Prospective Trial Comparing the Performance Profiles of Two Non-Cross-Linked Porcine Dermal Matrices in Abdominal Wall Reconstruction
Phase: NA
Conditions: Hernia, Ventral, Intestinal Fistula, Fibromatosis, Abdominal
Sponsor: Jeffrey Janis

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TITLE: Prospective, Single-Blinded, Randomized-Controlled 
Trial Comparing the Performance Profiles of Two Non-Cross-
Linked Porcine Dermal Matrices in Abdominal Wall 
Reconstruction 
 
Research Protocol V2 
Document Date: September 24, 2024 
NCT # NCT02228889 
 
Principal investigator: Jeffrey E. Janis, MD, FACS (Professor of Plastic Surgery) 

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Prospective, Single-Blinded, Randomized-Controlled Trial 
Comparing the Performance Profiles of Two Non-Cross-Linked 
Porcine Dermal Matrices in Abdominal Wall Reconstruction 
 
Research Protocol V2 
 
Principal investigator: Jeffrey E. Janis, MD, FACS (Professor of Plastic Surgery) 
 
Prospective, Single-Blinded, Randomized-Controlled Trial 
Comparing the Performance Profiles of Two Non-Cross-Linked 
Porcine Dermal Matrices in Abdominal Wall Reconstruction 
 
Research Protocol V2 
 
Principal investigator: Jeffrey E. Janis, MD, FACS (Professor of Plastic Surgery) 
 
 
I. Background and rationale 
 
250,000 ventral hernia repairs are performed in the United States every year,1 and 
hernia recurrence, as well as surgical site occurrences (SSOs), remain a significant 
problem. When hernias recur and require reoperation, the subsequent risk of recurrence 
increases significantly. In fact, Luijendijk et al have shown that the 5-year risk of hernia 
recurrence increases stepwise with every reoperation2 (24% after the first reoperation, 
35% after the second reoperation, 39% after the third reoperation), and this underscores 
the importance of performing the best possible hernia repair the first time. In order to 
design the operation with the best possible odds of success, high-quality level I evidence 
is needed. There is a scarcity of high-quality, randomized-controlled trials in the field of 
ventral hernia repair.3 
One aspect of hernia repair that still contains significant uncertainty due to the 
scarcity of high-quality data is the ideal type of mesh. Meshes used in hernia repair fall 
into two broad categories: synthetic and biologic. Synthetic meshes add strength to the 
fascial repair, but are plagued by a high rate of infection and formation of 
enterocutaneous fistulas.3 This led to the development of biologic meshes. These usually 
consist of human or animal dermis that has been treated to remove cells, thus leaving a 
collagen matrix and making the material non-immunogenic. They are less prone to 
fibrous encapsulation than synthetic meshes. In addition, those biologic meshes serve as 
scaffolds that allow ingrowth of new tissue, including new blood vessels. This makes 
them less prone to infection than synthetic meshes. The Ventral Hernia Working Group 
(VHWG) recommends using a biologic mesh rather than a synthetic mesh in patients 
with a VHWG hernia grade of 2 or above.3 Although many biologic meshes exist, it is 
unclear which one provides optimal ventral hernia repair with the lowest rate of SSOs. 
 

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Some biologic meshes commonly used in abdominal wall reconstruction include: 
-Strattice: non-cross-linked porcine acellular dermal matrix (LifeCell Corp., 
Branchburg, NJ) 
-XenMatrix: non-cross-linked porcine acellular dermal matrix (Davol, Warwick, 
RI) 
-SurgiMend: non-cross-linked bovine acellular dermal matrix (TEI Bioscience, 
Inc., Boston, MA) 

