Porcine Xenograft Versus Second Intention Healing: a Randomized, Evaluator-blinded Clinical Trial
Phase: NA
Conditions: Wound Healing and Scar Quality Following Mohs Surgery and Excisional Dermatologic Surgery
Sponsor: Northwell Health

 
 
 
 
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Title: Porcine Xenograft versus Second Intention 
Healing: A randomized, evaluator-blinded clinical trial 
NCT Number: 03931746 
Document Date: September 16, 2019 
 
 
 
 
 
 
 
 
 
 
 

Porcine Xenograft versus Second Intention Healing: A 
randomized, evaluator-blinded clinical trial 
Protocol Number: 18-0715 
National Clinical Trial (NCT) Identified Number:  03931746 
Principal Investigator: Dr. Victoria Sharon 
 Sponsor: Investigator Initiated 
 
 
Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
6.5.1 
We have added a description of the “rescue 
therapy” that may be provided if a patient’s 
wound has not healed at approximately 10 to 
12 weeks following the surgical date. This 
section was previously left blank. 
While typical healing time is within 12 weeks 
of the surgical date, it is standard of care to 
provide the rescue therapy at approximately 
10 to 12 weeks if a patient’s wound is not 
healing normally. Furthermore, it is not 
possible to assess the primary outcome 
(POSAS observer total score) if the wound 
has not healed. 
9.3 
We have added a sentence to this section to 
clarify that patients who receive the rescue 
therapy will be included in the Modified 
Intention-to-Treat Population. 
We plan to analyze the data according to the 
treatment to which a patient was 
randomized. This will provide an accurate 
estimate of the treatment effect in the 
setting of actual clinical practice. 
Furthermore, given that typical healing time 
is within 12 weeks, we do not expect a large 
number of patients to require rescue 
therapy. Accordingly, the effect of the 
rescue therapy on treatment effect 
estimates would be minimal. 

  
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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schema ................................................................................................................................................. 2 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 4 
2 
INTRODUCTION ............................................................................................................................................ 4 
2.1 
Study Rationale .................................................................................................................................... 4 
2.2 
Background........................................................................................................................................... 4 
2.3 
Risk/Benefit Assessment .................................................................................................................... 5 
2.3.1 
Known Potential Risks ..................................................................................................... 5 
2.3.2 
Known Potential Benefits ................................................................................................ 6 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 6 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 6 
4 
STUDY DESIGN ........................................................................................................................................... 10 
4.1 
Overall Design .................................................................................................................................... 10 
4.2 
Scientific Rationale for Study Design.............................................................................................. 11 
4.3 
Justification for Dose ......................................................................................................................... 11 
4.4 
End of Study Definition ..................................................................................................................... 12 
5 
STUDY POPULATION ................................................................................................................................ 12 
5.1 
Exclusion Criteria ............................................................................................................................... 12 
5.2 
Lifestyle Considerations .................................................................................................................... 12 
5.3 
Screen Failures .................................................................................................................................. 12 
5.4 
Strategies for Recruitment and Retention ...................................................................................... 12 
6 
STUDY INTERVENTION ............................................................................................................................ 13 
6.1 
Study Intervention(s) Administration ............................................................................................... 13 
6.1.1 
Study Intervention Description ..................................................................................... 13 
6.1.2 
Dosing and Administration ............................................................................................ 13 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................ 13 
6.2.1 
Acquisition and accountability ...................................................................................... 13 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 13 
6.2.3 
Product Storage and Stability ....................................................................................... 13 
6.2.4 
Preparation ...................................................................................................................... 14 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 14 
6.4 
Study Intervention Compliance ........................................................................................................ 14 
6.5 
Concomitant Therapy ........................................................................................................................ 14 
6.5.1 
Rescue Medicine ............................................................................................................ 14 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 15 
7.1 
Discontinuation of Study Intervention ............................................................................................. 15 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 15 
7.3 
Lost to Follow-Up ................................................................................................................................. 15 
8 
STUDY ASSESSMENTS AND PROCEDURES ....................................................................................................... 15 
8.1 
Efficacy Assessments ............................................................................................................................ 15 
8.2 
Safety and Other Assessments ....................................................................................................... 16 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 17 
8.3.1 
Definition of Adverse Events (AE) ............................................................................... 17 

  
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8.3.2 
Definition of Serious Adverse Events (SAE) .............................................................. 17 
8.3.3 
Classification of an Adverse Event .............................................................................. 17 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 18 
8.3.5 
Adverse Event Reporting .............................................................................................. 18 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 19 
8.3.7 
Reporting Events to Participants ................................................................................. 19 
8.3.8 
Events of Special Interest ............................................................................................. 19 
8.3.9 
Reporting of Pregnancy ................................................................................................ 19 
8.4 
Unanticipated Problems .................................................................................................................... 19 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................................. 19 
8.4.2 
Unanticipated Problem Reporting ................................................................................ 19 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 20 
9 
STATISTICAL CONSIDERATIONS .............................................................................................................. 20 
9.1 
STATISTICAL HYPOTHESES ............................................................................................................. 20 
9.2 
SAMPLE SIZE DETERMINATION ..................................................................................................... 21 
9.3 
POPULATIONS FOR ANALYSES ....................................................................................................... 21 
9.4 
STATISTICAL ANALYSES ................................................................................................................... 22 
9.4.1 
GENERAL APPROACH ................................................................................................... 22 
9.4.2 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) ........................................... 22 
9.4.3 
ANALYSIS OF THE SECONDARY ENDPOINT(S) ........................................................ 22 
9.4.4 
SAFETY ANALYSES ......................................................................................................... 23 
9.4.5 
BASELINE DESCRIPTIVE STATISTICS ......................................................................... 24 
9.4.6 
PLANNED INTERIM ANALYSES ................................................................................... 24 
9.4.7 
SUB-GROUP ANALYSES ................................................................................................ 25 
9.4.8 
TABULATION OF INDIVIDUAL PARTICIPANT DATA ............................................... 25 
9.4.9 
EXPLORATORY ANALYSES ........................................................................................... 25 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 25 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 26 
10.1.1 
Informed Consent Process ........................................................................................... 26 
10.1.2 
Study Discontinuation and Closure ............................................................................. 26 
10.1.3 
Confidentiality and Privacy ........................................................................................... 27 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 27 
10.1.5 
Key Roles and Study Governance .............................................................................. 27 
10.1.6 
Safety Oversight ............................................................................................................. 28 
10.1.7 
Clinical Monitoring .......................................................................................................... 28 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 29 
10.1.9 
Data Handling and Record Keeping ............................................................................ 29 
10.1.10 
Protocol Deviations ........................................................................................................ 29 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 30 
10.1.12 
Conflict of Interest Policy .............................................................................................. 30 
10.2 
Additional Considerations ................................................................................................................. 30 
10.3 
Abbreviations ...................................................................................................................................... 32 
10.4 
Protocol Amendment History ........................................................................................................... 34 
11 
REFERENCES ............................................................................................................................................. 36 
 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
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STATEMENT OF COMPLIANCE 
 
