Impact of Promogran Prisma™ on Pain of Split-thickness Skin Graft Donor Sites Compared to Standard of Care Alone
Phase: NA
Conditions: Skin Graft Disorder, Donor Site Complication
Sponsor: NYU Langone Health

 
 
Official Title: 
Impact of Promogran Prisma™ on Pain of Split-thickness Skin Graft 
Donor Sites Compared to Standard of Care Alone   
NCT Number: 
NCT04050124 
Study Number: 
19-00437 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
January 15, 2020 
 
 

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Study number: s19-00437 
Version: 3. 2 
Impact of Promogran Prisma™ on pain of split-thickness skin graft donor 
sites compared to standard of care alone – a pilot study 
Principal Investigator: 
Scott Gorenstein, MD 
Department of Surgery, Division of Wound Care 
120 Mineola Blvd, Suite 360 
Mineola, NY 11501 
Scott.Gorenstein@nyulangone.org 
516-663-8498 
Additional Investigators: 
Michael Castellano, Eric Slone, Brian Gillette, , Michael  Acerra,  
Cindy Alsamarraie, Helen Liu, Kenneth Droz, Noreen Troy-Nisi 
Department of Surgery, Division of Wound Care 
259 1st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 
516-663-9614 
NYULMC Study Number: 
s19-00437 
Funding Sponsor:  
Investigator-Initiated 
Scott Gorenstein, MD 
Department of Surgery, Division of Wound Care 
120 Mineola Blvd, Suite 360 
Mineola, NY 11501 
Scott.Gorenstein@nyulangone.org 
516-663-8498 
Study Product: 
Promogran Prisma™ 
Study Product Provider:  
KCI – An Acelity Company 
Initial version: 7 MAY 2019 
Version 2: 20 May 2019 
Version 3: 20 June 2019 
Version 3.1: 17 October 2019 
Version 3.2: 20 December 2019 

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STATEMENT OF COMPLIANCE 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable 
US government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred 
to as “ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS 
regulations. The Principal Investigator will assure that no deviation from, or changes to the protocol will 
take place without prior agreement from the sponsor and 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 Training. 
  
 

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3.2 
Table of Contents 
STATEMENT OF COMPLIANCE...........................................................................................................................II 
LIST OF ABBREVIATIONS....................................................................................................................................IV 
PROTOCOL SUMMARY 
...........................................................................................................................................1 
SCHEMATIC OF STUDY DESIGN ..........................................................................................................................2 
1 KEY ROLES...........................................................................................................................................................3 
2 INTRODUCTION, BACKGROUND AND RATIONALE....................................................................................5 
2.1 Background Information and Relevant Literature..........................................................................................5 
2.2 Potential Risks & Benefits...............................................................................................................................5 
3 RESEARCH OBJECTIVES AND PURPOSE OF THE STUDY ...........................................................................5 
4 STUDY DESIGN AND ENDPOINTS....................................................................................................................5 
4.1 Study Description............................................................................................................................................5 
4.2 Study Endpoints...............................................................................................................................................5 
5 STUDY ENROLLMENT AND WITHDRAWAL .................................................................................................6 
5.1 
Randomization: 
...............................................................................................................................................6 
5.2 
Inclusion 
Criteria:...........................................................................................................................................6 
5.3 
Exclusion 
Criteria:..........................................................................................................................................66 STUDY 
PROCEDURES AND SCHEDULE..........................................................................................................6 
7 ASSESSMENT OF SAFETY..................................................................................................................................7 
7.1 
Adverse Events 
................................................................................................................................................7 
7.2 
Classification of An Adverse 
Event.................................................................................................................7 
7.3 
Relationship To Study Agent 
...........................................................................................................................8 
7.4 
Expectedness 
...................................................................................................................................................9 
7.5 
Unanticipated Problem Reporting 
................................................................................................................10 

