Evaluation of Closed Incision Negative Pressure Dressing (PREVENA) to Prevent Lower Extremity Amputation Wound Complications
Phase: NA
Conditions: Amputation, Amputation; Postoperative, Sequelae, Wound Dehiscence, Seroma, Wound Infection, Surgical, Lymph Leakage
Sponsor: Thomas Jefferson University

STUDY PROTOCOL 
 
Evaluation of a Closed Incision Negative Pressure Dressing (PREVENA) To 
Prevent Lower Extremity Amputation Wound Complications 
SHORT TITLE: PREVENA-AMP 
 
ClinicalTrials.gov Identifier: TBD 
 
Compiled By: Jefferson Clinical Research Institute (JCRI) 
Version: 1.0 
Date: August 21, 2018 
 
 
Study Funding: Acelity/KCI Inc. 
Sponsor: Thomas Jefferson University 
Steering Committee Chair: Paul J. DiMuzio, MD 
William M. Measey Professor of Surgery 
Director, Division of Vascular and Endovascular Surgery 
Co-Director, Jefferson Vascular Center 
Protocol Development Team: Suzanne Adams, RN, MPH 
Melissa McCarey, MPH 
 
 
 
 
 
 
 
 
This protocol has been written in accordance with current applicable guidelines (IDE for USA) as well as all 
other relevant additional references, medical and legal. The information herein is confidential and to be 
used in confidence for the conduct of the clinical trial according to written agreement. 
PROTOCOL REVISION HISTORY 

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Version No. And Date 
Section 
Change 
Rationale 
Version 1.0 
AUGUST2018 
n/a 
n/a 
Original Release 
 
 
 

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TABLE OF CONTENTS 
1. 
SPONSOR RESPONSIBILITIES AND ADDRESSES ............................................................................. 5 
2. 
ABBREVIATIONS AND DEFINITIONS .............................................................................................. 5 
3. 
PROTOCOL SUMMARY .................................................................................................................. 7 
4. 
INTRODUCTION ............................................................................................................................. 8 
5. 
STUDY OBJECTIVES ........................................................................................................................ 8 
5.1. 
Primary Objective .......................................................................................................... 8 
5.2. 
Secondary Objectives .................................................................................................... 9 
6. 
STUDY DESIGN ............................................................................................................................... 9 
6.1. 
Enrollment ..................................................................................................................... 9 
6.2. 
Selection of Subjects ..................................................................................................... 9 
6.2.1. Informed Consent ............................................................................................. 9 
6.2.2. Number of Subjects ........................................................................................ 10 
6.2.3. Subject Inclusion Criteria ................................................................................ 10 
6.2.4. Subject Exclusion Criteria ............................................................................... 10 
7. 
STUDY DEVICE ............................................................................................................................. 10 
7.1. 
PREVENA™ PEEL & PLACE™ Dressing Kit ..................................................................... 10 
7.2. 
Packaging ..................................................................................................................... 11 
7.3. 
Instruction for Use ....................................................................................................... 11 
7.4. 
Required Training on Study Device ............................................................................. 11 
8. 
NEGATIVE PRESSURE WOUND THERAPY .................................................................................... 11 
8.1. 
Negative Pressure Wound Therapy using PREVENA™ PEEL & PLACE™ Dressing Kit .. 11 
9. 
STUDY INTERVENTION ................................................................................................................ 12 
9.1. 
Treatment Groups ....................................................................................................... 12 
10. 
STUDY FLOW ............................................................................................................................... 13 
11. 
STUDY SCHEDULE ........................................................................................................................ 14 
11.1. 
Detailed Visit Schedule ................................................................................................ 14 
11.1.1. Screening/Baseline ......................................................................................... 14 
11.1.2. Randomization ............................................................................................... 14 
11.1.3. Day of Surgery ................................................................................................ 14 
11.1.4. Post-Operative Day 1 – 3 ................................................................................ 14 
11.1.5. Post-Operative Day 5 or 6 .............................................................................. 14 
11.1.6. Post-Operative Day 5 or 6 to Discharge ......................................................... 14 
11.1.7. Post-Discharge Follow-Up at Day 30 .............................................................. 14 
11.2. 
Overview of visits ........................................................................................................ 15 
11.3. 
Duration of the study .................................................................................................. 15 
12. 
VISIT PROCEDURES ...................................................................................................................... 15 
12.1. 
Screening/Enrollment ................................................................................................. 15 
12.2. 
Baseline Data Collection .............................................................................................. 16 
12.3. 
Randomization ............................................................................................................ 16 
12.4. 
Day of Surgery ............................................................................................................. 16 
12.5. 
Dressing Monitoring (Post-Operative Days 1 to 5) ..................................................... 16 
12.6. 
Wound Monitoring (Post-Operative Day 5 to Discharge) ........................................... 16 
12.7. 
Discharge ..................................................................................................................... 17 
12.8. 
Follow-Up Visit (Discharge to Day 30 ± 5 days) ........................................................... 17 
13. 
SAFETY ......................................................................................................................................... 17 
13.1. 
Labeled Adverse Device Effects ................................................................................... 17 
14. 
STATISTICAL ANALYSIS ................................................................................................................ 17 
14.1. 
Study Hypothesis ......................................................................................................... 17 

