Treatment of Subcutaneous Abdominal Wound Healing Impairment After Surgery Without Fascial Dehiscence by Vacuum Assisted Closure™(SAWHI-V.A.C.® Study) Versus Standard Conventional Wound Therapy
Phase: NA
Conditions: Wound Healing Disorder, Impaired Wound Healing, Abdominal Wound Healing Disorder, Abdominal Wound Healing Impairment, Acute Postsurgical Subcutaneous Wound
Sponsor: University of Witten/Herdecke

2013_09_17_SAWHI_Study Protocol V 8.0 
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TITLE  
 
 
CLINICAL RESEARCH PROTOCOL 
Treatment of Subcutaneous Abdominal Wound Healing Impairment after 
surgery without fascial dehiscence by Vacuum Assisted Closure™ 
(SAWHI–V.A.C.® Study) versus standard conventional wound therapy 
 
 
SPONSOR 
 
Private University of Witten/Herdecke gGmbH,  
Faculty for Health 
Alfred-Herrhausen-Str. 50 
58448 Witten, Germany 
 
Principal Coordinating Investigator 
Dörthe Seidel, MD 
Centre for Clinical Trials and Innovation 
Institute for Research in Operative Medicine 
Director: Univ.- Prof. Dr. Prof. h.c. Edmund A. M. Neugebauer 
Faculty of Health 
University of Witten/Herdecke 
Ostmerheimer Str. 200, Building 38 
D- 51109 Cologne, Germany 
 
Protocol Number: VAC2010-56 
Version: 8.0 Released: 17 SEP 2013 
Clinical Trials.gov Number: NCT01528033 
DRKS Number:  00000648 
 
GOOD CLINICAL PRACTICE (GCP) STATEMENT 
This document is a protocol for a clinical research study involving human participants. This study is to be executed in 
accordance with all laws and regulatory standards governing the conduct of human clinical research in the jurisdiction in which 
the study is being performed.   
 
ISO STATEMENT 
This study was conducted in accordance with ISO 14155 and all applicable regulations, including the Declaration of Helsinki. 
 
CONFLICT OF LAWS AND/OR GCP STANDARDS 
In the event of a conflict between the rules, regulations, laws, and treaties of the United States and those of the international 
nation-state under whose jurisdiction any part of and/or all of the study is being performed, the more stringent of the 2 GCP 
standards shall be applied. 
 
CONFIDENTIALITY 
The information in this document is confidential and is the property of Kinetic Concepts, Inc. and the University of 
Witten/Herdecke. The information may be provided only to Investigators, sub-Investigators, appropriate trial personnel, 
members of the Ethics Committee, and personnel of the authorities to whom it is submitted. This protocol may not be 
photocopied or discussed with third parties not involved in the trial without the prior written authorization from Kinetic Concepts, 
Inc. and the University of Witten/ Herdecke. 

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TABLE OF CONTENTS 
SIGNATURES 
2 
TABLE OF CONTENTS 
3 
LIST OF ABBREVIATIONS 
7 
SYNOPSIS 
8 
1 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
11 
1.1 
Sponsorship 
11 
1.2 
Investigators 
11 
1.3 
Statistician 
12 
1.4 
Steering Committee 
12 
1.5 
Independent Data Monitoring Committee 
13 
2 
BACKGROUND 
15 
2.1 
The medical problem 
15 
2.2 
Wound healing impairment after abdominal surgery 
15 
2.3 
Wound Closure after Surgical Wound-Healing Impairment 
18 
2.4 
Vacuum-assisted wound closure (V.A.C.®) 
19 
2.5 
Recent History 
20 
3 
STUDY OBJECTIVES AND PURPOSE 
22 
3.1 
Purpose 
22 
3.2 
Hypothesis 
22 
3.3 
Primary and secondary objectives 
22 
4 
STUDY DESIGN 
24 
4.1 
Phase and Classification of the Trial 
24 
4.2 
Treatments 
24 
4.3 
Randomisation 
24 
4.4 
Stratification 
25 
4.5 
Primary Endpoint 
25 

