Post-market, Randomized, Open-Label, Multicenter, Study to Evaluate the Effectiveness of Closed Incision Negative Pressure Therapy Versus Standard of Care Dressings in Reducing Surgical Site Complications in Subjects With Revision of a Failed Total Knee Arthroplasty (PROMISES)
Phase: NA
Conditions: Surgical Wound, Revision Total Knee Arthroplasty, Wounds and Injuries, Joint Disease, Musculoskeletal Disease, Prosthesis-Related Infections, Infection, Postoperative Complications, Pathologic Processes
Sponsor: KCI USA, Inc

Protocol 
 
Post-market, Randomized, Open-Label, Multicenter, Study to Evaluate 
the Effectiveness of Closed Incision Negative Pressure Therapy 
versus Standard of Care Dressings in Reducing Surgical Site 
Complications in Subjects with Revision of a Failed Total Knee 
Arthroplasty (PROMISES) 
 
 
NCT Number 
NCT03274466 
 
 
Document Date 
06-OCT-2018 

KCI.PREVENA.2017.01
Post-market, Randomized, Open-Label, Multicenter, Study to Evaluate 
the Effectiveness of Closed Incision Negative Pressure Therapy versus 
Standard of Care Dressings in Reducing Surgical Site Complications 
in Subjects with Revision of a Failed Total Knee Arthroplasty 
(PROMISES) 
PROTOCOL NUMBER 
KCI.PREVENA.2017.01 
SPONSOR 
KCI USA, Inc. 
6203 Farinon Drive 
San Antonio, Texas 78249 
Fax: 210.255.6760 
 STUDY PRODUCTS 
ActiV.A.C.® Therapy Unit 
              or 
Prevena Plus™ 125 Therapy Unit 
           in combination with 
Prevena™ Incision Dressing        
ORIGINAL PROTOCOL 
VERSION/DATE 
Version 3.0, 6-Oct-18 
Confidentiality Statement:  This document is a confidential communication of KCI, an Acelity Company. 
Acceptance of this document constitutes the agreement by the recipient that no unpublished information 
contained herein will be published or disclosed without the prior written approval of KCI. This document 
may be disclosed to appropriate Institutional Review Boards (IRBs) so long as they are requested to 
maintain its confidentiality. 
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TITLE: 
Post-market, Randomized, Open-Label, Multicenter, Study to Evaluate 
the Effectiveness of Closed Incision Negative Pressure Therapy versus 
Standard of Care Dressings in Reducing Surgical Site Complications in 
Subjects with Revision of a Failed Total Knee Arthroplasty (PROMISES) 
PROTOCOL 
NUMBER: 
KCI.PREVENA.2017.01 
TYPE AND 
PHASE: 
Post-market, prospective, randomized, open-label 
STUDY 
PRODUCT(S): 
ActiV.A.C.® Therapy Unit  
              or 
Prevena Plus™ 125 Therapy Unit 
           and 
Prevena™ Dressing         
STUDY 
OBJECTIVE(S)
: 
The goal of this study is to evaluate surgical site complications (SSCs) 
in subjects undergoing a revision of a failed total knee arthroplasty 
(TKA) when closed incision negative pressure therapy (ciNPT) is used 
to manage the closed incision, as compared to standard of care 
dressing. 
STUDY 
DESIGN: 
This is a post-market, prospective, randomized, open-label, multicenter, 
controlled study.  
Subjects randomized to the ciNPT treatment arm will have a Prevena™ 
Dressing placed over the sutured incision immediately after surgery. 
Negative pressure therapy will be delivered by the ActiV.A.C.® or 
Prevena Plus™ 125 Therapy Units up to the maximum optimal use 
condition specified in the Instructions for Use (IFU) document of the 
selected PrevenaTM Dressing but no shorter than five days post-surgery. 
Subjects randomized to the standard of care treatment arm will receive 
Aquacel® Ag Surgical incision dressing, or another equivalent silver-
impregnated dressing, up to the maximum number of days specified in 
the IFU but no shorter than five days post-surgery, not inclusive of other 
negative pressure wound therapy devices or dressings for the duration 
of the study. Subjects will be regularly evaluated for SSCs through 90 
days after the TKA revision.  
PRIMARY 
ENDPOINT: 
The primary endpoint is the subject incidence of Investigator-assessed 
surgical site complications within 90 days of TKA revision. 
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SECONDARY 
ENDPOINTS: 
The two secondary endpoints for this study are the 90-day subject 
incidence of Investigator-assessed surgical site infection (superficial or 
deep) and the 90-day subject incidence of Investigator-assessed deep 
surgical site infection. 
SAFETY 
ENDPOINT: 
The safety endpoint is the subject incidence of adverse events. 
NUMBER OF 
SUBJECTS  
PLANNED and 
DURATION OF 
PARTICIPATIO
N: 
The study will randomize approximately 440 subjects from 
approximately 15 sites in a 1:1 ratio to receive either ciNPT or standard 
of care after a revision TKA.  
The duration of study participation for each subject is as follows: 
o
Screening: 30 days prior to and including day of TKA
revision (Day 0)
o
TKA revision
o
Treatment Period: According to the IFU document included
with the selected dressing but no shorter than five days
post-surgery.
o
Post Operation and Follow-up: through 90 days after TKA
revision
The maximum participation duration per subject is 134 days. 
NUMBER OF 
STUDY SITES: 
It is anticipated that approximately 15 study sites in North America will 
participate and each site will randomize and treat subjects in both 
treatment groups. 
INCLUSION 
CRITERIA: 
The subject must meet all the following inclusion criteria:  
o
is at least 22 years of age on the date of informed consent
o
is able to provide their own informed consent
o
requires a TKA revision defined as one of the following:

a one-stage aseptic revision procedure
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 a one-stage septic exchange procedure (requiring 
removal of all hardware) for acute postoperative 
infection 
 removal of cement spacer and re-implantation 
procedure  
 open reduction and internal fixation of peri-
prosthetic fractures 
o has one or more of the following:  
 a body mass index (BMI) greater than 35 kg/m2 
 a requirement for the use of blood thinners other 
than acetylsalicylic acid (ASA) after surgery 
 history of or current peripheral vascular disease 
 the presence of lymphedema in the operative limb 
 insulin-dependent diabetes mellitus 
 current tobacco use or previous history of smoking 
and quitting within the past 30 days 
 a history of prior infection of the operative site 
 current use of immunomodulators or steroids 
 current or history of cancer or hematological 
malignancy (excluding localized skin cancer) 
 rheumatoid arthritis 
 current renal failure or dialysis 
 malnutrition as determined by the investigator 
 liver disease as determined by the investigator 
 status post solid organ transplant 
 HIV 
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o
is willing and able to return for all scheduled study visits
o
if female and of child-bearing potential, has a negative
urine or serum pregnancy test at screening and day of
revision surgery
o
has undergone a TKA revision resulting in a closed
surgical incision
EXCLUSION 
CRITERIA: 
The subject must not meet any of the following criteria: 
o
is pregnant or lactating
o
will undergo a bilateral TKA within the same operative visit
o
will undergo a bilateral TKA in which the first TKA surgery
is on the knee selected for study
o
will undergo a staged bilateral TKA in which the TKA
revision surgery for the knee under study occurs within 30
days of the first TKA procedure
o
was previously randomized in this protocol
o
has a systemic active infection at the time of revision not
including chronic viral infections such as HIV or hepatitis
o
has a remote-site skin infection at the time of revision
o
was tattooed on the area of the incision within 30 days
prior to randomization
o
has known sensitivity to the study product components
(drape and/or dressing materials in direct contact with the
closed incision or skin)
o
has known sensitivity to silver
o
is currently enrolled in another investigational trial that
requires additional interventions
o
is planned to be enrolled in another investigational trial that
requires additional interventions at any time during the
study
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o has localized skin cancer around the incision site  
o has a surgical incision that precludes placement of 
dressing  
o has a TKA revision resulting in a muscle flap  
o has a TKA revision resulting in the placement of a spacer 
o has an incision drainage and debridement procedure only 
o has a surgical incision closed with skin glue 
STUDY 
EVALUATION/
VISIT 
SCHEDULE: 
Subjects will be seen during Screening (no more than 30 days before 
TKA revision), at the TKA revision, at the weekly study treatment visits 
(a minimum of 5 days to a maximum number of days indicated in the 
Instruction for Use document for the selected dressing), the Midterm 
Follow-up visit (day 30 to 45), the Long Term Follow-up visit (day 90 to 
104), or as initiated by either the Investigator or the subject 
(Unscheduled). All subjects will be followed for 90 days for outcomes 
regardless of the treatment received. 
SAMPLE SIZE 
AND 
STATISTICAL 
METHODOLO
GY: 
The incidence rates of SSC are different for septic and aseptic revisions; 
the assumed SSC rate is 33% for septic and 6.9% for aseptic. This 
study plans to enroll at least 50% septic revisions overall. These 
enrollment rates lead to an assumed pooled SSC rate of 20% in the 
standard of care dressing arm.  
Assuming an overall type 1 error rate of 0.05, with a two-sided 
hypothesis test, the study will have at least 80% power to detect a 
difference of 10% (50% reduction) in SSCs in the ciNPT arm with 199 
subjects in each treatment arm, with one interim analysis at about 50% 
of the evaluable subjects for a total of 398 subjects using the likelihood 
ratio test. With an estimated 5%-10% loss, a non-binding interim 
analysis for superiority at approximately 50% of the evaluable subjects 
using O’Brien-Fleming method for monitoring boundaries, the planned 
sample size will be inflated for potential loss of follow-up for a total of 
440 subjects. 
 
 
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CKO
'
Antelly Cornparsy
SIGNATURE PAGE
Approved by:
Date:
Chief Medical Officer
KCI USA , an Acelity Company
Approved by :
Date
Senior Director, Global Clinical Development
KCI USA, an Acelity Company
Approved by:
Date:
Interim Head, Global Clinical Safety
KCI USA, an Acelity Company
Approved by:
Date:
Vice President, Global Regulatory Affairs
KCI USA, an Acelity Company
Approved by:
Statistician, Global Biostatistics and Data Management
KCI USA, an Acelity Company
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PRINCIPAL INVESTIGATOR ACKNOWLEDGEMENT OF PROTOCOL 
I confirm that I have read the protocol entitled: “Post-market, Randomized, Open-Label, 
Multicenter, Study to Evaluate the Effectiveness of Closed Incision Negative Pressure 
Therapy versus Standard of Care Dressings in Reducing Surgical Site Complications in 
Subjects with Revision of a Failed Total Knee Arthroplasty (PROMISES)” Version 3.0, 
dated 6-Oct-18. I understand the protocol and agree to conduct the study according to 
the procedures therein in accordance with applicable local government regulations, 
institutional research policies and procedures, the Federal Drug Administration Code of 
Federal Regulations, the International Conference on Harmonisation principles of Good 
Clinical Practice, and in the spirit of the Declaration of Helsinki concerning medical 
research in humans.  
  