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14.2. 
Analysis Plan ................................................................................................................ 18 
14.3. 
Primary Endpoint Analysis ........................................................................................... 18 
14.4. 
Secondary Endpoint Analysis ...................................................................................... 18 
14.5. 
Justification of the Sample Size ................................................................................... 18 
14.6. 
Interim Analysis ........................................................................................................... 19 
15. 
DATA HANDLING AND RECORDKEEPING .................................................................................... 19 
15.1. 
Data Collection ............................................................................................................ 19 
15.2. 
Study Documentation ................................................................................................. 19 
15.3. 
Query Generation and Resolution .............................................................................. 20 
15.4. 
Data Storage ................................................................................................................ 20 
15.5. 
Inspection of Records .................................................................................................. 20 
15.6. 
Study Files and Record Retention ............................................................................... 20 
15.7. 
Regulatory Documentation ......................................................................................... 20 
16. 
ETHICAL CONSIDERATIONS ......................................................................................................... 21 
16.1. 
Institutional Review Board (IRB) ................................................................................. 21 
16.2. 
Protocol Deviations ..................................................................................................... 21 
16.3. 
Risk Analysis and Confidentiality ................................................................................. 21 
16.3.1. Risk Determination of the Study .................................................................... 21 
16.3.2. Subject Data Confidentiality ........................................................................... 22 
17. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................................................... 22 
17.1. 
Site Selection ............................................................................................................... 22 
17.2. 
Training ........................................................................................................................ 22 
17.3. 
Audits and Inspections ................................................................................................ 23 
18. 
RESPONSIBILITIES ........................................................................................................................ 23 
18.1. 
Clinical Investigator Responsibilities ........................................................................... 23 
18.2. 
Sponsor Responsibilities .............................................................................................. 23 
19. 
STUDY ORGANIZATION AND COMMUNICATION ........................................................................ 24 
19.1. 
Steering Committee, Study Team and Communications ............................................ 24 
20.  REFERENCES ................................................................................................................................. 25 
21.  SIGNATURES ................................................................................................................................ 26 
 
 
 

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1. SPONSOR RESPONSIBILITIES AND ADDRESSES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator: 
Paul J. DiMuzio, MD 
Thomas Jefferson University 
111 S. 11th Street, Suite G6270 
Philadelphia, PA 19107 
 
Sub-Investigators: 
Babak Abai, MD, FACS 
Thomas Jefferson University 
111 S. 11th Street, Suite G6270 
Philadelphia, PA 19107 
 
Dawn Salvatore, MD, FACS 
Thomas Jefferson University 
111 S. 11th Street, Suite G6270 
Philadelphia, PA 19107 
 
Coordinating Center: 
Jefferson Clinical Research Institute 
1015 Chestnut Street, Suite 317 
Philadelphia, PA 19107 
 

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2. ABBREVIATIONS AND DEFINITIONS  
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AKA 
Above-Knee Amputation 
BKA 
Below-Knee Amputation 
EC 
Ethics Committee 
CRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
HbA1C 
Hemoglobin A1c 
iNPWT 
Incisional Negative Pressure Wound Therapy 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
LOS 
Length of Stay 
NPWT 
Negative Pressure Wound Therapy 
ROR 
Reoperation Rate or Return to Operating Room 
SAE 
Serious Adverse Event 
SC 
Steering Committee 
SOP 
Standard Operation Procedures 
 
 
 

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3. PROTOCOL SUMMARY 
Objectives 
To evaluate the impact of a closed incision negative pressure dressing (PREVENA) on 
incidence of post-operative wound complications, and medical costs in patients undergoing 
lower extremity amputation who are enrolled in a clinical trial. 
Study Design 
This study is a prospective, multi-center, two-arm, unblinded, and randomized controlled 
trial. We will enroll up to 440 adults presenting for above-, or below-knee amputation 
across approximately five study sites. Consenting patients will be randomized to receive 
either the PREVENA dressing, or usual care dressing on their amputation incision for five or 
six days post-procedure. Patients will return for a follow-up assessment at 30 days. 
Number of 
Subjects 
Up to 440 subjects will be enrolled in this study 
Selection 
Criteria 
 
Inclusion criteria 
1. Male or female adults 18 years or older 
2. Patients undergoing above-knee amputation (includes the revision of emergency 
guillotine amputations) 
3. Patients undergoing below-knee amputation (includes the revision of emergency 
guillotine amputations) 
4. Informed Consent signed by patient  
Exclusion criteria  
1. Minors under 18 years 
2. Women who are pregnant or breastfeeding 
3. Patients undergoing emergent or guillotine amputation 
4. Patients having BOTH legs amputated 
5. Patients with sensitivity to silver 
6. Unwilling or unable to provide informed consent 
7. Inability to comply with planned study procedures  
Primary 
Endpoint 
 
Incidence of any post-operative wound complications at 30 days including: 
dehiscence (skin or fascia), seroma, lymph leak, infection (deep or superficial), 
hematoma, ischemia and necrosis 
Secondary 
Endpoints 
 
Index length of stay 
 
30 day return to operating room for wound complications 
 
30 day hospital readmissions for wound complications 
Exploratory 
Endpoints 
 
30 day hospitalization costs 
 
30 day variable hospital costs 
Scheduled 
follow up 
For evaluation of the primary and secondary endpoints, subjects will be followed for a 
period of 1 month (30 days). Data will be collected at the following time-points: 
 
Baseline for demographics, vital signs, and medical history 
 
Day of surgery 
 
At discharge for dressing and wound assessment data 
 
30 days (±5 days) after discharge for wound assessment data and clinical outcomes 
For evaluation of the exploratory endpoints, data on hospitalization and variable costs will 
be collected after final accounting is completed and UB04 billing data becomes available. 