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4.6 
Secondary Endpoints 
26 
4.7 
Verification of wound closure and wound size 
26 
4.8 
Safety Endpoints 
26 
4.9 
Patient Reported Outcome 
27 
4.10 
Health Economic Endpoints 
28 
4.11 
Blinding 
29 
4.12 
Cross-sectoral patient treatment 
29 
5 
PATIENT SELECTION AND RECRUITMENT 
31 
5.1 
Diagnosis 
31 
5.2 
Inclusion Criteria 
31 
5.3 
Exclusion Criteria 
32 
5.4 
Enrolment 
34 
5.5 
Description and justification for duration of treatment 
34 
5.6 
Description and justification for follow-up 
34 
6 
TRIAL THERAPY 
35 
6.1 
Description of Intervention 
35 
6.1.1 
General information 
35 
6.1.2 
Composition and functionality 
36 
6.1.3 
Contraindications and Precautions for Use of V.A.C.® Therapy 
37 
6.1.4 
Use within the trial 
38 
6.1.5 
Operating Conditions of V.A.C.® Therapy Systems and disposables within the trial 40 
6.2 
Description of Control Therapy: Standard Conventional Wound Therapy 
40 
6.2.1 
Operating Conditions of SCWT-material within the trial 
41 
6.3 
Wound Care Principles and Practices 
42 
6.3.1 
Wound Debridement 
42 
6.3.2 
Wound Cleansing 
42 
6.3.3 
Wound Infection Management 
43 
6.3.4 
Wound Pain Management 
43 
6.3.5 
Treatment Compliance 
44 
6.4 
Training on Study Products and Procedures 
44 
7 
STUDY PLAN 
45 
7.1 
Study Flow Chart 
45 
7.2 
Description of Study Visits 
46 
7.2.1 
Screening 
46 
7.2.2 
Randomisation and Initiation of Therapy 
47 
7.2.3 
Weekly wound visits until wound closure or end of active treatment period 
47 
7.2.4 
Hospital Discharge 
48 

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7.2.5 
End of treatment 
49 
7.2.6 
Wound closure 
49 
7.2.7 
Wound Closure Confirmation 
50 
7.2.8 
End of maximum treatment period 
51 
7.2.9 
Follow-up Visit at Day 87 for non-closed wound at Day 42 (EOMT) 
51 
7.2.10 
General Follow-up Visit at Day 132 
52 
7.3 
All Interim Dressing Changes 
53 
7.4 
Wound Assessment (Examination) 
53 
7.5 
Wound pain assessment 
54 
7.6 
Prior and Concomitant Medications  
54 
7.7 
Early Termination of Treatment and Trial Participation 
54 
7.8 
Early Study Termination 
55 
7.9 
Removal of Participants from Therapy or Assessment 
55 
7.10 
Exclusion/Closure of Study Centers and Investigators 
56 
8 
DATA 
57 
8.1 
Data Quality Assurance 
57 
8.2 
Data Collection and Documentation 
57 
8.3 
Data Handling and Management 
59 
8.4 
Record Storage and Retention 
60 
8.5 
Data Ownership 
61 
9 
STATISTICAL CONSIDERATIONS 
62 
9.1 
Determination of Sample Size 
62 
9.2 
Analysis Populations 
63 
9.3 
General Considerations and Baseline Parameters 
63 
9.4 
Efficacy Analysis 
64 
9.4.1 
Primary Efficacy Analysis (Time to Confirmed Wound Closure) 
64 
9.4.2 
Secondary Efficacy Analysis 
65 
9.4.3 
Patient-Reported Outcome 
66 
9.4.4 
Health economic parameters 
67 
9.5 
Safety Analysis 
67 
9.6 
Interim Assessment 
68 
9.7 
Handling of Missing and Spurious Data 
68 
10 
ETHICAL AND LEGAL ASPECTS 
69 
10.1 
Ethics Committee 
69 

