Evaluation of Negative Pressure Wound Therapy for Reduction of Postoperative Surgical Site Infection in Patients Undergoing Colorectal and Hepatopancreatobiliary Surgery
Phase: NA
Conditions: Patients Undergoing Hepatopancreatobiliary Surgery
Sponsor: Duke University

 
 
 
A Randomized Phase II Evaluation of Negative Pressure Wound Therapy for 
Reduction of Postoperative Surgical Site Infection in Patients Undergoing 
Colorectal and Hepatopancreatobiliary Surgery 
 
 
Trial: NCT01905397 
 
 
Protocol 
 
December 31, 2020 

PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
  
 
 
 
A Randomized Phase II Evaluation of  
Negative Pressure Wound Therapy for  
Reduction of Postoperative Surgical Site Infection  
in Patients Undergoing  
Colorectal and Hepatopancreatobiliary Surgery 
 
 
Sponsor and Lead Investigator:  
Dan Blazer III, MD 
Duke Cancer Institute 
Durham, NC 27710 
919-668-1861 
 
 
 
Supported By: 
Kinetic Concepts, USA Inc. 
 
 
 
 
 
 
 
 
 
The information contained in this document is regarded as confidential, and may not be disclosed to another party unless such 
disclosure is required to initiate the study, to conduct study-related activities, or to comply with national, state, or local laws and 
regulations.  Written authorization from the coordinating site and sponsor is required for disclosure otherwise. 

CONFIDENTIAL 
PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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Protocol Version and Amendment Tracking 
 
 
 
Version Number / Amendment 
Version Date 
Version 1.0 / Initial 
02JUL2013 
Version 2.0 
18DEC2013 
Version 3.0 
03NOV2014 
Version 4.0 
16JUN2016 
Version 5.0 
14NOV2016 
Version 6.0 
09JAN2017 
Version 7.0 
10AUG2018 
Version 8.0 
06JUL2020 
Version 9.0 
31DEC2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CONFIDENTIAL 
PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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TABLE OF CONTENTS 
Protocol Version and Amendment Tracking ............................................................................................ 2 
Table of Contents ..................................................................................................................................... 3 
List of Abbreviations ................................................................................................................................. 5 
1.0 Introduction ........................................................................................................................................... 6 
2.0 NPWT systems ...................................................................................................................................... 6 
2.1 Prevena Incision Management System .............................................................................................. 6 
2.2 ActiV.A.C. Therapy Unit ...................................................................................................................... 7 
3.0 Study Rationale ..................................................................................................................................... 8 
4.0 Study objectives .................................................................................................................................... 8 
4.1 Primary ................................................................................................................................................ 8 
4.2 Secondary ........................................................................................................................................... 8 
5.0 Study Design ......................................................................................................................................... 9 
5.1 Study Description ................................................................................................................................ 9 
5.2 Randomization .................................................................................................................................. 10 
6.0 Subject Selection ................................................................................................................................ 10 
6.1 Inclusion Criteria ............................................................................................................................... 10 
6.2 Exclusion Criteria .............................................................................................................................. 10 
6.3 Inclusion of Women and Minorities ................................................................................................... 10 
7.0 Study Assessments ............................................................................................................................ 11 
7.1 Study Calendar ................................................................................................................................. 11 
7.2 Screening and Baseline Evaluations ................................................................................................ 12 
7.3 Evaluations during Study .................................................................................................................. 12 
7.3.1 Throughout Study ...................................................................................................................... 12 
7.3.2 Day of Surgery........................................................................................................................... 12 
7.3.3 Post-op Visit Day 4-5 ................................................................................................................. 12 
7.3.4 Post-op Visit Day 30 (+/-14) ...................................................................................................... 12 
8.0 Classification of SSI by NSQIP .......................................................................................................... 13 
9.0 Subject Discontinuation ..................................................................................................................... 14 
10.0 Statistical Methods ........................................................................................................................... 14 
10.1 Statistical Analysis .......................................................................................................................... 15 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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11.0 Investigational Product .................................................................................................................... 15 
11.1 Investigational Product Storage and Accountability ....................................................................... 15 
12.0 Safety Reporting Requirements ...................................................................................................... 16 
12.1 Definitions ....................................................................................................................................... 16 
12.2 Procedures for Reporting ................................................................................................................ 17 
13.0 Data and Safety Monitoring ............................................................................................................. 17 
13.1 Monitoring ....................................................................................................................................... 17 
13.2 Safety Oversight Committee ........................................................................................................... 18 
13.3 SUBJECT CONFIDENTIALITY ...................................................................................................... 18 
13.4 INVESTIGATOR COMPLIANCE .................................................................................................... 18 
13.5 AUDITS ........................................................................................................................................... 19 
14.0 Data Management and Processing ................................................................................................. 19 
14.1 Study Documentation ..................................................................................................................... 19 
15.0 Administrative Section ..................................................................................................................... 20 
15.1 Regulatory and Ethical Compliance ............................................................................................... 20 
15.2 DUHS Institutional Review Board and DCI Cancer Protocol Committee ....................................... 20 
15.3 Informed Consent ........................................................................................................................... 20 
15.4 Privacy, Confidentiality, and Data Storage ..................................................................................... 21 
15.5 Study Closure ................................................................................................................................. 21 
16.0 references .......................................................................................................................................... 22 
APPENDIX 1 
Study Schema ................................................................................................................. 23 
 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
BMI 
Body Mass Index 
CRF 
Case report/Record form 
CRS 
Colorectal surgery 
DCI 
Duke Cancer Institute 
DUMC 
Duke University Medical Center 
FDA 
Federal Drug Administration 
HPBS 
Hepatopancreatobiliary surgery 
ICH 
International Conference on Harmonization 
I.V. 
intravenous 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational new drug 
IRB 
Institutional Review Board 
KCI 
Kinetic Concepts, Inc 
NPWT 
Negative Pressure Wound Therapy 
NSQIP 
National Surgical Quality Improvement Program 
REB 
Research Ethics Board 
PI 
Principal Investigator 
PIMS 
Prevena™ Incision Management System 
SAE 
Serious Adverse Event 
SOC 
Safety Oversight Committee 
SOP 
Standard Operating Procedure 
SSI 
Surgical Site Infection 
VAC 
Vacuum Assisted Closure 
 