(1) The trial will be conducted in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP), and applicable United States (US) Code of Federal Regulations (CFR). 
The Principal Investigator will assure that no deviation from, or changes to the protocol will take 
place without prior documented approval from the Institutional Review Board (IRB), except 
where necessary to eliminate an immediate hazard(s) to the trial participants. All personnel 
involved in the conduct of this study have completed Human Subjects Protection and ICH GCP 
Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB for review and approval.  Approval of both the protocol and the consent 
form must be obtained before any participant is enrolled.  Any amendment to the protocol will 
require review and approval by the IRB before the changes are implemented to the study.  All 
changes to the consent form will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form. 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Porcine Xenograft versus Second Intention Healing: A randomized, 
evaluator-blinded clinical trial 
Study Description: 
A comparison of porcine xenograft placement to second intent healing will 
be performed. Upon completion of dermatologic surgery following 
standard procedures, patients will be randomized into one of two groups 
(porcine xenograft placement or second intention healing). Weekly follow-
up via questionnaires will be conducted as well as a final office visit follow-
up at 3 months. Our study will allow surgeons to make informed decisions 
on whether porcine xenograft dressing is superior to that of second 
intention healing and thus worth considering. 
Objectives: 
 
 
 
Primary Objective: To compare overall scar quality and aesthetic outcome 
following second intention healing or porcine xenograft dressing of 
surgical wounds on the lower extremities. 
Secondary Objective: To compare patients’ assessment of scar quality, 
healing time, scar size, pain level, and complication rates following second 
intention healing or porcine xenograft dressing of surgical wounds on the 
lower extremities. 
Endpoints: 
Detailed descriptions of the endpoints below are included in the body of 
the protocol. 
 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
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NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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Primary Endpoint: 
 
1. POSAS observer scale total score 
Secondary Endpoints: 
1. POSAS patient scale total score 
2. Healing time 
3. Ratio of scare size to initial defect size 
4. Pain score at 1 week following surgery 
5. Number of weeks with pain score above 1 
 
Safety Endpoints: 
1. Infection 
2. Bleeding 
3. Pain 
Study Population: 
A total of 50 patients, over 18 years of age, post-operative defects greater 
than 8 mm (in greatest diameter or length of circular or oval geometric 
shape) on the lower extremities (including the feet) , single defect  
Phase: 
Device study (porcine xenograft) 
Description of 
Sites/Facilities Enrolling 
Participants: 
The two study sites are Dermatology Practices associated with Northwell 
Health. Northwell Health Physician Partners Division of Dermatology 1991 
Marcus Avenue Suite 302 Lake Success, NY 11042 and 332 East Main 
Street Suite 1 Bay Shore, NY 11706 
Description of Study 
Intervention: 
Patients will either be randomized to receive a porcine xenograft or 
randomized to allow the wound to granulate via second intention.  
Study Duration: 
A total of 24 months.  
Participant Duration: 
The study participants will present to the clinic for their initial surgery and 
then at the 3-month (± 1 month) for wound check and photograph of the 
wound.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2 
SCHEMA 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
Visit 1-Surgery 
 
 
 
 
 
 
 3-Month  
Period after  
Surgery 
 
 
Visit 2 
3-month 
Follow-up  
 
 
 
Total 50:  Obtain informed consent. Screen potential participants by inclusion and 
exclusion criteria; obtain history, document. 
Follow-up assessments of study 
endpoints and safety. 
Have scars assessed by two blinded 
investigators utilizing the physician 
observer scar assessment instrument 
(POSAS). 
 
Second Intent 
Healing 25 
participants 
Porcine 
Xenograft 25 
participants 
Weekly Questionnaires via email or phone. 
Randomize 
Perform baseline assessments. 
Administer initial study intervention. 
Educate patient on proper wound care instruction. 
Inform patient of weekly questionnaires that will be given via phone or email. 
Maintain consistent mode of treatment of wound throughout 3-month period.   

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screening 
 
Enrollment/Surgery 
Visit 1 
3-Month after surgery-
Weekly 
Questionnaires 
3 month follow-up 
visit 
±1 month after 
surgery date 
Informed consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
 
 
 
Randomization 
X 
 
 
 
Administer study 
intervention 
 
X 
 
 
Physical exam (including 
height and weight) 
X 
X 
 
X 
Vital signs 
X 
X 
 
X 
Height 
X 
X 
 
X 
Weight 
X 
X 
 
X 
Performance status 
X 
X 
 
X 
Hematology  
 
 
 
 
serum chemistry a 
 
 
 
 
Pregnancy test b 
 
 
 
 
EKG (as indicated) 
 
 
 
 
Adverse event review and 
evaluation 
X 
 
 
 
Complete Case Report 
Forms (CRFs) 
X 
X 
X 
X 
Questionnaire reporting 
 
 
X 
 
Blinded Wound/Scar 
Assessment 
 
 
 
X 
 
 
 
2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
There is no clear evidence to indicate whether porcine xenograft placement is more beneficial for 
wound healing following dermatologic surgery (Mohs surgery or excision surgery) versus allowing the 
wound to heal on its own. We will perform a comparison of porcine xenograft placement to second 
intent healing. 
2.2 
BACKGROUND  
Porcine xenograft has been used as a barrier to the skin for over 30 years, and due to its wound healing 
promoting factors, we believe that its use may result in decreased healing time, smaller scar size, better 
cosmetic outcomes, lower pain levels, and decreased rates of infection and other post-surgical 
complications. 
 
Upon completion of dermatologic surgery following standard procedures, patients will be randomized 
into one of two groups (porcine xenograft placement or second intention healing). Weekly follow-up via 
questionnaires will be conducted as well as a final office visit follow-up at 3 months. 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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The application of porcine xenograft dressings for wound healing was first studied in 1985, with 
evidence supporting several benefits when compared to traditional dressings [1].  Subsequent studies 
have substantiated the use of this dressing for a variety of clinical settings [2,3]. 
 
The EZ-DERM™ porcine xenograft is a biosynthetic dressing made from porcine collagen containing 
aldehyde crosslinking [1,3].  It has been most commonly applied to the management of 2nd degree 
burns, both partial-thickness and full-thickness defects [4].  This dressing can be used for two healing 
purposes, either for primary healing or as an intermediate in the preparation for a skin graft [2].   
 
Compared to other biosynthetic dressings, porcine xenografts afford longer wound adherence and can 
be stored at room temperature [1].  The xenograft triggers rejection by the surgical defect, increasing 
local vascularization [5].  It also allows for rapid granulation, a reduced risk of infection, as well as 
reduced wound-related fluid and thermal losses [6-8].  There is also evidence that the quicker wound 
healing reduces the frequency of dressings, hospitalization time, pain, and analgesic [9,10]. 
 
Several clinical case series have extended the use of porcine xenografts to Mohs Micrographic Surgery 
(MMS) to facilitate post-operative wound care.  Porcine xenograft dressings were determined to be 
safe, well-tolerated, and able to be applied to a wide anatomical range [3, 11,12]. 
 
In addition to biosynthetic dressings, healing via second intention remains an alternative [13,14]. The 
extremities of elderly patients are a common location for wound granulation. Drawbacks to second 
intention healing on the extremities include prolonged healing time and extended wound care for the 
patient [15]. 
 
Chern et. al. completed a review of biological dressings in dermatologic surgery and concluded that 
there is a limited number of studies focusing on the conclusive benefits of dressings [16].  Although 
studies have established that EZ-DERM™ was helpful for wound healing following Mohs surgery, there 
have not been any definitive statistical measures reported in the literature.  Additionally, there is a lack 
of studies assessing the direct comparison to second intention healing. 
 