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10.2 
Ethical Conduct of the Study 
70 
10.3 
Regulatory Authority Approvals/Authorizations 
70 
10.4 
Participant Information and Consent 
70 
10.5 
Insurance 
72 
10.6 
Confidentiality 
72 
11 
SAFETY 
74 
11.1 
Warnings/Precautions 
74 
11.2 
Expected Adverse Events 
74 
11.3 
Potential Risks Associated with Study Participation 
75 
11.4 
Potential Risks and Benefits Associated with V.A.C.® Therapy and SCWT 
75 
11.5 
Other Study-related Risks 
78 
11.6 
Risk-Benefit Analysis 
78 
11.7 
Adverse Event Monitoring 
80 
11.8 
Safety Monitoring 
80 
11.9 
Adverse Event Definitions 
81 
11.10 
Documentation of Adverse Events 
82 
11.11 
Reporting of Serious Adverse Events and Incidents 
82 
11.12 
Reporting Requirements 
82 
12 
REPORTING AND PUBLICATION 
84 
12.1 
Study Report 
84 
12.2 
Publication 
84 
13 
CHANGES IN TRIAL CONDUCT OR PLANNED ANALYSIS 
86 
TABLES AND PICTURES 
87 
REFERENCES 
88 
APPENDICES 
90 

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LIST OF ABBREVIATIONS  
 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
CCI 
Coordinating Clinical Investigator 
CE 
European Conformity 
CI 
Clinical Investigator 
cm 
Centimeter 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
DCF 
Data Clarification Form 
EC 
Ethics Committee 
EOT 
End of Treatment 
EOMT 
End of Maximum Treatment Time 
EU 
European Union 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ID 
Identification 
IDMC 
Independent Data Monitoring Committee 
IQWiG 
Institute for Quality and Efficiency in Health Care 
ISO 
International Organization for Standardization 
ITT 
Intent to Treat 
KCI 
Kinetic Concepts, Incorporated 
KCI USA Kinetic Concepts, Incorporated, United States of America  
MD 
Medical Doctor  
mm Hg 
Millimeters of Mercury 
NPWT 
Negative Pressure Wound Therapy 
PCI 
Principal Coordinating Investigator 
PP 
Per Protocol 
PRO 
Patient Reported Outcome 
PTT 
Partial Thromboplastin Time 
QALY 
Quality-Adjusted Life Year 
QOL 
Quality of Life 
RCT 
Randomized Controlled Trial 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SCWT 
Standard Conventional Wound Therapy 
SF-36® 
SF-36v2™ Health Survey 
UADE 
Unanticipated Adverse Device Effect 
V.A.C. 
Vacuum Assisted Closure 
ZKSI 
Zentrum für Klinische Studien und Innovation  
(Center for Clinical Trials and Innovation) 

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SYNOPSIS 
Study Title 
Treatment of Subcutaneous Abdominal Wound Healing Impairment after 
surgery without fascial dehiscence by Vacuum Assisted Closure™ 
(SAWHI–V.A.C.® Study) versus standard conventional wound therapy 
 
Investigators and 
Study Sites 
This multicenter study will be conducted in hospital departments with the 
required manpower as well as the structural and scientific qualifications. Study 
therapy will be started in ambulatory care or in-hospital and may be continued in 
ambulatory care. Study sites and investigators will be listed in a separate 
document. 
 
Classification and 
phase of trial 
Examination of the clinical application of a CE-marked medical device  
(risk category 2 b);  
Endpoints 
Primary Endpoint 
Time (number of days) to achieve complete wound closure 
Verified by photo documentation and blinded, computer-based assessment as 
well as wound closure confirmation after 14 consecutive days (14 days -0 / + 3) 
Complete wound closure is defined as: 
 100% epithelialization 
 No drainage from the wound 
 No need for adjuvant therapy or dressing  
 No presence of sutures 
 
Secondary Endpoints 
 
Incidence of confirmed and verified wound closure achieved after a 
maximum study observation / treatment period of 42 days (+ 14 days to 
observe sustained closure). 
 
Recurrence of wound opening after confirmed wound closure 
 
Reduction of wound size over time 
 Reduction in wound volume over time  
 Reduction in wound surface area over time  
 
Safety Endpoints 
Incidence of serious adverse events including mortality of any cause (within 
132 days from the time of initiation of therapy)  
Incidence of wound-related adverse events and adverse device events 
(within the study treatment period of maximum 42 days) 
 
 
Patient Reported Outcome (PRO) 
Quality of Life (QoL) (SF-36®) 
Pain 
Patient Satisfaction 
 
Health Economic Endpoints 
Direct medical resource use 
(diagnostics, medication, specific wound therapy, treatment 
and medical attendance, reinterventions, rehospitalisations) 
Indirect resource use  
(restrictions of productivity besides absence from the 
workplace (activities of daily living); non-productive time for 
gainfully employed)  
 
 