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7.6 
Reporting Procedures – Notifying the Study 
Sponsor...................................................................................10 8 CLINICAL MONITORING 
.........................................................................................................................................10 
9 STATISTICAL CONSIDERATION ....................................................................................................................11 
9.1Sample Size.....................................................................................................................................................11 
9.2 Statistical Analysis Plan................................................................................................................................11 
9.3 Primary endpoint...........................................................................................................................................11 
9.4 Secondary endpoints .....................................................................................................................................11 
10 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
.............................................11 11 ETHICS/PROTECTIONI OF HUMAN 
SUBJECTS..........................................................................................12 
11.1 Consent Procedures and Documentation....................................................................................................12 
11.2 Participant and Data Confidentiality..........................................................................................................13 
12 DATA HANDLING AND RECORD KEEPING ...............................................................................................13 
12.1 
Study Records 
Retention..............................................................................................................................14 
12.2 
Protocol 
Deviations.....................................................................................................................................1413 REFERENCES 
........................................................................................................................................................15 
14 SCHEDULE OF EVENTS..................................................................................................................................16 
LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 

Page v 
IRB 
Institutional Review Board 
MOP 
Manual of Procedures 
N 
Number (typically refers to participants) 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
POD 
Postoperative day 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOC 
Standard of Care 
STSG 
Split Thickness Skin Graft 
UP 
Unanticipated Problem 

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number: 
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PROTOCOL SUMMARY 
Title 
Impact of Promogran Prisma™ on pain of split-thickness skin graft donor sites 
compared to standard of care alone – a pilot study 
Short Title 
Impact of Prisma on donor site pain 
Brief Summary 
Twenty patients will be randomized into two groups: control and treatment. The control 
group will received standard of care (SOC) dressings at the split thickness skin graft 
(STSG) donor site and the treatment group will receive Promogran in direct contact 
with the donor site in addition to SOC. SOC at NYU Winthrop Hospital includes, but 
is not limited to, xeroform or semi-occlusive adhesive dressings. The primary outcome 
is to assess the feasibility of evaluatingPromogran in addition to SOC for the 
management of donor-site pain following STSG. The only difference between the two 
groups is the addition of Prisma in direct contact with the donor site under the SOC 
dressings in the treatment group. 
Objectives 
The primary objective of this study is to assess the feasibility of evaluating the use of 
a composite collagen, silver-oxidized regenerated cellulose matrix compared to the 
standard of care dressing on donor site pain for patients undergoing split-thickness skin 
grafting in preparation for a larger study.  
Methodology 
This is a prospective, randomized, open-label, single-center feasibility study. 
Endpoint 
The primary endpoint of this feasibility study is to evaluate if using Promogran in 
addition to SOC is associated with a clinically meaningful difference in pain score (≥2 
points on the visual analog pain scale) between the treatment and control arms on 
postoperative day (POD) 1. 
Study Duration 
Two years 
Participant Duration 
Six weeks 
Duration  
of  
administration 
IP  One application 
Population 
Twenty patients; 10 in the intervention group and 10 in the control group. All genders, 
≥18 years old, all demographics and geographic locations; scheduled to undergo STSG.  
Study Sites 
Single site: NYU Winthrop Hospital 
Number of participants 
20 participants 
Study compensation 
$70. Two payments of $35 will be given to participants – one at enrollment and one at 
collection of the 10-day pain diary. 
Description  
of 
 
Study 
Agent/Procedure 
Promogran Prisma™ is a composite collagen-silver-oxidized regenerated cellulose 
dressing that is a sheet applied topically to the STSG donor site. 
Reference Therapy 
The control group will receive a standard of care dressing on the STSG donor site (i.e., 
non-adherent dressing) 
Key Procedures 
Placement of either Prisma or standard of care dressing on the STSG donor site. Record 
daily pain score of the donor site for 10 days post-grafting. Return to clinic for weekly 
follow-up visits for 6 weeks. 