Our plan is to perform a direct comparison of porcine xenograft placement to second intent healing. 
Based on the previously studied benefits of the xenograft as a barrier to the skin and one which has 
wound healing promoting factors, we believe that its use may result in decreased healing time, smaller 
scar size, better cosmetic outcomes, lower pain levels, and decreased rates of infection and other post-
surgical complications. 
 
Our study will allow surgeons to make informed decisions on whether porcine xenograft dressing is 
superior to that of second intention healing and thus worth considering. 
 
2.3 
RISK/BENEFIT ASSESSMENT   
2.3.1 KNOWN POTENTIAL RISKS  
 
Second intention Healing: 
 
Risk of infection, bleeding, scarring, numbness 
 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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Xenograft Placement: 
 
Localized skin allergy: EZ-DERM Porcine Xenograft is latex-friendly and non-cytotoxic. 
Risk of slightly longer procedure: Application of the xenograft may increase the length of the procedure 
by up to 10 minutes. 
Risks of infection, bleeding, scarring, and numbness. 
Rates of infection followed skin surgery are less than 1%. 
 
For Both: 
 
Risk of Randomization: Your group might receive a less effective treatment and/or have more side 
effects than the other treatment group(s). 
Risk of loss of confidentiality: There is a possibility that documents will be seen by individuals not 
included in this study. However, patient data will be stored in a password-protected electronic data 
capture tool in order to reduce the risk of loss of confidentiality. 
 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
There is no direct benefit to individual subjects or to the group of participants in the study 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
This trial can eventually lead to porcine xenografts becoming the standard of care when it comes to 
wound healing. 
 
3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
To compare overall scar quality and 
aesthetic outcome following 
second intention healing or porcine 
xenograft dressing of surgical 
wounds on the lower extremities. 
 
 
1. POSAS observer scale total score. 
The primary outcome will be the total 
score of the POSAS observer scale, 
assessed at the 3-month follow-up 
visit by two blinded evaluators who 
will not be involved in the placement 
of the porcine xenograft. For each 
patient, scores from the two blinded 
investigators will be combined by 
calculating the mean. The POSAS 
(Patient and Observer Scar 
Assessment Scale) is a validated 
assessment tool used for the 
To determine whether 
porcine xenografts 
improve wound 
healing.  

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
assessment of all types of scars by 
professionals and patients [17-19]. 
The observer scale is comprised of 6 
items (vascularity, pigmentation, 
thickness, relief, pliability, and 
surface area) scored on a scale from 
1(“like normal skin”) to 10 (“worst 
scar imaginable”). The total score is 
calculated as the sum of the six items 
(range, 6-60).  
 
All patients will be evaluated by two 
blinded observers, who will be 
selected from the other attending 
physicians and/or resident physicians 
at the site. However, all patients will 
not be evaluated by the same set of 
observers due to differences in 
physician schedules. Agreement 
between the blinded evaluators will 
be assessed using the intraclass 
correlation coefficient (ICC). The form 
of the ICC will be the ICC (1,2). 
 
Secondary 
 
 
To compare patients’ assessment 
of scar quality, healing time, scar 
size, and pain level following 
second intention healing or porcine 
xenograft dressing of surgical 
wounds on the lower extremities. 
 
1. POSAS patient scale total score. 
Study participants will complete the 
POSAS patient scale at the 3-month 
follow-up visit. The POSAS patient 
scale consists of 6 items assessing 
patients’ subjective opinion of scar 
quality in terms of pain, itching, 
color, pliability, thickness, and relief. 
Each item is scored from 1 (normal 
pigmentation, no itching, etc.) to 10 
(“worst imaginable scar or 
sensation”). The total score of the 
POSAS patient scale is calculated as 
the sum of the six items (range, 6-
60). 
 
To determine whether 
porcine xenografts 
improve wound 
healing. 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
2. Healing time. Healing time will be 
measured in weeks based on 
patient’s responses to question 1 of 
the weekly follow-up questionnaire 
(“Is the wound completely healed 
(i.e., wound is completely closed with 
no open areas)?”). For example, a 
patient who first replies “Yes” to this 
question on the third weekly follow-
up questionnaire will be assigned a 
healing time of 3 weeks. A more 
objective measure of healing time 
would not be feasible given our 
resources and patient schedule. 
 
3. Ratio of scare size to initial defect 
size. The initial postoperative defect 
size will be measured by the 
investigator prior to intervention in 
terms of length and width using a 
sterile ruler. Initial defect area will be 
calculated as length times width. Scar 
size will be measured in terms of 
length and width at the 3-month 
follow-up visit, and scar area will be 
calculated as length times width. The 
outcome will be calculated by 
dividing the scar area by the initial 
defect area. 
 
4. Pain score at 1 week following 
surgery. Patients’ pain scores will be 
measured based on their response to 
question 2 of the weekly follow-up 
questionnaire. Patients will be asked 
to rate their current pain level at the 
operative site on a scale from 1 (no 
pain) to 10 (worst imaginable pain). 
 
5. Number of weeks with pain score 
above 1. Patients’ pain scores will be 
measured based on their response to 
question 2 of the weekly follow-up 
questionnaire. Patients will be asked 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
to rate their current pain level at the 
operative site on a scale from 1 (no 
pain) to 10 (worst imaginable pain). 
 
The POSAS observer scale, POSAS 
patient scale, healing time, and 
number of weeks with pain score 
above 1 are all subjective endpoints. 
The ratio of scar size to initial defect 
size and complication rates are 
objective endpoints. 
Tertiary/Exploratory/Safety  
 
 
To compare complication rates 
following second intention healing 
or porcine xenograft dressing of 
surgical wounds on the lower 
extremities. 
 
1. Infection. Patient’s charts will be 
reviewed at the completion of their 
3-month office visit follow-up in 
order to analyze if they visited the 
dermatologist between the date of 
surgery and 3-month office visit and 
if infection was diagnosed. 
 
2. Bleeding. During each of the 
weekly follow-up questionnaires and 
during the 3-month follow-up visit, 
patients will be asked if they have 
experienced any post-operative 
bleeding that led to a visit to the 
physician (yes/no) and if there was 
any intervention performed by the 
physician to stop the bleeding 
(yes/no). The number and 
percentage of patients who 
experienced bleeding at any time 
during the 3-month follow-up period 
will be reported. 
 
To help keep the 
patients as safe as 
possible. 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
3. Pain. The proportion of patients 
with a pain score > 6 at the operative 
site will be assessed at one week 
following surgery. This will be based 
on the patient’s response to the 
weekly follow-up questionnaire, with 
scores ranging from 1 (no pain) to 10 
(worst imaginable pain). 
 
 
 
 
 
 
 
 
4 
STUDY DESIGN  
4.1 
OVERALL DESIGN 
The authors will conduct a comparative two-arm study investigating outcomes of second intention 
healing versus porcine xenograft placement of post-operative Mohs surgery or excision wound defects. 
This will be a randomized evaluator blinded study with a prior power analysis. Basic demographic data 
will be obtained including date of birth, sex, and race. Medical record number will be retained to obtain 
phone number or address for patient call back should patient not show for their follow-up 
appointments.  
 