 
 
 
 
 
 
 
 
 
 
 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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1.0 INTRODUCTION 
Surgical Site Infection (SSI) is a major source of morbidity in both colorectal (CRS) and 
hepatopancreatobiliary (HPBS) surgery.  The SSI rate has been published to be between 20-35% 
[1-3]. Specifically, colectomy for the treatment of colorectal cancer is associated with a SSI rate 
of 10-30% [1] and hepatectomy for hepatocellular carcinoma has a SSI rate of 15-25% [4, 5].  
Pancreaticoduodenectomy for pancreatic adenocarcinoma has a SSI rate of 10-20% [2, 6]. Taken 
together, up to a third of patients undergoing these complex abdominal surgeries will suffer the 
additional morbidity of SSI despite interventions such as appropriately timed and selected 
antibiotics.  This added level of morbidity increases the complexity of patient care during recovery 
from surgery, lengthens post-operative hospitalizations and adds significant overall medical 
costs. Given these persistently high rates of SSI despite best practice standards, a low morbidity 
intervention such as the incisional wound vacuum assisted closure (V.A.C) system is an attractive 
technology to try to further improve SSI rates in these patients. 
 
V.A.C® technology or negative pressure wound therapy (NPWT) has revolutionized the 
management of complex open wounds but its role in closed wounds remains undefined.  Initial 
enthusiasm for its potential role in reducing SSI rates in closed laparotomy wounds came from a 
report in the cardiothoracic literature performed as a collaboration between Duke University 
Medical Center (DUMC) and the Durham VA Medical Center [7] .  Negative pressure wound 
therapy was applied to closed sternotomy wounds in 57 patients, with a 3% expected SSI rate.  
No sternal wound infections were seen in any patients.  Though this initial report had small 
numbers of patients, the potential for this low morbidity technique to decrease SSI in sternotomy 
wounds was seen.  
 
Several reports have investigated the preoperative patient-specific risk factors as well as 
surgically-related risk factors to predict risk of developing SSI [8].  However, there is no reported 
study in the medical literature indicating the role or efficacy of either conventional wound care 
with sterile dressings or the application of V.A.C.® to postoperative abdominal incisions in 
preventing SSI.  However, both methods of wound care are employed on a daily basis in Duke 
University hospital system (DUMC, Duke Raleigh Hospital and Durham Regional Hospital) as well 
as other academic and private hospitals across the country.  The conventional approach to 
postoperative surgical wound care has little evidence-based data to support its practice and 
surgeons have been using incisional V.A.C.® technology for several years in an attempt to curtail 
SSI in high risk patients.     
2.0 NPWT SYSTEMS   
2.1 PREVENA INCISION MANAGEMENT SYSTEM 
The Prevena Incision Management System (PIMS) is the first battery powered negative pressure 
product designed specifically for management of closed surgical incisions that continue to drain 
following sutured or stapled closure.  The PIMS covers and protects the incision from external 
infectious sources, while negative pressure removes fluid and infectious material from the surgical 
incision. 
The Prevena System accomplishes its intended purpose by means of a dressing that seals the 
area around the incision site.  This dressing is fitted with connections for fluid/air lines that provide 
the means of communication between the wound and the suction apparatus.  The pump creates 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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a negative pressure (vacuum) of -125 mmHg relative to the wound and causes wound exudate 
to be pumped into the collection canister as necessary. 
 
PIMS consists of: 
• 
a small, portable, battery-powered suction pump,  
• 
a canister for the collection of wound fluids, and  
• 
a sterile, single use dressing kit.    
 
PIMS-associated dressings include either the Peel and Place Dressing or the Customizable 
Dressing.  
 
The PIMS Peel and Place dressing is an integrated, one-piece dressing comprised of a 
polyurethane film with acrylic adhesive that provides adhesion of the dressing to the skin 
surrounding the incision and a polyurethane shell that encapsulates the foam bolster and interface 
layer, providing a closed system.  The polyurethane foam has a pore size of 400-600 microns 
and a violet colorant.  Additionally, the dressing has a built-in pressure indicator, which shows 
when system pressure is at an acceptable level, and a skin interface layer with 0.019% ionic 
silver, which wicks fluid from the skin surface.  The silver is not intended to treat infection but to 
reduce potential for contamination of the skin interface layer with microbes. This type of 
Prevena™ Incision Management System is a 510(k) – cleared, Class II device (K100821). 
 
The Prevena Incision Management System with Customizable Dressing (Prevena Customizable) 
provides a new dressing configuration that has been designed to allow the clinician to cut the 
dressing to fit the incision size and geometry. The skin contacting dressing components include: 
• 
a foam bolster with a skin interface layer, 
• 
a hydrocolloid ring that is attached to the foam bolster to assist dressing application and 
to help reduce dressing leaks,  
• 
hydrocolloid sealing strips for bridging foam dressing pieces, and 
• 
a polyurethane film (V.A.C. Drape). 
 
This product was recently cleared under 510(k) K121883. 
 