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Design 
Multicentre, multinational, randomized controlled, observer-blinded clinical 
superiority trial 
 
Number of Study 
Participants 
 
Adaptive trial design with a maximum number of 552 participants to be analysed 
with interim analysis after 250 patients 
Diagnosis 
Primary closed abdominal wound with wound healing disorder in the 
postoperative course after surgical intervention without fascial dehiscence 
manifested as one or more of the following: 
 
a wound with spontaneous dehiscence  
 
a wound that requires an active reopening of the suture by the treating 
physician 
 
a wound that cannot be closed by primary intention and requires further 
treatment to achieve permanent closure 
 
Inclusion Criteria 
 
 
 
 
 
 
 
 
 
 
 Written informed consent  
 Post-surgical subcutaneous abdominal wound healing impairment 
 Minimum wound size eligible for the application of the randomized 
treatment 
 Inclusion, randomization, adequate wound pre-treatment (Debridement) 
and start of therapy within 48 hours after reopening of the wound, 
diagnosis for nonclosable wound or in case of spontaneous wound 
dehiscence  
Exclusion Criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Age < 18 years 
 Noncompliance with study procedures, visit schedule or follow up  
 Pregnancy  
 Present or nonclosable defect of the abdominal fascia  
 Any pre-existing or ongoing organ system failure, that cannot be stabilized 
or solved by appropriate medical treatment 
 Necrotic tissue with eschar present 
 Non-enteric and unexplored fistulas 
 Malignancy of the wound 
 Use of any other device based on the principle of negative pressure wound 
therapy on the study wound within ≤ 8 days prior to screening  
 Competing therapies or procedures 
 Simultaneous participation in competing clinical trials 
 
Intervention 
Vacuum Assisted Closure® (V.A.C.®) Therapy 
Control  
 
 
Study Treatment 
Standard conventional wound therapy (SCWT) according to institutional clinical 
standards 
 
All patients at the time point of randomisation / inclusion or during the active 
treatment period of 42 days that are eligible for outpatient care and have 
reasonable access to it, have to be transferred to outpatient care. 
 
 
Duration of 
Treatment 
Up to 42 days (end of maximum treatment time (EOMT)) 
Follow up 
 
General follow-up at Day 132 
Additional follow up at Day 87 for study participants with nonclosed wounds at 
Day 42 
 
 

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Evaluation Criteria 
Effectiveness: The primary endpoint is defined as time to achieve complete 
wound closure (in study participants where wound closure was confirmed as 
sustained for a minimum of 14 days). 
Safety: Wound-related AE and adverse device events within the study treatment 
period of 42 days, and SAE including mortality of any cause within 132 days 
after randomisation. 
 
Statistics 
The primary efficacy parameter, time to complete wound closure, will be 
compared between the two treatment groups using a log rank test. In addition, 
as a supportive analysis, a Cox proportional hazards regression will also be 
used in order to assess if there is a difference between treatment groups while 
accounting for the effect of study center and wound size (appropriate baseline 
and medical history parameters will also be considered). The secondary efficacy 
parameter, incidence of complete wound closure, will be analyzed using a Chi-
square test comparing the two treatment groups. As a supportive statistical 
analysis, logistic regression will also be implemented with factors in to model to 
include treatment, study center, and wound size (appropriate baseline and 
medical history parameters will also be considered). Reduction in wound area 
(cm2) and wound volume (cm3) will be assessed using a 3-factor (treatment 
group, study center, and time) analysis of covariance with baseline wound area 
(or volume) recorded at baseline to be used as a covariate.  
One planned interim analysis will be performed when 250 study participants 
have completed the first phase of the study. The interim analysis will validate the 
assumptions made for the study sample size calculation and will determine if 
sample size re-estimation is warranted. 
 
Ethics 
This study will be conducted in accordance with Good Clinical Practice and 
applicable regulations. 
 
