Hydromechanical Cleansing With V.A.C. VERAFLO CLEANSE CHOICE™ Dressing and NPWTi-d vs. Collagenase Ointment in the Management of Full-thickness Wounds
Phase: NA
Conditions: Wounds and Injuries, Wound Healing, Granulation Tissue
Sponsor: KCI USA, Inc

 
KCI.CLEANSE.CHOICE.2017.02 
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Hydromechanical Cleansing With V.A.C. VERAFLO CLEANSE 
CHOICE™ Dressing and NPWTi-d vs. Collagenase Ointment in the 
Management of Full-thickness Wounds 
(ACCELERATE Trial) 
PROTOCOL 
NUMBER 
KCI.CLEANSE.CHOICE.2017.02 
SPONSOR 
KCI® USA, Inc. 
6203 Farinon Drive 
San Antonio, Texas 78249 
Fax: 210.255.6760 
PROTOCOL 
VERSION/DATE 
Version 1.0, 24 May 2018  
Version 2.0, 24 August 2018 
Version 3.0, 08 March 2019 
Version 4.0, 15 August 2019 
Version 5.0, 13 February 2020 
 
 
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Acceptance of this document constitutes the agreement by the recipient that no unpublished information 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. 
 
 
 
NCT#: NCT03722485

 
 
 
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Study Synopsis 
TITLE: 
Hydromechanical Cleansing With V.A.C. VERAFLO 
CLEANSE CHOICE™ Dressing and NPWTi-d vs. 
Collagenase Ointment in the Management of Full-
thickness Wounds (Accelerate Trial) 
PROTOCOL 
NUMBER: 
KCI.CLEANSE.CHOICE.2017.02 
TYPE AND PHASE: 
A Multi-Center, Randomized, Controlled, Post-Market Open-
Label Study 
STUDY 
PRODUCT(S): 
V.A.C. 
VERAFLO 
CLEANSE 
CHOICE™ 
Dressing, 
V.A.C.ULTA™ Therapy Unit, Normal Saline 
Or 
Collagenase ointment 
STUDY 
OBJECTIVE(S): 
The primary objective of this study is to compare the short-
term effects of the V.A.C.ULTA™ Negative Pressure Wound 
Therapy System with instillation therapy using normal saline 
and V.A.C. VERAFLO CLEANSE CHOICE™ Dressing to 
collagenase ointment in wounds (chronic, acute, traumatic, or 
dehisced wounds) and/or ulcers (ie, full-thickness wounds). 
STUDY DESIGN: 
This randomized, controlled, prospective multicenter study will 
enroll Subjects diagnosed with wounds (chronic, acute, 
traumatic, or dehisced wounds) and/or ulcers (ie, full-thickness 
wounds) that measure ≥ 16 cm2 of total surface area, have a 
minimum width of 2 cm (excluding undermining) before sharp 
and/or mechanical removal of eschar at the bedside, and are < 
20 cm across (edge-to-edge) at any point perpendicular to the 
wound edges. Subjects will receive either V.A.C. VERAFLO 
CLEANSE CHOICE™ Dressing and Negative Pressure Wound 
Therapy with instillation and dwell time (NPWTi-d; V.A.C. 
VERAFLO™ Therapy with saline solution) or collagenase 
ointment to manage their wound over a 6-9-day period. Bedside 
sharp and/or mechanical debridement procedures will be 
performed to remove eschar prior to treatment; however, sharp 
and/or mechanical debridement will not be performed after 

 
 
 
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randomization during the treatment phase of the study period 
(up to 9 days).  
The study will randomize approximately 60 subjects from 
approximately 15 sites in a 1:1 ratio to either the V.A.C. 
VERAFLO CLEANSE CHOICE™ (ie, Treatment) arm or the 
collagenase ointment (ie, Control) arm after obtaining informed 
consent, undergoing screening procedures, and meeting all the 
inclusion criteria and none of the exclusion criteria. 
V.A.C. VERAFLO CLEANSE CHOICE™ Dressing: 
V.A.C. VERAFLO CLEANSE CHOICE™ Dressing will be 
applied to the wound bed and covered with drape material, 
providing a sealed environment for the application of NPWTi-d 
for a duration of 6-9 days. The dressing will be applied on Day 
0 and changed twice during the treatment period, allowing at 
least 48 hours between each dressing change. The first 
dressing change will occur on Day 2-3, and the second 
dressing change will occur on Day 4-6. The dressing will be 
removed on Day 6-9 at the treatment endpoint. 
Collagenase Ointment: 
Collagenase ointment will be used as the control for this study 
as it is a commonly used option for wound cleansing. After 
application of the ointment, the wound will be covered with a 
compatible standard-of-care (SOC) dressing for up to nine (9) 
days. During this treatment period, the ointment can be 
reapplied once daily (or more frequently if the dressing requires 
replacement). 
PRIMARY 
ENDPOINT: 
The percent change in the wound bed surface area (cm2) 
considered to be clean, healthy, and viable from baseline to 
Day 6-9 upon the final dressing removal. 
SECONDARY 
ENDPOINTS: 
• 
Percent change in total wound volume (cm3) from 
baseline to Day 6-9 upon the final dressing removal  
• 
Percent change in total wound area (cm2) from baseline 
to Day 6-9 upon the final dressing removal 
• 
Physician 
assessment 
of 
the 
need 
for 
surgical 
debridement upon completion of study treatment up to 
Day 6-9 
SAFETY 
ENDPOINT: 
The safety endpoint is the Subject incidence of adverse 
event(s). 

 
 
 
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NUMBER OF 
SUBJECTS 
PLANNED AND 
DURATION OF 
PARTICIPATION: 
Approximately 60 subjects will participate in this study. The 
total duration of participation may include up to 10 days of 
screening and up to nine (9) days of treatment. Subjects may 
have up to an additional 30 days of follow-up for safety for 
treatment-related adverse events that have not resolved by 
the final follow-up visit on Day 6-9. 
NUMBER OF 
STUDY SITES: 
This will be a multi-center study conducted at approximately 
15 study sites. 
INCLUSION 
CRITERIA: 
The Subject:  
1. 
is anticipated to be hospitalized for the duration of 
treatment (minimum of 6 days).  
2. 
is ≥ 18 years of age. 
3. 
or their legally authorized representative is able to provide 
informed consent.  
4. 
has been diagnosed with a wound (chronic, acute, 
traumatic, or dehisced wounds) and/or ulcer (ie, full-
thickness wounds) that meets the following criteria: 
a) 
total surface area measuring ≥ 16 cm2, including a 
minimum width of 2 cm (before removal of eschar at 
the bedside and excluding undermining). 
b) 
< 20 cm across (edge-to-edge) at any point 
perpendicular to the wound edges. 
5. 
has, in the opinion of the investigator, no more than 2/3 of 
the wound bed surface area considered to be clean, 
healthy, and viable. If eschar is present at baseline, it 
must be removed by bedside debridement prior to 
assessing the percentage of clean, healthy, viable wound 
bed. 
6. 
has a negative urine or serum pregnancy test at screening 
(if female and has potential for pregnancy) and is willing 
to take precautionary measures to prevent pregnancy 
during the duration of the study (up to 9 days). 
EXCLUSION 
CRITERIA: 
The Subject: 
1. 
has been diagnosed with a malignancy in the wound.  
2. 
has untreated osteomyelitis. 
3. 
has an untreated systemic infection. 

 
 
 
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4. 
has active cellulitis in the periwound area. 
5. 
has a known allergy or hypersensitivity to study 
materials: collagenase ointment, dressing(s), and/or dressing 
components such as acrylic adhesives or polyurethane. 
6. 
has, in the opinion of the investigator, a clinically 
significant condition that would impair the Subject’s ability to 
comply with the study procedures. 
7. 
has had radiation directly to the wound area. 
8. 
has been diagnosed with a major vascular deficit limiting 
arterial inflow to the wound region, as determined by the 
Investigator’s interpretation of the Subject’s medical history. 
9. 
has eschar in the wound that cannot be removed by 
bedside sharp and/or mechanical debridement. 
10. 
is participating in another interventional clinical trial for 
the duration of the study. 
11. 
has unexplored fistulas in the wound or fistulas in the 
wound that connect to other body cavities. 
12. 
has a wound with any tunneling present. 
13. 
has inadequate hemostasis at the wound site, as 
determined by the investigator. 
STUDY 
EVALUATION/VISIT 
SCHEDULE: 
Visit 1: Screening within 10 Days prior to and including Day 0 
Visit 2: Randomization and Study Treatment/Day 0 
Visit 3: Day 2-3 
Visit 4: Day 4-6 
Visit 5: End of Treatment/Day 6-9 
SAMPLE SIZE AND 
STATISTICAL 
METHODOLOGY: 
Analysis Sets 
The Safety Set will consist of all consented Subjects who have 
received either the V.A.C. VERAFLO CLEANSE CHOICE™ 
Dressing and NPWTi-d or collagenase ointment for any length 
of time. Subjects will be analyzed as treated. 
The Intent-to-Treat (ITT) Set will consist of all randomized 
Subjects. Subjects will be analyzed as randomized.  
The Modified Intent-to-Treat (mITT) Set will consist of all 
randomized Subjects who:  
i) 
met all the inclusion criteria and none of the exclusion 

 
 
 
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criteria 
ii) 
has no more than 2/3 of the wound bed surface area 
considered to be clean, healthy, viable wound bed as 
determined at the baseline measurement confirmed 
with 3D images by an independent assessor 
iii) 
received either the V.A.C. VERAFLO CLEANSE 
CHOICE™ Dressing and NPWTi-d or collagenase 
ointment  
iv) 
had the primary endpoint assessment on Day 6-9   
The Per-Protocol Analysis Set will consist of Subjects in the 
mITT who 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. Subject data will be analyzed in the arm to 
which they were randomized and treated. 
Analysis Methods 
For the primary endpoint, the percent change in the wound bed 
surface area (cm2) considered to be clean, healthy, and viable 
from baseline.   
The primary endpoint  will be analyzed using a repeated 
measures analysis of covariance model (ANCOVA) with 
treatment arm, visit, wound undermining measurement, clinical 
site, and treatment by visit (Note: if clinical site or treatment by 
visit are not statistically significant, then the non-significant 
term(s) will be removed from the model and the updated model 
will be re-run).  
Sample Size Determination 
Sample size determination is based on the primary endpoint. It 
was estimated that slough reduced by almost 20% in the 
Tender Wet 24 group and 10% in the Iruxol N group.1 Assuming 
a 20% increase in clean, healthy, viable wound bed surface 
area in the collagenase ointment group and a 40% increase in 
clean, healthy, viable wound bed surface area in the V.A.C. 
VERAFLO CLEANSE CHOICE™ Dressing and NPWTi-d, and 
a common standard deviation of 22%, 23 evaluable Subjects 
per group will provide approximately 80% power to detect a 
statistically significant difference using the Wilcoxon Rank-Sum 
test (n Query Advisor® 7.0).   