PIMS is intended to manage the environment of surgical incisions that continue to drain following 
sutured or stapled closure by maintaining a closed environment and removing exudate via the 
application of negative pressure wound therapy.  The Prevena System is intended to be applied 
to the wound site immediately after surgery, and continue for a minimum of 2 days up to a 
maximum of 7 days, depending on the surgeon’s preference. 
2.2 ACTIV.A.C. THERAPY UNIT 
The ActiV.A.C. therapy unit can be used in special situations in which the incision is larger or has 
an unusual shape. It is also intended to manage the environment of surgical incisions that 
continue to drain following sutured or stapled closure by maintaining a closed environment and 
removing exudates via the application of negative pressure wound therapy.  The unit is lightweight 
and portable to help patients resume their activities of daily living while still receiving the benefits 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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of V.A.C.® Therapy. The ActiV.A.C. can be used with the Prevena Peel and Place dressing and 
the Customizable dressing.  
 
The ActiV.A.C unit consists of: 
• 
a small, portable, battery-powered suction pump,  
• 
a canister for the collection of wound fluids, 
The ActiV.A.C. is a 510(k) – cleared, Class II device (K120033). 
3.0 STUDY RATIONALE 
Patients undergoing colorectal (CRS) and hepatopancreatobiliary (HPBS) surgery are at high risk 
for postoperative complications such SSI and wound dehiscence.  Such complications increase 
the complexity of patient care during recovery from surgery, lengthen post-operative 
hospitalizations, add significant overall medical costs and may potentially diminish quality of life 
and economic livelihood. To date, there is no reported study to evaluate the efficacy of either 
conventional wound care with sterile dressings or the application of V.A.C.® to postoperative 
abdominal incisions in preventing SSI. Furthermore, there are currently no identifiable additional 
risks for receiving either conventional wound care or PIMS. Therefore, the proposed study will 
compare SSI rates for subjects receiving NPWT via PIMS or ActiV.A.C to conventional wound 
care with sterile dressing.   
 
We hypothesize that incisional NPWT via PIMS or ActiV.A.C.(Kinetic Concepts USA, Inc., San 
Antonio, TX) compared to conventionally closed laparotomy wounds may decrease the SSI rate 
in these subject populations which are associated with a high rate of postoperative wound 
complications. 
4.0 STUDY OBJECTIVES 
4.1 PRIMARY 
• 
To compare the incidence of SSI rates between conventional wound care versus the 
incisional NPWT via PIMS or ActiV.A.C. within CRS or HPBS-associated laparotomy 
wounds as assessed on postoperative day 4-5 and the first postoperative clinic visit. 
4.2 SECONDARY 
• 
Characterize the incidence of SSI as superficial incisional, deep incisional, and 
organ/space as defined by The American College of Surgeons National Surgical Quality 
Improvement Program (NSQIP) guidelines. 
 
• 
Assess (or compare) the length of hospital stay between subjects who receive standard 
of care and incisional NPWT via PIMS or ActiV.A.C. 
 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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5.0 STUDY DESIGN 
5.1 STUDY DESCRIPTION 
This study is a multi-center, open-label, randomized clinical trial conducted at Duke Cancer 
Institute and Indiana University to evaluate whether incisional NPWT can help reduce the rate of 
SSI in patients undergoing either colorectal or hepatopancreatobiliary surgery. Up to 170 subjects 
will be randomized in a 1:1 ratio to either conventional wound care (control group) or the incisional 
NPWT (experimental group) to ensure 138 evaluable subjects.  
 
The primary study endpoint will be SSI within the laparotomy wound, as assessed on 
postoperative day 4-5 and the first postoperative clinic visit, which is anticipated to be within 30 
days of surgery. Evaluable subjects are defined as those who have been randomized and 
completed both postoperative assessments. Non-evaluable subjects are those subjects who were 
randomized but did not complete both post-op visits.  Non-evaluable scenarios include aborted 
surgeries, cancelled surgeries, death unrelated to study, and early device removal related to 
device malfunction. Screen failures are defined as those subjects not randomized.   
 
Safety endpoints will be adverse events related to the device or dressing, including the presence 
of any abnormal skin findings (such as blisters or rash). These endpoints will be assessed from 
the day of surgery through the 30-day follow-up visit.   
 
Subjects randomized to conventional wound care (control group) will have their skin incisions 
closed with skin staples, sutures, or surgical glue (per judgment of the treating physician), covered 
with sterile medical gauze and a form of adherent (tape or clear adhesive) for which the subject 
does not have any allergy. This dressing will be removed per the treating physician’s discretion 
or institutional standards. 
 
Subjects randomized to the incisional NPWT (experimental group) will have their skin incisions 
closed with skin staples or sutures (per judgment of the treating physician), a layer of non-
adhesive dressing (Adaptic: Johnson & Johnson, New Brunswick, New Jersey) will cover the skin 
staples or sutures, followed by placement of an adhesive (Benzoin: generic), a Prevena™ Incision 
Management System peel and place or customizable dressing (KCI USA, Inc, San Antonio, 
Texas) covering only the skin staples or sutures.  Please note, surgical glue should not be used 
for the experimental group. NPWT will be delivered using either the Prevena pump or the 
ActiV.AC. The incisional NPWT will then be continued for a minimum of 2 days up to a maximum 
of 7 days depending on physician preference.   
 
Subjects will be clinically managed according to routine standard of care. Subjects will be 
assessed during their inpatient stay and at the time of routine postoperative clinic visits which is 
anticipated to be within 30 days of discharge. Presence or absence of SSI will be determined on 
postoperative day 4-5 and again at the time of the postoperative clinic visit, which is anticipated 
to be within 30 days of discharge.  Criteria for determination of SSI are listed in Section 8. 
 
Patients who are candidates for a laparoscopic approach will not be recruited. Note: patients 
scheduled for a staging laparoscopy followed by an open procedure are permitted to participate. 
 