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Statistical Analysis 
Proposed sample size (10 patients in each arm, a total of N=20) is obtained from a 
recruitment and cost feasibility point of view. For the primary endpoint, the pain score 
at POD 1 will be compared between treatment groups using Wilcoxon rank-sum 
(Mann-Whitney) test. The secondary endpoint, time from randomization to donor site 
healing, will be compared between treatment groups using time to event approach via 
Kaplan-Meier method. 
SCHEMATIC OF STUDY DESIGN 
Total 20: Obtain informed consent. Screen potential subjects by inclusion and exclusion  
Screening criteria. Perform physical examination and review medical, surgical, and medication  
Phase histories. Perform a urine pregnancy test for females of reproductive potential. Collect  
(Day -7 – 0) demographic data including: date of birth, gender, race, ethnicity and tobacco use. 
1 KEY ROLES 
Principal Investigator: 
Scott Gorenstein MD 
Clinical Director, Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
2591st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 
(516) 663-9768 
Scott.gorenstein@nyulangone.org 
Sub-investigator: 
Brian Gillette PhD 
Research Scientist, Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
2591st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 
(516) 663-9614 
Brian.gillette@nyulangone.org 
Sub-investigator: 
Michael Castellano MD 
Director, Wound Care Surgical Services, Division of Wound Healing and Regenerative Medicine NYU 
Winthrop Hospital 
2591st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 
(516) 663-8498 
Michael.castellano@nyulangone.org 
Sub-investigator: 
Eric Slone MD 
Physician, Wound Care Surgical Services, Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
2591st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 

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(516) 663-8498 
Eric.slone@nyulangone.org 
 
 Sub-investigator: 
Helen Liu, DO 
Research Fellow, Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
2591st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 
Helen.liu@nyulangone.org  
 
Sub-investigator: 
Kenneth Droz 
Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
Kenneth.droz@nyulangone.org 
Sub-investigator: 
Noreen Troy-Nisi 
Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
Noreen.Troy-Nisi@nyulangone.org 
 
Research Coordinator: 
Cindy Alsamarraie 
Clinical Research Coordinator, Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
259 1st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 
(516) 663 – 1669 
Cindy.Alsamarraie@nyulangone.org 
Data Coordinator: 
Michael Acerra 
Data Coordinator, Division of Wound Healing and Regenerative Medicine 
NYU Winthrop Hospital 
2591st Street 
Professional Residence Hall, Suite 147 
Mineola, NY 11501 
(516) 663-4936 
Michael.acerra@nyulangone.org 
2 INTRODUCTION, BACKGROUND AND RATIONALE  

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2.1 Background Information and Relevant Literature 
Split-thickness skin grafting (STSG) is the mainstay of therapy for the management of wounds that 
cannot be closed primarily or left open to close by secondary intention. However, the wounds created 
by STSG are often a source of pain and morbidity to patients. Multiple studies have compared various 
donor site dressings in attempt to decrease pain and morbidity1–4. This study will look specifically at 
the effect on patient-reported donor site by using of a collagen dressing. The addition of a composite 
collagen-silver-oxidized regenerated cellulose dressing (Promogran Prisma™) which has been cleared 
by the FDA(510k) in direct contact with the donor site is hypothesized to decrease pain at the donor 
site. 
2.2 Potential Risks & Benefits  
Risks involved with the procedures (i.e. surgical procurement of the STSG, use of advanced wound 
care therapies included in the SOC at NYU Winthrop Hospital Wound Center) are similar to risks in 
the standard treatment of wounds of this nature (i.e. infection; allergic reaction; excessive redness, pain, 
swelling, or blistering). Procurement of the STSG will be performed under sterile conditions in the 
operating room under monitored supervision and adequate pain control by a trained anesthetist. There 
is no difference between the treatment and control groups in the way that the STSG is obtained. 
Standard risks associated with anesthesia will be explained to the patient in detail prior to the operation. 
Skin grafting can cause localized pain with associated local bleeding that will be controlled in the 
operating room.  
Benefits include decreased pain at the STSG donor site, decreased time to heal, and decreased 
occurrence of adverse events (e.g. wound infection). Even in the event that no improvement is made to 
donor site pain or wound healing, information gained from the study will be used to help understanding 
and improve future treatment options for people undergoing STSG. 
3 RESEARCH OBJECTIVES AND PURPOSE OF THE STUDY  
The primary purpose of this study is to assess the feasibility of evaluating the use of a composite 
collagen, silver-oxidized regenerated cellulose matrix compared to the standard of care dressing on 
donor site pain for patients undergoing split-thickness skin grafting in preparation for a larger study.  
4 STUDY DESIGN AND ENDPOINTS 
4.1 Study Description 
This is a prospective, randomized, single-center feasibility study. Twenty patients will be randomized 
into two groups: control and treatment. The control group will receive standard of care (SOC) dressings 
at the STSG donor site and the treatment group will receive Promogran in direct contact with the donor 
site in addition to SOC. SOC at NYU Winthrop includes, but is not limited to, xeroform or 
semiocclusive adhesive dressings. Thrombin spray may be used for hemostasis. Patients are routinely 
followed in the outpatient wound clinic until wound healing occurs. Healing is defined as complete 
donor site epithelialization without drainage. 
4.2 Study Endpoints 
The primary aim of this feasibility study is to evaluate if using Promogran in addition to SOC will 
improve the pain score compared to SOC alone. Specifically, we would like to detect a clinically 
meaningful difference in pain score (≥2 points on the pain scale) between the treatment and control 
arms on postoperative day (POD) 1.  
Secondary aims include: 
1. Describe and compare the percent of patients healed between treatment groups 
2. Describe and compare weekly surface area between treatment groups 
3. Compare time to complete donor site healing between treatment groups 