 
 
 
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It is possible that some wounds assessed by the independent 
assessor will not meet the baseline requirement of no more 
than 2/3 area of clean, healthy, viable wound bed, as measured 
by a 3D camera, even though the Investigator assessed the 
wound at ≤ 2/3 area of clean, healthy, viable wound bed. Such 
Subjects will be excluded from the mITT for the analysis of the 
primary endpoint. To allow for this possibility, plus the 
possibility that some Subjects may be lost to follow-up prior to 
their first post-baseline assessment at the Day 6-9 visit, the 
sample size is increased to a total of 60 randomized Subjects 
(ie, 30 Subjects per group). 
 
 
 

 
 
 
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PRINCIPAL INVESTIGATOR ACKNOWLEDGEMENT OF PROTOCOL 
I confirm that I have read the protocol entitled: “Hydromechanical Cleansing With V.A.C. 
VERAFLO CLEANSE CHOICE™ Dressing and NPWTi-d vs. Collagenase Ointment in 
the Management of Full-thickness Wounds” Version 5.0, dated 13 February 2020. 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.  
  
Site Name:__________________________________  Site #:___________________ 
 
Principal Investigator Name:  ____________________________________________ 
 
Signed:  __________________________________     Date:  ___________________ 
 
 
 

 
 
 
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ABBREVIATIONS 
3D 
Three-dimensional 
AE 
Adverse event 
BMI 
Body mass index 
CFR 
Code of Federal Regulations 
cm 
Centimeter 
cm2 
Square centimeters 
CRF 
Case report form 
CSR 
Clinical Study Report 
eCRF 
Electronic Case Report Form 
DFU 
Diabetic foot ulcer 
FDA 
Food & Drug Administration 
GCP 
Good Clinical Practice 
hCG 
Human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IDE 
Investigational device exemption 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ITT 
Intention-to-treat 
KCI® 
Kinetic Concepts, Inc. 
mITT 
Modified intent-to-treat 
mL 
Milliliter 
mmHg 
millimeters of mercury 
NP 
Negative pressure 
NPWT 
Negative pressure wound therapy  
NPWTi-d Negative pressure wound therapy with instillation and dwell time 
NSAID 
Non-steroidal anti-inflammatory drug 
PHI 
Personal health information 
RCT 
Randomized controlled trial 

 
 
 
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ROCF 
Reticulated open cell foam 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
Standard of care 
TEAE 
Treatment-emergent adverse event 
UADE 
Unanticipated Adverse Device Effect 
US 
United States 
VFCC 
V.A.C. VERAFLO CLEANSE CHOICE™ Dressing  
VLU 
Venous leg ulcer 
 
 

 
 
 
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TABLE OF CONTENTS 
1. 
INTRODUCTION ................................................................................................................................ 16 
1.1. 
BACKGROUND .............................................................................................................................. 16 
1.1.1. Review of Negative Pressure Wound Therapy with Instillation and Dwell Time (NPWTi-d) 
and V.A.C. VERAFLO CLEANSE CHOICE™ Dressing (VFCC) ....................................................... 17 
1.1.2. Collagenase Ointment ........................................................................................................... 19 
1.1.3. Rationale for Studying the Specific Population/Condition ..................................................... 19 
1.1.4. Rationale for Study Design .................................................................................................... 20 
1.1.5. Study Products ...................................................................................................................... 20 
1.1.6. Regulatory Status .................................................................................................................. 21 
1.1.7. V.A.C.ULTA™ Negative Pressure Wound Therapy System ................................................. 22 
2. 
STUDY OBJECTIVES ....................................................................................................................... 24 
3. 
STUDY DESIGN ................................................................................................................................. 25 
3.1. 
DESIGN SUMMARY ....................................................................................................................... 25 
3.1.1. V.A.C. VERAFLO CLEANSE CHOICE™ Dressing .............................................................. 26 
3.1.2. Collagenase Ointment ........................................................................................................... 26 
3.1.3. Duration of Study Participation .............................................................................................. 26 
3.2. 
PRIMARY ENDPOINT ..................................................................................................................... 26 
3.3. 
SECONDARY ENDPOINTS .............................................................................................................. 27 
3.4. 
EXPLORATORY ENDPOINTS ........................................................................................................... 27 
3.5. 
SAFETY ENDPOINT ....................................................................................................................... 28 
4. 
STUDY PROCEDURES AND ASSESSMENTS ................................................................................ 28 
4.1. 
INFORMED CONSENT .................................................................................................................... 28 
4.2. 
INCLUSION/EXCLUSION ................................................................................................................. 29 
4.2.1. Inclusion Criteria .................................................................................................................... 29 
4.2.2. Exclusion Criteria................................................................................................................... 30 
4.3. 
PREMATURE STUDY TERMINATION ................................................................................................ 31 
4.3.1. By Sponsor ............................................................................................................................ 31 
4.3.2. By IRB ................................................................................................................................... 31 
4.4. 
SUBJECT WITHDRAWAL OR TERMINATION ...................................................................................... 32 
4.4.1. Reasons for Withdrawal or Termination ................................................................................ 32 
4.4.2. Handling of Withdrawal or Termination ................................................................................. 32 
4.5. 
DEMOGRAPHICS AND SUBJECT CHARACTERISTICS ......................................................................... 32 

 
 
 
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4.6. 
MEDICAL AND SURGICAL HISTORY ................................................................................................ 33 
4.7. 
LABORATORY ASSESSMENT FOR PREGNANCY ............................................................................... 33 
4.8. 
RANDOMIZATION AND SUBJECT NUMBERING .................................................................................. 33 
4.9. 
WOUND ASSESSMENTS ................................................................................................................ 33 
4.10. 
BEDSIDE ESCHAR DEBRIDEMENT .................................................................................................. 34 
4.11. 
INITIAL APPLICATION OF STUDY TREATMENTS ................................................................................ 34 
4.11.1. V.A.C. VERAFLO CLEANSE CHOICE™ Dressing .............................................................. 34 
4.11.2. Collagenase Ointment ........................................................................................................... 35 
4.12. 
DRESSING CHANGES .................................................................................................................... 35 
4.12.1. V.A.C. VERAFLO CLEANSE CHOICE™ Dressing .............................................................. 36 
4.12.2. Collagenase Ointment ........................................................................................................... 36 
4.13. 
TREATMENT REMOVAL ................................................................................................................. 36 
4.13.1. V.A.C. VERAFLO CLEANSE CHOICE™ Dressing .............................................................. 36 
4.13.2. Collagenase Ointment ........................................................................................................... 37 
4.14. 
3D IMAGING ................................................................................................................................. 37 
4.15. 
CONCOMITANT MEDICATIONS ....................................................................................................... 37 
4.16. 
PROHIBITED PROCEDURES AND TREATMENTS ............................................................................... 38 
4.17. 
END OF STUDY ............................................................................................................................ 38 
5. 
VISIT SCHEDULE AND DESCRIPTION OF STUDY VISITS ........................................................... 39 
5.1. 
SCHEDULE OF VISITS ................................................................................................................... 39 
5.2. 
DESCRIPTION OF STUDY VISITS .................................................................................................... 40 
5.2.1. Visit 1/Screening/Days -10 to 0 ............................................................................................. 40 
5.2.2. Visit 2/Randomization/Day 0 ................................................................................................. 40 
5.2.3. Visit 3 and Visit 4/Follow-up Visits/Days 2-3 and Days 4-6 .................................................. 41 
5.2.4. Follow-up Visits/Visit 5/End of Treatment/Days 6-9 .............................................................. 41 
5.2.5. Unscheduled Visits ................................................................................................................ 41 
6. 
RISKS ASSOCIATED WITH STUDY PARTICIPATION ................................................................... 43 
7. 
SAFETY AND ADVERSE EVENTS ................................................................................................... 44 
7.1. 
DEFINITIONS ................................................................................................................................ 44 
7.1.1. Adverse Event (AE) ............................................................................................................... 44 
7.1.2. Serious Adverse Event (SAE) ............................................................................................... 44 
7.2. 
CLASSIFICATION ........................................................................................................................... 45 
7.2.1. Relationship to Study Treatment ........................................................................................... 45 
7.2.2. Severity .................................................................................................................................. 45 

 
 