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4. INTRODUCTION 
Perioperative wound complications, are common following lower extremity amputation, with 
occurrence rates of 10% to 34% among amputees [1, 2]. At Thomas Jefferson University/Hospital 
(TJU/H), approximately 15% of patients experienced some form of wound complication following 
lower extremity amputation. Lower extremity amputation complications in vascular surgery can be 
devastating in terms of patient morbidity and mortality, and are costly for the institution in terms 
of extended length of stay or readmission. 
The PREVENA™ PEEL & PLACE™ Dressing Kit (“Prevena”; KCI USA, Inc., San Antonio, TX) is 
marketed in the U.S. as a dressing that is used with a negative pressure pump. Prevena is intended 
to manage the environment of clean, closed surgical incisions (i.e., sutured or stapled) that 
continue to drain via the application of negative pressure wound therapy (NPWT), maintaining a 
closed environment and removing exudate. NPWT was initially developed to assist patients with 
open chronic and acute wounds that were difficult to heal and then found to be useful over closed 
incisions. Several recent studies in cardiac and orthopedic surgery demonstrated significant 
reductions in wound complications in high-risk populations by applying a negative-pressure 
dressing over the primarily closed incision [3-5]. In addition, a recent meta-analysis of 10 studies 
(1089 patients, 1311 incisions) assessing negative pressure wound therapy suggested this as an 
effective strategy for reducing seroma formation and infections [6]. 
In a recently completed randomized controlled trial by the Principal Investigator (PI), Dr. DiMuzio, 
Prevena reduced rate of infection by as much as 50% in sternal and groin incisions (manuscript in 
review [7]). This finding informed the development of this project. The Prevena dressing is applied 
immediately post-surgery (i.e., in a sterile field) to clean, closed incisions for a minimum of 2 days 
and up to a maximum of 7 days. Prevena is a disposable, single-patient use dressing designed to 
protect incisions from external contaminants, and remove fluid and infectious materials by 
delivering continuous negative pressure. The proposed randomized controlled trial will assess the 
impact of the Prevena dressing plus NPWT versus usual care on wound complication rates for 
lower extremity amputations. 
5. STUDY OBJECTIVES 
5.1. Primary Objective 
The primary outcome of this study is reported wound complications, specifically: 
• 
Dehiscence (skin or fascia) 
• 
Seroma 
• 
Lymph leak 
• 
Infection (superficial or deep; see CDC Surgical Site Infection criteria on pg. 9.8 to 9.10 [8]) 
• 
Hematoma 
• 
Ischemia 
• 
Necrosis 
Complications will further be classified as major wound complication if they require intravenous or oral 
antibiotics, reoperation and/or hospital readmission. 

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5.2. Secondary Objectives 
We will assess the impact of the Prevena dressing on the following secondary outcomes:  
1. Length of stay (LOS): index LOS is defined as days from operation to discharge; 30d LOS is 
defined as the index LOS plus all readmission days within 30d related to any wound 
complication 
 
2. 30-day Return to Operating Room (ROR): Reoperation for wound complication within 30 
days involving incision and drainage in the operating room; opening the skin to drain a 
superficial soft tissue infection at bedside or in the office is not considered reoperation 
 
3. 30-day hospital readmissions: Rehospitalization for wound complication within 30 days 
5.3. Exploratory Objectives 
Finally, the following exploratory outcomes will be assessed: 
1. 30-day hospitalization costs: Index hospitalization costs as well as all readmission days 
within 30d related to any wound complication 
 
2. 30-day hospital variable costs: Variable costs (not charges) for each admission obtained 
from hospital administration. 
6. STUDY DESIGN 
The PREVENA-AMP study is a prospective, multi-center, two-arm, unblinded, and randomized 
controlled trial of patients undergoing lower extremity amputation (above- or below-the-knee). 
Patients will be randomized to receive either the Prevena dressing or usual care for five or six days after 
the procedure on a lower extremity amputation incision. Patients will complete a follow-up assessment 
at approximately 30 days post-discharge. Demographic and clinical information will be collected 
through medical record review at enrollment, post-procedure, and at approximately 30 days post-
discharge by participating sites. 
6.1. Enrollment 
Patients presenting to Vascular and Endovascular Surgery for above-knee amputation (AKA) or 
below-knee amputation (BKA) will be screened for study eligibility. If a subject is willing to 
participate in the study, a written informed consent for the study must be obtained prior to any 
study related procedure and all eligibility criteria must be confirmed.  
6.2. Selection of Subjects 
6.2.1. Informed Consent 
The consent form is written in accordance with applicable data privacy acts and FDA 
Regulations and approved by the responsible Institutional Review Board (IRB).  
The informed consent process will take place prior to the planned procedure. The 
investigator or responsible staff will explain the nature, purpose and risks associated 
with the study. The patient will be given sufficient time to consider the study’s 

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implications before deciding whether to participate. Patient information materials 
created by the Investigators and Coordinating Center must be approved by the IRB 
before use. 
A signed, IRB/EC-approved consent form must be obtained from the patient prior to the 
performance of any protocol-related testing or procedures unless obtained as part of 
standard care. The consent process must be performed by a designated clinical study 
team member authorized by the IRB to consent patients and listed on the Delegation of 
Authority Log as having privileges to consent patients. A signed/dated copy of the 
consent form must be maintained in the study files and a copy provided to the patient.  
6.2.2. Number of Subjects 
Up to 440 subjects will be included in this study, 220 in each of the two arms. 
6.2.3. Subject Inclusion Criteria 
1. Male or female adults 18 years or older 
2. Patients undergoing above-knee amputation (includes the revision of emergency 
guillotine amputations) 
3. Patients undergoing below-knee amputation (includes the revision of emergency 
guillotine amputations) 
4. Informed Consent signed by patient  
6.2.4. Subject Exclusion Criteria 
1. Minors under 18 years 
2. Women who are pregnant or breastfeeding 
3. Patients undergoing emergent or guillotine amputation 
4. Patients having BOTH legs amputated 
5. Patients with sensitivity or allergy to silver or adhesive. 
6. Unwilling or unable to provide informed consent 
7. Inability to comply with planned study procedures  
7. STUDY DEVICE 
7.1. PREVENA™ PEEL & PLACE™ Dressing Kit 
This study will assess the impact of a market-released surgical dressing that has been FDA-cleared 
in the US (K100821) on wound complications. The PREVENA™ PEEL & PLACE™ Dressing Kit 
(“Prevena”; KCI USA, Inc., San Antonio, TX) protects the incision from external contamination, 
helps hold incision edges together, removes fluid and infection materials, and delivers continuous 
negative pressure at up to -125mmHg for a maximum of seven days in combination with a 
negative pressure pump. The dressing is easy to apply and use in the operating room by the 
surgeon. Detailed information is found in the Prevena Clinician's Guide. 