See Appendix 1 for the study schema. 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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5.2 RANDOMIZATION 
Subjects who meet all inclusion criteria and no exclusion criteria and who consent to participate 
in the study will be randomized in a 1:1 ratio to receive either incisional NPWT via PIMS or 
ActiV.A.C or the standard-of care dressing following surgery. Randomization may occur up to 5 
business days prior to surgery. If a subject is randomized and surgery is subsequently delayed, 
they will not be re-randomized even if outside the 5-day window. 
 
Randomization will be stratified according to surgical site (colorectal vs hepatopancreatobiliary) 
and body mass index (BMI), < 30 vs ≥ 30. 
 
Randomization using permuted block scheme will be done via REDCap Randomization 
Application. Please refer to the randomization manual for detailed instructions. 
6.0 SUBJECT SELECTION 
6.1 INCLUSION CRITERIA  
1. Female and male patients 18 years of age or older 
2. Scheduled for an elective surgery in either open CRS or open HPBS. This includes, but 
is not limited to: ileocecectomy, right hemicolectomy, extended right hemicolectomy, 
transverse colectomy, left hemicolectomy, sigmoidectomy, proctectomy, low anterior 
resection or abdominoperineal resection, hepatectomy, bile duct reconstruction, 
duodenectomy, 
pancreatectomy, 
pancreaticoduodenectomy, 
or 
pancreatic 
duct 
reconstruction 
6.2 EXCLUSION CRITERIA 
1. The need for emergency surgery. 
2. The need for use of only laparoscopic surgery.  Note: Hand-assisted laparoscopic 
procedures are not exclusionary. Patients scheduled for a staging laparoscopy followed 
by an open procedure are permitted to participate. 
3. Presence of bowel obstruction, strangulation, peritonitis or perforation. 
4. The presence of local or systemic infection preoperatively. 
5. ASA class ≥4. 
6. Inability to provide informed consent and authorization. 
7. Known allergy or hypersensitivity to silver. 
8. Patients who are pregnant 
9. Any clinically significant condition that, in the investigator’s opinion, would significantly 
impair the subject’s ability to comply with the study. 
6.3 INCLUSION OF WOMEN AND MINORITIES 
Men and women of all races and ethnic groups are eligible for this trial. 

PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
7.0 STUDY ASSESSMENTS 
7.1 STUDY CALENDAR 
 
 
Baselinea 
 
Cycle Day 
Day of Surgery 
 
Post-op Visit  
4-5 days 
Post-op Visit  
30 days (+/-14) 
Informed Consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical and Surgical history 
X 
 
 
 
Physical Exam and Vital Signs 
X 
 
 
 
 
 
Pregnancy Testb 
X 
 
 
 
Randomizationc 
 
X 
 
 
Incisional NPWT via PIMS or 
ActiV.A.C or standard wound 
applicationd 
 
X 
 
 
Incision Assessment 
 
 
X 
X 
Adverse Event Assessment 
 
Throughout Study 
Concomitant Medication 
X 
 
 
a: Screening procedures will be performed within 42 days prior to surgery. 
b:  Serum or urine pregnancy test in women of childbearing potential will be performed within 30 days prior to surgery 
c: Randomization may occur within 5 business days of surgery. 
d: Wound application will be done in the operating room by the OR team. 

PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
7.2 SCREENING AND BASELINE EVALUATIONS 
All baseline assessments must be done within 42 days of surgery.  
 
• 
Physical Exam and vital signs 
• 
Medical History 
• 
Surgical History 
• 
Concomitant Medications (must be done or confirmed on the day of surgery): Include a 
list of pre-treatment chemotherapy and/or radiation for rectal cancer patients. Also include 
antibiotics within 30 days prior to surgery, steroid use within 1 week prior to surgery, 
medications related to anticoagulation within 30 days prior to surgery. 
A serum or urine pregnancy test will be conducted on women of childbearing age within 30 days 
prior to surgery. 
Eligibility will be reviewed by two key personnel prior to randomization to ensure eligibility 
(inclusion and exclusion) criteria have been met. The PI will review final eligibility prior to surgery.   
7.3 EVALUATIONS DURING STUDY 
7.3.1 Throughout Study 
• 
Adverse Event evaluation specific only to the NPWT units and dressings unit (e.g. 
blistering, redness) 
7.3.2 Day of Surgery 
• 
Randomization (or within 5 business days of surgery) 
• 
NPWT via PIMS or ActiV.A.C. or standard of care wound application; application will be 
done in the operating room by the OR team.  
7.3.3 Post-op Visit Day 4-5 
• 
Post-operative incision assessment 
• 
Review of any side effects or symptoms  
• 
This may be conducted by a review of clinical data 
• 
PI will confirm the clinical data of any finding indicative of infection (i.e. redness, fever, 
positive culture) 
7.3.4 Post-op Visit Day 30 (+/-14) 
• 
Post-operative incision assessment 
• 
Review of any side effects or symptoms  
• 
This may be conducted by a review of clinical data 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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• 
PI will confirm the clinical data of any finding indicative of infection (i.e. redness, fever, 
positive culture) 
8.0 CLASSIFICATION OF SSI BY NSQIP 
The following definitions will be used to classify SSI: 
Superficial Incisional SSI: Superficial incisional SSI is an infection that occurs within 30 days 
after the operation and infection involves only skin or subcutaneous tissue of the incision and at 
least one of the following:  
- Purulent drainage, with or without laboratory confirmation, from the superficial incision. 
- Organisms isolated from an aseptically obtained culture of fluid or tissue from the 
superficial incision.  
- At least one of the following signs or symptoms of infection: pain or tenderness, localized 
swelling, redness, or heat AND superficial incision is deliberately opened by the surgeon, 
unless incision is culture-negative.  
- Diagnosis of superficial incisional SSI by the surgeon or attending physician 
Deep Incisional SSI: Deep Incision SSI is an infection that occurs within 30 days after the 
operation and the infection appears to be related to the operation and infection involved deep soft 
tissues (for example, fascial and muscle layers) of the incision and at least one of the following:  
- Purulent drainage from the deep incision but not from the organ/space component of the 
surgical site. 
- A deep incision spontaneously dehisces or is deliberately opened by a surgeon when 
the patient has at least one of the following signs or symptoms: fever (> 38° C), localized 
pain, or tenderness, unless site is culture-negative. 
- An abscess or other evidence of infection involving the deep incision is found on direct 
examination, during reoperation, or by histopathologic or radiologic examination. 
- Diagnosis of a deep incision SSI by a surgeon or attending physician. 
- Report infection that involves both superficial and deep incision sites as deep incisional 
SSI. 
Organ/Space SSI: Organ/Space SSI is an infection that occurs within 30 days after the 
operation and the infection appears to be related to the operation and the infection involves any 
part of the anatomy (for example, organs or spaces), other than the incision, which was opened 
or manipulated during an operation and at least one of the following: 
- Purulent drainage from a drain that is placed through a stab wound into the 
organ/space. 
- Organisms isolated from an aseptically obtained culture of fluid or tissue in the 
organ/space. 
- An abscess or other evidence of infection involving the organ/space that is found on 
direct examination, during reoperation, or by histopathologic or radiologic examination. 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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- Diagnosis of an organ/space SSI by a surgeon or attending physician.  
Do not report the following conditions as SSI:  
- Stitch abscess (minimal inflammation and discharge confined to the points of suture 
penetration). 
- Infected burn wound.  
9.0 SUBJECT DISCONTINUATION 
Subjects may withdraw from this study at any time.   
 