 
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7.3. 
AE REPORTING PROCEDURES ...................................................................................................... 46 
7.4. 
AE COLLECTION/REPORTING PERIOD ........................................................................................... 46 
7.5. 
SAE REPORTING TO KCI® ............................................................................................................ 46 
7.6. 
UADE REPORTING - UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) ....................................... 46 
7.7. 
FOLLOW-UP PERIOD FOR ONGOING AES ....................................................................................... 47 
8. 
STATISTICAL CONSIDERATIONS .................................................................................................. 47 
8.1. 
ENDPOINT DEFINITIONS FOR ANALYSIS.......................................................................................... 47 
8.1.1. Primary Endpoint ................................................................................................................... 47 
8.1.2. Secondary Endpoints ............................................................................................................ 48 
8.1.2.1. 
Percent change in total wound volume ....................................................................................... 48 
8.1.2.2. 
Percent change in total wound area ........................................................................................... 48 
8.1.2.3. 
Physician assessment of need for debridement ......................................................................... 48 
8.1.3. Safety Endpoints ................................................................................................................... 49 
8.1.4. Exploratory Endpoints ........................................................................................................... 49 
8.2. 
ANALYSIS SETS............................................................................................................................ 49 
8.3. 
PLANNED ANALYSIS AND DATA SUMMARIES ................................................................................... 50 
8.3.1. General Analysis Techniques ................................................................................................ 50 
8.3.2. Subject Disposition ................................................................................................................ 50 
8.3.3. Demographic and Baseline Characteristics .......................................................................... 51 
8.3.4. Analysis of Primary Endpoint ................................................................................................ 51 
8.3.5. Analysis of Secondary Endpoints .......................................................................................... 52 
8.3.5.1. 
Percent change in total wound volume ....................................................................................... 52 
8.3.5.2. 
Percent change in total wound care ............................................................................................ 52 
8.3.5.3. 
Physician assessment of the need for debridement ................................................................... 52 
8.3.6. Exploratory Analyses ............................................................................................................. 52 
8.3.7. Analysis of Safety Endpoint ................................................................................................... 53 
8.4. 
ADDITIONAL STATISTICAL DETAILS ................................................................................................ 53 
8.4.1. Sample Size Determination ................................................................................................... 53 
8.4.2. Randomization....................................................................................................................... 54 
8.5. 
OPEN-LABEL STUDY REPORTING RESULTS ................................................................................... 54 
8.6. 
INTERIM ANALYSIS ....................................................................................................................... 54 
8.7. 
STATISTICAL ANALYSIS PLAN AND CHANGES IN ANALYSES ............................................................. 55 
9. 
HANDLING OF STUDY PRODUCTS ................................................................................................ 55 
10. DATA HANDLING AND RECORD KEEPING ................................................................................... 56 
10.1. 
INVESTIGATOR/STUDY SITE TRAINING ........................................................................................... 56 

 
 
 
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10.2. 
ELECTRONIC CASE REPORT FORM (ECRF) AND SOURCE DOCUMENTS .......................................... 56 
10.3. 
MONITORING OF STUDY DATA ....................................................................................................... 56 
10.4. 
DATA HANDLING .......................................................................................................................... 57 
10.5. 
RECORDS RETENTION .................................................................................................................. 57 
11. ADMINISTRATIVE REQUIREMENTS ............................................................................................... 57 
11.1. 
GOOD CLINICAL PRACTICE (GCP) ................................................................................................ 57 
11.2. 
ETHICAL CONSIDERATIONS ........................................................................................................... 57 
11.3. 
SUBJECT INFORMED CONSENT ..................................................................................................... 58 
11.4. 
CONFIDENTIALITY ......................................................................................................................... 58 
11.5. 
CLINICALTRIALS.GOV REGISTRATION ............................................................................................. 58 
11.6. 
AUDITING AND INSPECTING ........................................................................................................... 59 
12. REFERENCES ................................................................................................................................... 59 
 
 

 
 
 
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1. INTRODUCTION 
In the United States (US), nonhealing wounds are estimated to affect approximately 2% 
of the general population, and impaired wound healing is conservatively estimated to 
have an economic impact of $25 billion to $50 billion per year to the US economy.2;3 
Nonhealing wounds are thought to be in an unresolved pro-inflammatory state, which can 
result in the buildup of slough (proteinaceous exudate and fibrinous tissue form).4-6 This 
formation of slough along with nonviable tissue and other debris in a wound can promote 
an increase in bacterial bioburden, further contributing to delayed healing and wound 
chronicity. Therefore, a key aspect of wound management is the cleansing of wounds in 
order to remove slough, thick exudate, and potentially infectious materials (such as 
nonviable tissue) so as to obtain a clean, healthy, and viable wound bed. A major goal of 
wound cleansing is to clean the wound while avoiding trauma to the wound bed. Having 
a clean wound may help the wound progress through the inflammatory phase to the 
subsequent stages of healing. In fact, a clean, healthy, and viable wound bed is a 
necessary part of wound bed preparation so that wounds can heal, whether it be healing 
by secondary intention, or healing through a surgical intervention such as skin grafting, 
flap closure, or delayed primary intention.  
1.1. Background  
In the 1990s, Morykwas and Argenta introduced the use of negative pressure (NP) with 
a foam dressing.7 This method has been successfully commercialized and has become 
a standard of care among many wound types. In 1998, Fleischman et al combined the 
benefits of negative pressure wound therapy (NPWT) with timed, intermittent delivery of 
a topical solution via gravity.8 In 2003, KCI® commercialized the first gravity-based 
instillation NPWT (V.A.C. INSTILL™ Therapy) in combination with reticulated open cell 
foam (ROCF) into the wound healing arena. In 2010, KCI® re-engineered the product 
pump (V.A.C.ULTA™ Therapy Unit) to mechanically deliver the instillation solution to less 
hydrophobic foam dressing (V.A.C. VERAFLO™ Dressing, V.A.C. VERAFLO 
CLEANSE™ Dressing), which is referred to as negative pressure wound therapy with 
instillation and dwell time (NPWTi-d; V.A.C. VERAFLO™ Therapy; KCI®, an Acelity™ 

 
 
 
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Company). The combination of instilling a topical solution over the wound bed, soaking 
the wound in the solution, compressing and de-compressing the foam under cycles of 
negative pressure, and removing the fluids via NP is a gentle method of cleansing that 
appears to minimize the risk of cross-contamination9 and help decrease bacterial 
bioburden in the wound bed.10 However, NPWTi-d systems have historically been limited 
in their ability to remove large amounts of thick exudate through the foam dressing. 
Recently, a novel wound interface dressing containing an array of through holes (V.A.C. 
VERAFLO CLEANSE CHOICE™ Dressing) has been developed that may be an 
important technological advancement for NPWTi-d.  
1.1.1. 
Review of Negative Pressure Wound Therapy with Instillation and 
Dwell Time (NPWTi-d) and V.A.C. VERAFLO CLEANSE CHOICE™ Dressing 
(VFCC) 
While there is broad acceptance and a large body of evidence that supports NPWT as 
an important tool in aiding wound healing, the evidence for NPWTi-d to improve healing 
has been steadily growing throughout the years. Although there are no published 
randomized controlled trials (RCTs) involving the use of V.A.C. VERAFLO™ Therapy 
found during our literature review, KCI® has recently completed a clinical study titled, “A 
Prospective, Randomized, Multi-Center Trial Evaluating the Effectiveness of the 
V.A.C.ULTA™ Negative Pressure Wound Therapy System with V.A.C. VERAFLO™ 
Dressing System in Operatively Debrided Wounds.” Most evidence is limited to expert 
opinion, case reports, abstracts, small to large case series, and a few comparative 
studies. These publications describe the use of NPWTi-d on a variety of wound types, 
including open fractures,11 breast reconstruction,12 necrotizing fasciitis,11 upper and lower 
extremity wounds,13 pressure ulcers,11 venous leg ulcers (VLUs),14 diabetic foot ulcers 
(DFUs),14 and other complex wounds requiring surgical debridement.15;16 Significant 
variabilities in therapeutic methods (eg, number of cycles, dwell time, volume and type of 
instillate) exist in the literature; however, various clinical recommendations and guidelines 
have been developed to guide clinicians on the use of NPWTi-d.17-20 Furthermore, there 
are two (2) studies comparing NPWT to NPWTi-d.13;15 

 
 
 
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Since the introduction of V.A.C. VERAFLO™ Therapy, there have been several 
studies13;16;21 and clinical recommendations17-19 published on the use of instillation 
therapy across various wound types. However, the current literature is limited to two 
articles concerning NPWTi-d using V.A.C. VERAFLO CLEANSE CHOICE™ Dressing 
(VFCC). 
Teot et al22 retrospectively reviewed medical records from 21 patients with 21 large 
complex wounds that contained substantial areas of yellow, fibrinous slough who received 
treatment with V.A.C. VERAFLO™ Therapy using VFCC in an acute care setting. The 
wounds included a range of clinical situations, including difficult wounds with non-viable 
and/or fibrinous tissue on the wound surface. V.A.C. VERAFLO™ Therapy with VFCC 
was delivered by instilling normal saline with a 10-minute dwell time, followed by 3.5 hours 
of NP at -125 mmHg. The mean number of dressing changes was 2.9, and the mean 
duration of therapy was 8.7 days. V.A.C. VERAFLO™ Therapy with VFCC assisted in 
loosening, solubilizing, and detaching viscous exudate, dry fibrin, wet slough and other 
infectious materials. Wound management required an average of 1-3 VFCC dressing 
applications (3-9 days of V.A.C. VERAFLO™ Therapy), after which 18/21 (85.7%) 
wounds had ≤ 10% surface area with black non-viable tissue remaining and 12/21 
(57.1%) wounds had ≤ 10% surface area with yellow fibrinous slough remaining. A total 
of 20/21 (95.2%) wounds displayed enhanced granulation tissue formation and reduction 
in wound volume during use of V.A.C. VERAFLO™ Therapy with VFCC. The authors 
concluded that the adjunctive use of this therapy may be suitable for wound cleansing in 
chronic, complex wounds.22 
Fernandez et al23 recently reported on their initial experiences in the use of V.A.C. 
VERAFLO™ Therapy with VFCC in the treatment of five (5) complex pressure ulcer 
cases. The patients (3 females, 2 males) received debridement when possible, but were 
limited in undergoing surgery due to the presence of comorbidities or advanced age 
(range: 50-82 years). This article illustrates an algorithm approach used to determine the 
appropriate treatment to reach the goals of therapy for each patient. Treatment with 
V.A.C. VERAFLO™ Therapy with VFCC consisted of instillation of saline or a 

 
 