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-FlexHD: human acellular dermal matrix (Ethicon, Somerville, NJ) 
-AlloDerm: human acellular derman matrix (LifeCell Corp., Branchburg, NJ) 
-AlloMax: human acellular derman matrix (Davol, Warwick, RI) 
-Permacol: cross-linked porcine acellular dermal matrix (Covidien, Mansfield, 
MA) 
It is known that the lowest recurrence and complication rates are achieved when 
the fascia is closed primarily in the midline, with additional reinforcement using mesh.2,4 
Closure of the native fascia can be achieved via primary advancement and suture in the 
case of small hernias, or component separation (as described in Ramirez et al5) in the 
case of larger hernias. Meshes can be placed as an overlay (superficial to the fascial 
closure), underlay (deep to the fascial closure), or bridge (in cases where the fascia 
cannot be primarily closed) 
 
The senior author (J.E.J) performs hernia repair using a technique similar to the 
Minimally-Invasive Component Separation with Inlay Bioprosthetic Mesh technique 
(MICSIB) described by Butler et al.6 The technique involves division of the external 
oblique aponeurosis just lateral to the semilunar line via a narrow subcutaneous tunnel, 
without significant subcutaneous undermining. This can be performed unilaterally or 
bilaterally. This is followed by placement of biologic mesh for reinforcement, in an 
intraperitoneal or retro-rectus plane, with wide overlap with the native fascia (this is a 
departure from the MICSIB technique, where the mesh is placed in the pre-peritoneal 
plane). Finally, the rectus muscles are advanced medially and the fascia is primarily 
closed over the mesh. This technique improves skin flap vascularity by preserving the 
myocutaneous perforators to the abdominal skin, and by minimizing subcutaneous 
dissection and dead space, which can result in fluid collections. In their evaluation of 38 
patients with large abdominal hernias, Butler et al applied the MICSIB technique, 
achieving primary musculofascial closure with inlay mesh in 31 patients and bridged 
repair with mesh in 7 patients. Mean follow-up was 12.4 months. There were no hernia 
recurrences. There was one bulge. There were no seromas, and there were two instances 
of skin necrosis (compared to a rate of 20% in the literature for standard component 
separation7). In a subsequent report comparing minimally-invasive component separation 
to standard open component separation, Butler et al found the minimally-invasive 
technique to result in far fewer instances of skin dehiscence and wound healing 
complications.8 The same group has also found that primary repair of the fascia with 
mesh reinforcement results in far fewer instances of hernia recurrence than cases where 
the fascia cannot be primarily closed and where mesh is used as a bridge.9 
 
In the MICSIB study by Butler et al,6 all patients received non-cross-linked 
acellular porcine dermal matrix bioprosthetic mesh. There are several retrospective 
studies comparing various types of allogenic and xenogenic bioprosthetic meshes in 
abdominal wall reconstruction. Non-cross-linked porcine mesh has been shown to be 
superior to human acellular dermis, resulting in fewer instances of laxity/bulge.10,11 Non- 
cross-linked porcine acellular dermis has also been shown to be superior to cross-linked 
porcine acellular dermis.12 Non-cross-linked acellular porcine dermal matrix has been 
shown to result in successful hernia repair in 80% of patients with contaminated or 

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infected hernias in a retrospective review.13 Janfaza et al retrospectively compared 
SurgiMend, a non-cross-linked bovine acellular dermal matrix, to Flex HD, a non-cross- 
linked human acellular dermal matrix.14 They found higher rates of surgical site 
infections and hernia recurrence with Flex HD. Clemens et al conducted a prospectively 
collected, retrospectively analyzed study in which they compared hernia repair with 
Strattice, a non-cross-linked porcine acellular dermal matrix, and with SurgiMend, in 120 
patients with mean follow-up of 21.0 months.15 They found no difference in the rate of 
recurrent hernia or bulge, although the Strattice group had a higher rate of overall 
complications due to a relatively higher rate of medical complications (pneumonia, renal 
failure) in that group not directly related to the type of mesh used. 
At the Ohio State University Wexner Medical Center, the two most commonly 
used biologic meshes for hernia repair in the practice of the senior author (J.E.J) are 
Strattice and XenMatrix. These are both non-cross-linked porcine acellular dermal 
matrices, manufactured by different companies using different technologies. There are 
some structural differences between the two. For example, according to internal reports 
by the companies, XenMatrix has larger pores that allows more tissue ingrowth.16 
However, there are no published reports comparing the performance profile those two 
meshes in the clinical setting. 
II. Objectives 
Our goals in this study are: 
a. PRIMARY OUTCOME 
i. To compare the hernia recurrence rate between XenMatrix and 
Strattice at 30 days and 1 year postoperatively 
b. SECONDARY OUTCOMES 
i. To compare the bulge rate between XenMatrix and Strattice at 
30 days and 1 year postoperatively 
ii. To compare the rate of Surgical Site Occurrences (SSOs) 
between two non-cross-linked porcine dermal matrices 
(XenMatrix and Strattice) in abdominal wall reconstruction at 30 
days and 1 year postoperatively 
1. Infection 
2. Seroma 
3. Hematoma 
4. Wound dehiscence 
5. Skin necrosis 
6. Formation of enterocutaneous fistula 
7. Mesh infection 
iii. To compare to changes in patient pain, physical functioning and 
quality of life after hernia repair between XenMatrix and 
Strattice, preoperatively, and at 1 year postoperatively 
1. Pain assessment: PROMIS Pain Intensity survey, 
PROMIS Pain Interference survey 