Reason for discontinuation from the trial will be recorded. 
 
The Principal Investigator may discontinue a subject from the protocol regimen.  Reasons for 
subject discontinuation by the investigator may include but are not limited to the following:  
• 
Death 
• 
Investigator or PI determination that it is not in the subject’s best interest to continue 
participation 
• 
Lost to follow-up 
10.0 STATISTICAL METHODS 
Administrative Summary 
Between July 2016 and June 2017, institutional SSI rates were 29% and 9% for Whipple 
procedures and liver resections, respectively. Based on these lower than expected SSI rates we 
decided to compute the observed, overall infection rate among patients currently enrolled and 
treated on this trial to assess whether the trial hypotheses were reasonable assumptions. The 
current overall infection rate was estimated to be 11%. In addition, the observed percent of 
ineligible/non-evaluable patients was 14%. Consequently, the null and alternative hypotheses of 
the present trial are being amended from the previous null and alternative hypotheses of 30% 
and 15%, respectively to 17% and 5%, respectively, to reflect the overall, observed infection rate. 
The revised, maximum sample size will be inflated to reflect the observed percent of inevaluable 
patients, 14%. As of February 2018, 131 patients were randomized; no statistical analysis of the 
study endpoint has been conducted to date. 
 
Revised Statistical Considerations 
The primary study endpoint is SSI rate. Patients will be stratified by surgical site (colorectal vs 
hepatopancreatobiliary) and BMI (<30 vs ≥30), and randomly assigned to conventional wound 
care group or negative wound pressure group with 1:1 allocation. The hypothesized SSI rate is 
17% for the conventional wound care group (control group) [1].  We anticipate a reduction of the 
rate to 5% in the negative wound pressure group (experimental group).   
 
As this is a phase II study, a larger type I error rate of 0.1 will be used. Based on a chi-square 
test comparing two-sample binomial probabilities at a 1-sided significance level of 0.1, the study 
has approximately 85% power to detect the difference in SSI rates between 17% in the control 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
Page 15 of 23 
group and 5% in the experimental group. With the allowance of 14% ineligible/non-evaluable 
patients (based on the observed percentage of evaluable patients to date), up to 170 patients (85 
per arm) will be enrolled. Given that 143 patients have already enrolled on the study, up to 27 
additional patients will be accrued to meet the revised, maximum study sample size.   
 
With an accrual rate of 4 patients per month, we expect to complete the additional accrual in less 
than 8 months. 
 
Preoperative, intraoperative, and postoperative variables will be prospectively collected. 
10.1 STATISTICAL ANALYSIS 
The primary analysis will include all randomized and evaluable patients but exclude ineligible 
patients or patients who are canceled from the study before receiving any wound care. SSI is 
defined as an infection that occurs within 30 days of operation. The primary endpoint is the SSI 
rate.  The primary analysis of comparing the conventional wound care (control group) and the 
incisional V.A.C® (experimental group) will be conducted using a chi-square test for two-sample 
binomial probabilities with a one-sided significance level of 0.1. The observed SSI rates and 90% 
Upper Confidence Bound (UCB) estimates will be reported. Preoperative, intraoperative, and 
postoperative variables will be tabulated and appropriate summary statistics will be reported. As 
a secondary analysis, comparison of treatment groups for SSI will be adjusted for any significant 
preoperative, intraoperative, or postoperative variables using logistic regression.  
 
For secondary endpoints, the incidence of SSI as superficial incisional, deep incisional, and 
organ/space will be estimated along with the 90% UCBs. The secondary endpoint length of stay 
is a continuous variable.  A Wilcoxon rank sum test will be used to assess the significance of the 
difference between groups in median length of stay. Median length of stay, its range and quartiles 
will be reported.  
 
11.0 INVESTIGATIONAL PRODUCT  
The PIMS and ActiV.A.C. therapy units and associated dressings will be supplied by KCI. 
 
Incisional NPWT will be removed prior to hospital discharge. 
 