Surgical defects 8 mm in diameter or larger on the lower extremities will be eligible for enrollment. Only 
patients with one wound will be eligible for enrollment. Primary intention (also known as linear layered) 
repair is not feasible in many patients with defects on the foot, ankle, or distal extremity as these are 
sites under high tension and poor circulation. Patients with small post-op defects many also opt not to 
be sutured via primary intention to avoid physical activity restrictions due to the increased risk of wound 
dehiscence. When closed via primary intention, a 0.8cm defect results in a scar of greater than or equal 
to 2.4cm. 
 
Patients will be randomly assigned in a 1:1 ratio to receive either a porcine xenograft or to allow the 
wound to granulate via second intention. If primary/linear repair is not an acceptable option, the 
standard of care at Northwell is to allow the wound to heal on its own via second intention post-
operatively. Due to recently published retrospective studies, there is a suggestion that porcine 
xenografts may be a feasible alternative to second intent healing. Currently, it is the surgeon’s (and 
patient’s) choice, after a discussion of risks and benefits of each modality, what is done. 
 
A randomization schedule will be generated by the Biostatistics Unit at the Feinstein Institute for 
Medical Research to assign a repair method (porcine xenograft placement or second intention healing). 

Porcine Xenograft versus Second Intention Healing: A randomized, evaluator-blinded clinical trial 
Version 2.0 
Protocol 18-0715 
16 September 2019 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017  Northwell Version: 9/16/2019 
 
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Block randomization will be used to ensure balance in the number of patients allocated to each 
treatment group. The randomization schedule will be uploaded to REDCap by a statistician outside of 
the study team. The PI, who will screen eligible subjects, will not have user rights for the Randomization 
Setup module within REDCap, and will thus be blinded to which treatment arm is next on the 
randomization list. Due to the nature of the treatment, it will not be possible to blind the patients. 
Patients will be asked not to inform the blinded physician observers which treatment they received. The 
PI will use the “Randomize” button within REDCap to assign patients to porcine xenograft or second 
intention healing after they have been consented and enrolled in the study. 
 
Prior to intervention the defect size will be measured in terms of length and width using a sterile ruler. 
 
After procedure completion wound care instruction will include daily dressing changes and application 
of petroleum jelly using a cotton tipped applicator to the wound daily until it is healed.   
 
Weekly questionnaires will be given to the patients by phone or email follow-up. All complications and 
adverse events would be monitored and recorded for both study groups. Assessment of the scar will be 
blinded in nature.  
 
The mode of treatment for participants will remain consistent throughout the 3-month period, as both 
methods are reliable for this type of defect. It is not general practice to place a xenograft on a wound 
healing by second intention or to remove a xenograft after one has been placed to switch to second 
intention. Should there be any complications, a modified intention to treat principle, described in 
Section 9, will be adhered to. 
 
The scars for both study groups will be measured at a single follow up visit after 3 months ± 1 month, 
and two blinded investigators will then assess the scar for the primary efficacy endpoint at this time. The 
blinded evaluators will be other MDs not involved in the study who are working in the dermatology 
department. The Principle Investigator will speak with the physician to outline what needs to be 
recorded for each patient. The validated physician observer scar assessment instrument (POSAS) will be 
used for this purpose. Scar size will consist of a length x width measurement using a ruler.  
 
The research team consists of one physician who will perform all of the surgical procedures, which will 
remove bias in technique. The study statistician will be blinded to the treatment groups in order to avoid 
bias or the appearance of bias. The statistician will keep the information on which treatment is “A” and 
which treatment is “B”. 
 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
To compare overall scar quality, aesthetic outcome, healing time, scar size, pain level, and complication 
rates following second intention healing or porcine xenograft dressing of surgical wounds on the lower 
extremities. 
 
 
4.3 
JUSTIFICATION FOR DOSE 
This is a device study not a drug trial. 
 
 

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4.4 
END OF STUDY DEFINITION 
 A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), 
Section 1.3. 
 
The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial 
globally. 
 
 
5 
STUDY POPULATION 
• 
Over 18 years of age   
• 
Able to give informed consent themselves   
• 
Willing to return for follow-up visits   
• 
Post-operative defects greater than 8 mm (in greatest diameter or length of circular or oval 
geometric shape) on the lower extremities (including the feet)  
• 
Single defect 
 
5.1 
EXCLUSION CRITERIA 
• 
Mentally handicapped   
• 
Unable to understand written and oral English   
• 
Incarceration   
• 
Under 18 years of age   
• 
Unwilling to return for follow-up   
• 
Pregnant women   
• 
Wounds less than 8 mm in length   
• 
Wounds on the head, neck or digits 
• 
Patients in which primary linear closure is recommended 
5.2 
LIFESTYLE CONSIDERATIONS 
 
During this study, participants will discuss with the physician any limitations of activities based on the 
treatment provided, as is done with the normal protocol. 
 
5.3 
SCREEN FAILURES 
 
Patients will either qualify to receive the device or don’t. 
 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Patients scheduled for cutaneous surgery at the Northwell Health Dermatology Clinics at Lake Success 
and Bay Shore will be approached by the research staff to see if they are interested in participating in 
the study. A pre-operative surgical consultation for lower extremity cutaneous malignancies is not 
standard of care. As such, many dermatologic surgery patients receive same-day consult and surgery. 
Thus it is, in the majority of cases, not feasible to obtain consent prior to the day of surgery. It would 
pose a burden on the patient and surgeon and may result in delay of surgical care to require a pre-
operative surgical consultation prior to treatment of lower extremity cutaneous malignancies. 

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Patients will not be encouraged nor coerced in any way. We do not plan to advertise this study, as the 
patient population in the department will produce sufficient opportunities to identify patients. Subjects 
are not compensated for participation in this study. 
 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
Only patients with one wound will be eligible for enrollment. Primary intention (also known as linear 
layered) repair is not feasible in many patients with defects on the foot, ankle, or distal extremity as 
these are sites under high tension and poor circulation. Patients with small post-op defects many also 
opt not to be sutured via primary intention to avoid physical activity restrictions due to the increased 
risk of wound dehiscence. When closed via primary intention, a 0.8cm defect results in a scar of greater 
than or equal to 2.4cm. 
 
Patients will be randomized to either receive a porcine xenograft or allow the wound to granulate via 
second intention. If primary/linear repair is not an acceptable option, the standard of care at Northwell 
is to allow the wound to heal on its own via second intention post-operatively. Due to recently published 
retrospective studies, there is a suggestion that porcine xenografts may be a feasible alternative to 
second intent healing. Currently, it is the surgeon’s (and patient’s) choice, after a discussion of risks and 
benefits of each modality, what is done. 
 
Prior to intervention the defect size will be measured in terms of length and width using a sterile ruler. 
 
After procedure completion wound care instruction will include daily dressing changes and application 
of petroleum jelly using a cotton tipped applicator to the wound daily until it is healed. 
6.1.2 DOSING AND ADMINISTRATION 
 
 There will be no dosing since patients will either be randomized to receive the porcine xenograft or 
continue with second intent healing. 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
Normal porcine xenograft procedures that the dermatology practice follows. 
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
Normal porcine xenograft procedures that the dermatology practice follows. 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
Normal porcine xenograft procedures that the dermatology practice follows. 
 