PRINCIPAL INVESTIGATOR NAME: 
 
 _____________________________________________     
 
SITE NAMES AND IDENTIFICATION NUMBERS: 
 
_____________________________________________ 
 
PRINCIPAL INVESTIGATOR SIGNATURE: 
 
_____________________________________________ 
 
 
DATE:_____________________ 
 
 
 
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ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
adverse event 
AJRR 
American Joint Replacement Registry  
ANCOVA 
Analysis of Covariance 
ASC/AST 
Active Surveillance Culture/Testing  
BMI 
body mass index 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
ciNPT 
closed incision negative pressure therapy 
CMH 
Cochran-Mantel-Haenszel 
CSR 
Clinical Study Report 
DB 
database 
DEHP-free PVC (Di(2-ethylhexyl)phthalate-free polyvinyl chloride 
eCRF 
Electronic Case Report Form 
fSAP 
final Statistical Analysis Plan 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
IFU 
Instructions for Use 
iSAP 
interim Statistical Analysis Plan 
ISS 
Injury Severity Score 
ITT 
intention-to-treat 
IV 
 
intravenous 
KCI 
Kinetic Concepts, Inc. 
KOOS 
Knee injury and Osteoarthritis Outcome Score 
mITT 
modified Intention-to-Treat 
mmHG 
millimeters of mercury 
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mPP 
modified Per-Protocol  
NHSN 
National Healthcare Safety Network 
NPWT 
negative pressure wound therapy  
NSAID 
non-steroidal anti-inflammatory drug 
OR 
operating room 
PHI 
personal health information 
PRO 
patient-reported outcomes 
PROMIS 
Patient-Reported Outcomes Measurement Information System
QoL 
Quality of Life 
RCT 
randomized clinical trial 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
standard of care 
SSC 
surgical site complication 
SSI 
surgical site infection 
TEAE 
treatment-emergent adverse event 
THA 
total hip arthroplasty  
TKA 
total knee arthroplasty  
UADE 
Unanticipated Adverse Device Effect 
 
 
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TABLE OF CONTENTS 
1. 
INTRODUCTION .................................................................................................... 15 
1.1. 
Background Negative Pressure Wound Therapy ............................................ 15 
1.2. 
Total Knee Arthroplasty and Revision ............................................................. 16 
1.3. 
Review of Medical Literature – ciNPT  in TKA ................................................ 17 
1.4. 
Conclusion ...................................................................................................... 17 
1.5. 
Study Products ................................................................................................ 17 
1.5.1. 
Regulatory status ..................................................................................... 18 
1.5.2. 
Negative Pressure Wound Therapy Units ................................................ 18 
1.5.2.1. ActiV.A.C. ® .......................................................................................... 18 
1.5.2.2. Prevena Plus™ 125 ............................................................................. 19 
1.5.3. 
Prevena™ Peel & Place™ Dressing ........................................................ 20 
1.5.4. 
Prevena Plus™ Customizable™ Dressing ............................................... 22 
2. 
STUDY OBJECTIVES ........................................................................................... 24 
3. 
STUDY DESIGN .................................................................................................... 25 
3.1. 
Study Schematic ............................................................................................. 25 
3.2. 
Design Summary ............................................................................................ 26 
3.3. 
Duration of Study Participation ........................................................................ 26 
3.4. 
Primary Endpoint ............................................................................................ 26 
3.5. 
Secondary Endpoints ...................................................................................... 27 
3.6. 
Exploratory Endpoints ..................................................................................... 27 
3.7. 
Safety Endpoint ............................................................................................... 28 
4. 
STUDY PROCEDURES AND ASSESSMENTS .................................................... 29 
4.1. 
Informed Consent ........................................................................................... 29 
4.2. 
Inclusion/Exclusion ......................................................................................... 29 
4.2.1. 
Pre-Operative Inclusion Criteria ............................................................... 30 
4.2.2. 
Pre-Operative Exclusion Criteria .............................................................. 31 
4.2.3. 
Intra-Operative Inclusion Criteria ............................................................. 32 
4.2.4. 
Intra-Operative Exclusion Criteria ............................................................ 32 
4.3. 
Premature Study Termination ......................................................................... 32 
4.3.1. 
By Sponsor .............................................................................................. 32 
4.3.2. 
By IRB ...................................................................................................... 33 
4.4. 
Subject Withdrawal or Termination ................................................................. 33 
4.4.1. 
Reasons for Withdrawal or Termination ................................................... 33 
4.4.2. 
Handling of Withdrawal or Termination .................................................... 33 
4.5. 
Demographics and Subject Characteristics .................................................... 34 
4.6. 
Vital Signs ....................................................................................................... 35 
4.7. 
Medical/Surgical History ................................................................................. 35 
4.8. 
Laboratory Assessment for Pregnancy ........................................................... 35 
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4.9. 
Randomization and Subject Numbering .......................................................... 35 
4.10. 
Surgical Procedures and Assessments ....................................................... 36 
4.10.1. TKA Revision Procedure .......................................................................... 36 
4.10.2. Application of Study Treatments .............................................................. 36 
4.10.2.1. ciNPT ................................................................................................. 36 
4.10.2.2. Standard of Care (SOC) .................................................................... 37 
4.10.2.3. Documentation .................................................................................. 37 
4.10.3. Removal of Study Treatments ................................................................. 37 
4.10.3.1. ciNPT ................................................................................................. 37 
4.10.3.2. Standard of Care Dressing ................................................................ 38 
4.10.3.3. Documentation .................................................................................. 38 
4.11. 
Post-Operative Assessments ...................................................................... 38 
4.11.1. Investigator-Assessed Surgical Site Complication (SSC) ........................ 38 
4.11.1.1. SSC Components .............................................................................. 39 
4.11.1.2. Special Reporting Instructions for Superficial SSI ............................. 40 
4.11.1.3. Special Reporting Instructions for Continued Drainage ..................... 40 
4.11.2. Intervention Assessment .......................................................................... 41 
4.11.3. Healthcare Utilization Assessment .......................................................... 41 
4.12. 
Pain Assessment ......................................................................................... 41 
4.13. 
Patient Reported Outcomes (PRO) Assessments ....................................... 42 
4.13.1. Knee Injury and Osteoarthritis Outcome Score (KOOS) .......................... 42 
4.13.2. Patient-Reported Outcomes Measurement Information System (PROMIS) 
Global-10 Assessment ........................................................................................... 42 
4.14. 
Concomitant Medications ............................................................................ 43 
4.15. 
Prohibited Procedures and Treatments ....................................................... 43 
4.16. 
End of Study ................................................................................................ 44 
5. 
VISIT SCHEDULE AND DESCRIPTION OF STUDY VISITS ................................ 45 
5.1. 
Schedule of Visits ........................................................................................... 45 
5.2. 
Description of Study Visits .............................................................................. 46 
5.2.1. 
Screening/ Day -30 to 0 ........................................................................... 46 
5.2.2. 
TKA Revision – Pre-Surgery/ Day 0 ........................................................ 46 
5.2.3. 
TKA Revision –  Post-Surgery/ Day 0 ...................................................... 46 
5.2.4. 
Weekly Visit (Study Treatment Visits) ...................................................... 47 
5.2.5. 
Midterm Follow-up/Day 30 to 45 .............................................................. 47 
5.2.6. 
Long Term Follow-up/ Day 90 (+ 14 days) ............................................... 48 
5.2.7. 
Unscheduled Visits .................................................................................. 48 
6. 
RISKS ASSOCIATED WITH STUDY PARTICIPATION ........................................ 49 
7. 
SAFETY AND ADVERSE EVENTS ....................................................................... 50 
7.1. 
Definitions ....................................................................................................... 50 
7.1.1. 
Adverse Event (AE) ................................................................................. 50 
7.1.2. 
Serious Adverse Event (SAE) .................................................................. 50 
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7.2. 
Classification ................................................................................................... 51 
7.3. 
Relationship to Study Treatment ..................................................................... 51 
7.4. 
Severity ........................................................................................................... 51 
7.5. 
Expectedness ................................................................................................. 51 
7.6. 
AE Reporting Procedures ............................................................................... 52 
7.7. 
AE Collection/Reporting Period ....................................................................... 52 
7.8. 
SAE Reporting to KCI ..................................................................................... 52 
7.9. 
UADE Reporting - Unanticipated Adverse Device Effect (UADE) ................... 52 
7.10. 
Follow-up Period for Ongoing AEs .............................................................. 53 
8.
STATISTICAL CONSIDERATIONS ...................................................................... 54
8.1. 
Endpoint Definitions for Analysis ..................................................................... 54 
8.1.1. 
Primary Endpoint – Subject Incidence SSC ............................................. 54 
8.1.2. 
Secondary Endpoints ............................................................................... 54 
8.1.2.1. Subject Incidence SSI ......................................................................... 54 
8.1.2.2. Subject Incidence Deep SSI ................................................................ 55 
8.1.3. 
Exploratory Endpoints .............................................................................. 55 
8.1.3.1. Pain Assessment ................................................................................. 55 
8.1.3.2. Knee Injury and Osteoarthritis Outcome Subscale Score (KOOS) ...... 55 
8.1.3.3. Patient-Reported Outcomes Measurement Information System 
(PROMIS) Global-10 ........................................................................................... 56 
8.1.3.4. 30-Day Subject Incidence of SSC ....................................................... 56 
8.1.3.5. 45-Day Subject Incidence of SSC ....................................................... 56 
8.1.3.6. Safety Endpoint ................................................................................... 56 
8.2. 
Analysis Sets .................................................................................................. 57 
8.3. 
Planned Analysis and Data Summaries .......................................................... 57 
8.3.1. 
General Analysis Techniques .................................................................. 57 
8.3.2. 
Subject Disposition .................................................................................. 58 
8.3.3. 
Demographic and Baseline Characteristics ............................................. 58 
8.3.4. 
Analysis of Primary Endpoint ................................................................... 58 
8.3.5. 
Analysis of Secondary Endpoints ............................................................ 59 
8.3.6. 
Exploratory Endpoints .............................................................................. 59 
8.3.7. 
Analysis of Safety Endpoint ..................................................................... 60 
8.4. 
Additional Statistical Details ............................................................................ 60 
8.4.1. 
Hypothesis ............................................................................................... 60 
8.4.2. 
Sample Size Determination ..................................................................... 61 
8.4.3. 
Randomization ......................................................................................... 61 
8.4.4. 
Open-Label Study Reporting Results ...................................................... 61 
8.4.5. 
Interim Analysis ....................................................................................... 62 
8.4.6. 
Study Sites ............................................................................................... 62 
8.4.7. 
Statistical Analysis Plans and Changes in Analyses ................................ 62 
9.
HANDLING OF STUDY PRODUCTS .................................................................... 63
10.
DATA HANDLING AND RECORD KEEPING ................................................... 64
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10.1. 
Investigator/Study Site Training ................................................................... 64 
10.2. 
Electronic Case Report Form (eCRF) and Source Documents ................... 64 
10.3. 
Monitoring of Study Data ............................................................................. 64 
10.4. 
Data Handling .............................................................................................. 64 
10.5. 
Records Retention ....................................................................................... 64 
11. 
ADMINISTRATIVE REQUIREMENTS ............................................................... 66 
11.1. 
Good Clinical Practice (GCP) ...................................................................... 66 
11.2. 
Ethical Considerations ................................................................................. 66 
11.3. 
Subject Informed Consent ........................................................................... 66 
11.4. 
Confidentiality .............................................................................................. 66 
11.5. 
Clinicaltrials.gov Registration ...................................................................... 66 
11.6. 
Auditing and Inspecting ............................................................................... 67 
12. 
PUBLICATION POLICY ..................................................................................... 68 
13. 
REFERENCES ................................................................................................... 69 
14. 
APPENDICES .................................................................................................... 72 
14.1. 
KOOS Questionnaire ................................................................................... 72 
14.2. 
PROMIS 10 Questionnaire .......................................................................... 72 
 
List of Tables 
Table 1. Prevena™ Peel & Place™ Dressing Description ............................................ 21 
Table 2. Prevena Plus™ Customizable™ Dressing Description ................................... 22 
 
List of Figures 
Figure 1. ActiV.A.C.® Therapy Unit ................................................................................ 19 
Figure 2. Prevena Plus™ 125  Therapy Unit ................................................................. 20 
Figure 3. Prevena™ Peel & Place™ Dressing .............................................................. 21 
Figure 4. Prevena Plus™ Customizable™ Dressing ..................................................... 23 
Figure 5. Study Schematic ............................................................................................ 25 
 