Principal 
Coordinating 
Investigator 
Dörthe Seidel, MD 
Centre for Clinical Trials and Innovation (ZKSI) 
IFOM - Institute for Research in Operative Medicine 
Faculty of Health 
Private University Witten/Herdecke gGmbH 
Ostmerheimer Str. 200 , Building 38 
51109 Cologne, Germany 
Tel.: +49 (0)221 9895726  
Email: doerthe.seidel@uni-wh.de 
 
Sponsor  
Private University of Witten/Herdecke gGmbH 
Alfred-Herrhausen-Str. 50 
58448 Witten, Germany 
Statistician 
Prof. Dr. R. Lefering 
Institute for Research in Operative Medicine 
University of Witten/Herdecke 
Tel.: +49 (0)221 9895716  
Email: rolf.lefering@uni-wh.de 
 

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1 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
1.1 Sponsorship 
The Institute for Research in Operative Medicine (IFOM) as part of the Private 
University of Witten/Herdecke gGmbH is initiating the clinical investigation, whereas 
the Private University of Witten/Herdecke assumes responsibility as Sponsor. The 
clinical trial is funded by KCI. IFOM, acting for the University of Witten/Herdecke 
gGmbH, oversees implementation of the study and is responsible for data analysis, 
report, and publication.  
 
1.2 Investigators 
Principal Coordinating Investigator (PCI) 
The Principal Coordinating Investigator (PCI) has responsibility for the overall 
conduct of the clinical trial. The PCI is responsible for controlling the technical 
direction and academic quality of the project, and will ensure that the trial is carried 
out in compliance with the terms, conditions, and policies of the Sponsor.  
 
The Principal Coordinating Investigator (PCI) of this trial is: 
Dörthe Seidel, MD 
Centre for Clinical Trials and Innovation 
Institute for Research in Operative Medicine 
Faculty of Health 
University of Witten/Herdecke 
Ostmerheimer Str. 200, Building 38 
51109 Cologne, Germany 
 
Clinical Investigator (CI) 
The Clinical Investigator (CI) is defined as the responsible lead investigator at each 
study site. Clinical Investigators will be listed on a separate document. 
 
Subinvestigator (SI) 
The Subinvestigator is defined as any other physician involved in the conduct of the 
Clinical Trial at the respective trial site. 
 
 

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1.3 Statistician 
The statistician will conduct all analyses mentioned in chapter 9 including the interim 
analysis and safety analysis. 
 
The statistician of this trial is: 
Prof. Dr. Rolf Lefering  
Institute for Research in Operative Medicine 
Faculty of Health 
University of Witten/Herdecke 
Ostmerheimer Str. 200, Building 38 
51109 Cologne, Germany 
 
1.4 Steering Committee 
Responsibilities 
The Steering Committee‘s primary responsibility is to ensure that the study is 
conducted in accordance with the protocol, all pertinent countries’ laws; and 
regulatory authorities, industry, institutional and corporate-related laws, regulations, 
guidance, and standard operating procedures. The Steering Committee must ensure 
operational excellence and the delivery of quality data as well as its publication in an 
unbiased manner in an appropriate peer-reviewed journal.  
 
 
Membership 
The Steering Committee will be composed of the following individuals: 
 
Edmund A. Neugebauer 
Institute for Research in Operative Medicine (IFOM) 
Private University of Witten/Herdecke gGmbH 
 
Dörthe Seidel 
Institute for Research in Operative Medicine (IFOM) 
Private University of Witten/Herdecke gGmbH 
 
Rolf Lefering 

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Institute for Research in Operative Medicine (IFOM) 
Private University of Witten/Herdecke gGmbH 
 
Alex Hartnagel 
KCI Europe Holding B.V. 
 
1.5 Independent Data Monitoring Committee 
To ensure data integrity and unbiased clinical decisions, IFOM and KCI will convene 
an Independent Data Monitoring Committee (IDMC). An IDMC is an independent 
group of relevant experts, external to a study that reviews and evaluates 
accumulating study data from an ongoing research study. The structure and voting 
membership of the IDMC ensures that critical decisions made while the results of a 
study are still blinded will be free of conflicts of interest. Membership includes 
individuals with pertinent clinical, scientific, and statistical expertise in the therapeutic 
area. The IDMC members will develop a charter that will detail the functions the 
IDMC will be asked to perform for the study.   
 