 

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6.2.4 PREPARATION 
Normal porcine xenograft procedures that the dermatology practice follows. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
A randomization schedule will be generated by the Biostatistics Unit at the Feinstein Institute for 
Medical Research to assign a repair method (porcine xenograft placement or second intention healing). 
Block randomization will be used to ensure balance in the number of patients allocated to each 
treatment group. The allocation ratio will be 1:1. The randomization schedule will be uploaded to 
REDCap by a statistician outside of the study team. The PI, who will screen eligible subjects, will not have 
user rights for the Randomization Setup module within REDCap, and will thus be blinded to which 
treatment arm is next on the randomization list. The PI will use the “Randomize” button within REDCap 
to assign patients to porcine xenograft or second intention healing as they are enrolled. 
 
There will be one physician who will perform all of the surgical procedures, which will remove bias in 
technique. There will additionally be two blinded physicians who will be tasked with observing the scar 
and assessing the primary efficacy endpoint (POSAS observer scale total score). The study statistician 
will be blinded to the treatment groups in order to avoid bias or the appearance of bias. All data 
provided to the statistician will list the treatment group as “A” or “B”. 
 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
Porcine xenograft placement and second intention healing are methods of healing that are currently 
used and is the patient’s and physician’s choice. Administration of either porcine xenograft or second 
intention is part of the standard of care and will be completed as such. An initial visit form will be 
completed to log the method of treatment administered and will be reviewed to ensure that the 
randomized treatment was completed.  
 
6.5 
CONCOMITANT THERAPY 
For this protocol no prescription medication will be utilized as this is a device study. 
 
6.5.1 RESCUE MEDICINE 
   
 
 
The study sites will supply the topical application of rescue medication that will be obtained locally. The 
following rescue medications may be used: 
Silver Nitrate Wood Applicator Sticks 
Henry Schein Model: 1126994 
  
The use of rescue medication is allowable after the formation of hypergranulation tissue which may 
begin to occur 6-8 weeks post-operatively, but typically the use of rescue medications should be 
delayed, if possible, for at least 10-12 weeks following the surgical date. This is considered standard of 
care, as it allows the patient the chance to heal without adjunct medication. The date and time of rescue 
medication administration as well as the name and regimen of the rescue medication will be recorded in 
RedCAP. Follow-up after the application of the rescue medication will occur every 6 weeks or until 
healed, per our surgical standard of care. 

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For patients receiving rescue medication, the POSAS observer scale total score (primary outcome), 
POSAS patient scale total score (secondary outcome), and ratio of scar size to initial defect size 
(secondary outcome) will be recorded at the patient’s follow-up visit within 6 weeks of administering 
the rescue medication, or at a subsequent follow-up visit when the wound is fully healed. (Note that it is 
not possible to administer the POSAS instrument, a scar assessment tool, if the wound is not completely 
healed). 
 
As described in Section 9.3, a modified intention-to-treat analysis will be used, in which all patients who 
have been assessed for the primary study endpoint will be analyzed according to their randomized 
treatment group. 
 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Discontinuation from porcine xenograft placement does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study protocol.  If a clinically 
significant finding is identified (including, but not limited to changes from baseline) after enrollment, the 
investigator or qualified designee will determine if any change in participant management is needed. 
Any new clinically relevant finding will be reported as an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
Reason for discontinuation 
• 
Specific complications 
• 
Scar size 
• 
Pain score 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
If patients decide to withdraw from the study, there is no danger involved with early withdrawal. 
Patients will be advised to follow up with the surgeon as normal standard of care outside the research 
setting.  
 
Should patients wish to have their porcine xenograft removed following enrollment in the porcine 
xenograft arm or suffer from other complications resulting in porcine xenograft failure, they will be 
assessed in an intention to treat method. 
 
7.3 
LOST TO FOLLOW-UP 
If patients fail to show up for the follow-up visit, they will be withdrawn from the study. An evaluable 
patient will be one who completes the final 3 month follow -up office visit. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
EFFICACY ASSESSMENTS  
The authors will conduct a comparative two-arm study investigating outcomes of second intention 
healing versus porcine xenograft placement of post-operative Mohs surgery or excision wound defects. 

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This will be a randomized evaluator blinded study with a prior power analysis. Basic demographic data 
will be obtained including date of birth, sex, and race. Medical record number will be retained to obtain 
phone number or address for patient call back should patient not show for their follow-up 
appointments.  
 
Surgical defects 8 mm in diameter or larger on the lower extremities will be eligible for enrollment. Only 
patients with one wound will be eligible for enrollment. Primary intention (also known as linear layered) 
repair is not feasible in many patients with defects on the foot, ankle, or distal extremity as these are 
sites under high tension and poor circulation. Patients with small post-op defects many also opt not to 
be sutured via primary intention to avoid physical activity restrictions due to the increased risk of wound 
dehiscence. When closed via primary intention, a 0.8cm defect results in a scar of greater than or equal 
to 2.4cm. 
 
Patients will be randomized to either receive a porcine xenograft or allow the wound to granulate via 
second intention. If primary/linear repair is not an acceptable option, the standard of care at Northwell 
is to allow the wound to heal on its own via second intention post-operatively. Due to recently published 
retrospective studies, there is a suggestion that porcine xenografts may be a feasible alternative to 
second intent healing. Currently, it is the surgeon’s (and patient’s) choice, after a discussion of risks and 
benefits of each modality, what is done. 
 
 
Prior to intervention the defect size will be measured in terms of length and width using a sterile ruler. 
 
After procedure completion wound care instruction will include daily dressing changes and application 
of petroleum jelly using a cotton tipped applicator to the wound daily until it is healed.   
 
Weekly questionnaires will be given to the patients by phone or email follow-up until 12 weeks post-
surgery.  
 
The mode of treatment for participants will remain consistent throughout the 3-month period, as both 
methods are reliable for this type of defect. It is not general practice to place a xenograft on a wound 
healing by second intention or to remove a xenograft after one has been placed to switch to second 
intention. Should there be any complications, a modified intention to treat principle, described in 
Section 9, will be adhered to. 
 
The scars for both study groups will be measured at a single follow up visit after 3 months ± 1 month, 
and two blinded investigators will then assess the scar at this time. The blinded evaluators will be other 
MDs not involved in the study who are working in the dermatology department. The Principle 
Investigator will speak with the physician to outline what needs to be recorded for each patient. The 
validated physician observer scar assessment instrument (POSAS) will be used for this purpose. Scar size 
will consist of a length x width measurement using a ruler.  
 
The research team consists of one physician who will perform all of the surgical procedures, which will 
remove bias in technique.> 
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
 

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Each patient will undergo examination of the surgical defect. Any adverse effects will be recorded. 
Formal safety endpoints are described in Section 9.4.4. Standard protocol for porcine xenograft 
placement and secondary intention will be followed. 
   
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
Adverse events (AE) or suspected adverse reactions in dermatologic surgery are associated with 
postoperative hemorrhage and hematoma formation, graft necrosis, flap necrosis, postoperative 
infection, and wound dehiscence. However, the rate of complications is low at 1.6%. Important medical 
events that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the participant and may 
require medical or surgical intervention to prevent one of the outcomes listed in this definition.  
 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines 
will be used to describe severity.  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, 
occurs in a plausible time relationship to study intervention administration and cannot be explained by 
concurrent disease or other drugs or chemicals. The response to withdrawal of the study intervention 
(dechallenge) should be clinically plausible. The event must be pharmacologically or phenomenologically 
definitive, with use of a satisfactory rechallenge procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study intervention, is unlikely to be attributed to concurrent 
disease or other drugs or chemicals, and follows a clinically reasonable response on withdrawal 
(dechallenge). Rechallenge information is not required to fulfill this definition. 