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1. 
INTRODUCTION 
1.1. 
Background Negative Pressure Wound Therapy 
Negative pressure wound therapy (NPWT) was first introduced for the treatment of acute 
and chronic open wounds more than 25 years ago. This therapy has become a common 
and effective adjunct to wound healing, as evidenced by its use among surgeons and 
clinicians all over the world. NPWT is used in treating both open and closed wounds. 
Problems associated with wound healing frequently lead to infection, wound dehiscence, 
and additional procedures. 
Hyldig et al. performed a meta-analysis combining the results from ten randomized clinical 
trials (RCTs) which compared NPWT against standard post-operative dressings among 
1089 patients undergoing procedures requiring closed surgical incisions such as hip and 
knee arthroplasty, sternotomy, spinal fractures, abdominal wounds, and breast 
reconstruction.1 Each study measured and reported at least one of the following wound 
complications:  dehiscence, infection, or seroma. Most trials included in the meta-analysis 
were published in a peer-reviewed journal, however, three trials contributing 697 patients 
(64%), provided the results used in the meta-analysis via personal communication.  
While the results of the meta-analysis showed NPWT to be effective in reducing the risk 
of seroma formation (relative risk and 95% CI: 0.48 [0.27,0.84]) and would infection (0.54 
[0.33,0.89]) compared to the standard dressings, the effect on wound dehiscence did not 
reach statistical significance (0.69 [0.47,1.01]). The results of this meta-analysis should 
be interpreted cautiously. Heterogeneity among the studies included in the meta-analysis 
prevents general conclusions or recommendations across all closed surgical incisions. 
Also, the majority of the patient-data (64%) included in the meta-analysis came from un-
published results communicated directly with the study authors.  
In a multi-center, prospective RCT in patients with high-risk lower extremity fractures 
(calcaneus, pilon, and tibial plateau) Stannard et al. showed a lower frequency of infection 
and dehiscence among fractures in patients randomized to the NPWT group (14 [9.9%] 
and12 [8.5%]) compared to the fractures in patients randomized to the standard post-
operative dressing group (23 [18.8%] and 20 [16.4%]).2 The study population consisted 
of 249 patients; 130 patients with 141 fractures randomized to NPWT and 119 patients 
with 122 fractures randomized to standard of care.  
In a prospective, single-center study of obese patients undergoing cardiac surgery via 
sternotomy, patients allocated to NPWT had a lower rate of infection (4%) than those 
treated with standard of care (16% p-value= 0.0266)3. Retrospective studies also found 
lower rates of infection for patients with surgical incisions treated with NPWT compared 
to standard of care. 4;5  
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Innovations and successes with NPWT have led to the development of devices that 
simplify and provide options for the application of NPWT, such as ActiV.A.C.® Therapy 
Unit in conjunction with the Prevena™ Peel & Place Dressing and the Prevena Plus™ 
Customizable™ Dressing for closed incisions. Closed incision negative pressure therapy 
(ciNPT) is now used as an adjunct therapy in all types of closed incisions, including 
incisions resulting from knee replacement surgery. 
1.2. 
Total Knee Arthroplasty and Revision 
Replacement of a knee joint with a prosthesis, or Total Knee Arthroplasty (TKA), is an 
increasingly common surgical procedure in the United States. In a study using the 
Nationwide Inpatient Sample, US Census data, and National Health Expenditure data 
from 1993 through 2010, Kurtz and colleagues found steady growth of both primary and 
revision TKAs between 2000 and 2010. They concluded that the economic downturn did 
not substantially affect the growth trends for these procedures in the United States 
(2014).6 As a large percentage of the population ages, the number of these procedures 
is expected to increase.  
A TKA may fail for a variety of reasons causing pain, swelling, stiffness, and instability. 
When a TKA fails, a second surgery (revision) may be performed, where some or all parts 
of the original prosthesis are replaced. The most common reasons for TKA revision 
include infection, aseptic loosening, instability, mechanical complications, wear, and 
fracture. 7-11 The 2014 annual report from the American Joint Replacement Registry 
(AJRR) considered TKA revisions for 639 patients and finds that infection and 
inflammatory reaction (27.2%) were the most frequently reported causes of TKA revision 
and that among revisions with complete data, 43% occurred within 3 months post primary 
TKA. Although the revision has the same goal as the primary TKA – to relieve pain and 
improve function – revision surgery is longer and more complex, requires extensive 
planning, and requires the use of specialized implants and tools to achieve the desired 
result.  
Among patients undergoing orthopedic surgeries, including TKA and revisions, published 
literature shows that patients with multiple co-morbidities, such as obesity, diabetes, 
dyspnea, hypertension, and smoking are at an even higher risk for infections than patients 
without co-morbidities.11-13 Infections can cause prolonged hospital stays, can create 
significant burden on the healthcare system, and can result in substantial morbidity and 
quality of life (QoL) deterioration for the patient. 14 
A reduction in the occurrence of these negative and costly outcomes by closed incision 
negative pressure therapy (ciNPT) would have a significant benefit for TKA revision 
patients.  
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1.3. 
Review of Medical Literature – ciNPT  in TKA 
A retrospective study of revision TKAs and total hip arthroplasties (THAs) with 138 
patients (30 treated with ciNPT and 108 patients with antimicrobial dressings) undergoing 
procedures by a single surgeon, found that patients treated with ciNPT developed fewer 
overall wound complications (6.7% vs. 26.9%) and fewer surgical site infections (3.3% 
vs. 18.5%) as compared to patients whose wounds were treated using antimicrobial 
dressings.15   
The authors concluded that ciNPT decreases the incidence of surgical site complications 
– including dehiscence, suture granuloma, prolonged drainage, and surgical site 
infections – and may have the potential to lower the need for another reoperation in this 
population of TKA and THA revision patients. 
1.4. 
Conclusion 
Surgical Site Complications (SSCs) arising from aseptic and septic TKA revisions, 
particularly surgical site infection, are well documented in the literature, with patient co-
morbidities further impacting the rate of SSCs. The use of ciNPT has been shown to 
reduce complication rates related to closed surgical incisions in a variety of indications. 
An interest in exploring the benefits of ciNPT in orthopedic closed incisions is growing, 
such as impact on deep infection and dehiscence. There is a need for higher level 
evidence from a large, randomized, well-controlled study. This study will assess how 
ciNPT impacts the rate of SSCs and the components in patients undergoing TKA revision 
after primary TKA compared to the rate of complication associated with standard of care 
surgical wound dressings. 
1.5. 
Study Products 
The following devices and dressings will provide the ciNPT system used for this study in 
comparison to standard of care (SOC) surgical dressings. The system consists of any 
United States Food and Drug Administration (FDA)-cleared PrevenaTM Incision 
Management System dressing, including but not limited to: 
o Prevena™ Peel & Place™ Dressings (section 1.5.3), or  
o Prevena Plus™ Customizable™ Dressing (section 1.5.4)  
 applied at the time of the surgery and one of the following negative pressure pumps:   
o ActiV.A.C.® Therapy Unit (section 1.5.2.1), or  
o Prevena Plus™ 125 Therapy Unit (section 1.5.2.2).   
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The products provide surgical incision management via the application of negative 
pressure wound therapy over an incision site that has been surgically closed with sutures 
or staples. 
1.5.1. 
Regulatory status 
The Prevena Plus™ Incision Management System was cleared by the United States FDA 
via a 510(k) clearance affirming that the system is substantially equivalent in terms of 
indication and technology to the predicate device, the Prevena™ Incision Management 
System. The system’s indications, contraindication, warnings, precautions, and 
instructions for use can be found in the Prevena Plus™ Therapy System Clinician 
Guide.16 The Prevena Plus™ Incision Management System is intended to manage the 
environment for 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.  
1.5.2. 
Negative Pressure Wound Therapy Units 
The Therapy Unit creates a negative pressure vacuum of the closed surgical incision and 
causes exudate to be pumped into a collection canister attached to the unit. The Therapy 
Units described in this section were designed to be used in conjunction with any 
PrevenaTM Dressings used in this study immediately after the dressing is applied to the 
subject’s closed incision. 
Both Therapy Units are lightweight, portable, electric and battery-powered devices that 
the surgeon will attach to the dressing immediately after it is applied to the subject’s 
closed incision. Subjects will maintain the Therapy Unit after being discharged from the 
hospital. The unit will be programmed to deliver continuous 125 mmHg negative pressure 
for the duration of the ciNPT treatment.  
1.5.2.1. 
ActiV.A.C. ®  
The ActiV.A.C.® Therapy Unit (Figure 1) delivers continuous negative pressure to a wound 
in the selectable range of 25 mmHg to 200 mmHg. It weighs 2.4 pounds, has alarm 
notifications, and a 14-hour battery. A 300 mL canister is attached to the device to collect 
wound fluid.   
 
 
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Figure 1. ActiV.A.C.® Therapy Unit 
                 
 
1.5.2.2. 
Prevena Plus™ 125  
The Prevena Plus™ 125 Therapy Unit (Figure 2) delivers continuous negative pressure 
at 125 mmHg for up to seven days. A 150 mL canister is attached to the device to store 
exudates away from the incision site. Audible and visual alerts notify subjects and 
Investigators of leaks, full canister, and low battery.  
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Figure 2. Prevena Plus™ 125  Therapy Unit 
 
 
1.5.3. 
 Prevena™ Peel & Place™ Dressing 
The Prevena™ Peel & Place™ dressing is an integrated one-piece dressing that is 
applied to the closed surgical incision without sizing or cutting. The foam dressing has an 
integrated pressure indicator to ensure adequate negative pressure and PrevenaTM 
patches used to seal leaks at the time of application. Each dressing has a V.A.C.® 
Therapy Unit Connector to allow connection to the therapy unit. The dressings are 
designed for linear incisions and are constructed of 3 layers, as described in Table 1 and 
shown in Figure 3. 
 
 
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 Table 1. Prevena™ Peel & Place™ Dressing Description 
Layer/Material 
Function 
Skin Interface layer (Subject skin contacting) 
Wicking Interface Fabric (polyurethane-
coated polyester fabric with 0.019% silver) 
Placed directly over the incision. Wicks 
fluid away from the skin/tissue; contains 
silver ions to reduce potential for 
contamination of the fabric with microbes. 
Polyurethane film with acrylic adhesive 
Secures dressing to application site  
Foam Bolster (Subject skin noncontacting) 
Polyurethane foam with pigment violet 23  
Manifolds negative pressure to the 
surgical incision area through the 
underlying interface fabric 
Polyurethane film shell 
Maintains the negative pressure 
environment in conjunction with the 
therapy unit
PIMS Pressure Pad with Sterile Tubing (Subject skin noncontacting) 
Polyurethane film with acrylic adhesive  
Connects dressing to the therapy unit, 
transfers negative pressure and removes 
exudate 
DEHP-free PVC, medical grade 
 
 
Figure 3. Prevena™ Peel & Place™ Dressing 
 
 
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1.5.4. 
Prevena Plus™ Customizable™ Dressing 
The Prevena Plus™ Customizable™ Dressing is designed to be altered such that the 
dressing can cover closed surgical incisions of different sizes and shapes. 
The dressing is fitted with SENSAT.R.A.C.TM Pad and connector enabling attachment to 
the Therapy Units (Section 1.5.2). The dressing comes with V.A.C.® Drapes used to cover 
the dressing and hydrocolloid sealing strips used to create a continuous adhesive seal 
around the dressing. The Prevena Plus™ Customizable™ Dressing is constructed of 
three layers, as described in Table 2 and shown in Figure 4. 
Table 2. Prevena Plus™ Customizable™ Dressing Description 
Layer/Material 
Function 
Skin Interface layer (Subject skin contacting) 
Wicking Interface Fabric (polyurethane-
coated polyester fabric with 0.019% silver)  
Placed directly over the incision. Wicks fluid 
away from the skin/tissue; contains silver ions 
to reduce potential for contamination of the 
fabric with microbes. 
Polyurethane film with acrylic adhesive 
Secures dressing to application site on 
subject
Hydrocolloid Ring (Subject skin contacting) 
Hydrophilic polymer ring attached to the 
outside edge of the foam bolster 
Assists with dressing application and helps 
reduce dressing leaks  
Foam Bolster (Subject skin non-contacting) 
Polyurethane foam with pigment violet 23  
Manifolds negative pressure to the surgical 
incision area through the underlying 
interface fabric 
Polyurethane film shell 
Maintains the negative pressure 
environment in conjunction with the therapy 
unit
Pressure Pad with Sterile Tubing (Subject skin non-contacting) 
Polyurethane film with acrylic adhesive  
Connects dressing to the therapy unit, 
transfers negative pressure and removes 
exudate 
DEHP-free PVC, medical grade 
 
 
 
 
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Figure 4. Prevena Plus™ Customizable™ Dressing  
 
 
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2. 
STUDY OBJECTIVES 
The goal of this study is to evaluate surgical site complications (SSC) in subjects 
undergoing a revision of a failed total knee arthroplasty when ciNPT is used to manage 
the closed incision, as compared to standard of care dressing. The individual components 
for SSC (section 4.11.1) will also be assessed by collecting data associated with each 
complication. Safety and quality of life will also be evaluated.  
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3. 
STUDY DESIGN 
3.1. 
Study Schematic 
Figure 5. Study Schematic 
 
 
 
 
 
 
 
 
 
 
 