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2. Physical functioning assessment: PROMIS Physical 
Function 
3. Quality of life assessment: HerQLes survey 
III. Procedures 
a. Research design 
This is a prospective, randomized-controlled trial. It is single-blind (patients are 
blinded to the type of mesh used while surgeons are not). 
b. Sample 
Inclusion criteria: 
-Age > 18 
-Patients presenting for elective hernia repair, with VHWG grade 2 or above 
-Patients deemed to be good surgical candidates, with no active life-threatening cardiac 
disease, pulmonary disease, renal disease, hematologic disease 
-Patients presenting for resection of large abdominal wall tumors who are expected to 
undergo have tumor extirpative defect that would require biologic mesh for closure 
Exclusion criteria: 
-Known allergy to porcine products 
-Active smokers (within the past 4 weeks) presenting for elective hernia repair 
-Patients with active life-threatening cardiac disease, pulmonary disease, renal disease, 
hematologic disease presenting for elective hernia repair 
-Patients presenting for emergent hernia repair (in the setting of bowel strangulation, 
necrosis, penetrating trauma) as it will be difficult to consent those patients for the study 
preoperatively 
-Patients with severe systemic sepsis 
-Patients with frank purulence in the wound 
Sample size (power analysis) 
Our primary outcome is hernia recurrence rate at 30 days and 1 year postoperatively. 
According to two industry-sponsored studies, the rate of hernia recurrence with 
XenMatrix is approximately 7%.17,18 
According to the large series by Clemens et al, the rate of hernia recurrence with Strattice 
is approximately 2.9%.15 
Assuming an alpha error of 5%, a power of 80%, and assuming a large standard deviation 
(3), the number of patients in each group that is needed to demonstrate a significant 
difference is 5. 
 
In order to adequately power the study to analyzethe secondary outcomes, we plan to 
enroll 35 patients in each group (70 patients total) 

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a. Detailed study procedures 
When a patient with a ventral hernia or an abdominal wall tumor presents to the 
senior author for evaluation for abdominal wall reconstruction, a full history and physical 
examination will be performed. Patient who satisfy the study inclusion and exclusion 
criteria will be offered the opportunity to participate in the study. If they agree to 
participate, informed consent and HIPAA forms will be filled out and signed. 
 
Patients will then be randomized to group A (Strattice) or group B (XenMatrix) 
using a random number generator made in Microsoft Excel. They will not be told which 
group they are in, and only the principal investigator, co-investigators and operating room 
staff will be aware of which mesh is being used. 
 
The patients will be asked to fill out 4 surveys preoperatively: PROMIS Pain 
Intensity survey, PROMIS Pain Interference survey, PROMIS physical function survey 
and HerQLes survey. 
 
They will then undergo surgery, and will be followed weekly for a month, then 
every 3 months for a year, and as needed. They will be evaluated for hernia recurrence, 
bulge, or other SSOs throughout the follow-up period. 
 