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PREVENA™ PEEL & PLACE™ Dressing Kit components include: 
1. The PREVENA™ PEEL & PLACE™ Dressing that is applied over clean, sutured or stapled incisions 
in a simple peel-and-place process, with multiple dressing options for linear incisions between 
5 to 17 inches long. 
• 
The dressing has a built-in pressure indicator that when compressed indicates that the 
negative pressure in the system is between -75mmHg to -125mmHg. A raised pressure 
indicator button indicates that the negative pressure is less than 75mmHg.  
• 
A polyurethane coated, polyester fabric interface layer with 0.019% ionic silver wicks fluid 
from the skin surface. The silver is not intended to treat infection but only to reduce 
bacterial colonization within the fabric.  
• 
The polyurethane foam bolster that covers the interface layer has a pore size of 400-600 
microns and a violet colorant; the foam magnifies negative pressure to the incision site. 
• 
A polyurethane film with acrylic adhesive provides adhesion of the dressing to the skin 
surrounding the incision.  
• 
A polyurethane shell encapsulates the foam bolster and interface layer, providing a closed 
system that allows patients to shower with dressing in place. 
• 
A connecting tube that is integrated with the dressing for connection to a negative 
pressure pump. 
2. PREVENA™ Therapy V.A.C. ® Connector, which is required for connection of PREVENA™ 
Incision Dressings to approved V.A.C. ® Therapy Units. 
3. PREVENA™ Patch Strips, which may be used to help seal leaks around the dressing. 
4. All patient-contact materials are free of latex and DEHP [Di(2-ethylhexl)phthalate]. 
7.2. Packaging 
The PREVENA-AMP study device is FDA 510(k) cleared and will be used with the standard 
packaging. 
7.3. Instruction for Use 
The device will be used as specified in the relevant Instructions for Use. 
7.4. Required Training on Study Device 
Negative pressure dressings are now commonplace throughout the hospital and operating room. 
As such, formal education regarding the proper application of the Prevena dressing is considered 
an ongoing process during the practitioner’s surgical education. 
8. NEGATIVE PRESSURE WOUND THERAPY 
8.1. Negative Pressure Wound Therapy using PREVENA™ PEEL & PLACE™ Dressing Kit 
In combination with a negative pressure pump (V.A.C. ® Therapy Unit, KCI USA, Inc.), the Prevena 
dressing is designed to provide negative pressure wound therapy (NPWT) over surgical incisions 
(incisional NPWT). Negative pressure wound therapy is the controlled application of 
subatmospheric pressure to a wound using an electrical pump to intermittently or continuously 
convey subatmospheric pressure through connecting tubing to a specialized wound dressing. 
Application of negative pressure to an incision site that is closed via staples or sutures helps draw 

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the incision edges together and removes fluid from the incision site. The occlusive drape of the 
dressing provides a negative pressure environment and protects the incision from external 
contamination. The Prevena dressing contains 0.019% ionic silver that may help reduce bacterial 
colonization within the fabric.  
For initiation of therapy, the Prevena dressing can be connected to a KCI V.A.C. ® Therapy Unit to 
deliver continuous negative pressure at -125 mmHg through the dressing to the incision site. The 
following Therapy Units are compatible with the Prevena dressing and can be used by study sites 
to provide negative pressure (Detailed information is found in the Clinician's Guide for each 
respective Therapy Unit): 
• 
INFOV.A.C. ™ 
• 
V.A.C.RX4™ 
• 
V.A.C. SIMPLICITY™ 
• 
ACTIV.A.C. ™ 
• 
V.A.C. FREEDOM™ 
• 
V.A.C.ULTA™  
Dressing application, negative pressure application, and dressing removal will only be conducted 
by a physician or designee. Patients using Prevena should contact the physician or nurse if the 
therapy unit turns off before therapy ends or if any of the following findings occur: 
• 
Bleeding develops suddenly or in large amounts during therapy 
• 
There are signs of allergic reaction or infection 
• 
The canister is full of fluid 
• 
System alerts need to be addressed 
9. STUDY INTERVENTION 
9.1. 
Treatment Groups 
Enrolled subjects will be randomized to one of two groups prior to their surgical procedure: 
• 
Group 1: PREVENA 
• 
Group 2: Usual Care 
Subjects randomized to the PREVENA group will have the Prevena dressing applied to their surgical 
incision while in the operating room and will receive NPWT using an V.A.C. ® Therapy Unit that is 
compatible with the dressing. Subjects randomized to the Usual Care group will have a sterile gauze 
dressing supplemented with an Ace wrap applied to their incision while in the operating room. For 
both treatment groups, the surgical team will examine the surgical dressing daily until post-
operative day (POD) 5 or 6. On POD 5 or 6, all surgical dressing will be removed and replaced with 
sterile gauze covered by an Ace bandage. After the initial surgical dressing is removed, the care 
team will examine the incision daily until the patient is discharged from the hospital. Dressing and 
wound examination notes documented in the subject medical record will be abstracted by study 
personnel for inclusion in the Case Report Form (CRF). 

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10.  Study Flow 
Identify potential subject 
(Above-, or below-the-knee amputation scheduled) 
Screening/Enrollment 
Obtain informed consent and 
document baseline data 
Excluded? 
Post-Operative Day 1 to 4 
Daily examination of the external appearance 
of the surgical dressing 
4 Week Follow-up 
Collect follow-up data and conduct wound 
examination 
No 
Yes 
Post-Operative Day 5 or 6 
Surgical dressing (PREVENA or Usual Care) 
removed  
Document screen 
failure  
Post-Operative Day 5 or 6 to Discharge 
Daily sterile gauze dressing changes and 
wound exams until discharge 
Randomization – Day of Surgery 
Group 1: PREVENA 
Group 2: Sterile Gauze dressing  

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11. STUDY SCHEDULE 
11.1. Detailed Visit Schedule 
The following visit schedule applies to subjects who met all eligibility criteria, and are enrolled in 
the PREVENA-AMP study.  
11.1.1. Screening/Enrollment 
Determination of eligibility and enrollment 
Collect demographics and baseline data from medical record 
 