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• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other factors 
may have contributed to the event (e.g., the participant’s clinical condition, other concomitant events). 
Although an AE may rate only as “possibly related” soon after discovery, it can be flagged as requiring 
more information and later be upgraded to “probably related” or “definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship improbable (e.g., 
the event did not occur within a reasonable time after administration of the study intervention) and in 
which other drugs or chemicals or underlying disease provides plausible explanations (e.g., the 
participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an alternative, 
definitive etiology documented by the clinician. 
 
 
8.3.3.3 EXPECTEDNESS  
Dr. Victoria Sharon, MD will be responsible for determining whether an adverse event (AE) is expected 
or unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
Dr. Victoria Sharon will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs since the 
last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
8.3.5 ADVERSE EVENT REPORTING  
Events will be documented accordingly and reported to Northwell Health’s IRB. 

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8.3.6 SERIOUS ADVERSE EVENT REPORTING  
The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit to the 
study sponsor and to the reviewing Institutional Review Board (IRB) as soon as possible, but in no event 
later than 10 working days after the investigator first learns of the effect.  The study sponsor is 
responsible for conducting an evaluation of an unanticipated adverse device effect and shall report the 
results of such evaluation to the Food and Drug Administration (FDA) and to all reviewing IRBs and 
participating investigators within 10 working days after the sponsor first receives notice of the effect. 
Thereafter, the sponsor shall submit such additional reports concerning the effect as FDA requests. 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
N/A 
 
8.3.8 EVENTS OF SPECIAL INTEREST  
N/A 
 
8.3.9 REPORTING OF PREGNANCY  
N/A 
 
 
8.4 
UNANTICIPATED PROBLEMS 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
This definition could include an unanticipated adverse device effect, any serious adverse effect 
on health or safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects (21 CFR 812.3(s)). 
 
8.4.2  UNANTICIPATED PROBLEM REPORTING  
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the Data Coordinating Center (DCC)/lead principal investigator (PI). The UP report will 
include the following information: 

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• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to the DCC/study 
sponsor within <insert timeline in accordance with policy> of the investigator becoming aware 
of the event.  
• 
Any other UP will be reported to the IRB and to the DCC/study sponsor within <insert timeline in 
accordance with policy> of the investigator becoming aware of the problem.  
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within <insert timeline in accordance with policy> of the 
IRB’s receipt of the report of the problem from the investigator. 
 
An investigator shall submit to the sponsor and to the reviewing Institutional Review Board (IRB) a 
report of any unanticipated adverse device effect occurring during an investigation as soon as possible, 
but in no event later than 10 working days after the investigator first learns of the effect (21 CFR 
812.150(a)(1)), A sponsor who conducts an evaluation of an unanticipated adverse device effect under 
812.46(b) shall report the results of such evaluation to the Food and Drug Administration (FDA) and to 
all reviewing IRB's and participating investigators within 10 working days after the sponsor first receives 
notice of the effect. Thereafter the sponsor shall submit such additional reports concerning the effect as 
FDA requests (21 CFR 812.150(b)(1)) 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
N/A 
 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
• 
Primary Efficacy Endpoint(s):  The primary efficacy endpoint is the POSAS observer scale total 
score, evaluated at the 3-month follow-up visit (detailed in Section 9.4.2). The Mann-Whitney U 
test will be used to assess the superiority of porcine xenograft to second intention healing with 
respect to this endpoint. A two-sided hypothesis test will be used. 
 
H0: The distributions of POSAS observer scale total score are equal for patients treated with 
porcine xenograft and second intention healing. 
H1: The distributions of POSAS observer scale total score are not equal for patients treated with 
porcine xenograft and second intention healing. 

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• 
Secondary Efficacy Endpoint(s): The Mann Whitney U test will be used to assess the superiority 
of porcine xenograft to second intention healing for each of the secondary endpoints below. 
Additional details for each endpoint are provided in Section 9.4.3. Two-sided hypothesis tests 
will be used. 
 
1. POSAS patient scale total score, evaluated at the 3-month follow-up visit by study participants.  
2. Healing time, measured in weeks based on patient’s responses to question 1 of the weekly 
follow-up questionnaire. 
3. Ratio of scare size to initial defect size 
4. Pain score at 1 week following surgery 
5. Number of weeks with pain score above 1 
 
9.2 
SAMPLE SIZE DETERMINATION 
 
A total of 50 patients (25 per group) will be recruited in order to ensure adequate power to compare 
groups on the primary efficacy endpoint, POSAS observer scale total score. Based on a two-sample t-
test, a total sample size of 38 will provide 80% power to detect a significant difference between groups, 
assuming a true difference of 6 points, pooled standard deviation of 6.5 [20], and an alpha level of .05. 
Given that the asymptotic relative efficiency (ARE) of the Mann-Whitney U test relative to the two-
sample t-test is no less than 0.864 [21], regardless of the underlying distribution, a sample size of 44 
(38/0.864) will achieve equal power. In order to account for 10% attrition, we will recruit a total of 50 
patients. 
 
The assumed difference of 6 points was based on the PI’s clinical judgment of the minimal clinically 
important difference for the POSAS observer scale, which ranges from 6 to 60. It was also informed by 
previous research which considered 6 points the minimal clinically important difference when 
comparing second intention healing to an alternative closure method. [20] The mean POSAS observer 
score among patients treated with second intention healing was estimated at 19.9 in this prior study. 
Based on this estimate, an improvement of 6 points or more would correspond to a mean POSAS score 
of 13.9 or lower for patients treated with porcine xenograft. 
 
9.3 
POPULATIONS FOR ANALYSES 
 
A modified intention to treat analysis will be performed. All patients will be analyzed according to 
randomized treatment assignment, unless a patient prefers an alternative treatment method between 
the time he/she is randomized and the procedure (in which case the patient will be excluded from the 
study). The Modified Intention-to-Treat (mITT) Population will consist of all patients who receive the 
study intervention and show up for the 3-month office visit follow-up, during which the primary 
endpoint is evaluated. The Modified Intention-to Treat Population will also include patients who 
required the rescue therapy, and had the primary endpoint assessed at a follow-up visit when the 
wound had completely healed. This population will be used to analyze the primary endpoint and all 
secondary endpoints. 
 
The Safety Population will consist of all patients who receive the randomized study intervention. This 
population will be used to analyze all safety endpoints.  

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9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
Descriptive statistics will be produced to summarize the demographic and clinical characteristics of the 
two study arms. For continuous variables, means and standard deviations (SD) will be provided, as well 
as medians and interquartile ranges (IQR). For categorical variables, frequencies and percentages will be 
provided. 
 