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4. Describe and compare adverse events between groups 
5. Describe and compare decreased use of narcotics and other pain medications between groups 
6. Describe and compare percent of granulation tissue at the donor site between treatment groups. 
Granulation will be reported in quartiles (0-25%, 26-50%, 51-75%, and 76-100%). 
5 STUDY ENROLLMENT AND WITHDRAWAL  
Participants will be recruited from the NYU Winthrop Hospital Wound Care center, inpatient service, 
and other outpatient surgical services. Consent will be obtained by the principal and sub-investigators 
of the study.  
5.1 Randomization: 
Randomization will be performed 1:1 at enrollment. A computer generated randomized block 
assignment list will be given to the study coordinator. Each block of 2 or 4 subjects will contain an 
equal number of the two groups: 1) SOC, 2) Promogran+SOC. SAS PROC PLAN will be used to 
generate this list. 
5.2 Inclusion Criteria: 
1. Patient ≥18 years of age 
2. Male or female 
3. Patient scheduled to undergo STSG for any reason 
4. Patientis able to provide informed consent and has read and signed the IRB-approved informed 
consent form. 
5.3 Exclusion Criteria: 
1. Active infection or history of radiation to the donor site 
2. Patient has a known sensitivity to Promogran Prisma™ or silver 
3. Elevated INR >3.0 
4. Insensate at the donor site 
5. Chronic narcotic use (>6 months of daily use) 
6. Patient is currently pregnant and/or breastfeeding 
The target number of enrolled patients will be 20, with 10 patients in the control and treatment groups, 
respectively. Patients will be allowed to withdraw consent at any time, with no adverse effect on the 
care received at NYU Winthrop Hospital.  
6 STUDY PROCEDURES AND SCHEDULE 
The study will last six weeks. After consent and enrollment, patients in both the control and treatment 
groups will undergo STSG as scheduled. Promogran will be available in the operating room and applied 
by the operating surgeon (study or non-study surgeon) directly to the donor site of patients randomized 
to the treatment group. Patients in the control group will receive SOC dressings per the attending 
surgeon’s clinical judgment. SOC dressings include a primary non-adherent dressing, a secondary 
gauze and transparent film or tape. The only difference between the two groups is the addition of Prisma 
in direct contact with the STSG donor site under the primary dressing in the treatment group. 
Pain will be patient-reported using the visual analogue/Wong-Baker pain rating scale (VAS), which is 
reported on a scale from 0-10. Pain will be measured once at each of the following 12 time points: 
preoperatively, post-operatively (POD 1), and each subsequent postoperative day for ten days. After 
day 10, pain will be recorded by the assessing clinic provider during the weekly visits, until week six. 
Patients will be followed daily while inpatient and weekly while outpatient for six weeks. The number 
of study visits will be between 6-10.  The study visits will be combined with SOC vists and there will 