 
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hypochlorous solution with a dwell time of 10 minutes, followed by 2-3 hours of -125 
mmHg negative pressure. After an average of six (6) days of therapy, all wounds showed 
a reduction of non-viable tissue and rapid granulation tissue formation. In these cases, 
V.A.C. VERAFLO™ Therapy with VFCC provided effective and rapid removal of thick 
exudate and infectious materials and promoted the development of healthy tissue in the 
wound bed.23 
1.1.2. 
Collagenase Ointment  
One well-established method of cleansing wounds is to utilize collagenase ointment, 
which cleanses wounds through the enzymatic cleavage of denatured collagen in non-
viable tissue. Collagenase ointment is applied topically once daily and covered with a 
dressing until cleansing is complete.  
A recent systematic review and meta-analysis of RCTs supported the use of collagenase 
ointment over placebo or alternative therapies for wound healing (eg, wound size 
reduction or proportion of healed wounds) or wound cleansing (eg, time to clean wound 
bed or proportion of wounds completely cleansed) of pressure ulcers and DFUs.24 
Individual RCTs have also shown collagenase ointment to be effective in treating chronic 
ulcers and VLUs, but based on the limited number of RCTs for these wound types, the 
meta-analysis could not conclude that collagenase was favored.24 An independent review 
of RCTs and data from the US Wound Registry showed that collagenase ointment led to 
better wound healing outcomes (eg, wound closure) in pressure ulcers and VLUs when 
compared to alternative therapies.25 Assessment of cost-effectiveness in this review 
showed collagenase to also be more economical for pressure ulcers and DFUs when 
compared to other therapies.25    
1.1.3. 
Rationale for Studying the Specific Population/Condition 
Results from the published studies by Teot et al and Fernandez et al (summarized in 
Section 1.1.1 above) have provided the evidence needed to pursue this study. It is 
hypothesized that the mechanisms of action for NPWTi-d will offer a superior method of 
cleansing the wound and removing exudate, cellular debris, and infectious material. This 

 
 
 
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could help improve wound healing rates and reduce the risk for complications, thus 
resulting in clean, healthy, and viable wounds that lead to better outcomes for patients. 
Currently, NPWTi-d is only available in the inpatient hospital setting. The most common 
wounds in the inpatient hospital setting are traumatic wounds, post-surgical wounds, and 
pressure ulcers/injuries. Of these three types of wounds, pressure ulcers tend to present 
in a more consistent manner and often would benefit from wound cleansing. However, 
this study will not restrict the types of wounds that will be assessed.  
1.1.4. 
Rationale for Study Design 
In order to have the highest level of evidence, a prospective, multi-center RCT was the 
study design chosen. Collagenase ointment was selected as the comparator as it is 
utilized for wound cleansing in various types of wounds (see Section 1.1.2). The proposed 
study is designed to examine the potential benefits of V.A.C. VERAFLO™ Therapy using 
VFCC in wounds (eg, chronic, acute, traumatic, or dehisced wounds) and/or ulcers (ie, 
full-thickness wounds). It is hypothesized that NPWTi-d, in combination with VFCC will 
use hydromechanical cleansing action to loosen, disrupt and remove non-viable tissue, 
thereby increasing the wound bed surface area (cm2) considered to be clean, healthy, 
and viable. Using a volume of normal saline determined by the treating physician and 
default device settings for dwell time and NP, the effects of VFCC and V.A.C. 
VERAFLO™ Therapy will be studied and compared to collagenase ointment. The follow-
up time period of 6-9 days is selected due to the series published by Teot et al, where 
V.A.C. VERAFLO™ Therapy using VFCC was reported to increase the percent surface 
area of viable tissue (granulation tissue) in the majority of patients after an average of 1-
3 dressing changes (3-9 days).22 
1.1.5. 
Study Products 
The following devices and dressings will be the therapies for the two (2) treatment groups: 
• V.A.C.ULTA™ Negative Pressure Wound Therapy System with instillation therapy 
(ie, V.A.C. VERAFLO™ Therapy) using VFCC and normal saline 
• Collagenase ointment with compatible standard dressing 

 
 
 
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1.1.6. 
Regulatory Status 
The prospective, post-market clinical study described in this protocol will assess the 
effectiveness and functional performance of the V.A.C.ULTA™ Negative Pressure 
Wound Therapy System using VFCC and the instillation of saline. 
The V.A.C.ULTA™ Negative Pressure Wound Therapy System is a 510(k)–cleared, 
Class II device (K100657) with the following indication for use:  “the V.A.C.ULTA™ 
Negative Pressure Wound Therapy System is an integrated wound management system 
that provides negative pressure wound therapy with an instillation option. Negative 
pressure wound therapy in the absence of instillation is intended to create an environment 
that promotes wound healing by secondary or tertiary (delayed primary) intention by 
preparing the wound bed for closure, reducing edema, promoting granulation tissue 
formation and perfusion, and by removing exudates and infectious material. The 
instillation option is indicated for patients who would benefit from vacuum-assisted 
drainage and controlled delivery of topical wound treatment solutions and suspensions 
over the wound bed. The V.A.C.ULTA™ Negative Pressure Wound Therapy System, with 
and without instillation, is indicated for patients with chronic, acute, traumatic, sub-acute 
and dehisced wounds, partial-thickness burns, ulcers (such as diabetic, pressure and 
venous insufficiency), flaps and grafts”. The V.A.C.ULTA™ Therapy Unit is for use with 
only V.A.C.® Dressings (V.A.C.® GRANUFOAM™ Dressing, V.A.C. GRANUFOAM 
SILVER™ Dressing, V.A.C. WHITEFOAM™ Dressing, V.A.C. VERAFLO™ Dressing 
Systems) and disposables. For those Subjects who are randomized into the Treatment 
arm, V.A.C. VERAFLO™ Therapy will be applied using the V.A.C.ULTA™ Unit and 
VFCC. VFCC is intended for use with V.A.C. VERAFLO™ Therapy as provided by the 
V.A.C.ULTA™ Therapy Unit. VFCC was cleared under the V.A.C.ULTA™ Negative 
Pressure Wound Therapy System 510(k) (K160451). It is recommended for use with open 
wounds, including wounds with shallow undermining or tunnel areas where the distal 
aspect is visible. 
In this study, various types of wounds will be studied. For this study, the V.A.C.ULTA™ 
Negative Pressure Wound Therapy System and VFCC will be used in accordance with 

 
 
 
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their cleared labeling and indications for use and are, therefore, exempt from the 
investigational device exemptions (IDE) regulation because they meet the conditions for 
an exempt investigation as provided in 21 CFR 812.2 (c) (2). The system’s indications, 
contraindications, warnings, precautions, and instructions can be found in the 
V.A.C.ULTA™ Negative Pressure Wound Therapy System Instructions for Use (IFU) 
document.  
1.1.7. 
V.A.C.ULTA™ Negative Pressure Wound Therapy System 
The V.A.C.ULTA™ Negative Pressure Wound Therapy System offers two methods of 
therapy. The therapy unit delivers both V.A.C.® Therapy (V.A.C.ULTA™ Therapy without 
instillation) and V.A.C. VERAFLO™ Therapy (V.A.C.ULTA™ with instillation). 
The SENSAT.R.A.C.™ Dressing/Technology allows egress of fluid from the wound bed, 
measures pressure at the wound site, and connects the dressing to the canister tubing.  
An exudate canister attaches to the side of the therapy unit and holds the wound and 
instillation fluid collected from the wound bed.  
The V.A.C. VERAFLO™ Therapy option allows for NPWT and instillation of topical wound 
solutions. The VERAFLO™ Therapy cycle is comprised of an instillation period, a solution 
dwell or soak period, and an NP period. The user programs the volume of solution to be 
delivered to the wound bed, the length of time the solution will be allowed to dwell in the 
wound, and the length of time NP will be applied before the instillation cycle repeats. 
V.A.C. VERAFLO™ Therapy using the V.A.C.ULTA™ Negative Pressure Wound 
Therapy System also includes (Table 1): 
• An instillation cassette (V.A.C. VERALINK™ Cassette) connects a solution 
bag/bottle and the dressing tubing to the therapy unit. The cassette holds and 
delivers user-provided wound solutions to the wound bed via the automated 
volumetric pump.  
• The V.A.C. VERAT.R.A.C.™ Pad incorporates tubing for fluid input, exudate/fluid 
removal, as well as pressure sensing at the wound site. 

 
 
 
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• The V.A.C. VERAFLO CLEANSE CHOICE™ Dressing Kit contains VFCC, which 
is similar to the V.A.C.® GRANUFOAM™ Dressing but is less hydrophobic for 
enhanced fluid distribution. VFCC also has improved mechanical properties, 
including a higher tensile strength. The V.A.C. VERAFLO CLEANSE CHOICE™ 
Dressing Kit also contains a polyurethane drape (V.A.C.® Advance Drape) with 
acrylic adhesive, a V.A.C. VERAT.R.A.C.™ Pad, a ruler and 3M™ Cavilon™ No 
Sting Barrier Film. 
• Disposable canisters for the collection of wound exudate are available in three 
sizes:  300 mL, 500 mL, and 1000 mL. For this study, the 1000-mL canisters will 
be provided due to instillation. 

 
 
 
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Table 1: V.A.C.ULTA™ Therapy and V.A.C. VERAFLO CLEANSE CHOICE™ Dressing 
Kit components. 
Name/Description 
Picture/Diagram 
V.A.C.ULTA™ Therapy Unit 
 
Exudate Canisters 
Single-patient use, disposable canister 
(1000 mL). 
 
Instillation 
Cassette 
(V.A.C. 
VERALINK™ Cassette) 
Single patient use, disposable cassette 
with a spike. 
 
V.A.C. VERAFLO CLEANSE CHOICE™ 
Dressing Kit 
For 
Subjects 
in 
the 
V.A.C.ULTA™ 
Therapy with instillation Treatment arm 
only.  
Contains: V.A.C. VERAFLO CLEANSE 
CHOICE™ Dressing; V.A.C.® Advanced 
Drape; V.A.C. VERAT.R.A.C.™ Pad; 
Ruler; Cavilon™ No Sting Barrier 
 
2. STUDY OBJECTIVES 
The primary objective of this study is to compare the short-term effects of the 
V.A.C.ULTA™ Negative Pressure Wound Therapy System with instillation therapy using 
normal saline and V.A.C. VERAFLO CLEANSE CHOICE™ Dressing to collagenase 
ointment in wounds (eg, chronic, acute, traumatic, or dehisced wounds) and/or ulcers (ie, 
full-thickness wounds). 