Study Treatment Visits/ 
Dressing Removal  
Day 5 to max days per 
dressing IFU 
Up to 30 days 
Midterm Follow-up 
Day 30 to 45 
45-74 days 
23-40 days 
Long Term Follow-Up 
Day 90 to 104 
Screening (Day -30 to 0) 
TKA Revision (Day 0)/ 
Randomization & Treatment 
ciNPT Prevena Plus 
(n=220)
Standard of Care 
Dressing (n=220) 
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3.2. 
Design Summary 
This post-market, prospective, randomized, open-label, multicenter, controlled study will 
evaluate the effectiveness of closed incision negative pressure therapy (ciNPT) compared 
to standard of care (SOC) surgical dressing in reducing the surgical site complications 
(SSCs) in subjects with revision of a failed total knee arthroplasty (TKA).  
The study will randomize approximately 440 subjects from approximately 15 sites in a 1:1 
ratio to receive either ciNPT or SOC after a revision TKA. Subjects randomized to the 
ciNPT treatment arm will receive the placement of a Prevena™ Dressing in conjunction 
with ActiV.A.C.® or Prevena Plus™ 125 Therapy Units for a duration consistent with the 
Instructions for Use (IFU) document for the selected dressing but no shorter than five 
days post-surgery. Subjects randomized to the SOC treatment arm will receive Aquacel® 
Ag Surgical incision dressing, or another equivalent silver-impregnated dressing, up to 
the maximum number of days specified in the IFU but no shorter than five days post-
surgery, not inclusive of other negative pressure wound therapy devices or dressings for 
the duration of the study.    
Subjects will be seen during Screening (no more than 30 days before TKA revision) at 
the TKA revision, at weekly study treatment visits (a minimum of 5 days to a maximum 
number of days indicated in the Instruction for Use document for the selected dressing), 
the Midterm Follow-up visit (day 30 to 45), the Long Term Follow-up visit (day 90 to 104), 
or as initiated by either the Investigator or the subject (Unscheduled). All subjects will be 
followed for 90 days for outcomes regardless of the treatment received.  
3.3. 
Duration of Study Participation 
The duration of study participation for each subject is as follows: 
o Screening: 30 days prior to and including day of TKA revision (Day 0) 
o TKA revision 
o Treatment Period: According to the IFU document included with the 
selected dressing but no shorter than five days post-surgery 
o Post Operation and Follow-up: through 90 days after TKA revision 
The maximum participation duration per subject is 134 days. 
3.4. 
 Primary Endpoint 
The primary endpoint is the subject incidence of Investigator-assessed surgical site 
complications (SSCs) within 90 days of TKA revision. SSCs include any of the following: 
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o
Superficial Surgical Site Infection (SSI)
o
Deep SSI
o
Full thickness skin dehiscence
o
Seroma or hematoma requiring drainage or surgery
o
Skin necrosis
o
Continued drainage
Specific details regarding SSC determination and measurement can be found in section 
4.11.1. 
3.5. 
Secondary Endpoints 
The two secondary endpoints for this study are the 90-day subject incidence of 
Investigator-assessed: 
o
Any SSI (superficial or deep)
o
Deep SSI only
3.6. 
Exploratory Endpoints 
Exploratory endpoints in this study are self-reported, except where indicated, and include: 
o
Worst pain last 24 hours
o
Average pain in last 24 hours
o
Knee-Related Quality of Life – as assessed by the Knee injury and
Osteoarthritis Outcome Score (KOOS)
o
Function in Sport and Recreation (KOOS)
o
Function in Daily Living (KOOS)
o
Pain (KOOS)
o
Other Symptoms (KOOS)
o
Mental health – as assessed by PROMIS Global 10 t-score
o
Physical health – as assessed by PROMIS Global 10 t-score
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o Investigator-assessed: 
 30-Day subject incidence of SSC 
 45-Day subject incidence of SSC  
3.7. 
Safety Endpoint 
The safety endpoint is the subject incidence of adverse events. 
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4. 
STUDY PROCEDURES AND ASSESSMENTS 
4.1. 
Informed Consent 
The Investigator, or designee, will discuss the purpose of this study with potential 
subjects. Each individual will review the Informed Consent Form (ICF) approved by the 
local Institutional Review Board (IRB). The subject and the Investigator (or medically 
licensed sub-Investigator), must both sign and date the ICF before the subject can 
undergo any study-related procedures. The subject’s informed consent will be obtained 
under these conditions: 
o Subjects must be made aware of the purpose of the study and the potential 
risks and benefits known or that can be reasonably predicted or expected. 
o Subjects must be given the opportunity to ask the Investigator questions 
and must be provided time to consider participation in the study. 
o ICFs will be written in a manner that is non-technical and understandable to 
the subject.   
o Subjects will not be led to believe that they are waiving their legal rights to 
release the Investigator, KCI, the study site, or any of their agents from 
liability from negligence. 
o Subjects will be asked to sign and date the ICF indicating their informed 
consent to participate in the study. 
o The Investigator’s responsibilities during the ICF process include: 
o screening out potential subjects who may not be able or willing to comply 
with the study protocol, and 
o ensuring that subjects have signed the ICF prior to undergoing any 
study-related assessments, and  
o ensuring that each subject receives a copy of their signed ICF. 
4.2. 
Inclusion/Exclusion 
In order to be considered for randomization, a subject must meet all pre-operative 
eligibility criteria, assessed no more than 30 days prior to the planned TKA revision, and 
the intra-operative eligibility criteria assessed on the day of surgery. Subjects who do not 
meet all eligibility criteria will not be eligible for randomization, will discontinue from the 
study, and will be considered a screen failure.  
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4.2.1. 
Pre-Operative Inclusion Criteria 
The subject:  
o is at least 22 years of age on the date of informed consent 
o is able to provide their own informed consent 
o requires a TKA revision defined as one of the following: 
 a one-stage aseptic revision procedure  
 a one-stage septic exchange procedure (requiring removal of all 
hardware) for acute postoperative infection 
 removal of cement spacer and re-implantation procedure  
 open reduction and internal fixation of peri-prosthetic fractures 
o has one or more of the following:  
 a body mass index (BMI) greater than 35 kg/m2 
 a requirement for the use of blood thinners other than acetylsalicylic 
acid (ASA) after surgery 
 history of or current peripheral vascular disease 
 the presence of lymphedema in the operative limb 
 insulin-dependent diabetes mellitus 
 current tobacco use or previous history of smoking and quitting within 
the past 30 days 
 a history of prior infection of the operative site 
 current use of immunomodulators or steroids 
 current or history of cancer or hematological malignancy (excluding 
localized skin cancer) 
 rheumatoid arthritis 
 current renal failure or dialysis 
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 malnutrition as determined by the investigator 
 liver disease as determined by the investigator 
 status post solid organ transplant 
 HIV 
o is willing and able to return for all scheduled study visits 
o if female, has a negative urine or serum pregnancy test at screening and 
day of revision surgery. Women who have had surgical sterilization by a 
medically accepted method such as tubal ligation, hysterectomy, or 
oophorectomy or are post-menopausal, defined as not having menstruation 
for > 12 months will be excluded from requiring this test. 
4.2.2. 
Pre-Operative Exclusion Criteria 
The subject: 
o is pregnant or lactating 
o will undergo a bilateral TKA within the same operative visit 
o will undergo a bilateral TKA in which the first TKA surgery is on the knee 
selected for study 
o will undergo a staged bilateral TKA in which the TKA revision surgery for 
the knee under study occurs within 30 days of the first TKA procedure  
o was previously randomized in this protocol 
o has a systemic active infection at the time of revision not including chronic 
viral infections such as HIV or hepatitis 
o has a remote-site skin infection at the time of revision 
o was tattooed on the area of the incision within 30 days prior to 
randomization 
o has known sensitivity to the study product components (drape and/or 
dressing materials in direct contact with the closed incision or skin) 
o has known sensitivity to silver 
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o is currently enrolled in another investigational trial that requires additional 
interventions 
o is planned to be enrolled in another investigational trial that requires 
additional interventions at any time during the study  
o has localized skin cancer around the incision site 
4.2.3. 
Intra-Operative Inclusion Criteria 
The subject: 
o continues to meet all pre-operative inclusion criteria 
o has undergone a TKA revision resulting in a closed surgical incision 
4.2.4. 
Intra-Operative Exclusion Criteria 
The subject: 
o is found to meet any of the pre-operative exclusion criteria 
o has a surgical incision that precludes placement of dressing  
o has a TKA revision resulting in a muscle flap  
o has a TKA revision resulting in the placement of a spacer 
o has an incision drainage and debridement procedure only 
o has a surgical incision closed with skin glue 
4.3. 
Premature Study Termination  
If the study is terminated prematurely or suspended, study subjects and the IRB will be 
informed promptly and provided with the reason(s) for the termination or suspension by 
KCI or by the Investigator. If applicable, regulatory authorities and the personal physicians 
of the subjects will also be informed. 
4.3.1. 
By Sponsor 
KCI reserves the right to discontinue any clinical study for business or ethical reasons at 
any time, such as, but not limited to: 
o The study is not conducted in accordance with the approved protocol. 
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o Information regarding the study product causes doubt as to the benefit/risk 
ratio. 
o Changes in medical practice limit utility of the data obtained from the study. 
KCI reserves the right to terminate a study at a site at any time, including, but not limited 
to, any of the following reasons: 
o Investigator(s) lack of compliance to the study protocol and/or with 
applicable regulatory or IRB guidelines in conducting the study 
o Incidence or severity of AEs indicates a potential health hazard or poses an 
unreasonable risk to the study participants 
o Subject enrollment is unsatisfactory. 
4.3.2. 
By IRB 
The IRB may choose to discontinue the study at the site for which they granted approval. 
If the IRB discontinues the study, the Investigator will report a withdrawal of IRB approval 
to KCI within five (5) working days. 
4.4. 
Subject Withdrawal or Termination  
4.4.1. 
Reasons for Withdrawal or Termination  
Subjects may withdraw from participation in the study at any time upon request.  
The Investigator may choose to terminate participation of the subject from the study with 
or without their consent for any of the following reasons: 
o Adverse events 
o Noncompliance 
o For any reason that may, in the opinion of the Investigator, negatively affect 
the safety or well-being of the subject. 
An Investigator must terminate participation of a subject from the study for any of the 
reasons indicated in section 4.15.   
4.4.2. 
Handling of Withdrawal or Termination 
Every effort should be made to assess SSCs and adverse events prior to the subject 
withdrawal. If a subject does not return for a scheduled visit, every effort should be made 
to contact the subject. 
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For subjects who are lost to follow-up, the Investigator will make attempts to collect at 
least the vital status (e.g., whether the subject is alive) before formally withdrawing the 
subject from the study. Prior to considering a subject lost to follow-up at least two 
documented attempts should be made to contact the subject through all available routes, 
and a certified letter should be sent to the permanent address on file. 
Once the subject withdraws from the study, no further study evaluations will be performed, 
and no additional data will be collected. The Investigator may retain and continue to use 
any data collected before withdrawal. The subject will not be replaced.  
If for any reason the subject is withdrawn by the Investigator from this study, the 
Investigator will inform the subject and KCI. 
4.5. 
Demographics and Subject Characteristics 
The following demographic data and subject characteristics will be collected and 
documented after the subject signs the informed consent and before the TKA revision:  
o Date of birth 
o Sex 
o Race 
o Ethnicity 
o Co-morbidities 
o Primary TKA characteristics 
o Date of surgery 
o Diagnosis (osteoarthritis, rheumatoid arthritis, other) 
o Unilateral or bilateral 
o Primary reason for failure  
o Aseptic loosening 
o Infection 
o Wear 
o Mechanical causes 
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o Instability 
o TKA revision septic/aseptic  
4.6. 
Vital Signs 
The subject’s height and weight will be collected and documented at the screening visit. 
If the screening visit and the TKA revision occur on different days, only weight will be 
taken and documented on Day 0, prior to the revision procedure.  
4.7. 
Medical/Surgical History 
As part of screening procedures, the Investigator, or medically licensed sub-investigator, 
will collect a complete medical and surgical history for each subject. If the screening visit 
and the TKA revision occur on different days, the medical and surgical history will be 
updated on Day 0, prior to the revision procedure. 
4.8. 
Laboratory Assessment for Pregnancy 
Serum or urine hCG assessment to determine pregnancy status in female subjects of 
child-bearing potential will be conducted during screening and prior to surgery, if the 
screening visit and the TKA revision occur on different days. If the subject’s pregnancy 
test is positive, she will not be eligible for randomization, will discontinue from the study, 
and will be considered a screen failure. 
4.9. 
Randomization and Subject Numbering 
Subjects who sign an informed consent will be assigned a unique subject identifier. The 
identifier will be unique to the subject. Study data will be reported according to this unique 
subject identifier. 
Subjects who satisfy all inclusion criteria and none of the exclusion criteria will be eligible 
for randomization which will occur in the operating room after the TKA revision procedure 
has been completed and the surgical incision has been closed. Randomization to study 
treatment will be centralized, electronic, and web-based. Subjects will be randomized in 
a 1:1 ratio (ciNPT vs. SOC) stratified by type of revision (septic vs. aseptic). For details, 
see section 8.4.3.   
If a screened subject does not meet inclusion criteria or meets any exclusion criteria, the 
subject will not be randomized and will be considered a screen failure. 
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4.10. 
Surgical Procedures and Assessments 
4.10.1. 
TKA Revision Procedure  
The surgical procedure will be performed in accordance with the Investigator’s standard 
practice and the resultant surgical incision will be closed with sutures (resorbable or 
permanent) or staples. Incisional skin glue (e.g., Dermabond) must not be used. 
The following information regarding the TKA revision will be documented after the 
surgery: 
o Material used (polyethylene, cross-linked polyethylene, antioxidant 
polyethylene) 
o Location (left or right knee)  
o Length of the incision  
o Method of closure (sutures or staples)  
o Start and stop time of the surgical procedure 
4.10.2. 
Application of Study Treatments 
4.10.2.1. ciNPT 
Subjects randomized to ciNPT will receive treatment for a duration consistent with the 
IFU document included with the selected PrevenaTM Dressing but no shorter than five 
days post-surgery. Depending on the length of the incision, an appropriate Prevena™ 
Dressing will be used to cover the closed surgical incision, according to the instructions 
for use included with the product. Total treatment time should not exceed the maximum 
number days indicated in the IFU document included with the PrevenaTM Dressing applied 
immediately following surgery.  
For the delivery of negative pressure, an ActiV.A.C.® or Prevena PlusTM 125 Therapy Unit 
will be attached to the dressing tubing and ciNPT will be initiated in the operating room. 
The ActiV.A.C.® Unit must be set to 125mmHg of continuous negative pressure. If the 
dressing leaks and a seal cannot be maintained, replacement of the initial ciNPT dressing 
is acceptable and will be documented.  
In the event that the Therapy Unit malfunctions, a replacement unit may be used. A 
dressing may also be replaced during the treatment period. 
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4.10.2.2. Standard of Care (SOC) 
Subjects randomized to standard of care will have their closed surgical incision covered 
with the silver-impregnated dressing, Aquacel® Ag Surgical or other equivalent, up to the 
maximum number of days specified in the IFU but no shorter than five days post-surgery. 
Total treatment time should not exceed the maximum number days indicated in the IFU 
document included with the dressing applied immediately following surgery. 
4.10.2.3. Documentation 
The following information regarding the application of study treatments will be 
documented after the surgery: 
o
SOC
o
Type of dressing applied
o
ciNPT