In the event that the clinician or study designee encounters issues with PIMS or control dressings 
prior to the desired time for removal, dressing replacement/reinforcement is acceptable but must 
be documented in the case report form (CRF).  The PIMS unit may also be switched to use an 
ActiV.A.C unit.  Any loss of negative pressure will be documented and will not determine subject 
evaluability. Please refer to the PIMS Instructions manual for guidance on operational questions. 
 
A PIMS canister filled with 45 mL of wound fluid will lead to a “canister full” alarm.  
11.1 INVESTIGATIONAL PRODUCT STORAGE AND ACCOUNTABILITY 
The PIMS and ActiV.A.C. therapy units and associated dressings are to be stored in a secure, 
limited-access location with ambient room temperature away from direct sun exposure and 
moisture. 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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No investigational product will be released until the KCI receives written confirmation that the IRB 
has approved the clinical study. 
Prior to the release of product to the site, the funding source, KCI shall complete the appropriate 
Investigational Product Release and Inventory Control Forms, which will accompany the shipment 
of the investigative product and serve as a shipping record from the funding source. 
 
Upon receipt of product, the Principal Investigator (PI), or designee, will inventory the shipment 
and verify the lot numbers (PIMS) and serial numbers (ActiV.A.C units) against the information 
provided on the Investigational Product Release Form. The PI, or designee, will sign the form and 
return it to the funding source, or designee, with notations regarding any missing investigational 
product or other discrepancies. 
 
The PIMS and ActiV.A.C. therapy units and associated dressings that are not dispensed for the 
study will be returned to KCI at the end of the study. 
 
12.0 SAFETY REPORTING REQUIREMENTS 
12.1 DEFINITIONS 
The definitions in this section have been adapted from the Code of Federal Regulations (CFR) 
and the International Conference on Harmonization (ICH) Guidelines for Good Clinical Practices 
(GCPs). Please refer to the complete regulations and guidelines for additional details regarding 
these definitions. This study will only evaluate adverse events that are probably or possibly related 
to the NPWT units and dressings (e.g. blistering, redness, etc). 
 
Adverse Event (AE) [ICH GCP]: An Adverse Event (AE) shall mean any untoward medical 
occurrence. For the purposes of this study, only adverse events thought to be related to the 
dressing will be collected and recorded. 
 
Unanticipated adverse device effects [21 CFR 812.150]: Any serious adverse effect on health 
or safety, 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 application; or any other unanticipated serious problem associated with a device that relates 
to the rights, safety, or welfare of subjects. An investigator shall submit to the sponsor and to the 
reviewing 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. 
 
Deviations from the investigational plan [21 CFR 812.150]: An investigator shall notify the 
sponsor and the reviewing IRB of any deviation from the investigational plan to protect the life or 
physical well-being of a subject in an emergency. Such notice shall be given as soon as possible, 
but in no event later than 5 working days after the emergency occurred. Except in such an 
emergency, prior approval by the sponsor is required for changes in or deviations from a plan, 
and if these changes or deviations may affect the scientific soundness of the plan or the rights, 
safety or welfare of human subject, FDA and IRB approval is also required. 
 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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12.2 PROCEDURES FOR REPORTING 
All adverse events deemed possibly or probably related to the NPWT unit and dressings that are 
identified from the time of placement of the NPWT or standard of care wound application through 
30 days post-surgery should be recorded on the CRFs. 
 
Serious Adverse Events (SAEs) must ALSO be reported within 2 business days of learning of an 
event. The DCI Safety SAE Review Form must be completed and promptly submitted to the 
funding company. The forms should include at minimum the following information but should not 
be held until all information is available. The funding source, KCI, will be notified using the KCI 
USA, Inc. SAE Report Form. The Duke study team will send SAE Report Form to KCI USA, Inc. 
within 2 business days of knowledge of the SAE. External sites should report SAEs to the Duke 
study team within 24 hours. Reporting instructions for external sites can be found in the REDCap 
study eManual. The Duke study team will be responsible for reporting to the supporting company 
as well as the Duke IRB and/or FDA, where applicable. In accordance with applicable regulations, 
Investigators must report SAEs to their local IRB according to their institutional guidelines. 
 
Additional information and/or corrections may be submitted as they are obtained. All SAEs must 
be followed through resolution or stabilization.  
 
The initial report for each SAE should include at minimum the following information: 
• 
protocol # and title 
• 
patient initials, study identification number, sex, age 
• 
date the event occurred  
• 
description of the SAE 
• 
description of the patient’s condition 
• 
indication whether the patient remains on study 
• 
causality or causal relationship 
 
SAEs should be reported by fax to the following: 
 
KCI USA, INC 
Fax: 1-800-275-4290 
Email: SAE@kci1.com 
 
 
Events will be reviewed and reported to the Duke IRB according to local IRB guidelines. 
 
13.0 DATA AND SAFETY MONITORING 
13.1 MONITORING 
The Duke Cancer Institute (DCI) Monitoring Team will conduct monitoring visits to ensure subject 
safety and to ensure that the protocol is conducted, recorded, and reported in accordance with 
the protocol, standard operating procedures, good clinical practice, and applicable regulatory 
requirements.  As specified in the DCI Data and Safety Monitoring Plan, the DCI Monitoring Team 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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will conduct routine monitoring after the third subject is enrolled, followed by annual monitoring of 
1 – 3 subjects until the study is closed to enrollment and subjects are no longer receiving study 
interventions that are more than minimal risk.   
 