All hypothesis tests will be two-sided, and evaluated at the .05 level of significance. 95% confidence 
intervals will be provided for inferential tests. Statistical analysis will be performed using SAS software, 
Version 9.4 (SAS Institute Inc., Cary, NC). 
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
1. POSAS observer scale total score. The primary efficacy endpoint will be the total score of the POSAS 
observer scale, assessed at the 3-month follow-up visit by two blinded evaluators who will not be 
involved in the placement of the porcine xenograft. For each patient, scores from the two blinded 
investigators will be combined by calculating the mean. The POSAS (Patient and Observer Scar 
Assessment Scale) is a validated assessment tool used for the assessment of all types of scars by 
professionals and patients [17-19]. The observer scale is comprised of 6 items (vascularity, 
pigmentation, thickness, relief, pliability, and surface area) scored on a scale from 1(“like normal skin”) 
to 10 (“worst scar imaginable”). The total score is calculated as the sum of the six items (range, 6-60). 
This is a subjective endpoint, given that it is based on the evaluating physician’s judgment of each scale 
item. 
All patients will be evaluated by two blinded observers, who will be selected from the other attending 
physicians and/or resident physicians at the site. However, all patients will not be evaluated by the same 
set of observers due to differences in physician schedules. Agreement between the blinded evaluators 
will be assessed using the intraclass correlation coefficient (ICC). The form of the ICC will be the ICC(1,2). 
Statistical Analysis: The Mann Whitney U test will be used to compare the two study arms on the 
primary efficacy endpoint based on the mITT Population defined in Section 9.3. No adjustments for 
multiplicity will be made because there is only one primary endpoint, and this endpoint will not be 
evaluated during the planned interim safety analysis. 
 
We will summarize the POSAS observer scale score for the two study arms using the mean (SD), and 
median (IQR). As a measure of effect size between the porcine xenograft and second intention healing 
groups, we will calculate the Hodges-Lehmann estimate of the median difference, and corresponding 
95% confidence interval. This is equal to the median of all paired differences between observations in 
the porcine xenograft and second intention healing groups. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 

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Analysis of all secondary endpoints will be considered exploratory. Thus, the analysis of secondary 
endpoints is not dependent on findings of the primary endpoint, and no adjustments for multiplicity will 
be made. 
1. POSAS patient scale total score. Study participants will complete the POSAS patient scale at the 3-
month follow-up visit. The POSAS patient scale consists of 6 items assessing patients’ subjective opinion 
of scar quality in terms of pain, itching, color, pliability, thickness, and relief. Each item is scored from 1 
(normal pigmentation, no itching, etc.) to 10 (“worst imaginable scar or sensation”). The total score of 
the POSAS patient scale is calculated as the sum of the six items (range, 6-60). 
2. Healing time. Healing time will be measured in weeks based on patient’s responses to question 1 of 
the weekly follow-up questionnaire (“Is the wound completely healed (i.e., wound is completely closed 
with no open areas)?”). For example, a patient who first replies “Yes” to this question on the third 
weekly follow-up questionnaire will be assigned a healing time of 3 weeks. A more objective measure of 
healing time would not be feasible given our resources and patient schedule. 
3. Ratio of scare size to initial defect size. The initial postoperative defect size will be measured by the 
investigator prior to intervention in terms of length and width using a sterile ruler. Initial defect area will 
be calculated as length times width. Scar size will be measured in terms of length and width at the 3-
month follow-up visit, and scar area will be calculated as length times width. The outcome will be 
calculated by dividing the scar area by the initial defect area. 
4. Pain score at 1 week following surgery. Patients’ pain scores will be measured based on their 
response to question 2 of the weekly follow-up questionnaire. Patients will be asked to rate their 
current pain level at the operative site on a scale from 1 (no pain) to 10 (worst imaginable pain). 
5. Number of weeks with pain score above 1. Patients’ pain scores will be measured based on their 
response to question 2 of the weekly follow-up questionnaire. Patients will be asked to rate their 
current pain level at the operative site on a scale from 1 (no pain) to 10 (worst imaginable pain). 
The POSAS patient scale, healing time, and number of weeks with pain score above 1 are all subjective 
endpoints. The ratio of scar size to initial defect size is an objective endpoints. 
Statistical Analysis: The Mann Whitney U test will be used to compare the two study arms on each of 
the secondary endpoints based on the mITT Population defined in Section 9.3.  
 
We will summarize each secondary endpoint for the two study arms using the mean (SD), and median 
(IQR). As a measure of effect size between the porcine xenograft and second intention healing groups, 
we will calculate the Hodges-Lehmann estimate of the median difference, and corresponding 95% 
confidence interval. This is equal to the median of all paired differences between observations in the 
porcine xenograft and second intention healing groups. 
 
9.4.4 SAFETY ANALYSES 
 
Safety Endpoints: 

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1. Infection. Patient’s charts will be reviewed at the completion of their 3-month office visit follow-up in 
order to analyze if they visited the dermatologist between the date of surgery and 3-month office visit 
and if infection was diagnosed. 
2. Bleeding. During each of the weekly follow-up questionnaires and during the 3-month follow-up visit, 
patients will be asked if they have experienced any post-operative bleeding that led to a visit to the 
physician (yes/no) and if there was any intervention performed by the physician to stop the bleeding 
(yes/no). Bleeding will be considered an adverse event if an intervention by a physician was required to 
stop the bleeding. The number and percentage of patients who experienced bleeding at any time during 
the 3-month follow-up period will be reported. 
3. Pain. The proportion of patients with a pain score > 6 at the operative site will be assessed at one 
week following surgery. This will be based on the patient’s response to the weekly follow-up 
questionnaire, with scores ranging from 1 (no pain) to 10 (worst imaginable pain). 
 
Statistical Analysis: We will report the frequency and proportion of patients experiencing each of the 
safety endpoints above, based on the Safety Population defined in Section 9.3.The proportion of 
patients experiencing each type of complication (infection, bleeding, pain) will be compared between 
porcine xenograft and second intention healing using Fisher’s exact test. 
 
In addition to the planned safety analysis at the completion of the study, one interim analysis will be 
conducted by the study statistician after 26 patients have been randomized and complete the final study 
visit at 3 months post-intervention. This is equal to approximately 50% of the planned enrollment goal 
of 50 patients. The purpose of this interim analysis will be to review the safety endpoints. There will be 
no formal stopping rule based on the statistical significance of the interim safety analysis. The principal 
investigator will alert the IRB immediately if there is any evidence or suggestion of a difference between 
treatment groups with regard to AEs or SAEs. Additional details on this interim safety analysis are 
included in Section 9.4.6. 
 
 
 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
Baseline demographic and clinical characteristics will be provided for the two study arms. Continuous 
variables will include age and initial post-op defect size (length x width, cm2). Categorical variables will 
include sex, race, ethnicity, procedure type (Mohs, Excisions), surgical site, current tobacco use, use of 
other antibiotics at time of surgery, use of topical or systemic prophylaxis after surgery, and past 
medical history of: blood thinners, immunosuppresants, diabetes, venous stasis, and skin infection. Past 
medical history will be self-reported by the patient. 
 
Continuous variables will be summarized using means (SD) and medians (IQR). Categorical variables will 
be summarized using frequencies and percentages. Significance tests will not be used for baseline 
comparisons. 
 