Type of dressing applied (eg, Prevena Plus™ Customizable™
Dressing, Prevena™ Peel & Place™ Dressing)
o
Type of therapy unit

ActiV.A.C.®

Prevena Plus™ 125
o
Replacement of the initial dressing to maintain the seal
4.10.3. 
Removal of Study Treatments 
4.10.3.1. ciNPT 
All subjects must receive ciNPT for a duration consistent with the IFU document included 
with the selected PrevenaTM Dressing but no shorter than five days post-surgery. A 
maximum duration indicated in the IFU document of the PrevenaTM Dressing applied 
immediately following surgery is encouraged. The dressing should not be lifted or 
removed for reasons other than those related to the device such as initial malfunction or 
leak alarm.  
At the end of the ciNPT treatment period, the dressing and unit are to be removed; 
re-application of the PrevenaTM dressing is prohibited after the treatment period. If 
continued drainage is determined by the Investigator’s visual inspection of the incision at 
the time of dressing removal, an SSC event should be documented. 
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4.10.3.2. Standard of Care Dressing 
The Aquacel® Ag Surgical or other equivalent dressing may be replaced as needed for 
the duration of the treatment period. Total treatment time should be no shorter than five 
days post-surgery and should not exceed the maximum number days indicated in the IFU 
document included with the dressing applied immediately following surgery. 
4.10.3.3. Documentation 
The following information regarding the application of study treatments will be 
documented after the surgery: 
o Date of removal 
o SOC only 
o The number of dressing replacements  
o Type of dressing (if any) applied after removal of study treatment 
o ciNPT only 
o Replacement of therapy unit 
o Number and dates of dressing replacements (Prevena™ Peel & Place™ or 
Prevena Plus™ Customizable™) 
o Type of dressing (if any) applied after removal of ciNPT 
4.11. 
Post-Operative Assessments 
4.11.1. 
Investigator-Assessed Surgical Site Complication (SSC)  
The Investigator will examine the subject and the surgical incision at the scheduled 
assessment visits – Weekly, Midterm Follow-up, and Long Term Follow-up – as well as 
any unscheduled visits initiated by the subject or the Investigator. The Investigator will 
evaluate the subject for all complications at each visit, regardless if the subject has a 
documented SSC event.  
For all SSC events, the date of onset will be recorded. Not all reported adverse events 
that are surgical complications will meet the criteria for an SSC event.  
Subjects with a documented SSC event will continue to be assessed through the Long 
Term Follow-up visit or study withdrawal and all newly occurring complications will be 
recorded.  
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4.11.1.1. SSC Components 
1. Superficial Incisional Surgical Site Infection (SSI) involves only skin and subcutaneous 
tissue of the incision and meets at least one of the following criteria: 
o purulent drainage from superficial incision; 
o organisms identified from an aseptically-obtained specimen from the 
superficial incision or subcutaneous tissue by a culture or non-culture based 
microbiologic testing method which is performed for purposes of clinical 
diagnosis or treatment (e.g., not Active Surveillance Culture/Testing 
[ASC/AST]); 
o both of the following: 
 superficial incision that is deliberately opened by Investigator and 
culture or non-culture based testing is not performed, and 
 at least one of the following signs or symptoms:  
 pain or tenderness;  
 localized swelling;  
 erythema; or  
 heat. 
o diagnosis of superficial SSI by the Investigator.  
2. Deep Incisional SSI which involves deep soft tissue of the surgical incision, occurs 
within 90 days after the revision, and has at least one of the following: 
o purulent drainage from the deep surgical incision; 
o both of the following:  
 a deep incision that spontaneously dehisces, or is deliberately 
opened or aspirated by the Investigator and organism is identified by 
a culture or non-culture based microbiologic testing method which is 
performed for purposes of clinical diagnosis or treatment (e.g., not 
Active Surveillance Culture/Testing (ASC/AST) or culture or non-
culture based microbiologic testing method is not performed: 
 at least one of the following signs or symptoms: 
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 fever(>38°C);  
 localized pain, or 
 tenderness.  
Note: A culture or non-culture based test that has a negative finding does 
not meet this criterion. 
o an abscess or other evidence of infection involving the deep incision that is 
detected on gross anatomical or histopathologic exam, or imaging test.  
3. Full thickness skin dehiscence, defined as a separation of the closed incision at least 
through the subcutaneous tissue or deeper and at least one mm wide. 
4. Seroma or hematoma requiring drainage or surgery. The fluid accumulation will be 
classified as hematoma (bloody fluid) or seroma (clear or serous fluid) after drainage. 
The drainage may be percutaneous, an open technique at the bedside, or open 
surgical drainage. 
5. Skin necrosis is defined as the presence of necrotic tissue/skin eschar at the incision 
site that requires intervention with antibiotics, excision, and/or re-operation. 
6. Continued drainage determined by an Investigator’s visual inspection of the incision 
after completion of the study treatment period and removal of the study treatment 
dressing.   
4.11.1.2. Special Reporting Instructions for Superficial SSI 
Assessments of SSI will follow the CDC classification of superficial infections.17 
Specifically, the following do not qualify as criteria for meeting the National Healthcare 
Safety Network (NHSN) definition: 
o Diagnosis/treatment of cellulitis (redness/warmth/swelling), by itself, does 
not meet the last criterion for superficial incisional SSI. Conversely, an 
incision that is draining or that has organisms identified by culture or non-
culture based testing is not considered a cellulitis. 
o A stitch abscess alone (minimal inflammation and discharge confined to the 
points of suture penetration). 
 
4.11.1.3. Special Reporting Instructions for Continued Drainage  
It is typical for a closed incision to drain up to 72 hours after surgery. However, if the 
closed incision continues to drain at the time of dressing removal (> 5 days) as determined 
by the Investigator to require significant medical intervention, then the occurrence will be 
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documented as an SSC. Investigators will assess any signs of infection, including 
purulent discharge or pus, for an SSI and document accordingly. 
 
4.11.2. 
Intervention Assessment 
Information related to all interventions that are performed for an SSC will be documented 
at all post-surgery visits including unscheduled visits. Information collected will include 
but is not limited to:  
o
Date of intervention
o
Type of interventions
o
Types of interventions may include open surgical or percutaneous drainage,
debridement, excision, or re-operation.
4.11.3. 
Healthcare Utilization Assessment 
Information related to additional hospital procedures and/or follow-up care after the 
subject’s TKA revision during the study period will be documented at all post-surgery 
visits, scheduled or unscheduled. Data to be collected will include: 
o
Relatedness to the TKA revision
o
Duration of stay for TKA revision
o
Length of hospital stay (days)
o
Days in ICU
o
Re-admission after TKA revision (yes/no)
o
Length of hospital stay (days)
o
Days in ICU
o
Number of home health visits after hospital discharge
o
Number of clinic visits after hospital discharge
o
Number of rehab/physical therapy visits
4.12. 
Pain Assessment  
Subjects will answer two questions asking them, on a scale from 0 (no pain) to 10 (pain 
as bad as you can imagine), to recall and rate their worst and average pain in the last 24 
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hours. Subjects will answer these questions prior to the TKA revision, at the earlier of 
discharge or 24 hours (± 2 hours) after the TKA revision, and at the weekly study 
treatment visits. Subjects will document whether they completed the assessment before 
or after consultation with the Investigator. At the weekly study treatment visits, the subject 
will record whether the pain assessment was performed before or after the dressing 
removal.  
4.13. 
Patient Reported Outcomes (PRO) Assessments 
4.13.1. 
Knee Injury and Osteoarthritis Outcome Score (KOOS)  
The KOOS is a 42-item disease-specific patient reported outcome (PRO) measure 
designed to assess short-term and long-term symptoms and function in subjects with 
knee injury and osteoarthritis. The KOOS has been validated for several orthopaedic 
interventions including total knee replacement.18-21 The KOOS consists of five subscales: 
 Knee-related Quality of Life,  
 Function in Sport and Recreation,  
 Function in Daily Living,  
 Pain, and  
 Other Symptoms. 
Intended for use over short-term or long-term intervals to assess changes from visit to 
visit, subjects will be asked to complete the KOOS questionnaire on their own at the 
Screening, weekly study treatment visits, Midterm Follow-up, and the Long Term Follow-
up visits.  
Subjects will record whether they completed the assessment at a particular visit before or 
after consultation with the Investigator. 
4.13.2. 
Patient-Reported Outcomes Measurement Information System (PROMIS) 
Global-10 Assessment 
The PROMIS Global-10 is a generic health assessment that measures the physical, 
social, and emotional health of individuals and is often used for those living with chronic 
conditions. 
Subjects will be asked to complete the PROMIS Global-10 questionnaire on their own at 
the Screening, weekly study treatment visits, Midterm Follow-up, and Long Term Follow-
up visit.  
Subjects will record whether they completed the assessment at a particular visit before or 
after consultation with the Investigator. 
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4.14. 
Concomitant Medications 
Concomitant medications will be collected from the time of informed consent through the 
Long Term Follow-up visit. The medication name, start date, end date, and indication will 
be reported. 
Special consideration should be given to report medications given to treat SSCs or that 
may affect the healing process such as:  
o
all antimicrobial medications taken by the subject from time of informed
consent throughout the duration of the study especially IV, which may be
given to the subject for pre-op prophylaxis within 24 hours of surgery
followed by a course of oral antibiotics post-TKA revision
o
opioid medications (e.g., morphine) taken by the subject within 14
consecutive days after randomization
o
immunosuppressants
o
corticosteroids
o
non-steroidal anti-inflammatory drugs (NSAID)
o
anti-coagulants (e.g., Lovenox, aspirin, Coumadin)
o
all medications with a prophylactic indication
o
all medications the subject is given to treat an AE during the study
4.15. 
Prohibited Procedures and Treatments 
Subjects who undergo a subsequent surgery involving the initial TKA incision within 90 
days must withdraw from the study.  
Subjects who receive a subsequent TKA revision on the same knee within 90 days of the 
study revision must withdraw from the study prior to the procedure. Sites will record any 
SSCs that occur prior to the subsequent TKA revision and document the revision as the 
reason for the withdrawal from the study. 
In the absence of an SSC, subjects receiving cross-over therapy after completing the 
original study treatment (ie, therapy from the arm in which the subject was not initially 
treated) must withdraw from the study.   
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4.16. 
End of Study 
Subjects may withdraw or be discontinued from this study at any time (Section 4.4.1). The 
Investigator may discontinue a subject’s study participation if the Investigator feels it is in 
the best interest of the subject. Subjects who consent to participate in the study but do 
not satisfy the inclusion and exclusion criteria will be considered screen failures.  
The following information will be documented: 
o Date of study termination 
o Completion of the study (yes/no) 
o Primary reason for discontinuation  
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5.
VISIT SCHEDULE AND DESCRIPTION OF STUDY VISITS
5.1. 
Schedule of Visits 
Pre 
Post
Day
-30 to 0
Day 0
Day 0
Per 
Dressing 
IFU
Day 30-45
Day 90 
(+14 days)
Informed Consent
X
Pre-Operative Inclusion & Exclusion Criteria
X
Demographics & Subject Characteristics
X
Vital Signs
X
X2
Medical & Surgical History
X
X3
Laboratory Assessment for Pregnancy1
X
X
Intra-operative Inclusion & Exclusion Criteria
X
TKA Revision Procedure
X
Randomization
X
Application of Study Treatment
X
Removal of Study Treatment
X
SSC Assessment
X
X
X
X
Intervention Assessment
X
X
X
X
Pain Assessment
X
X4
X
Patient-Reported Outcomes Assessments
(KOOS and PROMIS Global-10)
X
X
X
X
Healthcare Utilization Assessment
X
X
X
X
End of Study
X
X5
Concomitant Medications
X
X
X
X
X
X
X
Adverse Event Assessment and SAE Reporting
X
X
X
X
X
2 - Weight only
4 - Pain w ill be assessed at the earlier of discharge or 24 hours (± 2 hours) after the TKA Revision.
5 - End of Study assessed at an unscheduled visit only w hen a subject discontinues prior to the 90-day visit.
3 - Updates to medical and surgical history to be documented.
TKA Revision
End of 
Treatment
1 - Assessed on w omen of child-bearing potential
Midterm
 Follow-up
Long Term 
Follow-up
Unscheduled 
Screening
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5.2. 
Description of Study Visits 
5.2.1. 
Screening/ Day -30 to 0 
The following procedures and assessments will be performed and documented. 
o Informed Consent 
o Pre-Operative Inclusion and Exclusion Criteria  
o Demographics and Subject Characteristics 
o Vital Signs 
o Medical and Surgical History  
o Laboratory Assessment for Pregnancy 
o PRO Assessments (KOOS and PROMIS Global-10)  
o Concomitant Medications 
5.2.2. 
TKA Revision – Pre-Surgery/ Day 0 
The following procedures and assessments will be performed and documented. 
 If Screening Visit occurs prior to Day 0: 
o Vital Signs  
o Medical and Surgical History 
o Laboratory Assessment for Pregnancy 
o Concomitant Medications 
For all subjects regardless of timing of Screening Visit: 
o Pain Assessment  
5.2.3. 
TKA Revision –  Post-Surgery/ Day 0 
o Intra-Operative Inclusion and Exclusion Criteria Evaluation 
o TKA Revision Procedure 
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o
Randomization to either the ciNPT arm or the SOC arm (in operating room
[OR])
o
Application of Study Treatment
o
Pain Assessment – assessed at the earlier of discharge or 24 hours (± 2
hours) after the TKA revision
o
Concomitant Medications
o
AE Assessment and SAE Reporting
5.2.4. 
Weekly Visit (Study Treatment Visits) 
The following procedures and assessments will be performed and documented. 
o
Removal of Study Treatment
o
SSC Assessment
o
Intervention Assessment
o
Pain Assessment
o
PRO assessments (KOOS and PROMIS Global-10)
o
Healthcare Utilization Assessment
o
Concomitant Medications
o
AE Assessment and SAE Reporting
5.2.5. 
Midterm Follow-up/Day 30 to 45  
The following procedures and assessments will be performed and documented. 
o
SSC Assessment
o
Intervention Assessment
o
PRO assessments (KOOS and PROMIS Global-10)
o
Healthcare Utilization Assessment
o
Concomitant Medications
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o AE Assessment and SAE Reporting  
5.2.6. 
Long Term Follow-up/ Day 90 (+ 14 days)  
The following procedures and assessments will be performed and documented. 
o SSC Assessment  
o Intervention Assessment  
o PRO assessments (KOOS and PROMIS Global-10) 
o Healthcare Utilization Assessment  
o Concomitant Medications 
o AE Assessment and SAE Reporting  
o End of Study  
5.2.7. 
Unscheduled Visits 
Outside of scheduled study visits, if the subject needs to be assessed by the Investigator 
for any reason, the following procedures and assessments will be performed and 
documented.  
o SSC Assessment  
o Intervention Assessment 
o Healthcare Utilization Assessment 
o Concomitant Medications 
o AE Assessment and SAE Reporting  
o End of Study (only when a subject discontinues prior to the 90-day visit) 
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6.
RISKS ASSOCIATED WITH STUDY PARTICIPATION
The following are the risks associated with the devices and dressings used in this study, 
specifically, ActiV.A.C.® Therapy Unit, Prevena PlusTM 125 Therapy Unit, and Prevena™ 
Dressings. 
Risks 
Disorders/Conditions 
Skin and 
Subcutaneous 
Tissue  