Additional monitoring may be prompted by findings from monitoring visits, unexpected frequency 
of serious and/or unexpected toxicities, or other concerns and may be initiated upon request of 
DUHS and DCI leadership, the DCI Cancer Protocol Committee, the Safety Oversight Committee 
(SOC), the funding source, the Principal Investigator, or the IRB.  All study documents must be 
made available upon request to the DCI Monitoring Team, the Duke School of Medicine Office of 
Regulatory Affairs and Quality (ORAQ) and other authorized regulatory authorities, including but 
not limited to the National Institute of Health, National Cancer Institute, and the FDA.  Every 
reasonable effort will be made to maintain confidentiality during study monitoring. 
13.2 SAFETY OVERSIGHT COMMITTEE 
The Duke Cancer Institute SOC is responsible for annual data and safety monitoring of DUHS 
sponsor-investigator phase I and II, therapeutic interventional studies that do not have an 
independent Data Safety Monitoring Board (DSMB). The primary focus of the SOC is review of 
safety data, toxicities and new information that may affect subject safety or efficacy. Annual safety 
reviews include but may not be limited to review of safety data, enrollment status, stopping rules 
if applicable, accrual, toxicities, reference literature, and interim analyses as provided by the 
sponsor-investigator. The SOC in concert with the DCI Monitoring Team oversees the conduct of 
DUHS cancer-related, sponsor-investigator therapeutic intervention and prevention intervention 
studies that do not have an external monitoring plan, ensuring subject safety and that the protocol 
is conducted, recorded and reported in accordance with the protocol, standing operating 
procedures (SOPs), Good Clinical Practice (GCP), and applicable regulatory requirements. 
13.3 SUBJECT CONFIDENTIALITY 
In order to maintain subject privacy, all case report forms (CRFs), study drug accountability 
records, study reports, and communications will identify the subjects by initials or the assigned 
subject number.  The investigator will grant monitor(s) and auditor(s) from the funding source, or 
designee and regulatory authority(ies) access to subject original medical records for verification 
of data gathered on the CRFs and to monitor/audit the data collection process.  The subject’s 
confidentiality will be maintained and will not be made publicly available to the extent permitted 
by the applicable laws and regulations. 
13.4 INVESTIGATOR COMPLIANCE 
The investigator will conduct the study in compliance with the protocol provided by the sponsor 
and funding source and will obtain approval by the IRB and appropriate regulatory authority(ies).  
Modifications to the protocol should not be made without agreement of the investigator and 
funding source. Changes to the protocol will require written IRB approval prior to the 
implementation, except when the modification is needed to eliminate an immediate hazard(s) to 
subjects.  If applicable regulatory authority(ies) permit, the IRB may provide expedited review and 
approval for minor changes in ongoing studies that have the approval of the IRB. Sponsor or 
designee will submit all protocol modifications to the regulatory authority(ies) in accordance with 
the governing regulations. 
 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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When immediate deviation from the protocol is required to eliminate an immediate hazard(s) to 
subjects, the investigator will contact the funding source or designee, if circumstances permit, to 
discuss the planned course of action.  All departures from the protocol must be fully documented. 
13.5 AUDITS 
The Duke School of Medicine Office of Regulatory Affairs and Quality (ORAQ) may conduct audits 
to evaluate compliance with the protocol and the principles of GCP. The PI agrees to allow the 
ORAQ auditor(s) direct access to all relevant documents and to allocate his/her time and the time 
of the study team to the ORAQ auditor(s) in order to discuss findings and any relevant issues. 
 
ORAQ audits are designed to protect the rights and well-being of human research subjects. 
ORAQ audits may be routine or directed (for cause). Routine audits are selected based upon risk 
metrics generally geared towards high subject enrollment, studies with limited oversight or 
monitoring, Investigator initiated Investigational Drugs or Devices, federally-funded studies, high 
degree of risk (based upon adverse events, type of study, or vulnerable populations), Phase I 
studies, or studies that involve Medicare populations. Directed audits occur at the directive of the 
IRB or an authorized Institutional Official. 
 
ORAQ audits examine research studies/clinical trials methodology, processes and systems to 
assess whether the research is conducted according to the protocol approved by the DUHS IRB. 
The primary purpose of the audit/review is to verify that the standards for safety of human subjects 
in clinical trials and the quality of data produced by the clinical trial research are met. The 
audit/review will serve as a quality assurance measure, internal to the institution. Additional goals 
of such audits are to detect both random and systemic errors occurring during the conduct of 
clinical research and to emphasize “best practices” in the research/clinical trials environment. 
 
14.0 DATA MANAGEMENT AND PROCESSING 
A Medidata Rave database will be the data collection tool for the study.   
 
An audit trail is maintained automatically by the electronic CRF management system.  All users 
of this system will complete user training. 
14.1 STUDY DOCUMENTATION 
Study documentation includes but is not limited to source documents, case report forms, 
monitoring logs, appointment schedules, study team correspondence with sponsors, funding 
source or regulatory bodies/committees, and regulatory documents that can be found in the DCI-
mandated “Regulatory Binder”, which includes but is not limited to signed protocol and 
amendments, approved and signed informed consent forms, FDA Form 1572, CAP and CLIA 
laboratory certifications, and clinical supplies receipts and distribution records. 
 
Source documents are original records that contain source data, which is all information in original 
records of clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  Source documents include but are not limited to hospital 
records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
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transcriptions certified after verification as being accurate copies, 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. When 
possible, the original record should be retained as the source document.  However, a photocopy 
is acceptable provided that it is a clear, legible, and an exact duplication of the original document. 
 
15.0 ADMINISTRATIVE SECTION 
15.1 REGULATORY AND ETHICAL COMPLIANCE 
This protocol was designed and will be conducted and reported in accordance with the 
International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good 
Clinical Practice, the Declaration of Helsinki, and applicable federal, state, and local regulations. 
15.2 DUHS INSTITUTIONAL REVIEW BOARD AND DCI CANCER PROTOCOL 
COMMITTEE 
The protocol, informed consent form and pertinent protocol-related documents must be submitted 
to the DUHS Institutional Review Board (IRB) and DCI Cancer Protocol Committee (CPC) for 
review. The study may be initiated only after the Principal Investigator has received written and 
dated approval from the CPC and IRB. 
 