11.1.2. Randomization 
Randomized to either PREVENA Group or Usual Care (Sterile Gauze Dressing) Group 
 
11.1.3. Day of Surgery 
Given either Prevena dressing or Usual Care (Sterile Gauze Dressing) 
 
11.1.4. Post-Operative Days 1 – 4 
Daily examination of the external appearance of the surgical dressing and assessments 
of the dressing documented in medical record 
 
11.1.5. Post-Operative Day 5 or Day 6 
Surgical dressings (PREVENA and Usual Care) removed, and replaced with sterile gauze 
dressing supplemented with an Ace wrap 
 
11.1.6. Post-Operative Day 5 or 6 to Discharge 
Wound examined and dressing changed daily until discharge; wound assessments 
documented in medical record 
Collect POD 1 to Discharge dressing/wound assessment data from medical record 
 
11.1.7. Post-Discharge Follow-up at Day 30 
On day 30 (±5 days), incision examined and wound assessment documented in medical 
record 
Collect follow-up wound assessment data from medical record 
Collect follow up data on readmissions, ROR, LOS, and wound complications from 
medical record 
Collect data on costs from hospital administration records 
 
 
 

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11.2. Overview of visits 
 
Screening/ 
Enrollment 
Prior to 
Surgery 
Surgery POD 1 to 3 
POD 5 
(±1 day) 
POD 5 or 6 
to 
Discharge 
Discharge to 
30 Days 
(±5 days) 
"1 month" 
Enrollment 
X 
 
 
 
 
 
 
Baseline data collection 
X 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
Dressing application (PREVENA 
or Usual Care) 
 
 
X 
 
 
 
 
Daily dressing examinations  
 
 
 
X 
 
 
 
PREVENA and Usual Care 
surgical dressings removed on 
post-operative day 5 or day 6 
 
 
 
 
X 
 
 
Daily wound examinations and 
dressing changes until 
discharge 
 
 
 
 
 
X 
 
Follow-up visit with surgical 
team to examine wound 
 
 
 
 
 
 
X 
11.3. Duration of the study 
An individual subject’s participation is expected to be 30 days. With an expected enrollment period 
of up to 15 months for 440 subjects, and a follow-up period of 1 month, the overall study duration 
is calculated to be approximately 22-30 months. 
12. VISIT PROCEDURES 
12.1. Screening/Enrollment 
Patients presenting for above-knee amputation (AKA) or below-knee amputation (BKA) will be 
screened for inclusion in the study. If they are not eligible for study participation, study personnel 
will document the reason for screen failure, and patients who do not meet the eligibility criteria 
will not be approached about the PREVENA-AMP study. Patients who meet eligibility criteria will 
be approached and asked about study participation. If a patient is unsure about participating in 
the study, they will be informed that they have the right to refuse participation and that the study 
is voluntary. They will be told that they will still receive standard of care regardless of their 
decision to participate. If a patient is not interested in the study, study personnel will 
accommodate the patient’s preference and no additional recruitment attempts will be made. 
If the patient continues to be eligible for participation in the study and expresses interest in 
participating, the study team will: 
1. Document eligibility criteria data 
2. Obtain informed consent and enroll the patient in the PREVENA-AMP study 
3. Document informed consent process 

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12.2. Baseline Data Collection 
Upon enrollment, the following data will be collected for each subject:  
• 
age, gender, race, ethnicity 
• 
indication for amputation (tissue loss, rest pain) 
• 
classification of tissue loss (ulceration, gangrene, presence of infection) 
• 
prior vascular procedures (specifically prior prosthetic bypass which will be transected) 
• 
medical co-morbidities (diabetes mellitus/HbA1C, dialysis dependence, active smoker, chronic 
venous insufficiency, end-stage renal disease, congestive heart failure) 
• 
BMI, blood pressure, pulse examination, and ankle-brachial index (if available) 
12.3. Randomization 
Prior to the surgical procedure, subjects will be randomized on a 1:1 basis to either the PREVENA 
arm or the Usual Care arm.  
Randomization will be stratified by site and conducted in permuted blocks. The stratification 
insulates the randomization of one site from another which allows for subgroup analyses by site, 
while permuted blocks ensures balanced allocation between treatment arms. 
Each site will receive a randomization scheme that contains a series of randomized group 
assignments and randomization IDs. As subjects are enrolled in the study, their subject ID will be 
assigned to a corresponding randomization ID. This information will be recorded in the CRF.  
12.4.  Day of Surgery 
All subjects will undergo their amputation procedure as scheduled. While in the operating room, 
after flap closure, subjects will receive the dressing that corresponds to their group assignment: 
- 
Group 1 (PREVENA Arm): Subjects randomized to the PREVENA arm will receive the Prevena 
negative pressure dressing on their incision 
- 
Group 2 (Usual Care): Subjects randomized to usual care will receive sterile gauze and Ace 
wrap compression dressing on their incision 
The use of an external splint will be determined by the attending surgeon.  
12.5. Dressing Monitoring (Post-Operative Days 1 to 4) 
The external appearance of the surgical dressing for both PREVENA and Usual Care groups will be 
examined by the surgical team on daily inpatient rounds.  
12.6. Wound Monitoring (Post-Operative Day 5 or Day 6 to Discharge) 
On post-operative day 5 or day 6, the surgical dressings (both PREVENA and usual care) will be 
removed and replaced with a new sterile gauze dressing supplemented by an Ace wrap. The sterile 
gauze dressing will be changed daily, and the incision will be assessed for wound complications 
during the dressing change every day until discharge from the acute care setting. 