Epidermal (skin) stripping.

Contusion (bruising)

Local cutaneous reaction (i.e., redness, rash, significant
pruritis, urticaria)

Maceration

Minor soft tissue damage

Minor bleeding

Pain
Other 

Allergic reaction

Bleeding complications (associated with the surgical procedure,
concomitant therapies and co-morbidities)

Increased risk of bleeding from the incision associated with the
use of anticoagulants and/or platelet aggregation inhibitors

Deterioration of the wound (due to lack of visibility of incision
site through dressing)

Exposure related infection

First degree burn (if device gets warm)

Localized infection

Minor desiccation (due to dressing leak)

Moderate soft tissue damage (i.e., due to trip hazard, tubing
entanglement)

Physical discomfort

Surgical Site disruption
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7. 
SAFETY AND ADVERSE EVENTS 
7.1. 
Definitions 
7.1.1. 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including clinically significant abnormal laboratory findings) in subjects, users or 
other persons, whether or not related to the investigational medical device. 
7.1.2. 
Serious Adverse Event (SAE) 
An AE is considered serious if it results in any of the following outcomes:  
o Death; 
o Life-threatening; 
o Hospitalization (initial or prolonged);  
o Persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
o Congenital anomaly/birth defect; 
o Required intervention to prevent permanent impairment or damage  
o Other important medical events may be considered serious when, based 
upon appropriate medical judgment, they may jeopardize the subject and 
may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition. 
Any planned hospitalization for a pre-existing condition, or a procedure required by the 
protocol, without serious deterioration in health, is not considered an SAE. 
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7.2. 
Classification 
7.3. 
Relationship to Study Treatment 
The Investigator will assess the relationship of the AE as: 
o
Related to the study product:  any adverse event for which there is a
reasonable possibility that the study product caused the adverse event.
o
Not Related to the study product:  when is determined that there is no
relationship between the adverse event and the use of the study product.
7.4. 
Severity 
The study investigator will assign severity as follows: 
o
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations
only; no intervention indicated
o
Moderate; minimal, local or non-invasive intervention indicated;
o
Severe or medically significant but not immediately life- threatening;
hospitalization or prolongation of hospitalization indicated; disabling;
7.5. 
Expectedness 
All SAEs will be classified for expectedness by the Sponsor based on the following 
definitions: 
o
Expected, Anticipated: the effect, problem, or death has been previously
identified in the study or product documentation.
Adverse  Event 
( AE)  
Serious?= YES
Complete SAE 
report 
Complete   AE in 
clinical  DB
Serious? = NO 
Complete   AE in 
clinical  DB
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o Unexpected, Unanticipated: if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the study 
or product documentation. 
The Sponsor will provide the Investigator with the classification of the event based on the 
information reported by clinical sites.   
7.6. 
AE Reporting Procedures 
The Investigator is responsible for monitoring the safety of all subjects enrolled in the 
study, and reporting AEs as described in this protocol.   
7.7. 
AE Collection/Reporting Period 
The AE collection/reporting period will begin after the subject has been randomized. 
Investigators should assess for AEs at each visit. In addition, study subjects should be 
instructed to report any AE that they experience to the Investigator.    
All AEs, regardless of perceived relationship to study product, will be reported and 
recorded on the appropriate CRFs in a timely manner. In addition, the worsening of a 
medical condition previously reported in the medical history should also be recorded as 
an AE.  
The reporting of all AEs is to continue for the duration of the study or until the patient 
receives an alternative therapy, whichever occurs first. Any SAE that occurs after 
treatment with alternative therapy is to be reported only if the Investigator or treating 
physician assesses the SAE as related to the study treatment. 
The AE description will include the nature of the experience (AE term), the start date, the 
end date, the severity of each sign or symptom, the seriousness of the event or 
experience, relationship to study treatment, the course of action taken, and the outcome 
of the experience. Indicate if the AE caused the subject to be discontinued from the study. 
7.8. 
SAE Reporting to KCI 
SAEs will be reported via the KCI SAE Report Form. This form should be completed by 
the Investigator, or designee, and submitted (fax or email) to KCI within 24 hours of the 
Investigator becoming aware of the event. The KCI SAE line is available for SAE reporting 
24 hours per day and is monitored during normal business hours.  
7.9. 
UADE Reporting - Unanticipated Adverse Device Effect (UADE) 
A UADE is any SAE on health or safety or any life-threatening problem or death caused 
by, or associated with, a device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan or 
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application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects. (21 CFR 812.3)  
The Sponsor (KCI) will immediately conduct an evaluation of the received SAEs to 
determine whether the event meets the UADE definition. If the event is determined to be 
an UADE, KCI will report the results of the evaluation to FDA, and participating 
Investigators.  
If KCI determines that the event presents an unreasonable risk to the study subjects, it 
will terminate all clinical studies or parts of studies presenting risk as soon as possible.  
7.10. 
Follow-up Period for Ongoing AEs 
Treatment-related AEs (serious and non-serious) which are ongoing at the final study visit 
will be followed until resolution or stabilization. All other adverse events will be considered 
closed (outcome = “ongoing”) at the time the subject completes participation in the study. 
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8. 
STATISTICAL CONSIDERATIONS 
8.1. 
Endpoint Definitions for Analysis 
8.1.1. 
Primary Endpoint – Subject Incidence SSC 
The primary endpoint is the incidence of surgical site complications (SSCs) within 90 days 
of TKA revision in subjects treated with ciNPT as compared to standard of care surgical 
dressing. The SSC endpoint includes any occurrence of superficial SSI, deep SSI, 
dehiscence, seroma, hematoma, skin necrosis, or continued drainage as outlined in 
section 4.11.1. For this endpoint there are three possible outcomes: 
o “Occurred”, which is assigned if the subject had one or more occurrences 
of any complication and the onset date of the complication was between the 
time of the TKA revision and not later than 90 days after; 
o “No occurrences”, which is assigned if the subject had no known 
occurrences of a complication within 90 days of the TKA revision and was 
assessed at least once on or after the 90th day following the TKA revision; 
o “Incomplete follow-up”, which is assigned if the subject had no occurrences 
of the complication within 90 days of the TKA revision and did not have an 
assessment at least 90 days after the date of the revision surgery. 
If a subject experiences one occurrence of any of the six complications, the primary 
outcome will be considered “Occurred”.  
For each component of the SSC, the start date of the complication will be recorded in 
order to calculate the number of days from the revision surgery until occurrence of the 
event. If the complication did not occur, the number of days will be calculated using the 
last assessment which confirmed the subject to be complication-free.  
8.1.2. 
Secondary Endpoints 
8.1.2.1. 
Subject Incidence SSI 
This secondary endpoint is the incidence of any SSI (superficial or deep) within 90 days 
of TKA revision in subjects treated with ciNPT as compared to SOC dressing. Superficial 
SSI is a component of the primary endpoint and specific instructions for ascertainment 
are described in sections 4.11.1. Subjects will be categorized using methods similar to 
those described in section 8.1.1.  
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8.1.2.2. 
Subject Incidence Deep SSI 
This secondary endpoint is the incidence of deep SSI within 90 days of TKA revision in 
subjects treated with ciNPT as compared to SOC dressing. Deep SSI is a component of 
the primary endpoint and specific instructions for ascertainment are described in section 
4.11.1. Subjects will be categorized using methods similar to those described in section 
8.1.1. 
8.1.3. 
Exploratory Endpoints 
8.1.3.1. 
Pain Assessment 
The pain assessment consists of two self-administered questions used to evaluate the 
severity of a subject’s pain in the past 24 hours. Both questions are measured from 0 (no 
pain) to 10 (pain as bad as you can imagine).   
Subjects will respond using the integer value. Subjects who have withdrawn prior to the 
scheduled assessments will be categorized as “Discontinued study prior to assessment”; 
otherwise subjects who do not have an assessment recorded at a particular visit will be 
summarized as “Assessment not done”.   
8.1.3.2. 
Knee Injury and Osteoarthritis Outcome Subscale Score (KOOS) 
The KOOS instrument is a patient-reported questionnaire to assess short-term and long-
term symptoms and functions.  
The KOOS consists of 42 items asked on a 5-point Likert scale. The items will be 
converted to numeric values and summarized into five domain scores: Knee-Related 
Quality of Life, Function in Sport and Recreation, Function in Daily Living, Pain, and Other 
Symptoms. The subscales are scored separately and interpreted separately. Each 
subscale score will be normalized from 0 (extreme symptoms) to 100 (no symptoms).  
All efforts will be made to ensure the subjects complete the entire assessment at each 
scheduled visit. Each subscale will be scored using the most recent KOOS Users Guide 
and Scoring Instruction manuals which outline methods for imputing missing data.18;19  
 For the subscale scores, four possible outcomes will be summarized and listed: 
o
Normalized numeric subscale score;
o
Assessment done but incomplete (sufficient number of items not complete);