St u d y n u m ber: s 1 9- 0 0 4 3 7   
Pa ge 6 
Versi o n: 3. 2  
be n o st u d y relate d pr oce d ures ot her t ha n assessi n g pai n at t he d o n or site.  Dressi n gs will be c ha n ge d 
a n d w o u n ds assesse d acc or di n g t o t he sta n dar d of care at N Y U Wi nt hr o p H os pital.  
Scree ni n g P h ase  - Wee k - 1 ( wit hi n 7 d a ys pri or t o tre at me nt visit) 
• 
E val uati o n of eli gi bilit y f or st u d y i ncl usi o n  
• 
O btai n i nf or me d c o nse nt  
• 
Scree ni n g of i ncl usi o n/e xcl usi o n criteria  
• 
Assi g n a u ni q ue s u bject i de ntificati o n n u m ber ( SI D). 
• 
Ra n d o mize t o treat me nt or c o ntr ol ar m   
• 
Perf or m p h ysical e xa mi nati o n a n d re vie w me dical, s ur gical, a n d me dicati o n hist ories.  
• 
Perf or m a uri ne pre g na nc y test f or fe males of re pr o d ucti ve p ote ntial.  
• 
C ollect de m o gra p hic data i ncl u di n g: date of birt h, ge n der, race, et h nicit y a n d t o bacc o use. 
• 
Gi ve pa tie nt pai n diar y a n d pa y me nt of $ 3 5 patie nt sti pe n d. 
Tre at me nt P h ase - D a y 0  
• 
E ns ure s u bject re mai ns eli gi ble pri or t o st u d y pr o d uct a p plicati o n.  
• 
C o nfir m ne gati ve uri ne pre g na nc y test f or fe males of re pr o d ucti ve p ote ntial pri or t o i nitial pr o d uct 
a p plicati o n. 
• 
A p plicati o n of Pris ma t o S T S G d o n or site f or patie nts i n t he treat me nt gr o u p  Rec or d S T S G d o n or 
site le n gt h a n d wi dt h 
• 
Rec or ds all pai n me dicati o ns use d i n p ost o perati ve rec o ver y r o o m o n P O D 0 
F oll o w -U p – D a y 1 t o 1 0  
• 
Dail y rec or d of pai n le vel  i n pai n j o ur nal wit h t he i nitial rec or d o nce d uri n g 8a m t o 1 2 p m a n d pri or 
t o eac h pai n me dicati o n use 
• 
Rec or d ti me of a n y pai n me dicati o n use 
• 
Rec or d pai n of b ot h d o n or a n d reci pie nt S T S G site 
F oll o w -U p - Wee ks 1 t o 6 ( 6 wee k d urati o n wit h 1 visit per wee k) 
• 
E val uati o n a n d rec or d of S T S G d o n or site – p h ot o gra p h y, le n gt h, wi dt h 
• 
Rec or d pai n le vel of d o n or site 
• 
Rec or d a n y a d verse e ve nts  
• 
C ollecti o n of pai n diar y a n d sec o n d pa y me nt of $ 3 5 sti pe n d. 
7 A S S E S S M E N T O F S A F E T Y 
7. 1 A d verse E v e nts 
A d verse E ve nts ( A Es) will  be ca pt ure d fr o m t he ti me t he s u bject is ra n d o mize d i nt o t he st u d y.  A n A E 
is defi ne d as f oll o ws: 
• A n y a d verse c ha n ge i n t he s u bj ect's me dical stat us w he n c o m pare d wit h t he s u bject's baseli ne 
c o n diti o n, w het her or n ot t he e ve nt is relate d t o t he de vice or a pr oce d ure; or 
• A n e xacer bati o n (eit her i n fre q ue nc y or se verit y) i n a s u bj ect's pre-e xisti n g c o n diti o n. 
7. 2 Classificati o n of a n A d verse E v e nt 
K n o w n se q uelae, j u d ge d b y t he I n vesti gat or t o be ass ociate d wit h tar get w o u n d pr oce d ures (e. g., pai n 
or blee di n g ass ociate d wit h S T S G har vest) a n d/ or t he c o urse of n or mal w o u n d heali n g (e. g., sl o u g h or 
mil d e x u date) s h o ul d n ot be rec or de d as a n A E u nless: 1) a n a d diti o nal treat me nt/ pr oce d ure is re q uire d 
(e. g., use of a c o nc o mita nt me dicati o n); or 2) t he fre q ue nc y, se verit y a n d/ or d urati o n de viates fr o m t he 
e x pecte d c o urse. T hese i ncl u de b ut are n ot li mite d t o:  
• I nfecti o n/se psis 
• W orse ni n g of w o u n d be d/fail ure t o heal 
• I ncrease d c hr o nic i nfla m mati o n 
• Aller gic reacti o n  