The Principal Investigator must submit and obtain approval from the IRB for all subsequent 
protocol amendments and changes to the informed consent form. The CPC should be informed 
about any protocol amendments that potentially affect research design or data analysis (i.e. 
amendments affecting subject population, inclusion/exclusion criteria, agent administration, 
statistical analysis, etc.). 
 
The Principal Investigator must obtain protocol re-approval from the IRB within 1 year of the most 
recent IRB approval. The Principal Investigator must also obtain protocol re-approval from the 
CPC within 1 year of the most recent IRB approval, for as long as the protocol remains open to 
subject enrollment. 
15.3 INFORMED CONSENT 
The informed consent form must be written in a manner that is understandable to the subject 
population. Prior to its use, the informed consent form must be approved by the IRB. 
 
The Principal Investigator or authorized key personnel will discuss with the potential subject the 
purpose of the research, methods, potential risks and benefits, subject concerns, and other study-
related matters. This discussion will occur in a location that ensures subject privacy and in a 
manner that minimizes the possibility of coercion. Potential subjects will have the opportunity to 
contact the Principal investigator or authorized key personnel with questions, and will be given as 
much time as needed to make an informed decision about participation in the study. 
 
Before conducting any study-specific procedures, the Principal Investigator must obtain written 
informed consent from the subject or a legally acceptable representative.  The original informed 
consent form will be stored with the subject’s study records, and a copy of the informed consent 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
Page 21 of 23 
form will be provided to the subject. The Principal Investigator is responsible for asking the subject 
whether the subject wishes to notify his/her primary care physician about participation in the 
study. If the subject agrees to such notification, the Principal Investigator will inform the subject’s 
primary care physician about the subject’s participation in the clinical study. 
 
The Investigator must ensure that patients or their legally acceptable representatives are clearly 
and fully informed about the purpose, potential risks and other critical issues regarding clinical 
trials in which they volunteer to participate. Preparation of the consent form is the responsibility 
of the Investigator and must include all elements required by CFR 21 Part 50.25 and the local 
IRB. 
15.4 PRIVACY, CONFIDENTIALITY, AND DATA STORAGE 
The Principal Investigator will ensure that subject privacy and confidentiality of the subject’s data 
will be maintained. 
 
Upon completion of the study, research records will be archived and handled per DUHS HRPP 
policy.     
 
Subject names or identifiers will not be used in reports, presentations at scientific meetings, or 
publications in scientific journals. 
15.5 STUDY CLOSURE 
Following completion of the studies, the PI will be responsible for ensuring the following activities: 
 
• 
Data clarification and/or resolution 
• 
Accounting, reconciliation, and destruction/return of used and unused study drugs 
• 
Review of site study records for completeness 
 
 

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PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
Page 22 of 23 
16.0 REFERENCES 
1. 
Itani KM, Wilson SE, Awad SS, Jensen EH, Finn TS, Abramson MA (2006) Ertapenem 
versus cefotetan prophylaxis in elective colorectal surgery. N Engl J Med 355: 2640-51 
2. 
Parikh P, Shiloach M, Cohen ME, Bilimoria KY, Ko CY, Hall BL, Pitt HA (2010) 
Pancreatectomy risk calculator: an ACS-NSQIP resource. HPB (Oxford) 12: 488-97 
3. 
Ceppa EP, House MG, Pitt HA, Kilbane EM, Janitz SK, Nakeeb A, Howard TJ, Schmidt 
CM, Maluccio MA, Zyromski NJ, Lillemoe KD (2012) Reducing Surgical Site Infections in 
Hepato-pancreato-biliary Surgery AHPBA: AHPBA20121026 
4. 
Nanashima A, Tobinaga S, Abo T, Takeshita H, Hidaka S, Sawai T, Nagayasu T (2010) 
Comparison of outcome of hepatectomy with thoraco-abdominal or abdominal approach. 
Hepatogastroenterology 57: 336-43 
5. 
Okabayashi T, Nishimori I, Yamashita K, Sugimoto T, Yatabe T, Maeda H, Kobayashi M, 
Hanazaki K (2009) Risk factors and predictors for surgical site infection after hepatic 
resection. J Hosp Infect 73: 47-53 
6. 
Mezhir JJ, Brennan MF, Baser RE, D'Angelica MI, Fong Y, DeMatteo RP, Jarnagin WR, 
Allen PJ (2009) A matched case-control study of preoperative biliary drainage in patients 
with pancreatic adenocarcinoma: routine drainage is not justified. J Gastrointest Surg 13: 
2163-9 
7. 
Atkins BZ, Wooten MK, Kistler J, Hurley K, Hughes GC, Wolfe WG (2009) Does negative 
pressure wound therapy have a role in preventing poststernotomy wound complications? 
Surg Innov 16: 140-6 
8. 
Khuri SF, Daley J, Henderson W, Barbour G, Lowry P, Irvin G, Gibbs J, Grover F, 
Hammermeister K, Stremple JF, et al. (1995) The National Veterans Administration 
Surgical Risk Study: risk adjustment for the comparative assessment of the quality of 
surgical care. J Am Coll Surg 180: 519-31 
 
 
 

PI: Dan Blazer III, M.D.                                                                                        Version Date: 31DEC2020 
 
 
APPENDIX 1 
STUDY SCHEMA  
 
S
C
R
E
E
N 
 
R
A
N
D
O
M
I
Z
E 
 
Up to 42 days 
S
U
G
E
R
E
Y 
 
Within 5  
business days 
 
 
STANDARD DRESSING 
NPWT via PIMS or ActiV.A.C. 
 
 
SSI Assessment 1 
Post-op 4-5 days 
SSI Assessment 2 
Post-op 30 days 
(+/- 14)