They will be asked to fill out the PROMIS Pain Intensity survey, PROMIS Pain 
Interference survey, PROMIS physical function survey and HerQLes survey at 1 year. 
c. Measurements 
The patient characteristics that will be collected will include: 
1) Age 
2) Comorbidities 
a. Diabetes 
i. Hemoglobin A1c 
b. Current tobacco use (defined as <4 weeks prior to surgery) 
c. Former tobacco use (defined as >4 weeks prior to surgery) 
d. Chronic Obstructive Pulmonary Disease 
e. Coronary Artery Disease 
f. Malnutrition (defined as prealbumin < 18 or albumin < 3.5) 
g. Corticosteroid use 
h. Use of other immunosuppressants 
i. BMI 
j. History of chemotherapy 
k. History of radiation to abdomen 
3) Hernia characteristics 
a. Size on abdominal CT scan in cm2 
b. Ventral Hernia Working Group (VHWG) grade3 

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i. Grade 1 (low risk): no comorbidities, no history of wound 
infection, no contamination 
ii. Grade 2 (comorbid): 
smoker/obese/diabetic/immunosuppressed/COPD 
iii. Grade 3 (potentially contaminated): previous wound infection, 
stoma present, GI tract violated 
iv. Grade 4 (infected): infected mesh, septic dehiscence 
c. Number of prior hernia repairs 
 
The surgical details that will be collected will include 
1) Surgeon 
2) Date of surgery 
3) Wound class 
a. Class I = clean 
b. Class II = clean-contaminated 
c. Class III = contaminated 
d. Class IV = dirty 
4) Whether bowel resection performed 
5) Whether component separation technique (CST) performed 
a. If yes, standard CST versus minimally-invasive CST 
6) Whether fascia able to be primarily closed 
7) Type of mesh used 
8) Location of mesh 
a. Overlay (superficial to the primary fascial repair) 
b. Underlay (deep to the primary fascial repair) 
i. Sub-rectus 
ii. Intraperitoneal 
The outcome data that will be collected will include 
a. Hernia recurrence 
b. Bulge 
c. SSOs 
a. Infection 
b. Seroma 
c. Hematoma 
d. Wound dehiscence 
e. Skin necrosis 
f. Formation of enterocutaneous fistula 
g. Mesh infection 
d. Score on PROMIS Pain Intensity survey 
e. Score on PROMIS Pain Interference survey 
f. Score on PROMIS Physical Function 
g. Score on HerQLes survey 
d. Internal validity 

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Since this is a randomized-controlled trial, we expect the baseline demographics and 
patient characteristics to be similar between the two groups, and we expect out results to 
be internally valid. 
e. External validity 
The study results will reflect the outcomes within our study population at the Ohio State 
University Medical Center, and may not be generalizable to other institutions. 
f. Data analysis 
Baseline patient characteristics will be compared between the two groups to ensure that 
the two groups are similar and that there are no confounders 
Multiple binary logistic regression will be performed to detect predictors of hernia 
recurrence, bulge and other SSOs. It will also be used to determine whether one mesh has 
a higher rate of complications compared to the other. 
IV. Regulatory & Continuing Review Completion Plan 
Step-by-Step Communication Plan 
The primary additional contact (department regulatory officer) listed on the IRB study 
team will be responsible for initiating the CR. when the CR notification is automatically 
sent by the IRB system 90 days prior to study expiration. Department contact will email 
study team notifying them that CR has been opened and set a timeline that is 8 weeks prior 
to study expiration for CR submission. 
A study team member, in the key personnel, co-investigator, or principal investigator role, 
will be asked to complete the details of the CR to include participant numbers, status of 
project, or any events that require reporting. This ensures that all “engaged” study team 
members participate in the CR and may serve in completing the CR. 
The department additional contact will follow-up with the study team via email 2x before 
setting up a meeting with PI to complete the CR. 
The PI will submit the ready CR at least 48hrs prior to the 8 week deadline. 
The 8 week deadline insures that at least 4 IRB board meetings occur prior to study 
expiration to account for request for modifications, delays from IRB, or other unforeseen 
circumstances that may cause a lapse in study. 
 