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• Unexplained fever or chills 
• Death 
• Neurologic symptoms such as light headedness, headache 
• Gastrointestinal symptoms including nausea and vomiting 
An AE or suspected adverse reaction is considered "serious" if, in the view of either the Investigator or 
Sponsor, it results in any of the following outcomes:  
• Death 
• A life-threatening adverse event 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
• A congenital anomaly/birth defect 
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 
patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed 
in this definition.  
Unanticipated adverse device effect is any serious adverse effect on health or safety, any lifethreatening 
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 application, or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects. 
The Investigator will be asked to assess the severity of the AE using the following categories: 
• 
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. 
7.3 Relationship to Study Agent 
For all collected AEs, the clinician who examines and evaluates the participant will determine the AE’s 
causality based on temporal relationship and his/her clinical judgment. The degree of certainty about 
causality will be graded using the categories below.  
• 
Definitely Related: The relationship of the AE and the study device or the study procedure can 
definitely be established. 
• 
Probably Related: While a clear relationship to the study device or to the study procedure 
cannot be established, the AE is associated with an expected AE or there is no other medical 
condition or intervention, which could explain the occurrence of such an event. 
• 
Possibly Related: There is no clear relationship between the AE and the study device or study 
procedure; however, one cannot definitely conclude that there is no relationship. 
• 
Unrelated Related: There is no relationship between the AE and the study device or study 
procedure.  This may include but is not limited to the incident being an expected outcome of a 

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previously existing or concurrent disease, concomitant medication or procedure the subject 
experienced. 
7.4 Expectedness 
The PI will be responsible for determining whether an 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 agent. 
The occurrence of an AE or 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 RF. 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. UPs will be recorded in the data collection system 
throughout the study. 
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. 
The PI 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.  
All unresolved adverse events should be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator should instruct each subject to report any subsequent event(s) that the subject, or the 
subject’s personal physician, believes might reasonably be related to participation in this study.  The 
investigator should notify the study sponsor of any death or adverse event occurring at any time after a 
subject has discontinued or terminated study participation that may reasonably be related to this study.  
The sponsor should also be notified if the investigator should become aware of the development of 
cancer or of a congenital anomaly in a subsequently conceived offspring of a subject that has 
participated in this study.  
7.5 Unanticipated Problem Reporting 
Incidents or events that meet the OHRP criteria for UPs require the creation and completion of an UP 
report form. It is the site investigator’s responsibility to report UPs to their IRB and to the DCC/study 
sponsor. The UP report will include the following information: 
• 
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. 

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To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
• 
UPs that are SAEs will be reported to the IRB and to the DCC/study sponsor within 5 business 
days of the investigator becoming aware of the event. 
• 
Any other UP will be reported to the IRB and to the DCC/study sponsor within 5 business days 
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 OHRP 
within<insert timeline in accordance with policy> of the IR’s receipt of the report of the 
problem from the investigator. 
7.6 Reporting Procedures – Notifying the Study Sponsor 
The study clinician will complete a SAE Form within the following timelines: 
• 
All deaths and immediately life-threatening events, whether related or unrelated, will be 
recorded on the SAE Form and submitted to the DCC/study sponsor within 24 hours of site 
awareness. See Section 1, Key Roles for contact information. 
• 
Other SAEs regardless of relationship will be submitted to the DCC/study sponsor within 72 
hours of site awareness. 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the event 
to be chronic or the adherence to be stable. Other supporting documentation of the event may be 
requested by the DCC/study sponsor and should be provided as soon as possible.  
As a follow-up to the initial report, within the following 48 hours of awareness of the event, the 
investigator shall provide further information, as applicable, on the unanticipated event or the 
unanticipated problem in the form of a written narrative.  This should include a copy of the 
completed Unanticipated Problem form, and any other diagnostic information that will assist the 
understanding of the event.  Significant new information on ongoing unanticipated adverse effects 
shall be provided promptly to the study sponsor. 
8 Clinical Monitoring 
Clinical site monitoring will be conducted to ensure that the rights and well-being of human subjects 
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 Good Clinical 
Practice (GCP), and with applicable regulatory requirement(s). 
Data safety monitoring will be done by the Clinical Research Coordinator.  Events that will be monitored 
are infection at donor site, increasing pain at donor site, and allergic reaction to dressing.  Monitoring will 
occur on a weekly basis once patients are enrolled.  There are no predefined stopping points and reviews 
will be disseminated at the weekly research meeting. 
9 STATISTICAL CONSIDERATION 
9.1Sample Size 
A pilot study is limited in terms of statistical power due to its small sample size. As a result, no formal 
power computation was carried out. Proposed sample size (10 patients in each arm, a total of N=20) is 
obtained from a recruitment and cost feasibility point of view. The main aim of the study is to determine 
feasibility of the intervention, recruitment, randomization, retention a priori to a large full scale 
randomized clinical trial. No inferential decision will be made based on p-values; however the direction 
and size of the effect of the intervention on the outcomes observed will be critical for designing future 
randomized controlled trial where efficacy of the intervention will be determined.  
9.2 Statistical Analysis Plan 