o
Discontinued study prior to assessment;
o
Assessment not done
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8.1.3.3. 
Patient-Reported Outcomes Measurement Information System (PROMIS) 
Global-10 
The PROMIS Global-10 is a generic health assessment that measures the physical, 
social, and emotional health of individuals and is often used for those living with chronic 
conditions. All efforts will be made to ensure the subject completes the entire assessment, 
which consists of 10 questions, at each scheduled visit. 
Two domains will be scored separately and each will be interpreted separately:  Global 
Physical Health and Global Mental Health. For each subscale, there are three possible 
outcomes: 
o Raw numeric subscale score and converted t-score; 
o Assessment done but incomplete (sufficient number of items not complete);  
o Discontinued study prior to assessment; 
o Assessment not done. 
8.1.3.4. 
30-Day Subject Incidence of SSC 
This endpoint is the incidence of the SSC within 30 Days post TKA revision in subjects 
treated with ciNPT as compared to SOC dressing. Section 4.11.1 describes the methods 
for ascertaining surgical site complications. Subject outcomes will be categorized using 
methods similar to those described in section 8.1.1. 
8.1.3.5. 
45-Day Subject Incidence of SSC 
This endpoint is the incidence of the SSC within 45 Days post TKA revision in subjects 
treated with ciNPT as compared to SOC dressing. Section 4.11.1 describes the methods 
for ascertaining surgical site complications. Subject outcomes will be categorized using 
methods similar to those described in section 8.1.1. 
8.1.3.6. 
Safety Endpoint 
Adverse events will be coded using the MedDRA dictionary. Treatment-emergent adverse 
events (TEAE) are those which first appear or worsen after the application of the study 
treatment. Subject incidence of TEAEs will be summarized by system organ class and 
preferred term by treatment group.  
All adverse events occurring during the study will be listed by subject in data listings.  
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8.2. 
Analysis Sets 
The following analysis sets will be used: 
o
ITT Analysis Set – The ITT (intention-to-treat) Analysis Set will consist of all
randomized subjects. Subjects will be analyzed according to the treatment
allocated at randomization.
o
Safety Analysis Set – The Safety Analysis Set will consist of all randomized
subjects who received any study-related treatment procedures. It is
expected that all randomized subjects will be treated. All safety results will
be presented based on the Safety Analysis Set. Subjects will be analyzed
according to the study treatment they received immediately following the
TKA revision.
o
Modified ITT (mITT) Analysis Set – This set will include subjects in the ITT
Analysis Set with the following: 1) an SSC on or before 90 days post-TKA
revision or 2) no known occurrence of an SSC within 90 days of the TKA
revision and was assessed at least once on or after the 90th day following
the TKA revision. Subjects will be analyzed according to their randomized
treatment assignment.
o
Per-Protocol Analysis Set – This will include subjects in the mITT Analysis
Set and had no disqualifying protocol deviation(s) that would impact the
interpretation of the primary endpoint. The disqualifying protocol
deviation(s) for exclusion from this set will be defined and documented in a
blinded fashion prior to the final database lock by the Protocol Deviation
Review Committee. Subjects will be analyzed according to their randomized
treatment assignment.
o
Modified Per-Protocol (mPP) Analysis Set – This will include subjects in the
Per-Protocol Analysis Set excluding any subjects that received prohibited
therapy as described in section 4.15 or any subjects that received
alternative therapy following the study treatment period.
8.3. 
Planned Analysis and Data Summaries 
8.3.1. 
General Analysis Techniques 
In general, continuous variables will be summarized by providing the number of subjects 
with available data (n), the mean, median, standard deviation, minimum, and maximum 
values. For categorical variables, the number and percentage of subjects that are in each 
category will be provided. Unless otherwise specified, the denominator for percentages 
will be all relevant subjects in a particular analysis, including those for whom data are not 
available, i.e., “not reported” or “not available” will generally be considered a separate 
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category and included in the displays of data, with the denominator for percentages 
including these subjects. Subjects will be summarized by their assigned and actual 
treatment group (e.g., ciNPT and SOC).   
8.3.2. 
Subject Disposition 
Summaries of disposition will be tabulated by treatment group. The number and 
percentage of subjects in each analysis set will be described, as will the number (and 
percentage, if relevant) of subjects who: 
o provided informed consent; 
o failed screening, and reason for failing screening; 
o were randomized; 
o were randomized and treated; 
o discontinued early from the study for any reason, along with the reason for 
discontinuation (if the reason is adverse event, the system organ class and 
preferred term); and 
o completed the study as planned.  
Subject disposition also will be described in a flowchart (CONSORT diagram22). 
8.3.3. 
Demographic and Baseline Characteristics 
Demographic characteristics (age, sex, race, and ethnicity), baseline characteristics, and 
other disease characteristics, will be summarized according to the general techniques in 
section 8.3.1. Subjects in the Safety, ITT, mITT, Per-Protocol, and/or mPP Analysis Sets 
will be summarized within each treatment group and overall.  
8.3.4. 
Analysis of Primary Endpoint 
The analyses described in this section will be performed for the overall primary endpoint, 
“Any Surgical Site Complication (SSC)”, within 90 days of TKA revision, and repeated for 
each type of complication. 
The proportion of subjects with each possible result – “Occurred”, “No occurrences”, or 
“Incomplete follow-up” will be reported, using the mITT Analysis Set as the denominator. 
See section 8.1.1 for definitions of these outcomes. 
The comparative analysis of the primary endpoint will only consider subjects in the mITT 
Analysis Set, i.e., subjects with “Incomplete Follow-up” will be excluded. The proportions 
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of subjects with “Occurred” will be calculated within each treatment group and compared 
between treatment arms using a Cochran-Mantel-Haenszel (CMH) p-value stratified for 
type of revision (aseptic vs. septic). The difference between the proportions (ciNPT – 
SOC) and asymptotic 95% confidence interval will be computed. At the final analysis, a 
two-sided significance level adjusted for the interim efficacy analyses and potential 
sample size recalculation (e.g., α = 0.048 if interim look is at t=0.50 and no sample size 
adjustment is made) will be used to compare the SSC proportions between the two 
treatment arms. 
Supportive/exploratory analyses of the primary efficacy endpoint, SSC, may include: 
o
analyses comparing the treatment groups for the septic and aseptic
revisions;
o
analyses comparing the treatment groups for age, BMI, race/ethnicity,
material used in the revision, and sex subgroups;
o
analyses comparing the heterogeneity of the treatment groups across
clinical sites;
o
multivariable analyses comparing the treatment groups with covariate
adjustment where possible covariates might include (but not limited to) age,
BMI, sex, type of revision (aseptic or septic), and subject co-morbidities;
o
Fisher’s exact test presenting the unstratified p-value;
o
A repeat of any analysis above using the Per-Protocol and/or mPP Analysis
Sets;
and other exploratory analyses as deemed appropriate. 
8.3.5. 
Analysis of Secondary Endpoints 
Any SSI (superficial or deep) and Deep SSI will be analyzed in a similar fashion as the 
primary endpoint described in section 8.3.4. Superficial and Deep SSI will be analyzed 
separately and jointly; individual infection components will be summarized descriptively.  
8.3.6. 
Exploratory Endpoints 
In general, analyses will be performed on subjects in the ITT and/or mPP Analysis Sets 
using methods outlined in section 8.3.1. The number of subjects in each treatment arm 
at each scheduled visit with adequate assessments will be summarized for each visit. 
Assessments performed outside the scheduled visit windows may not be included in the 
models but will be listed separately. The patterns of missing data will be presented using 
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descriptive analyses. Other statistical analyses exploring the effects of imputation 
methods for non-response may be generated as appropriate. 
Because the analyses are exploratory, no adjustment will be made for multiple 
comparisons. Confidence intervals may not be created for subsets with less than ten 
subjects, although standard errors or deviations will be presented to provide a measure 
of variability. Complete details for all endpoints will be outlined in the Statistical Analysis 
Plan. 
8.3.7. 
Analysis of Safety Endpoint 
Treatment-emergent adverse events (TEAEs) will be summarized by treatment arm. For 
each coded medical term, the proportion of subjects who experience at least one 
treatment-emergent: 
o adverse event(s); 
o adverse event(s) related to treatment; 
o serious adverse event(s); 
o serious adverse event(s) related to treatment; 
o adverse event(s) leading to treatment/study discontinuation; or 
o serious adverse event(s) leading to treatment/study discontinuation 
will be reported. Subject incidence of TEAEs by severity (mild, moderate, severe) will also 
be presented. Events will be reported by MedDRA system organ class and preferred term. 
A listing of death(s), subjects who died of any cause during study, will be presented. 
8.4. 
Additional Statistical Details 
8.4.1. 
Hypothesis 
This study will assess whether closed incision negative pressure therapy (ciNPT) reduces 
the surgical site complications (SSCs) compared to standard of care (SOC) among 
subjects who undergo a total knee arthroplasty (TKA) revision. The primary endpoint is 
measured by the proportion of subjects with SSC within 90 days of TKA revision among 
subjects in the mITT Analysis Set; the corresponding null and alternative hypotheses are: 
Null:   ∆ciNPT-SOC = 0   
 
