair in clean-contaminated and contaminated wounds. Am Surg, 2002. 68(6): 
p. 524-8; discussion 528-9. 
10. 
Campanelli, G., et al., Intestinal resection and multiple abdominal hernia mesh 
repair: is the combination safe and feasible? Chir Ital, 2004. 56(6): p. 839-42. 
11. 
Birolini, C., et al., Elective colonic operation and prosthetic repair of incisional 
hernia: does contamination contraindicate abdominal wall prosthesis use? J Am 
Coll Surg, 2000. 191(4): p. 366-72. 
12. 
Engelsman, A.F., et al., In vivo evaluation of bacterial infection involving 
morphologically different surgical meshes. Ann Surg, 2010. 251(1): p. 133-7. 
13. 
Engelsman, A.F., et al., Morphological aspects of surgical meshes as a risk factor 
for bacterial colonization. Br J Surg, 2008. 95(8): p. 1051-9. 
14. 
Iqbal, C.W., et al., Long-term outcome of 254 complex incisional hernia repairs 
using the modified Rives-Stoppa technique. World J Surg, 2007. 31(12): p. 2398-
404. 
15. 
Burger, J.W., et al., Long-term follow-up of a randomized controlled trial of 
suture versus mesh repair of incisional hernia. Ann Surg, 2004. 240(4): p. 578-
83; discussion 583-5. 
16. 
Cobb, W.S., et al., Infection risk of open placement of intraperitoneal composite 
mesh. Am Surg, 2009. 75(9): p. 762-7; discussion 767-8. 
17. 
Engelsman, A.F., et al., The phenomenon of infection with abdominal wall 
reconstruction. Biomaterials, 2007. 28(14): p. 2314-27. 
18. 
Geisler, D.J., et al., 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): 
p. 1118-23. 
19. 
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hernia repair in clean-contaminated and ontaminated surgical sites.  Abstract 
accepted for oral presentation at the 2013 Clinical Congress of the American 
College of Surgeons, Washington DC, October 2013. 
 
 
 
 
 
 
 
Figure 1: 
A rodent model of incisional hernia and chronic infection after exposure to 10'4 
colony forming units of MRSA.  Bacterial clearance as measured by total 

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resolution of bacterial growth. Strattice versus Soft Mesh p=0.32.
 
 
 
Appendix 1: HerQLes Questionnaire 
Appendix 2: EQ-5D Quality of Life Tool 
Appendix 3: CDC Wound Classification 
Appendix 4: CDC Definitions for Surgical Site Infections 
Appendix 5: Glossary of Terms 
Appendix 6: Definitions and Treatment Plans for Surgical Site Occurrences 
Appendix 7:  Continuation of Study Follow-up Visits for Patients Previously 
Enrolled