 
 
 
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3. STUDY DESIGN 
3.1. Design Summary 
ACCELERATE Study Schema 
Up to 10 Days 
Day 0 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
Day 9 
SCREENING 
RANDOMIZATION 1:1 
Collagenase Ointment Treatment 
Daily treatment for 6-9 days 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
VFCC and NPWTi-d Treatment 
Total treatment 6-9 days 
  
  
First change 
  
  
Second change 
  
  
End of Treatment 
  
  
  
  
  
  
  
  
  
This randomized, controlled, prospective multicenter study will enroll Subjects diagnosed 
with wounds (eg, chronic, acute, traumatic, or dehisced wounds) and/or ulcers (ie, full-
thickness wounds) that measure ≥ 16 cm2 of total surface area, have a minimum width of 
2 cm (excluding undermining) before sharp and/or mechanical removal of eschar at the 
bedside, and are < 20 cm across (edge-to-edge) at any point perpendicular to the wound 
edges. Subjects will receive either VFCC and NPWTi-d (V.A.C. VERAFLO™ Therapy 
with saline solution) or collagenase ointment to manage their wound over a 6-9-day 
period. Bedside sharp and/or mechanical debridement procedures will be performed to 
remove eschar before randomization; however, sharp or mechanical debridement will not 
be performed after randomization during the treatment phase of the study period (up to 9 
days).  
For the purposes of this study, we will define and assess viable tissue. Viable tissue will 
not include the following:  non-viable tissue, which can be loose or firmly adherent, hard, 
soft, dry, or wet. Slough is defined as a type of non-viable fibrinous tissue that consists of 
fibrin, pus, and proteinaceous material, and could be yellow, white, tan, gray, or green in 
appearance.  

 
 
 
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The study will randomize approximately 60 Subjects from approximately 15 sites in a 1:1 
ratio to either the VFCC (ie, Treatment) arm or the collagenase ointment (ie, Control) arm 
after obtaining informed consent, undergoing screening procedures, and meeting all the 
inclusion criteria and none of the exclusion criteria. 
3.1.1. 
V.A.C. VERAFLO CLEANSE CHOICE™ Dressing 
VFCC dressing will be applied to the wound bed and covered with drape material, 
providing a sealed environment for the application of NPWTi-d for a duration of 6-9 days. 
The dressing will be applied on Day 0 and changed twice during the treatment period, 
allowing at least 48 hours between each dressing change. The first dressing change will 
occur on Day 2-3, and the second dressing change will occur on Day 4-6. The dressing 
will be removed on Day 6-9 at the treatment endpoint. 
3.1.2. 
Collagenase Ointment 
Collagenase ointment will be used as the control for this study as it is a commonly used 
option for wound cleansing. After application of the ointment, the wound will be covered 
with a compatible standard-of-care (SOC) dressing for up to nine (9) days. During this 
treatment period, the ointment can be reapplied once daily (or more frequently if the 
dressing requires replacement). 
3.1.3. 
Duration of Study Participation 
The duration of study participation for each Subject is as follows: 
• Screening Period: up to 10 days (Day -10 to Day 0) 
• Treatment Period: up to nine (9) days (Day 0 to Day 9) 
The maximum participation duration per Subject is up to 19 days.   
3.2.  Primary Endpoint 
The percent change in the wound bed surface area (cm2) considered to be clean, healthy, 
and viable from baseline to Day 6-9 upon the final dressing removal. 
 

 
 
 
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3.3. Secondary Endpoints 
The secondary endpoints are as follows:  
• Percent change in total wound volume (cm3) from baseline to Day 6-9 upon the 
final dressing removal  
• Percent change in total wound area (cm2) from baseline to Day 6-9 upon the final 
dressing removal 
• Physician assessment of the need for surgical debridement upon completion of 
study treatment up to Day 6-9 
3.4. Exploratory Endpoints 
The exploratory endpoints are as follows: 
• The absolute change from baseline to Day 6-9 upon the final dressing removal in 
the wound bed surface area (cm2) considered to be clean, healthy, and viable, in 
the total wound area, and in the total wound volume 
• The percent change and absolute change of granulation tissue from baseline to 
Day 6-9 upon the final dressing removal 
• Number of treatment applications and/or dressing changes per Subject (ie, 
collagenase ointment applications versus VFCC applications) 
• Total time to perform treatment applications and/or dressing changes per Subject 
In addition to these exploratory endpoints, the following data will be collected from 
Subjects in one of the groups: 
• Total number of collagenase ointment tubes used per Subject 
• Number of blockage and leak alarms (obtained from the V.A.C.ULTA™ Therapy 
Unit log) 
Additional exploratory endpoints may be added and will be detailed in the statistical 
analysis plan (SAP). 

 
 
 
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3.5. Safety Endpoint 
The safety endpoint is the Subject incidence of adverse event(s) (AEs). 
4. STUDY PROCEDURES AND ASSESSMENTS 
4.1. Informed Consent 
The Investigator, or designee, will discuss the purpose of this study with potential 
Subjects or their legally authorized representative if the Subject is unable to provide their 
own informed consent. Each individual will review the Informed Consent Form (ICF) 
approved by the local Institutional Review Board (IRB). The ICF must be signed according 
to IRB requirements before the Subject can undergo any study-related procedures. 
Informed consent will be obtained under these conditions: 
• Subjects or their legally authorized representatives 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. 
• Subjects or their legally authorized representatives must be given the opportunity 
to ask the Investigator questions and must be provided time to consider 
participation in the study. 
• ICFs will be written in a manner that is non-technical and understandable to the 
Subject or their legally authorized representative.   
• Subjects or their legally authorized representatives 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 for negligence. 
• Subjects or their legally authorized representatives will be asked to sign and date 
the ICF indicating their informed consent to participate in the study. 
• The Investigator’s responsibilities during the ICF process include: 

 
 
 
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o screening out potential Subjects who may not be able or willing to comply with 
the study protocol. 
o ensuring that Subjects or their legally authorized representatives have signed 
the ICF prior to undergoing any study-related assessments.  
o ensuring that each Subject or their legally authorized representative receives a 
copy of the signed ICF. 
4.2. Inclusion/Exclusion 
In order to be considered for randomization, a Subject must meet all eligibility criteria and 
be assessed no more than 10 days prior to the treatment application. 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. Inclusion and exclusion criteria will be 
reconfirmed immediately prior to randomization if Visit 1 and Visit 2 are on different dates. 
4.2.1. 
Inclusion Criteria 
The Subject: 
1. is anticipated to be hospitalized for the duration of treatment (minimum of 6 days).  
2. is ≥ 18 years of age. 
3. or their legally authorized representative is able to provide informed consent. 
4. has been diagnosed with a wound (eg, chronic, acute, traumatic, or dehisced 
wounds) and/or ulcer (ie, full-thickness wounds) that meets the following criteria: 
a) total surface area measuring ≥ 16 cm2, including a minimum width of 2 cm 
(before removal of eschar at the bedside and excluding undermining). 
b) < 20 cm across (edge-to-edge) at any point perpendicular to the wound 
edges. 
5. has, in the opinion of the investigator, no more than 2/3 of the wound bed surface 
area considered to be clean, healthy, and viable. If eschar is present at baseline, 
it must be removed by bedside debridement prior to assessing the percentage of 

 
 
 
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clean, healthy, and viable wound bed. 
6. has a negative urine or serum pregnancy test at screening (if female and has 
potential for pregnancy) and is willing to take precautionary measures to prevent 
pregnancy during the duration of the study (up to 9 days). 
4.2.2. 
Exclusion Criteria 
The Subject: 
1. has been diagnosed with malignancy in the wound. 
2. has untreated osteomyelitis. 
3. has an untreated systemic infection. 
4. has active cellulitis in the periwound area. 
5. has a known allergy or hypersensitivity to study materials: collagenase ointment, 
dressing(s), and/or dressing components such as acrylic adhesives or 
polyurethane. 
6. has, in the opinion of the investigator, a clinically significant condition that would 
impair the Subject’s ability to comply with the study procedures. 
7. has had radiation directly to the wound area. 
8. has been diagnosed with a major vascular deficit limiting arterial inflow to the 
wound region, as determined by the Investigator’s interpretation of the Subject’s 
medical history. 
9. has eschar in the wound that cannot be removed by bedside sharp and/or 
mechanical debridement. 
10. is participating in another interventional clinical trial for the duration of the study. 
11. has unexplored fistulas in the wound or fistulas in the wound that connect to other 
body cavities. 
12. has a wound with any tunneling present. 

 
 
 
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13. has inadequate hemostasis at the wound site, as determined by the investigator. 
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 the clinical study for business or ethical reasons at 
any time, such as, but not limited to: 
• Information regarding the study product causes doubt as to the benefit/risk ratio. 
• 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: 
• Investigator(s) lack of compliance with the approved study protocol and/or 
applicable regulatory or IRB guidelines in conducting the study 
• Incidence or severity of AEs indicates a potential health hazard or poses an 
unreasonable risk to the study participants 
• Subject enrollment is unsatisfactory 
• Fraud or misconduct 
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. 