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12.7. Discharge 
Following discharge, the patient and/or caregivers will provide standard wound care that involves 
keeping the incision clean, dry and covered with a gauze dressing supplemented by an Ace wrap. 
12.8. Follow-Up Visit (Discharge to Day 30 ± 5 days) 
The final study visit will take place approximately 30 days after discharge. During this follow-up 
visit, the wound will be assessed for wound complications. For incisions closed with staples, these 
would be removed between post-operative days 30-42 at the discretion of the surgeon. 
13. SAFETY 
The investigator is responsible for monitoring the safety of subjects enrolled into the study at the 
study site. The investigator or qualified designee will enter the required initial and follow-up 
information regarding events on the appropriate CRF. Investigators are responsible for following 
all serious adverse events (SAEs) until resolution, stabilization, or the event is otherwise explained, 
and to report serious adverse events as well as serious injury or death that were related to (caused 
by or contributed to) the Prevena dressing in accordance with their local IRB/EC requirements. 
Investigators should follow usual clinical practice at their institutions for reporting serious events 
to the regulatory authorities. 
13.1. Labeled Adverse Device Effects 
Expected adverse device events are determined to be mild and are related to the interface 
(polyurethane drape) between the device (Prevena dressing) and the subject. In this study, any 
skin irritation that is transient (i.e., resolves within 24 hours following device use and requires no 
medical intervention), will not be classified as an adverse device effect. 
Dressing  
• 
Mild skin irritation of the skin under the enclosed dressing 
• 
Discomfort with having to wear an occlusive dressing that may be twice the size of 
normal dressing  
V.A.C. ® Therapy Unit 
• 
Inadequate seal of the Prevena dressing over the patient’s skin due to improper 
placement or the patient shifting position could prevent adequate negative pressure 
delivery upon the wound 
• 
The inconvenience of having to keep the negative pressure pump attached to the 
incision site 
14. STATISTICAL ANALYSIS 
14.1. Study Hypothesis 
The primary hypothesis for this study asserts that the application of a negative pressure wound 
therapy dressing (Prevena) and negative pressure pump over a closed lower extremity amputation 

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incision will decrease the wound complication rate at 30 days in patients undergoing lower 
extremity amputation, as compared to patients receiving standard care. The secondary hypothesis 
suggests that patients who receive Prevena will have reduced LOS, ROR, and readmission rates 
compared with patients who receive usual care. 
14.2. Analysis Plan 
We will carry out initial descriptive analysis to identify outliers, such as measurement and 
recording errors, logical inconsistencies in data, and values extreme in the marginal distributions of 
all study variables. Data summaries will be produced both for the combined sample, and 
separately by treatment arm. Continuous variables will be presented as means and standard 
deviations or, if substantially skewed, presented as medians and first and third quartiles and then 
transformed using a Box-Cox power transformation for parametric analysis. Categorical variables 
will be presented as frequencies and percentages. The baseline characteristics will be compared 
between the treatment arms to identify potential confounding variables. Men and women will be 
examined separately first to assess whether the treatment effect might depend on sex. Similarly, 
the associations and interaction effects of other variables (e.g., age and race) will be explored. 
Participant flow will be described using a CONSORT style diagram. 
14.3. Primary Endpoint Analysis 
The primary endpoint will be the difference in mean wound complication rates after 1 month. A 
Yates Chi-Square test (2x2 contingency table) will be used to determine if the differences between 
the wound complication rates of the two randomized treatment groups (PREVENA versus Usual 
Care) are statistically significant at the 0.05 level. 
14.4. Secondary and Exploratory Endpoint Analysis 
Descriptive analyses of the secondary and exploratory endpoints will be conducted using the 
previously described methods for continuous and categorical endpoints in order to characterize 
both the combined sample, and to compare by treatment group. Student’s t-test will be used to 
evaluate if the difference in the secondary endpoints (index and 30-day LOS; total number of 
hospitalizations at 30 days) and exploratory endpoints (hospitalization costs; hospital variable 
costs) between the two groups is statistically significant at the 0.05 level. In addition, Yates Chi-
Square test will be used to compare the proportion of patients in each group with reported ROR, 
or readmission within 30 days (P<.05 considered significant). Finally, respective multivariable 
logistic regression models will characterize the odds of 30 day ROR and odds of 30 day 
readmission, using study variables found to be related to return and readmission in descriptive 
analysis. 
14.5. Justification of the Sample Size 
Based on a review of the literature, perioperative wound complications occur among 10% to 34% 
of lower extremity amputees. We postulate a wound complication rate of 22% for this study. 

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Previous studies have shown that, among femoral incision patients, Prevena reduced the relative 
risk of major wound complications by 60.8% (from 21.7% among controls to 8.5% using Prevena). 
Assuming a similar, but somewhat attenuated, risk reduction of 50% among amputees, we would 
expect the major wound complications among patients treated with Prevena to be 11.0% in this 
study. Assuming major wound complication rates are 22% and 11% in the control and Prevena 
populations, and using an O’Brien-Fleming early stopping boundary[9] for an interim look at the 
data, suggests that in order to maintain an overall 5% type I error rate, the study would need data 
on up to n = 210 patients per group to have 80% power for detecting this (or a greater) difference 
in complication rates by two-sided Z-tests. The operating characteristics of this group sequential 
testing approach are provided in the table below. We expect 5% attrition from mortality and/or 
loss to follow-up, so our overall recruitment goal will be n = 220 per group (N = 440 overall). 
Interim analysis operating characteristics using O’Brien-Fleming stopping bounds. 
 
 
 
  
 
14.6. Interim Analysis 
Interim analysis for early stopping of the trial for efficacy will be conducted once prior to enrolling 
the planned complete sample size. This analysis will be conducted at 75% of the expected number 
of patients having the primary endpoint (i.e., 52 patients with major wound complications).  
15. DATA HANDLING AND RECORDKEEPING 
15.1. Data Collection 
The investigator, sub-investigator(s), or study coordinator participating in the study will document 
all data required by the protocol. 
Each participating site will provide data on LOS, variable costs, and hospitalization costs for each 
subject to facilitate analysis of the secondary endpoints. 
In addition, any contact with the subject via telephone or other means that provide significant 
clinical information must be documented. 
Any changes to information in the source documents must be initialed and dated on the date the 
change is made by a clinician authorized to make the change. 
Look 
Expected 
Complications 
Expected 
Sample Size 
Z-test 
Lower 
Bound 
Z-test 
Upper 
Bound 
Alpha 
Power 
Interim 
52 (75%) 
315 (75%) 
-2.34 
2.34 
0.019 
0.55 
Final 
70 (100%) 
420 (100%) 
-2.01 
2.01 
0.044 
0.80 