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Data will be summarized using descriptive statistics such as mean (standard deviation), median 
(Interquartile Range) based on the distribution of the continuous variables. Categorical variables will 
be presented as count (percentage).  
9.3 Primary endpoint 
Reducing pain at POD 1 was thought to be clinically important. Hence, the pain score at POD 1 will be 
compared between treatment groups using Wilcoxon rank-sum (Mann-Whitney) test. For demographic 
and other clinical covariates, we will test whether baseline characteristics are well balanced between 
two groups. If a baseline variable is not balanced or correlated with outcome (r>0.30), we will develop 
an ANCOVA model for POD 1 pain score and include it as a covariate in addition to baseline pain 
score and treatment groups.  
9.4 Secondary endpoints 
Time from randomization to donor site healing will be compared between treatment groups using time 
to event approach via Kaplan-Meier (KM) method. The log-rank test will be used to compare the KM 
curves. Adverse events will be summarized between groups using counts and percentages. Percent of 
patients healed, percent use of narcotics and other pain medication (ie amount of medication used) and 
percent of granulation will be compared between groups using Fisher’s exact test.  
All analyses will be performed using SAS version 9.4 for Windows (SAS Institute Inc.). Nominal P< 
values will be presented. 
10 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Source data is all information, original records of clinical findings, observations, or other activities in 
a clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in 
source documents.  Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, 
and at medico-technical departments involved in the clinical trial. It is acceptable to use CRFs as source 
documents. If this is the case, it should be stated in this section what data will be collected on CRFs 
and what data will be collected from other sources. 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
requested on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is 
left blank because the procedure was not done or the question was not asked, write “N/D”.  If the item 
is not applicable to the individual case, write “N/A”.  All entries should be printed legibly in black ink.  
If any entry error has been made, to correct such an error, draw a single straight line through the 
incorrect entry and enter the correct data above it.  All such changes must be initialed and dated.  DO 
NOT ERASE OR WHITE OUT ERRORS.  For clarification of illegible or uncertain entries, print the 
clarification above the item, then initial and date it. 
Access to study records will be limited to IRB-approved members of the study team. The investigator 
will permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government 
regulatory bodies, and University compliance and quality assurance groups of all study related 
documents (e.g. source documents, regulatory documents, data collection instruments, study data etc.).  
The investigator will ensure the capability for inspections of applicable study-related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.). 