 
 
 
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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 the participation of a Subject from the study 
with or without their consent for any of the following reasons: 
• Adverse events 
• Noncompliance 
• For any reason that may, in the opinion of the Investigator, negatively affect the 
safety or well-being of the Subject 
4.4.2. 
Handling of Withdrawal or Termination 
Every effort should be made to complete wound and AE assessments prior to the Subject 
withdrawal. 
For Subjects who are lost to follow-up, the Investigator will make attempts to collect at 
least the vital status (eg, 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 or legally authorized representative signs the informed 
consent and before treatment application:  

 
 
 
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• Subject characteristics 
• Comorbidities 
• Wound history and characteristics 
4.6. Medical and Surgical History 
As part of screening procedures, the Investigator or a medically licensed sub-investigator, 
or a practitioner working under the licensure of the Investigator or sub-investigator, will 
collect a complete medical and surgical history for each Subject. If the screening visit and 
randomization occur on different days, the medical and surgical history will be updated (if 
changes have occurred) at the randomization visit prior to treatment application. 
4.7. Laboratory Assessment for Pregnancy 
Serum or urine assessment for human chorionic gonadotropin (hCG) to determine 
pregnancy status in female Subjects of child-bearing potential will be conducted during 
screening. 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. 
4.8. Randomization and Subject Numbering 
Consented Subjects will be assigned a unique Subject identifier. 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. Randomization to study treatment will be centralized, electronic, and 
web-based.   
If a screened Subject does not meet all inclusion criteria or meets any exclusion criteria, 
the Subject will not be randomized and will be considered a screen failure. 
4.9. Wound Assessments 
Wound assessments will be performed by the Investigator or a medically licensed sub-
investigator, or a practitioner working under the licensure of the Investigator or sub-
investigator, according to the schedule of visits in order to capture key features of study 

 
 
 
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wounds (such as odor). A measurement of the study wound will be performed only to 
determine Subject eligibility. 
4.10. Bedside Eschar Debridement  
Bedside sharp and/or mechanical debridement procedures will be allowed before 
randomization to remove eschar. However, sharp or mechanical debridement of the study 
wound after randomization is not permitted. For those Subjects having bedside sharp 
and/or mechanical debridement prior to randomization, there will be two wound 
assessments prior to initiation of treatment.  
1) Prior to debridement, the investigator or a medically licensed sub-investigator, or 
a practitioner working under the licensure of the Investigator or sub-investigator, 
will measure the wound to confirm that the wound size matches inclusion criteria 
#4 in Section 4.2.1. In addition, a three-dimensional (3D) image of the wound will 
be taken prior to debridement. 
2) After debridement, the investigator will assess the wound to confirm the wound 
has no more than 2/3 viable tissue. In addition, a 3D image of the wound will be 
taken after debridement. This 3D image will be used for the baseline measurement 
that subsequent images are compared to for any changes in size/tissue 
composition. 
4.11. Initial Application of Study Treatments 
4.11.1. 
V.A.C. VERAFLO CLEANSE CHOICE™ Dressing  
For Subjects randomized to the Treatment arm, VFCC will be placed in the wound 
according to the manufacturer’s instructions (safety information and application 
instructions are provided with the study products). The dressing will be covered with semi-
occlusive V.A.C.® Advanced Drape with a quarter-sized hole cut in the drape for the 
V.A.C. VERAT.R.A.C.™ Pad. The pad should be placed directly over the hole. The 
normal saline solution will be connected to the system. The pre-programmed therapy unit 
will then be set to V.A.C. VERAFLO™ Therapy and initiated to deliver a volume 
determined by the physician along with a 10-minute soak time followed by 3.5 hours of 

 
 
 
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V.A.C.® Therapy with a pressure of -125 mmHg. During the unit’s initial drawdown, the 
Investigator will evaluate that there is no indication of a system leak using the Seal Check 
tool. The Investigator or a medically licensed sub-investigator, or a practitioner working 
under the licensure of the Investigator or sub-investigator, will document therapy unit 
settings (dwell time, pressure, and cycle time), that the system is operational, and that 
application of the assigned therapy is successful. Additional V.A.C.® Advanced Drape 
can be applied to the dressing if needed to assist in mitigating leaks. 
The Fill Assist feature on the pump allows the user to monitor initial wound fill by manually 
starting and stopping instillation to determine correct instill volume after the dressing is 
applied. The Fill Assist procedure will be performed twice each time a new dressing is 
placed in the wound. The first time the Fill Assist is performed, the dressing is completely 
saturated to assist in filling or priming the dressing with a solution and purging the air in 
the foam. The second Fill Assist procedure is done to determine the appropriate volume 
to be instilled during therapy. The volume determined from the second Fill Assist 
procedure will be recorded.  
Dressing changes are addressed in Section 4.12. Treatment removal is addressed in 
Section 4.13. 
4.11.2. 
Collagenase Ointment 
For Subjects randomized to the Control arm, the collagenase ointment will be placed in 
the wound according to the manufacturer’s instructions (application instructions are 
provided with the study products). The approximate therapy amount (such as the total 
number of tubes used) will be documented. The wound will be covered with a compatible 
standard dressing, and dressing materials will be documented. 
Dressing changes are addressed in Section 4.12. Treatment removal is addressed in 
Section 4.13. 
4.12. Dressing Changes 
The date, start time, and end time of each dressing change for both treatment groups 
(see Sections 4.12.1 and 4.12.2 below) will be documented by the Investigator or a 

 
 
 
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medically licensed sub-investigator, or a practitioner working under the licensure of the 
Investigator or sub-investigator. 
4.12.1. 
V.A.C. VERAFLO CLEANSE CHOICE™ Dressing  
Dressing changes and treatment application can occur at the bedside. Therapy 
application instructions are provided with the study products. Dressing change frequency 
will follow the study schedule of visits (refer to Section 5.1). Dressing changes should not 
occur more frequently than 48 hours from the previous dressing change unless a 
replacement is required to maintain therapy. At each dressing change, the Investigator or 
a medically licensed sub-investigator, or a practitioner working under the licensure of the 
Investigator or sub-investigator, will document therapy unit settings (dwell time, pressure, 
and cycle time), that the system is operational, and that application of the assigned 
therapy is successful for all dressing changes.  
4.12.2. 
Collagenase Ointment 
Dressing changes and treatment application can occur at the bedside. Therapy 
application and dressing changes should be made following the instructions available in 
the package insert of the product. Dressing changes can occur daily for patients 
randomized to the collagenase ointment group (or more frequently if dressings become 
soiled). The approximate therapy amount (such as the total number of tubes used) will be 
documented for all dressing changes. The wound will be covered with a compatible 
standard dressing, and dressing materials will be documented for all dressing changes. 
4.13. Treatment Removal 
4.13.1. 
V.A.C. VERAFLO CLEANSE CHOICE™ Dressing  
Subjects will remain hospitalized and on Study Treatment therapy for two (2) dressing 
changes (ie, 6 to 9 days). Dressing removal should not occur prior to 48 hours from the 
previous dressing change unless a replacement is required to maintain therapy. The 
Investigator may then use their wound treatment of preference to ensure the continuation 
of wound care. The date and time of dressing removal will be documented. 

 
 
 
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4.13.2. 
Collagenase Ointment 
Subjects will remain on Study Treatment therapy for six (6) to nine (9) days. The 
Investigator may then use their wound treatment of preference to ensure the continuation 
of wound care. The date and time of dressing removal will be documented. 
4.14. 3D Imaging 
Three-dimensional wound images will be captured for each study visit using a specialized 
imaging system. Imaging guidelines, equipment, and supplies will be provided to the 
investigational sites by KCI®. 
The 3D images collected from each site will be aggregated into a single database. The 
aggregated images will be analyzed/measured by the independent assessor. The 
independent assessor will determine and plot the wound perimeter, the clean, healthy, 
viable tissue, and other tissue types for each image. The imaging software will be used 
to calculate wound length, width, surface area, and wound volume. The values of these 
parameters/assessments will be used for calculations of the primary endpoint as 
described in section 8.1.1 and the secondary endpoints described in sections 8.1.2.1 and 
section 8.1.2.2. The 3D wound images should not be used to guide patient treatment. 
4.15. Concomitant Medications 
Concomitant medications will be collected from the time of randomization through the end 
of the study. The medication name, start date, end date, and indication will be reported. 
Special consideration should be given to report medications that may affect the healing 
process, such as:  
• opioid medications (such as morphine)  
• immunosuppressants 
• corticosteroids 
• non-steroidal anti-inflammatory drugs (NSAID) 
• anticoagulant agents (such as heparin)   

 
 
 
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• all medications with a prophylactic indication 
• all medications the Subject is given to treat an AE during the study 
4.16. Prohibited Procedures and Treatments 
Temporary coverage of the wound for the duration of the study with cell-based skin 
substitute products such as Apligraf® (Organogenesis), Dermagraft® (Advanced 
BioHealing), and cadaveric skin is prohibited. For patients in the Control group 
(collagenase ointment), ointment removal should be performed in a gentle manner and is 
not intended to be an aggressive mechanical debridement. For Subjects in both groups, 
no forms of mechanical debridement should be performed for the duration of the study. 
4.17. End of Study 
The following information will be documented: 
• Last day of study participation 
• Completion status – Did Subject complete the study (ie, 6-9 days of therapy)? 
• Reason for study discontinuation 

 
 
 
 
 
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5. VISIT SCHEDULE AND DESCRIPTION OF STUDY VISITS  
5.1. Schedule of Visits  
Procedure Description 
Visit 1 
Visit 2 
Visit 31 
Visit 41 
Visit 51 
Unscheduled 
Screening 
Randomization 
 
 
End of Treatment 
 
Day -10 to 0 
Day 0 
Day 2-3 
Day 4-6 
Day 6-9 
 
Informed Consent 
X 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X2 
 
 
 
 
Demographics and Subject 
Characteristics 
X 
 
 
 
 
 
Medical and Surgical History 
X 
X3 
 
 
 
 
Laboratory Assessment for 
Pregnancy 
X 
 
 
 
 
 
Wound Assessments 
X 
X4 
X 
X 
X 
X 
Bedside Eschar Debridement  
(if needed) 
 
X 
 
 
 
 
Initial Treatment Application 
 
X 
 
 
 
 
Dressing Change 
 
 
X5 
X5 
 
X5 
Dressing Removal 
 
 
 
 
X 
X6 
3D Imaging 
 
X4 
X 
X 
X 
X 
End of Study 
 
 
 
 
X 
X6 
Concomitant Medication 
 
X 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
1 Visit should not occur prior to 48 hours from the previous visit. 
2 Inclusion/Exclusion Criteria will be reconfirmed immediately prior to randomization if Visit 1 and Visit 2 are on different dates. 
3 If the screening visit and randomization occur on different days, the medical and surgical history will be updated (if changes have occurred). 
4 For patients undergoing eschar debridement prior to randomization, the procedure is performed before and after debridement (see Section 4.10). 
5 Dressing changes can occur daily for patients randomized to the collagenase ointment group (or more frequently if dressings become soiled). 
6 If the Subject is withdrawn early. 