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15.2. Study Documentation 
Throughout the conduct of the study, all required data will be entered into the CRF for each 
subject. The investigator should ensure the accuracy, completeness, and timeliness of the data 
reported to the in the CRFs and in all required reports. Data entered into the CRF must be 
consistent with source documents. Any change or correction to CRF will be captured. The clinical 
site will provide study data by recording data in CRF. In cases of subject-reported data, the CRF will 
be the source record. 
15.3. Query Generation and Resolution 
Queries will be generated based upon anomalous or missing data and will be tracked. Once all 
queries are resolved, the database will be verified by ensuring all study files were loaded 
completely and correctly.  
15.4. Data Storage 
Access to data maintained in the EDC System is strictly limited to authorized personnel. 
15.5. Inspection of Records 
Periodically the Coordinating Center may review the Investigator study file and the study data to 
verify compliance with applicable regulations and the protocol, and to verify accuracy of the data.  
15.6. Study Files and Record Retention 
The investigator must maintain adequate and accurate records as specified in Essential Documents 
for the Conduct of a Clinical Trial (E6, Section 8 of the ICH Guideline for GCP) to enable the conduct 
of the study to be fully documented and the study data to subsequently be verified. 
Essential documents must be retained until at least 2 years after notification that the 
investigations have been discontinued OR 2 years after the last approval of a marketing 
application. The investigator must notify the Coordinating Center prior to destroying any clinical 
study records. 
15.7. Regulatory Documentation 
Documents that must be provided to the Coordinating Center prior to study initiation are: 
• 
Signed, dated current (within 2 years) curriculum vitae of Investigator and Sub-Investigator(s) 
• 
Current professional license for Investigators and study personnel  
• 
Financial disclosure for Investigators and study personnel 
• 
Proof of current human subjects training for Investigators and study personnel 
• 
Signed (original), dated Protocol 
• 
Signed (original), dated IRB Authorization Agreement (including the institution’s Federal-Wide 
Assurance (FWA) number if available) naming Jefferson as the IRB of record  
OR 

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• 
Assurance that the IRB/EC complies with requirements set forth in Title 21 Part 56 of the Code 
of Federal Regulations (required documentation consists of name and address of the IRB/EC, a 
current list of members including title, gender, occupation and any institutional affiliation of 
each member or the FWA number from the Department of Health and Human Services may be 
substituted for this list) 
• 
Written notification (copy) to the Investigator from the IRB/EC approving the protocol 
• 
IRB/EC approved informed consent (copy) and any other adjunctive materials to be used in the 
study as required 
16. ETHICAL CONSIDERATIONS 
16.1. Institutional Review Board (IRB) 
The investigator must have written and dated approval from the IRB for the protocol, consent 
form, subject recruitment materials/process (if used), and any other written information to be 
provided to subjects. The investigator should also provide the IRB with a copy of the product 
labeling information and any updates. The investigator will provide the IRB with reports, updates, 
and other information (e.g., safety updates and protocol amendments) as required by regulations. 
16.2. Protocol Deviations 
An investigator is required to conduct this study in accordance with the signed Investigator's 
Agreement, this Investigational Plan, applicable laws and FDA regulations, and any conditions of 
approval imposed by the reviewing IRB and FDA. According to FDA regulation 21 CFR § 
812.150(a)(4), an investigator shall notify the sponsor (Thomas Jefferson University) 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 no later 
than five working days after the emergency occurred. Except in such an emergency, prior approval 
by the Coordinating Center is required for a change in or deviations from a plan and, if these 
changes or deviations could affect the scientific soundness of the plan or the rights, safety or 
welfare of human subjects, FDA and IRB/EC approval may also be required in accordance with 21 
CFR § 812.35(a). 
A list of subjects with protocol deviations will be compiled based on entry criteria deviations as 
well as deviations from study conduct and assessments. Prior to data base lock, an evaluation of 
subjects with significant protocol deviations will be performed to assess the appropriateness of 
their inclusion in the analysis. 
16.3. Risk Analysis and Confidentiality 
16.3.1. Risk Determination of the Study 
The Prevena dressing has been cleared by FDA to provide negative pressure wound therapy to 
surgical incisions. The dressing is intended for hospital use, with placement occurring within the 

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operating room. The purpose of this study is to evaluate the effect of the Prevena dressing on 
wound complication rates for adult patients undergoing lower extremity amputation.  
This study is considered to be of minimal risk to the patients receiving Prevena. NPWT is widely 
accepted and effective for treating deep wounds, and the risks associated with its use in this study 
are reasonable in terms of knowledge gained and potential benefits to patients. By its nature, use 
of NPWT on surgical incisions may be associated with minor side effects. Prevena may cause minor 
discomfort, especially in a patient who has not previously used NPWT. In this study, these side 
effects will not be classified as adverse events unless they do not resolve within a reasonable 
period of time when NPWT is discontinued. 
Subjects should be encouraged to discuss any issues they are having with NPWT during the study. 
The investigator should assess for changes in the health or well-being of the subject in response to 
general, non-directed questioning. Side effects should be documented on the site’s source 
documents. Any transient side effects, at a minimum, should be documented in the clinic record.  
16.3.2. Subject Data Confidentiality 
All information and data collected for the PREVENA-AMP study concerning subjects or their 
participation in this investigation will be considered confidential. Only authorized site personnel or 
Coordinating Center personnel will have access to these confidential files. All data will be handled 
in accordance with applicable local laws. Authorized FDA personnel or Regulatory Authorities have 
the right to inspect and copy all records pertinent to this investigation. All data used in the analysis 
and reporting of this investigation will be without identifiable reference to specific subject name. 
17. QUALITY CONTROL AND QUALITY ASSURANCE 
Quality Control is defined as the operational techniques and activities, such as monitoring, 
undertaken within the quality assurance system to verify that the requirements for quality of the 
study related activities have been fulfilled. Quality Control should be applied to each stage of data 
handling to ensure that all data are reliable and have been processed correctly. 
17.1. Site Selection 
The sites must have adequate experience, time, staff, and facilities to perform all required duties. 
Sites must agree to permit clinical trial related monitoring, audits, IRB review, and regulatory 
inspections, providing access to source data/documents, as appropriate. 
17.2. Site Training 
The Coordinating Center will conduct a site initiation conference call with each site to review 
relevant documentation such as the clinical protocol, Prevena device usage instructions, and 
investigator’s obligations with site study personnel. In addition, training on the Case Report Form 
(data collection) will be conducted. If new study staff members are employed by the site after the 
initiation meeting, experienced site personnel must train new employees as noted above and 
document the training using the Training log provided by the Coordinating Center. 