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11 ETHICS/PROTECTIONI OF HUMAN SUBJECTS 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
the Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 
CFR Part 56, and/or the ICH E6. 
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 previously consented participants 
need to be re-consented. 
Consent forms describing in detail the study agent, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study product. The informed consent is submitted with this protocol. 
11.1 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. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants and their families. Consent forms will be 
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. All participants 
will receive a verbal explanation in terms suited to their 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 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. The participants may withdraw consent at any time 
throughout the course of the trial. A copy of the signed informed consent document will be given to the 
participants for their records. 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. 
A copy of the signed informed consent document will be stored in the subject’s research record. The 
consent process, including the name of the individual obtaining consent, will be thoroughly documented 
in the subject’s research record. Any alteration to the standard consent process (e.g. use of a translator, 
consent from a legally authorized representative, consent document presented orally, etc.) and the 
justification for such alteration will likewise be documented.  
11.2 Participant and Data Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements 
of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Study photos will be kept 
confidential by not including any identifying features (e.g. patient face, tattoo). De-identifies photos will 
be kept on the secure NYU Winthrop hospital computer network and only accessed by study personnel.  
Those regulations require a signed subject authorization informing the subject of the following:  
• 
What protected health information (PHI) will be collected from subjects in this study 
• 
Who will have access to that information and why 
• 
Who will use or disclose that information  
• 
The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 

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subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
12 DATA HANDLING AND RECORD KEEPING 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
PI. 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. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 
documents should be consistent with the source documents or the discrepancies should be explained and 
captured in a progress note and maintained in the participant’s official electronic study record. 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into a local database kept and maintained at NYU Winthrop Hospital by 
the Wound Care team. Access to 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. 
12.1 Study Records Retention 
Study documents will be retained for the longer of 3 years after close-out, 5 years after final 
reporting/publication, or 2 years after the last approval of a marketing application is approved for the 
drug for the indication for which it is being investigated or 2 years after the investigation is discontinued 
and FDA is notified if no application is to be filed or if the application has not been approved for such 
indication. No records will be destroyed without the written consent of the sponsor, if applicable. It is 
the responsibility of the sponsor to inform the investigator when these documents no longer need to be 
retained. 
12.2 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, 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 E6: 
• 
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 PI/study staff to use continuous vigilance to identify and record 
deviations within 2 working days of identification of the protocol deviation, or within 2 working days 
of the scheduled protocol-required activity. 
13 References 
1. 
Healy C, Greig AVH, Murphy AD, et al. Prospective randomized controlled trial: Fibrin sealant 
reduces split skin graft donor-site pain. Plast Reconstr Surg. 2013;132(1):139-146. 
doi:10.1097/PRS.0b013e318299c6f4. 

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2. 
Ramesh BA, Jayalakshmi BK, Mohan J. A Comparative Study of Collagen Dressing versus 
Petrolatum Gauze Dressing in reducing Pain at the Donor Area. J Cutan Aesthet Surg. 
2017;10(1):18-21. doi:10.4103/JCAS.JCAS_110_16. 
3. 
Sinha S, Schreiner AJ, Biernaskie J, Nickerson D, Gabriel VA. Treating pain on skin graft donor 
sites: Review and clinical recommendations. doi:10.1097/TA.0000000000001615. 
4. 
García-Salinas AS, Mecott GA, García-Pérez M, et al. Decreased pain in split-thickness skin graft 
donor sites with the use of a non-adherent polyurethane dressing. Med Univ. 2015;17(69):196-202. 
doi:10.1016/j.rmu.2015.07.001. 
 

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14 SCHEDULE OF EVENTS 
Activity 
Screening  
Visit 
[Day -7-0] 
Treatment  
Visit 
[Day 0] 
Follow-Up  
Phase 
[Day 1-10] 
FollowUp 
Visit 1 
[Day 7±3] 
Follow-Up  
Visit 2 
[Day 14±3] 
Follow-Up  
Visit 3 
[Day 28±3] 
Follow-Up  
Visit 4 
[Day 35±3] 
Follow-Up  
Visit 5 
[Day 42 ±3] 
Final Visit 6 
[Day 49  ±3] 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
 
 
 
 
 
 
 
 
Significant  
Medical,  
Surgical,  
Medication History 
X 
 
 
 
 
 
 
 
 
Baseline demographics: gender, age, 
height, weight 
X 
 
 
 
 
 
 
 
 
Pain score at STSG donor site 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
 
Application of Promogran Prisma™, 
for intervention group 
 
X 
 
 
 
 
 
 
 
STSG donor site evaluation and 
management 
(SOC 
dressing, 
photography, length, width,  
assessment of appearance) 
 
 
 
X 
X 
X 
X 
X 
X 
Closure assessment 
 
 
 
X 
X 
X 
X 
X 
X