 
 
 
 
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5.2. Description of Study Visits 
5.2.1. 
Visit 1/Screening/Days -10 to 0 
The following procedures and assessments will be performed and documented in the 
Subject’s medical records/source notes: 
• Informed consent 
• Inclusion and exclusion criteria  
• Demographics and Subject characteristics 
• Medical and surgical history  
• Laboratory assessment for pregnancy 
• Wound assessment, including assessment of wound undermining 
5.2.2. 
Visit 2/Randomization/Day 0 
• Inclusion and exclusion criteria confirmation immediately prior to randomization 
• Medical and surgical history update, if the Screening Visit and Randomization 
occur on different days. 
• Wound assessment, including assessment of wound undermining (if the patient 
had eschar sharp and/or mechanical debridement prior to randomization refer to 
Section 4.10) 
• Bedside eschar sharp and/or mechanical debridement (if needed) prior to 
randomization 
• Initial treatment application 
• Concomitant medications 
• 3D imaging (if the patient had eschar sharp and/or mechanical debridement prior 
to randomization refer to Section 4.10) 
• AE assessment and serious adverse event (SAE) reporting after randomization 

 
 
 
 
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5.2.3. 
Visit 3 and Visit 4/Follow-up Visits/Days 2-3 and Days 4-6 
Visits should not occur prior to 48 hours from the previous visit. The following procedures 
and assessments will be performed and documented in the Subject’s medical 
records/source notes: 
• Wound assessment 
• Dressing change 
• Concomitant medications 
• 3D imaging 
• AE assessment and serious adverse event (SAE) reporting  
5.2.4. 
Follow-up Visits/Visit 5/End of Treatment/Days 6-9 
Visit should not occur prior to 48 hours from the previous visit. The following procedures 
and assessments will be performed and documented in the Subject’s medical 
records/source notes: 
• Wound assessment 
• Dressing removal 
• 3D imaging 
• End of study 
• Concomitant medications 
• AE assessment and SAE reporting 
5.2.5. 
Unscheduled Visits 
Outside of scheduled study visits, if the Subject needs to be assessed by the Investigator 
or a medically licensed sub-investigator for any reason, the following procedures and 
assessments will be performed and documented in the Subject’s medical records/source 
notes:  
• Wound assessment 

 
 
 
 
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• Dressing change 
• Dressing removal, if Subject is withdrawn early 
• 3D imaging 
• End of study, if Subject is withdrawn early 
• Concomitant medications 
• AE assessment and SAE reporting  
 
 

 
 
 
 
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6. RISKS ASSOCIATED WITH STUDY PARTICIPATION 
Participation in the clinical investigation presents low risks to Subjects. Some risks are 
generalized and are listed in Tables 2 and 3. 
Table 2. Risks Associated With NPWTi-d/VFCC 
Risks 
Disorders/Conditions 
Skin and Subcutaneous 
Tissue Reaction/Allergy 
• 
Skin rash, irritation, blistering 
• 
Pruritus/itching 
• 
Skin excoriation/breakdown/stripping 
• 
Skin scarring if significant skin irritation were to occur 
• 
Maceration 
• 
Skin hyper/hypo-pigmentation at and/or around dressing application 
area 
• 
Erythema/redness, edema, inflammation, or swelling at and/or around 
dressing application area 
Mild Pain or Discomfort 
• 
Tenderness/minor ache at and/or around dressing application area  
• 
Perspiration associated with wearing dressing 
• 
Auditory irritation (due to a mild buzzing sound of negative pressure unit) 
• 
Decreased sleep or sleep quality 
• 
Paresthesia (numbness, tingling, prickling, creeping sensation) 
• 
Pain upon dressing removal 
Other 
• 
Bleeding 
• 
Localized infection 
• 
Autonomic dysreflexia (in Subjects with spinal cord injury) 
• 
Retained foreign debris (eg, foam) in the wound 
• 
Impairment of mobility/activity (limitation secondary to weight and 
attachment of therapy unit) 
• 
Possible tubing entanglement/trip or slip hazard leading to fracture, 
tissue damage 
• 
Stalled healing/non-progression of healing 
• 
Deterioration of the wound 
• 
Systemic reaction (due to an allergic reaction to dressing materials) 
 
 
 

 
 
 
 
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Table 3: Risks Associated with collagenase ointment 
Risks 
Disorders/Conditions 
Skin and Subcutaneous 
Tissue Reaction/Allergy 
• 
Collagenase ointment is contraindicated in patients who have shown 
local or systemic hypersensitivity to collagenase. 
• 
A slight transient erythema has been noted occasionally in the 
surrounding tissue, particularly when collagenase ointment was not 
confined to the wound. 
• 
Pain or burning sensation in the wound 
Other 
• 
The optimal pH range of collagenase is six (6) to eight (8). Higher or 
lower pH conditions will decrease the enzyme’s activity and appropriate 
precautions should be taken. 
• 
The enzymatic activity is adversely affected by certain detergents and 
heavy metal ions such as mercury and silver, which are used in some 
antiseptics. 
• 
Debilitated patients should be closely monitored for systemic bacterial 
infections because of the theoretical possibility that debriding enzymes 
may increase the risk of bacteremia. 
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:  
• Death 
• Life-threatening 
• Hospitalization (initial or prolonged) 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly/birth defect 

 
 
 
 
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• Required intervention to prevent permanent impairment or damage  
• 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. 
7.2. Classification 
 
 
 
 
 
7.2.1. 
Relationship to Study Treatment 
The Investigator will assess the relationship of the AE as: 
• Related to the study product: any AE for which there is a reasonable possibility 
that the study product caused the AE. The Sponsor will review all SAEs for 
expectedness. 
• Not Related to the study product: when it is determined that there is no relationship 
between the AE and the use of the study product.  
7.2.2. 
Severity 
The Investigator will assign severity as: 
• Mild – asymptomatic or mild symptoms; clinical or diagnostic observations only; 
no intervention indicated 
• Moderate – minimal, local, or non-invasive intervention indicated  
Adverse  Event        
( AE)  
Serious? = YES
Complete SAE 
report 
Complete AE in 
clinical database
Serious? = NO 
Complete AE in 
clinical database

 
 
 
 
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• Severe – medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling 
7.3. 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. 
7.4. 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 case report forms (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 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. It will be indicated if the AE caused the Subject to be discontinued from 
the study. 
7.5. SAE Reporting to KCI® 
The SAE collection/reporting period will begin after the Subject has been randomized. 
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 inbox is available for SAE 
reporting 24 hours per day and is monitored during normal business hours.  
7.6. 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 

 
 
 
 
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identified in nature, severity, or degree of incidence in the investigational plan or 
application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of 
Subjects.  
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 
a UADE, KCI® will report the results of the evaluation to the United States Food & Drug 
Administration (FDA) and to 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.  
7.7. Follow-up Period for Ongoing AEs 
Treatment-related AEs (serious and non-serious) that are ongoing at the final study visit 
will be followed up to 30 days to assess resolution or stabilization. All unrelated AEs will 
be considered closed at the time the Subject completes participation in the study. 
8. STATISTICAL CONSIDERATIONS 
8.1. Endpoint Definitions for Analysis 
8.1.1. 
Primary Endpoint  
The primary endpoint is the percent change in the wound bed surface area (cm2) 
considered to be clean, healthy, and viable from baseline to Day 6-9 upon the final 
dressing removal, which is defined as the difference between the final post-baseline 
assessment value and baseline value. The percent change in the wound bed surface 
area (cm2) considered to be clean, healthy, and viable over time will also be explored and 
defined in a similar fashion as above utilizing values collected at each visit. 

 
 
 
 
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8.1.2. 
Secondary Endpoints 
8.1.2.1. Percent change in total wound volume 
This secondary endpoint is the percent change in total wound volume (cm3) from baseline 
to Day 6-9 upon the final dressing removal, which is defined as the difference between 
the final post-baseline assessment value and baseline value, divided by the baseline 
value and multiplied by 100. The percent change in total wound volume over time will also 
be explored and defined in a similar fashion as above utilizing values collected at each 
visit. 
8.1.2.2.  Percent change in total wound area 
This secondary endpoint is the percent change in total wound area (cm2) from baseline 
to Day 6-9 upon the final dressing removal, which is defined as the difference between 
the final post-baseline assessment value and baseline value, divided by the baseline 
value and multiplied by 100. The percent change in total wound area over time will also 
be explored and defined in a similar fashion as above utilizing values collected at each 
visit. 
8.1.2.3. Physician assessment of need for debridement 
This secondary endpoint is the need for debridement of the wound upon completion of 
study treatment up to Day 6-9, as assessed by the Investigator. For each Subject, there 
are three possible outcomes for this endpoint: 
• “Yes”, which is assigned if the Subject had a need for wound debridement after the 
completion of treatment. 
• “No”, which is assigned if the Subject had no need for wound debridement after 
the completion of treatment. 
• “Incomplete Treatment”, which is assigned if the Subject did not complete assigned 
treatment for at least six (6) days. 

 
 
 
 
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8.1.3. 
Safety Endpoints  
Treatment-emergent adverse events (TEAE) are those that first appear or worsen after 
the initial application of the assigned study treatment (ie, V.A.C. VERAFLO™ Therapy 
using VFCC or collagenase ointment). Adverse events will be coded using the MedDRA 
dictionary. 
8.1.4. 
Exploratory Endpoints 
Additional exploratory endpoints may be added and will be detailed in the SAP. Definitions 
regarding exploratory endpoints will also be included in the SAP. 
8.2. Analysis Sets 
The following analysis sets will be used: 
• Safety Analysis Set – The Safety Analysis Set will consist of all consented Subjects 
who received either VFCC and NPWTi-d or collagenase ointment for any length of 
time. Subjects will be analyzed as treated. 
• Intention-to-treat (ITT) Analysis Set – The ITT Set will consist of all randomized 
Subjects. Subjects will be analyzed as randomized. 
• Modified Intent-to-treat (mITT) – The mITT will consist of all randomized Subjects 
with the following:  
i. 
met all the inclusion criteria and none of the exclusion criteria,  
ii. 
has no more than 2/3 of the wound bed surface area considered to be clean, 
healthy, viable wound bed as determined at the baseline measurement 
confirmed with 3D images by an independent assessor, 
iii. 
received either the V.A.C. VERAFLO CLEANSE CHOICE™ Dressing and 
NPWTi-d or collagenase ointment,  
iv. 
had the primary endpoint assessment on Day 6-9. 
• Per-Protocol Analysis Set – This set will include Subjects in the mITT who had no 
disqualifying protocol deviation(s) that would impact the interpretation of the 

 
 
 
 
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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. Subject data will be analyzed in the arm to which they were randomized and 
treated. 
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 specified analysis set, including those for whom data are 
not available, ie, “not reported” or “not available” – those data will generally be considered 
a separate category and included in the displays of data, with the denominator for 
percentages including these Subjects. Subjects will be summarized by treatment group 
and overall.   
8.3.2. 
Subject Disposition 
Summaries of disposition will be tabulated by treatment group. The number and 
percentage of Subjects in the specified analysis set will be described, as will the number 
and percentage of Subjects who: 
• provided informed consent 
• failed screening, and the reason for screen failure 
• were randomized and treated 
• discontinued early from the study for any reason, along with the reason for 
discontinuation (if the reason is an AE, the system organ class and preferred term)  
• completed the study as planned  
Subject disposition also will be described in a flowchart (CONSORT diagram). 