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17.3. Audits and Inspections 
The Sponsor (or designee), FDA, NIH and any other regulatory agencies may request access to all 
study records, including source documents, for inspection and copying, in keeping with Federal 
regulations. The investigator must immediately notify the Coordinating Center of an upcoming FDA 
or other regulatory agency inspection. Audits may also be conducted by representatives of the 
Coordinating Center. 
18. RESPONSIBILITIES 
18.1. Clinical Investigator Responsibilities 
With the approval of their institution‘s IRB/EC, qualified investigators will conduct the PREVENA-
AMP study in accordance with the Declaration of Helsinki: “Recommendations Guiding Medical 
Doctors in Biomedical Research Involving Human Subjects”. Each site principal investigator and 
their sub-investigators are responsible for the following: 
• 
Completion of all required agreements  
• 
Screening and evaluation of subjects 
• 
Strict adherence to the Clinical Protocol, Manual of Procedures and all Federal Regulations 
• 
Supervising device use 
• 
Obtaining informed consent prior to study related procedures and the collection of data 
during study and follow-up examinations in a timely manner 
• 
Timely reporting of all SAEs and UADEs 
• 
Providing death notes, when applicable 
It is acceptable for the site principal investigator to delegate one or more of the above functions to 
an associate or sub-investigator, however, the site principal investigator remains responsible for 
proper conduct of the clinical investigation and signing an investigator agreement. The 
investigation is non-transferable to other centers attended by the investigator unless prior 
approval is obtained from the appropriate IRB/EC and the Coordinating Center. 
18.2. Sponsor Responsibilities 
The Sponsor (Thomas Jefferson University) will provide each site with study materials. The 
Coordinating Center (Jefferson Clinical Research Institute) will train study personnel on the clinical 
study protocol and procedures. Randomization procedures for all enrolling sites will be managed 
centrally through the Coordinating Center and the permuted block sizes will be kept confidential 
from study personnel conducting enrollment. Coordinating Center representatives will ensure that 
the study is progressing as expected, study data are accurate and up to date, data recording is 
complete, and protocol deviations are recorded and reviewed with the PI. Throughout the study 
period, the Coordinating Center representative will be available to address any issues that may 
arise. This availability includes access by phone and/or e-mail.  

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19. STUDY ORGANIZATION AND COMMUNICATION 
19.1. Steering Committee, Study Team and Communications 
The Steering Committee (SC) includes the lead investigators from each site. Any required 
modifications to the protocol will be reviewed and approved by the SC prior to implementation.  
 
The Study Team, PI, Sub-I, or designee(s) will meet monthly via telephone/video conference call, or 
in-person. 

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20. REFERENCES  
1. 
Hasanadka, R., et al., Predictors of wound complications following major amputation for critical limb 
ischemia. J Vasc Surg, 2011. 54(5): p. 1374-82. 
2. 
Belmont, P.J., Jr., et al., Risk factors for 30-day postoperative complications and mortality after 
below-knee amputation: a study of 2,911 patients from the national surgical quality improvement 
program. J Am Coll Surg, 2011. 213(3): p. 370-8. 
3. 
Stannard, J.P., et al., Incisional negative pressure wound therapy after high-risk lower extremity 
fractures. J Orthop Trauma, 2012. 26(1): p. 37-42. 
4. 
Pachowsky, M., et al., Negative pressure wound therapy to prevent seromas and treat surgical 
incisions after total hip arthroplasty. International Orthopaedics, 2012. 36(4): p. 719-722. 
5. 
Grauhan, O., et al., Prevention of poststernotomy wound infections in obese patients by negative 
pressure wound therapy. The Journal of Thoracic and Cardiovascular Surgery, 2013. 145(5): p. 1387-
1392. 
6. 
Hyldig, N., et al., Meta‐analysis of negative‐pressure wound therapy for closed surgical incisions. 
BJS, 2016. 103(5): p. 477-486. 
7. 
Kwon, J., et al., A Randomized Clinical Trial Evaluating Negative-Pressure Therapy to Decrease 
Vascular Groin Incision Complications. 2018, Journal of Vascular Surgery. 
8. 
National Healthcare Safety Network. Surgical Site Infection (SSI) Event. 2018 [cited 2018 June 25]; 
Available from: http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf. 
9. 
O'Brien, P.C. and T.R. Fleming, A multiple testing procedure for clinical trials. Biometrics, 1979. 
35(3): p. 549-56. 
 
 
 
 

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21. SIGNATURES  
 
The trial will be conducted in accordance with the ICH E6 Good Clinical Practice, and applicable Federal and 
state Regulations or guidelines and the executed institutional agreements. Furthermore, the Investigator 
attests to the following: 
• 
I confirm that I have read the above-mentioned protocol and its attachments.  
• 
I agree to conduct the described trial in compliance with all requirements from the protocol.  
• 
I agree that changes to the protocol will not take place without prior agreement from the Sponsor 
and documented approval from the designated Institutional Review Board (IRB), except where 
necessary to eliminate an immediate hazard(s) to the trial participants.  
• 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
Investigator’s Signature: _______________________________________ Date: ______________________ 
Investigator’s Name: ______________________________________________________________________ 
Investigator’s Institution: __________________________________________________________________