 
9.4.6 PLANNED INTERIM ANALYSES  

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One interim analysis will be conducted after 26 patients have been randomized and complete the final 
study visit at 3 months post-intervention. This is equal to approximately 50% of the planned enrollment 
goal of 50 patients. The purpose of this interim analysis will be to review the safety endpoints delineated 
in Section 9.4.4. The primary efficacy endpoint (Observer POSAS score) and all secondary endpoints will 
not be evaluated. Thus, the interim analysis will not impact the Type I error rate for the primary efficacy 
analysis. 
The number and proportion of patients who experience each of the adverse events below will be 
summarized, and compared between study arms using Fisher’s exact test. Definitions and assessment 
procedures for these endpoints have been described in Section 9.4.4. 
• 
Infection 
• 
Bleeding 
• 
Pain score at the operative site > 6 at week 1 post-intervention 
 
The number and proportion of patients who experience any serious adverse event (SAE), as defined in 
Section 8.3.2, will be summarized and compared between study arms using Fisher’s exact test. Given the 
minimal risk associated with dermatologic surgery, we do not anticipate any serious adverse events [22]. 
The interim safety analysis will be performed by Andrew Strunk, the study statistician. The statistician 
will be blinded to the treatment groups. All data provided to the statistician will list the treatment group 
as “A” or “B”. The results of the interim safety analysis will be presented to the Principal Investigator, Dr. 
Victoria Sharon, who will be unblinded to the groups corresponding to “A” and “B”. 
There will be no formal stopping rule based on the statistical significance of the interim safety analysis. 
The principal investigator will alert the IRB immediately if there is any evidence or suggestion of a 
difference between treatment groups with regard to AEs or SAEs. 
 
 
 
9.4.7 SUB-GROUP ANALYSES 
 
N/A 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
Individual participant data will not be listed by measure and time point. 
 
9.4.9 EXPLORATORY ANALYSES 
 
N/A 
 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 

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10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.  The following consent materials are submitted with this 
protocol, ICF. Participants will also be asked to sign the Northwell A/V recording authorization for 
permission to photograph their wounds. 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study participants, and regulatory authorities.  If the 
study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform study 
participants, the Institutional Review Board (IRB), and sponsor and will provide the reason(s) for the 
termination or suspension.  Study participants will be contacted, as applicable, and be informed of 
changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 

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Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff 
and their interventions. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to the clinical information relating to participants. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. 
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at the 1991 Marcus Avenue Suite 302 Lake Success, NY 11042 Dermatology 
Practice and 332 East Main Street Suite 1 Bay Shore, NY 11706 Dermatology Practice. This will not 
include the participant’s contact or identifying information. Rather, individual participants and their 
research data will be identified by a unique study identification number. The study data entry and study 
management systems used by clinical sites and by 1991  Marcus Avenue Suite 302 Lake Success, NY 
11042 Dermatology Practice and 332 East Main Street Suite 1 Bay Shore, NY 11706 Dermatology 
Practice research staff will be secured and password protected. At the end of the study, all study 
databases will be de-identified and archived at the 1991 Marcus Avenue Suite 302 Lake Success, NY 
11042 Dermatology Practice and 332 East Main Street Suite 1 Bay Shore, NY 11706 Dermatology 
Practice. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
Data collected for this study will be analyzed and stored at the 1991 Marcus Avenue Suite 302 Lake 
Success, NY 11042 Dermatology Practice. Data will be stored electronically via REDCap.  
 
Biological samples will not be obtained in this study. 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator 
Medical Monitor 
Victoria Sharon, MD, Director of 
Dermatologic Surgery & 
N/A 

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Dermato-Oncology and Attending 
Physician, Department of 
Dermatology  
Northwell Health Physician 
Partners Division of Dermatology  
 
1991 Marcus Avenue Suite 302 
Lake Success, NY 11042 
 
(516) 719-3376 
 
vsharon@northwell.edu 
 
 
 
 
 
10.1.6 SAFETY OVERSIGHT 
Safety oversight will be conducted by the study team during the planned interim analysis. Safety data 
will be assessed for each arm of the study as described in Section 9.4.6. 
 
 
10.1.7 CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with International 
Conference on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s).  
 
• 
Monitoring for this study will be performed by Dr. Victoria Sharon and Joshua Burshstein, a 
research assistant who is part of the study team. 
• 
Dr. Sharon is the physician performing the surgery and applying the method of healing. Dr. 
Sharon will monitor the clinical safety of the patients via analysis of the follow-up data. 
• 
Monitoring activities will focus on the following processes: informed consent process, timely 
completion of eCRF forms, participant follow-up, review of data entry, and missing data. 
• 
An initial monitoring assessment will be conducted after the fifth patient has been enrolled, and 
subsequent assessments will be completed after approximately every 20 patients have been 
enrolled.  
• 
During monitoring assessments, the study team will  
o Verify that appropriate signatures and dates were obtained for consent documents for 
all participants. 
o Review 100% of data contributing to the primary endpoint. 
o Review documentation of adverse events and reporting of serious adverse events 

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10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  An individualized quality management plan will be 
developed to describe a site’s quality management.] 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated and biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good 
Manufacturing Practices (GMP)).  
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing, and inspection by local and regulatory authorities. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into REDCap a 21 CFR Part 11-compliant data capture 
system. The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be 
entered directly from the source documents. 
 
10.1.9.2 STUDY RECORDS RETENTION  
 
All study documents will be retained as part of standard patient protocol as the participants are patients 
of the practice as well. There is no sponsor for this study. 
 
10.1.10 
PROTOCOL DEVIATIONS  

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A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation, or within 10 working days 
of the scheduled protocol-required activity.  All deviations must be addressed in study source 
documents, and reported to the reviewing Institutional Review Board (IRB) per their policies. The site 
investigator is responsible for knowing and adhering to the reviewing IRB requirements.  
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals. 
 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  The study 
leadership in conjunction with the <specify NIH Institute or Center (IC)> has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest> 
 
 
 
 
10.2 ADDITIONAL CONSIDERATIONS 
N/A 

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10.3 ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 

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UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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the healing of split-thickness skin graft donor sites. Burns. 1992; 18(2): 145-148 
2. Duteille F, Perrot P. Management of 2nd-degree facial burns using the Versajet hydrosurgery system and 
xenograft: A prospective evaluation of 20 cases. Burns. 2012; 38: 724-729 
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treatment of inpatient partial-thickness thermal burns. J Trauma 1988;28:1265-9.  
7. Hansbrough JF, Zapata-Sirvent R, Carroll WJ, Dominic WJ, Wang XW, Wakimoto A. Clinical experience with 
Biobrane biosynthetic dressing in the treatment of partial thickness burns. Burns Incl Therm Inj 
1984;10:415–9. 
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allografts—preliminary results. Burns 2005;31:597–602. 
9. Becker D. Temporary wound dressings of burns with fresh, sterile, frozen porcine skin. Ann Burns Fire 
Disasters 1998;11:171–5. 
10. Hosseini SN, Mousavinasab SN, Fallahnezhat M. Xenoderm dressing in the treatment of second degree 
burns. Burns. 2007; 33:776–81. 
11. Marzolf, Sean et al. Porcine xenografts for surgical defects: Experience of a single center with 128 cases. J 
Am Acad Dermatol. 2017; 78(5): 1005 - 1007 
12. Yang, Y.W. and Ochoa, S.A. Use of porcine xenografts in dermatology surgery: the Mayo Clinic 
experience. Dermatol Surg. 2016; 42: 985–991 
13. Diwan R, Tromovitch TA, Glogau RG, Stegman SJ. Secondary intention healing. The primary approach for 
management of selected wounds. Arch Otolaryngol Head Neck Surg. Oct 1989;115(10):1248-1249. 
14. Howe NR, Lang PG, Jr. Daily observations during healing of a full-thickness human surgical wound by 
second intention. J Dermatol Surg Oncol. Dec 1991;17(12):933- 935. 
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