 
V. Bibliography 
1. Millennium Research Group. US markets for soft tissue repair 2009. Toronto, 
ON: Millennium Research Group, Inc; 2008. 
2. Luijendijk RW, Hop WC, van den Tol MP, et al. A comparison of suture repair 
with mesh repair for incisional hernia. N Engl J Med 2000;343:392-398. 
3. Breuing K, Butler CE, Ferzoco S, Franz M, Hultman CS, Kilbridge JF, Rosen 
M, Silverman RP, Vargo D. Incisional ventral hernias: review of the literature 
and recommendations regarding the grading and technique of repair. Surgery 
2010;148:544-558. 
4. Espinosa-de-los-Monteros A, de la Torre JI, Marrero I, Andrades P, Davis 
MR,Vasconez LO. Utilization of human cadaveric acellular dermis for 
abdominal hernia reconstruction. Ann Plast Surg 2007;58:264-267. 
5. Ramirez OM, Ruas E, Dellon AL. ‘‘Components separation’’ method for 
closure of abdominal-wall defects: an anatomic and clinical study. Plast 
Reconstr Surg 1990;86:519-526. 

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6. Butler CE, Campbell KT. Minimally invasive component separation with inlay 
bioprosthetic mesh (MICSIB) for complex abdominal wall reconstruction. Plast 
Reconstr Surg 2011;128:698-709. 
7. Lowe JB, Garza JR, Bowman JL, Rohrich RJ, Strodel WE. Endoscopically 
assisted “components separation” for closure of abdominal wall defects. Plast 
Reconstr Surg. 2000;105:720-729. 
8. Ghali S, Turza KC, Baumann DP, Butler CE. Minimally invasive component 
separation results in fewer wound-healing complications than open component 
separation for large ventral hernia repairs. J Am Coll Surg 2012;214:981-989. 
9. Booth JH, Garvey PB, Butler CE et al. Primary fascial closure with mesh 
reinforcement is superior to bridged mesh repair for abdominal wall 
reconstruction. J Am Coll Surg 2013; EPub ahead of print. 

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10. Sacks JM, Butler CE. Outcomes of complex abdominal wall reconstruction with 
bioprosthetic mesh in cancer patients. Plast Reconstr Surg. 2008;121:39. 
11. Candage R, Jones K, Reed RL et al. Use of human acellular dermal matrix for 
hernia repair: friend or foe? Surgery 2008;144:703-711. 
12. Butler CE, Burns NK, Campbell KT, Mathur AB, Jaffari MV, Rios CN. 
Comparison of cross-linked and non-cross-linked porcine acellular dermal 
matrices for ventral hernia repair. J Am Coll Surg. 2010;211:368-376. 
13. Itani KM, Rosen M, Vargo D, et al. NP2010-9938: Prospective multicenter 
clinical study of single-stage repair of infected or contaminated abdominal 
incisional hernias using Strattice reconstructive tissue matrix. In: Proceedings of 
the American College of Surgeons 96th Annual Clinical Congress; Washington, 
DC; October 3–7, 2010. 
14. Janfaza M, Martin M, Skinner R. A preliminary comparison study of two 
noncrosslinked biologic meshes used in complex ventral hernia repair. World J 
Surg 2012;36:1760-1764. 
15. Clemens MW, Selber JC, Butler CE et al. Bovine versus porcine acellular 
dermal matrix for complex abdominal wall reconstruction. Plast Reconstr Surg 
2013;131:71-79. 
16. XenMatrix Surgical Graft Brochure. Located online at 
http://www.davol.com/default/assets/File/DAV%201872%20XenMatrix%20Br 
o%20FINAL.pdf 
17. Pomahac B, Aflaki P. Use of a non-cross-linked porcine dermal scaffold in 
abdominal wall reconstruction. Am J Surg. 2010;199:22-27. 
18. 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;77:144-150.