Alternative:   ∆ciNPT-SOC ≠ 0 
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where ∆ciNPT-SOC is the difference in the proportion of subjects in the ciNPT group 
population with at least one SSC – proportion of subjects in the SOC dressing group with 
at least one SSC.
8.4.2. 
Sample Size Determination 
The primary endpoint of this study is the subject incidence of SSC as defined in section 
4.11.1. The incidence rates of SSC are different for septic and aseptic revisions; the 
assumed SSC rate is 33% for septic and 6.9% for aseptic. This study plans to enroll at 
least 50% septic revisions overall. These enrollment rates lead to an assumed pooled 
SSC rate of 20% in the SOC dressing arm.  
Assuming an overall type 1 error rate of 0.05, with a two-sided hypothesis test, the study 
will have at least 80% power to detect a difference of 10% (50% reduction) in SSCs in the 
ciNPT arm with 199 subjects in each treatment arm, with one interim analysis at about 
50% of the evaluable subjects for a total of 398 subjects using the likelihood ratio test. 
With an estimated 5%-10% loss, a non-binding interim analysis for superiority at 
approximately 50% of the evaluable subjects using O’Brien-Fleming method for 
monitoring boundaries, the planned sample size will be inflated for potential loss of follow-
up for a total of 440 subjects. 
8.4.3. 
Randomization 
Subjects who meet all inclusion criteria and no exclusion criteria will be randomized in a 
1:1 ratio to either the ciNPT or SOC dressing treatment arm. The randomization will be 
stratified by status at revision (septic versus aseptic).   
For each stratum, a randomization schedule including randomization numbers and 
treatment assignments will be generated and maintained centrally in the web-based 
clinical database management system. Once randomized, a subject’s assignment cannot 
be altered or changed; a subject should not be randomized twice.  
8.4.4. 
Open-Label Study Reporting Results  
In order to reduce operational bias that can be introduced during the analysis, while the 
study is ongoing summary statistics by treatment groups across all sites will be limited to 
a small analytical group at the Sponsor not involved in the daily operations of the study. 
Treatment groups will be masked in the summary outputs (tables, listings, and figures) in 
order to reduce the inference should results be inadvertently accessed. The limited results 
of the interim analysis will be shared with Investigators and IRBs as necessary to conduct 
the study.  
Upon study completion, the full results will be shared with all investigators and clinical 
sites.  
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8.4.5. 
Interim Analysis 
An interim analysis may be conducted at information-time t=0.5, i.e., when approximately 
half the planned study subjects [n=200] have had their primary endpoint assessed. The 
interim analysis will be performed at the α=0.0052 level; if the p-value for the primary 
endpoint is < 0.0052, the study will be stopped and null hypothesis rejected. Otherwise, 
the final analysis will be conducted at α=0.048 (i.e., by constructing a 95.2% confidence 
interval) to preserve overall Type I error rate at 5%. These α values were chosen using 
an O’Brien-Fleming α-spending function assuming t = 0.5. The alpha levels that will be 
used at the interim and final will be calculated according the precise information time at 
the interim analysis.   
If warranted, based on the unblinded interim results, the final sample size may be 
increased using appropriate statistical methodology as described in Chen.23 The increase 
to the final sample size would only occur if the interim results had conditional power of 
success ≥ 50%, would be subject to the restrictions in Chen, and would not be considered 
statistically binding.  
At the interim analysis, the rate of SSC for septic and aseptic revisions will be examined 
to confirm assumptions of the sample size calculations.24 In addition, the rate of SSC will 
be independently assessed for septic and aseptic revisions at the interim analysis to 
determine if a modification of enrollment from a 1:1 ratio of septic:aseptic revisions to 
focus on enrollment for either revision type is needed. This type of adaptive enrichment 
design will be further detailed in the interim statistical analysis plan.25  
8.4.6. 
Study Sites 
This is a multi-center study following the same protocol and procedures. It is anticipated 
that approximately 15 study sites in North America will participate, and each site will 
randomize and treat subjects in both treatment groups. The data and the results of the 
study will be pooled across clinical sites and centers.   
8.4.7. 
Statistical Analysis Plans and Changes in Analyses 
Statistical Analysis Plans (SAPs) containing full details of the statistical analyses and 
execution will be prepared for both the interim analysis and the final analysis. The interim 
SAP (iSAP) will be finalized prior to conducting interim analysis. The final SAP (fSAP) will 
be finalized prior to locking the study database and the final analysis. Any changes from 
the planned analyses in this protocol, the iSAP, and/or the fSAP will be noted in the 
Clinical Study Report (CSR). 
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9.
HANDLING OF STUDY PRODUCTS
Study product receipt, use, dispensation, destruction, and return records will be 
maintained throughout the study.  
Upon receipt of product, the Investigator, or designee, will inventory the shipment and 
immediately notify KCI if study product or other study supplies are missing. The KCI 
monitor will verify that study product documentation is maintained appropriately during 
monitoring visits. 
At the completion of the study, there will be a final reconciliation of study product shipped, 
used, and unused. Any unused study product and associated supplies will be returned to 
KCI. 
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10. 
DATA HANDLING AND RECORD KEEPING 
10.1. 
Investigator/Study Site Training 
The Investigator and site staff will be trained on the protocol, the study products, and any 
specialized procedures prior to enrolling subjects into the study. KCI will provide support 
to site staff for any questions or concerns related to study products and procedures. KCI 
will not have influence on subject medical care.   
10.2. 
Electronic Case Report Form (eCRF) and Source Documents 
Source documents include all information in original records, certified copies of original 
records, observations, or other activities necessary for the reconstruction and evaluation 
of the study. All source documents should be completed in their entirety in a neat, legible 
manner to ensure accurate interpretation of the data.   
Data from source documents of each subject will be entered into the subject’s electronic 
Case Report Form (eCRF). Guidance for eCRF completion will be provided and reviewed 
with the site staff prior to receiving study product. 
10.3. 
Monitoring of Study Data 
The Investigator will allow access to his/her clinical study records for periodic on-site 
monitoring visits by a designated KCI representative, with the understanding that the 
representative is bound by professional secrecy and will not disclose a subject’s personal 
identity or personal medical information. The representative will review eCRFs for 
completeness during on-site monitoring visits and after the eCRFs are submitted; any 
discrepancies will be resolved with the Investigator or designee, as appropriate. The data 
will be entered into the clinical study database and verified for accuracy. 
10.4. 
Data Handling 
KCI is responsible for compilation and verification of the clinical study data, retention of 
the clinical study database, performance of statistical analysis, and preparation of the 
clinical study report. 
10.5. 
Records Retention 
The study site will maintain all study documentation and institute measures to prevent 
accidental or premature destruction of any data and/or documents related to the study.   
After formal discontinuation or completion of the study, the Investigator will retain all 
clinical study documentation for a minimum of two (2) years from the date the investigation 
is terminated or completed or in accordance with the regulations in effect for the 
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jurisdiction where the site is located. The Investigator will contact KCI prior to the 
destruction of any study records. 
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11. 
ADMINISTRATIVE REQUIREMENTS 
11.1. 
Good Clinical Practice (GCP) 
This study is to be conducted according to US and international standards of good clinical 
practice (FDA Title 21 part 812 and International Conference on Harmonization 
guidelines), applicable government regulations and institutional research policies and 
procedures.  
11.2. 
Ethical Considerations 
This study will be conducted in accordance with ethical principles founded in the 
Declaration of Helsinki. Approving IRBs will be provided all relevant study documentation 
in order to safeguard the rights, safety, and well-being of subjects as mandated. 
Participating Investigators will obtain IRB approval of the study prior to initiation at their 
sites. The protocol, Instructions for use, informed consent, written information given to 
subjects, safety updates, and any revisions to these documents will be provided to the 
IRB by the Investigator. 
11.3. 
Subject Informed Consent 
Written informed consent will be obtained from a potential Subject after the study has 
been fully explained and prior to the conduct of any study-related procedures. Obtaining 
informed consent is a process that must be documented in compliance with GCP, IRB 
and other applicable regulatory requirements (21 CFR part 50). The Investigator is 
responsible for continuing an open conversation with the subject in regard to their 
continued participation in the study. KCI will conduct periodic monitoring to ensure 
informed consent is obtained from each Subject prior to any study procedures. 
11.4. 
Confidentiality 
Information collected about subjects during the study will be kept confidential and 
managed according to the requirements of the IRB and Health Insurance Portability and 
Accountability Act of 1996 (HIPAA).   
In the event that a subject revokes authorization to collect or use Personal Health 
Information (PHI), the Investigator retains the ability to use all information collected prior 
to the revocation of subject authorization.   
11.5. 
Clinicaltrials.gov Registration 
A description of this study will be available on http://www.ClinicalTrials.gov as required by 
U.S. law. This website will not include information that identifies subjects. At most, the 
website will include a summary of the results of the study and will be available for public 
review at any time. 
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11.6. 
Auditing and Inspecting 
Participation as an Investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable compliance and quality assurance 
offices.  
The Investigator will permit study-related monitoring, audits, and inspections of all study 
related documents (e.g., source documents, regulatory documents, data collection 
instruments, study data) by the IRB/IEC, KCI, and government regulatory bodies.  
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12. 
PUBLICATION POLICY 
The publication policy for this study will be addressed in a separate agreement. 
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13.
REFERENCES
(1)  Hyldig N, Birke-Sorensen H, Kruse M et al. Meta-analysis of negative-pressure 
wound therapy for closed surgical incisions. Br J Surg 2016;103:477-486. 
(2)  Stannard JP, Volgas DA, McGwin G et al. Incisional negative pressure wound 
therapy after high-risk lower extremity fractures. J Orthop Trauma 2012;26:37-42. 
(3)  Grauhan O, Navasardyan A, Hofmann M, Muller P, Stein J, Hetzer R. Prevention of 
poststernotomy wound infections in obese patients by negative pressure wound 
therapy. J Thorac Cardiovasc Surg 2013;145:1387-1392. 
(4)  Matatov T, Reddy KN, Doucet LD, Zhao CX, Zhang WW. Experience with a new 
negative pressure incision management system in prevention of groin wound 
infection in vascular surgery patients. J Vasc Surg 2013;57:791-795. 
(5)  Bonds A, Novick T, Bearden J, Araghizadeh F, Olson C. Incisional negative pressure 
wound therapy significantly reduces surgical site infection in open colorectal surgery. 
(Proceedings of the American Society of Colon & Rectal Surgeons 2013 Annual 
Meeting, April 27 - May 1, 2013, Phoenix, AZ) [abstract]Bonds A, Novick T, Bearden 
J, Araghizadeh F, Olson C. Dis Colon Rectum 2013;56:e77 
(6)  Kurtz SM, Ong KL, Lau E, Bozic KJ. Impact of the economic downturn on total joint 
replacement demand in the United States: updated projections to 2021. Journal of 
Bone and Joint Surgery American Volume 2014;96:624-630. 
(7)  Suarez J, Griffin W, Springer B, Fehring T, Mason JB, Odum S. Why do revision 
knee arthroplasties fail? J Arthroplasty 2008;23:99-103. 
(8)  Bozic KJ, Lau E, Kurtz S, Ong K, Berry DJ. Patient-related risk factors for 
postoperative mortality and periprosthetic joint infection in medicare patients 
undergoing TKA. Clin Orthop 2012;470:130-137. 
(9)  American Joint Replacement Registry. Annual Report 2014: Second AJRR Annual 
Report on Hip and Knee Arthroplasty Data. American Joint Replacement Registry . 
2015. 
Rosemont, 
IL, 
American 
Joint 
Replacement 
Registry. 
Ref Type: Report 
(10)  Frosch P, Decking J, Theis C, Drees P, Schoellner C, Eckardt A. Complications after 
total knee arthroplasty: a comprehensive report. Acta Orthop Belg 2004;70:565-569. 
(11)  Debreuve-Theresette A, Diallo S, Siboni R, Ohl X, Dehoux E, Bajolet O. Infections 
in Total Hip and Total Knee Arthroplasty: Development of a Score To Assess 
Endogenous Risk of Surgical Site Infections. Surgical Infections 2015;16:794-798. 
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(12)  Yuan K, Chen HL. Obesity and surgical site infections risk in orthopedics: a meta-
analysis. International Journal of Surgery 2013;11:383-388. 
(13)  Pugely AJ, Martin CT, Gao Y, Schweizer ML, Callaghan JJ. The Incidence of and 
Risk Factors for 30-Day Surgical Site Infections Following Primary and Revision 
Total Joint Arthroplasty. J Arthroplasty 2015;30:47-50. 
(14)  Manoharan V, Grant AL, Harris AC, Hazratwala K, Wilkinson MP, McEwen PJ. 
Closed Incision Negative Pressure Wound Therapy vs Conventional Dry Dressings 
After Primary Knee Arthroplasty: A Randomized Controlled Study. J Arthroplasty 
2016;31:2487-2494. 
(15)  Cooper HJ, Bas MA. Closed-Incision Negative-Pressure Therapy Versus 
Antimicrobial Dressings After Revision Hip and Knee Surgery: A Comparative Study. 
J Arthroplasty 2016;31:1047-1052. 
(16)  No Authors. Prevena Incision Management System: Instructions for Use for 
Clinicians: Featuring Peel & Place Dressing and Customizable Dressing. 390218, 1-
33. 
2013. 
San 
Antonio, 
TX, 
KCI 
USA, 
Inc.  
Ref Type: Report 
(17)  Centers for Disease Control and Prevention. Surgical Site Infection (SSI) Event.  1-
31. 2017. Centers for Disease Control and Prevention, Atlanta, GA.  
Ref Type: Report 
(18)  KOOS. 
KOOS 
Scoring 
2012. 
 
2012. 
5-30-2017.  
Ref Type: Report 
(19)  KOOS. The 2012 User's Guide to: Knee injury and Osteoarthritis Outcome Score 
(KOOS). 
 
2012. 
5-30-2017.  
Ref Type: Report 
(20)  Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score 
(KOOS): from joint injury to osteoarthritis. Health and Quality of Life Outcomes 
2003;1:64. 
(21)  Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and 
Osteoarthritis Outcome Score (KOOS)--development of a self-administered 
outcome measure. J Orthop Sports Phys Ther 1998;28:88-96. 
(22)  CONSORT. The CONSORT Statement. www consort-statement org [serial online] 
2015; Available from: The CONSORT Group. Accessed January 23, 2015. 
(23)  Chen YH, DeMets DL, Lan KK. Increasing the sample size when the unblinded 
interim result is promising. Stat Med 2004;23:1023-1038. 
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(24)  Wang SJ, Hung HM, O'Neill RT. Adaptive patient enrichment designs in therapeutic 
trials. Biometrical Journal 2009;51:358-374. 
(25)  Food and Drug Administration (FDA). Adaptive Designs for Medical Device Clinical 
Studies: Guidance for Industry and Food and Drug Administration Staff.  7-27-2016. 
Silver 
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and 
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(FDA). 
Ref Type: Report 
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14. 
APPENDICES 
14.1. 
KOOS Questionnaire 
14.2. 
PROMIS 10 Questionnaire 
 
 
 
 
 
 
 
 
 
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