 
 
 
 
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8.3.3. 
Demographic and Baseline Characteristics 
Demographic characteristics (eg, age, sex, race, and ethnicity), baseline characteristics, 
and other disease characteristics will be summarized per the general techniques in 
Section 8.3.1. Subjects in the mITT, ITT, and/or Per-Protocol Analysis Sets will be 
summarized by treatment arm and overall.  
8.3.4. 
Analysis of Primary Endpoint 
The primary endpoint will be calculated per the definition in Section 8.1.1. Based on the 
mITT analysis set, the primary endpoint will be summarized by treatment group and 
overall. 
The null and alternative hypotheses for the primary endpoint are: 
Null:   ΔVFCC – Control = 0  
Alternative:   ΔVFCC - Control ≠ 0 
where ΔVFCC - Control is the difference in the percent change in the wound bed surface area 
(cm2)  considered to be clean, healthy, and viable between the VFCC and NPWTi-d group 
and Control group. 
Assessments will be taken at multiple visits for each Subject during the study. The primary 
endpoint will be analyzed using a repeated measures analysis of covariance model 
(ANCOVA) with treatment arm, visit, wound undermining measurement, clinical site, and 
treatment by visit (Note: if clinical site or treatment by visit are not statistically significant, 
then the non-significant term(s) will be removed from the model and the updated model 
will be re-run). The analysis will be based on the mITT analysis set. 
If appropriate, supportive/exploratory analyses of the primary endpoint may include: 
• repeat the analysis above on the ITT and Per-Protocol analysis sets 
• a two-sample t-test or a Wilcoxon Rank-Sum test without adjusting for wound 
undermining 
• analyses comparing the treatment groups considering covariates (eg, age, body 
mass index [BMI], race/ethnicity, sex, wound undermining, and co-morbidities) and 
subsets of the data 

 
 
 
 
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8.3.5. 
Analysis of Secondary Endpoints 
8.3.5.1. Percent change in total wound volume 
This secondary endpoint will be calculated per the definition in Section 8.1.2.1 and will be 
analyzed in a similar fashion as the primary endpoint described in Section 8.3.4. 
8.3.5.2. Percent change in total wound care 
This secondary endpoint will be calculated per the definition in Section 8.1.2.2 and will be 
analyzed in a similar fashion as the primary endpoint described in Section 8.3.4. 
8.3.5.3. Physician assessment of the need for debridement 
This secondary endpoint will be calculated per the definition in Section 8.1.2.3. Based on 
the mITT analysis set, the proportion of Subjects with each possible result will be 
summarized by treatment group and overall. 
The comparative analysis of this secondary endpoint will only consider Subjects in the 
mITT set. Treatment groups (VFCC and NPWTi-d vs collagenase ointment) will be 
compared with a Chi-square or Fisher’s exact test, as appropriate.  
If appropriate, supportive/exploratory analyses of this secondary endpoint may include: 
• repeat the analysis above on the ITT and Per-Protocol analysis sets 
• analyses comparing the treatment groups considering covariates (eg, age, BMI, 
race/ethnicity, sex, wound undermining, and co-morbidities) and subsets of the 
data 
• analyses comparing the heterogeneity of the treatment groups across clinical sites. 
8.3.6. 
Exploratory Analyses 
In general, all exploratory, supplementary or sensitivity analyses/endpoints will be 
performed using methods outlined in Section 8.3.1. Because the analyses are 
exploratory, no adjustment will be made for multiple comparisons. Additional exploratory 
endpoints and specifics regarding analyses will be specified in the SAP.  

 
 
 
 
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8.3.7. 
Analysis of Safety Endpoint 
All safety results will be presented based on the Safety Analysis Set. All TEAEs will be 
summarized by treatment arm. Subject incidence of TEAEs will be summarized by 
treatment arm and by MedDRA system organ class and preferred term. For each coded 
medical term, the proportion of Subjects who experience at least one treatment-emergent: 
• adverse event(s); 
• adverse event(s) related to treatment 
• serious adverse event(s); 
• serious adverse event(s) related to treatment  
• adverse event(s) by severity (mild, moderate, severe); 
• adverse event(s) leading to treatment/study discontinuation, or 
• serious adverse event(s) leading to treatment/study discontinuation will be 
reported. 
A listing of death(s), Subjects who died of any cause during the study, will be presented. 
8.4. Additional Statistical Details 
8.4.1. 
Sample Size Determination 
Sample size determination is based on the primary endpoint. It was estimated that slough 
reduced by almost 20% in the Tender Wet 24 group and 10% in the Iruxol N group in M. 
Konig et al.1 Assuming a 20% increase in clean, healthy, viable wound bed surface area 
in the collagenase ointment group and a 40% increase in clean, healthy, viable wound 
bed surface area in the VFCC and NPWTi-d group, and a common standard deviation of 
22%, 23 evaluable Subjects per group will provide approximately 80% power to detect a 
statistically significant difference using the Wilcoxon Rank-Sum test (n Query Advisor® 
7.0).   
It is possible that some wounds assessed by the independent assessor will not meet the 
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measured by a 3D camera, even though the investigator assessed the wound at ≤ 2/3 
area of clean, healthy, viable wound bed. Such Subjects will be excluded from the mITT 
for the analysis of the primary endpoint. To allow for this possibility, plus the possibility 
that some Subjects may be lost to follow-up prior to their post-baseline assessment at the 
Day 6-9 visit, the sample size is increased to a total of 60 randomized Subjects (ie, 30 
Subjects per arm). 
8.4.2. 
Randomization 
Subjects who meet all inclusion criteria and no exclusion criteria will be randomized in a 
1:1 ratio to either the VFCC and NPWTi-d arm or the collagenase ointment treatment arm. 
The randomization will be stratified for the clinical site using permuted blocks to achieve 
equal numbers of Subjects assigned to the treatment groups within each clinical site.   
A randomization schedule, including randomization numbers and treatment assignments, 
will be generated and maintained centrally in a web-based clinical database management 
system. Once randomized, a Subject’s assignment cannot be altered or changed; a 
Subject should not be randomized more than once. 
8.5. Open-Label Study Reporting Results  
All precaution will be taken to avoid operational bias introduced by statistical analysis. 
While the study is ongoing, summary statistics by treatment arms across all sites may be 
limited to a small analytical group not involved in the daily operations of the study. 
Treatment arms may be masked in the summary reports or outputs (tables, listings, and 
figures) if needed. The limited analysis results 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.  
8.6. Interim Analysis 
A nonbinding, unblinded interim analysis will be performed when approximately 30 
evaluable subjects have had their assessments for the primary endpoint (percent change 
on wound bed surface area considered to be clean, healthy and viable from baseline to 

 
 
 
 
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Day 6-9). The purpose of the interim analysis is to evaluate the need for early stopping 
due to futility, efficacy, and/or sample size re-calculation. 
The primary endpoint will be analyzed as outlined in Section 8.3.4. If the resulting p-value 
for the primary analysis is less than α=0.006 as determined utilizing the O’Brien-Fleming 
α-spending function (O’Brien 1979),26 the null hypothesis will be rejected, and the study 
may be stopped for efficacy. 
If the null hypothesis could not be rejected, conditional power will be calculated to assess 
for futility and/or sample size adjustment. If the conditional power is lower than the pre-
specified boundary in the interim SAP, the trial may be stopped for futility. If the conditional 
power is above the futility boundary, the conditional power will be evaluated utilizing 
methods described in Chen et al (Chen 2004) to determine if a sample size increase is 
required.27  
The final analysis will be conducted at α=0.048 to maintain the overall type I error rate at 
α=0.05 as determined by the O’Brien-Fleming spending function. Details of the interim 
analysis will be described in the interim SAP before the interim analysis is conducted. 
8.7. Statistical Analysis Plan and Changes in Analyses 
A separate SAP containing full details of the statistical analysis and execution will be 
finalized prior to the study database lock and the final analysis. Any changes from planned 
analyses in the study protocol or from the SAP will be noted in the Clinical Study Report 
(CSR). 
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 monitor 

 
 
 
 
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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®. 
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 an 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 data will be entered into the clinical study database by Investigative Site staff and 
verified for accuracy by a KCI® representative. 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 

 
 
 
 
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monitoring visits, and after the eCRFs are submitted; any discrepancies will be resolved 
with the Investigator or designee, as appropriate.   
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 
CSR. 
10.5. Records Retention 
The study site will maintain all study documentation and institute measures to prevent the 
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 
jurisdiction where the site is located. The Investigator will contact KCI® prior to the 
destruction of any study records. 
11. ADMINISTRATIVE REQUIREMENTS 
11.1. Good Clinical Practice (GCP) 
This study is to be conducted according to the US and international standards of good 
clinical practice such as the International Conference on Harmonization guidelines, 
applicable government regulations (eg, FDA CFR Title 21 part 812), 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, IFUs, informed consent, written information given to Subjects, safety 

 
 
 
 
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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 or their legally 
authorized representative if the Subject is unable to provide their own informed consent 
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 
or their legally authorized representative in regard to their continued participation in the 
study. KCI® will conduct periodic monitoring to ensure informed consent is obtained for 
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 an 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 (eg, source documents, regulatory documents, data collection 
instruments, study data) by the IRB/IEC, KCI® or its designee, and government regulatory 
bodies.  
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