The IDMC will be independent of IFOM, KCI, PCI, regulatory agencies, Ethics 
Committees (ECs), CI, or Subinvestigators. IFOM and KCI will appoint an IDMC chair 
who may make recommendations for IDMC members and will give final approval of 
all members. The IDMC will assist in maintaining the quality of study conduct. 
Whenever possible, the IDMC will communicate directly with and receive data from 
IFOM’s 
data 
management 
group. 
The 
IDMC 
will 
provide 
an 
endpoint 
assessment/adjudication function, which will involve reviewing important endpoints 
reported by CIs to determine whether the endpoints meet protocol-specified criteria. 
Members of the IDMC will be designated by the Steering Committee. The IDMC is 
responsible for examining efficacy as well as participant-safety issues and is 
independent from the Steering Committee as well as from IFOM and KCI. The IDMC 
reviews the cumulative safety data for evidence of treatment harm and benefit; the 
IDMC will be supplied regularly with the tabulation of SAEs. A safety review will occur 
at every IDMC meeting. The IDMC may decide in the interest of healthcare to 
terminate the trial or a treatment arm of the trial before recruitment is finished – for 
instance, if an unacceptably high rate of AEs is seen in participants or if issues arise 

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that prevent successful completion of the study. Throughout the study, the IDMC will 
closely examine the incidence rates of SAEs.  
 
Other than serving a review and oversight role, the IDMC will not be involved in the 
conduct of the trial. For this study, only blinded data will be provided to the IDMC. 

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2 
BACKGROUND 
2.1 The medical problem 
Wound healing impairment after surgical procedures is a common problem of health 
care. The occurrence of wound healing impairment of the abdominal wall represents 
a multi-disciplinary, treatment, and cost-intensive problem of clinical life whether it is 
caused by infectious or non-infectious reasons. [1-3] 
Only a few clinical trials have been conducted regarding the use of negative pressure 
wound therapy for subcutaneous abdominal wound healing impairment [4-6]; thus, a 
large randomized clinical trial that is able to make a statement concerning 
effectiveness and universal validity of this innovative therapy option is still missing. 
 
2.2 Wound healing impairment after abdominal surgery 
Complications associated with surgical incisions range from annoying to life 
threatening and can be more common and serious than those related to the primary 
surgical procedure. These complications include wound healing disorders caused by 
the surgical procedure itself, by patient-related factors, or both. (Table 1) 
Table 1: Factors that affect surgical wound healing 
Surgical factors 
Patient-related factors 
Other factors 
Contamination status 
Pre-existing infection 
Performed procedures 
Skin preparation 
Site, duration and complexity 
of surgery 
Presence of suture or foreign 
body 
Suturing quality 
Prophylactic antibiotics 
Haematoma 
Mechanical stress on wound 
Diabetes 
Smoking 
Poor nutrition 
Alcoholism 
Chronic renal failure 
Jaundice 
Obesity 
Advanced age 
Poor physical condition 
Medication 
Previous radio-or 
chemotherapy 
Tissue perfusion 
Normovolaemia / 
Hypovolaemia 
Perioperative Body 
Temperature 
Pain 
etc. 
 
 
These factors are typically interrelated, complex in nature, and often difficult to 
prevent or treat successfully. 
 

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The most common postoperative wound healing impairments are seroma or 
haematoma, necrosis of wound margins or adjacent soft tissue, and infections, all 
with potential to cause dehiscence of the primarily closed wound. 
 
Wound dehiscence 
Wound dehiscence in general signals the inability of a wound margin to adequately 
heal after surgical closure. After surgical wound dehiscence, a defect can extend 
from partial up to full thickness depending on the layers of the abdominal wall 
involved. According to which wound layers are dehisced, these wounds can be 
classified into incomplete (open skin, with fascia and peritoneal suture intact), 
complete (all layers involved), or inapparent (skin suture intact, dehiscence of fascia 
and peritoneal suture) wound dehiscence. After laparotomy, wounds are endangered 
by a massively expanded abdomen (atony of the bowel or ileus, mesenteric edema, 
ascites) and postoperative coughing. Wound infections, including abscesses, are one 
of the major causes of abdominal and other types of wound dehiscence.  
 
Seroma or Hematoma 
Seroma and haematoma involve an accumulation of lymph or blood, respectively, in 
a preformed cavity or resulting space. Additionally, subcutaneous bleeding 
(ecchymosis) can lead to haematoma if there is no possibility for drainage. The 
resulting pressure leads to poor perfusion and delayed wound healing. Furthermore, 
these fluids are an ideal matrix for bacterial colonization. Reasons for the 
development of seroma and haematoma are tissue damage, insufficient hemostasis, 
constrained blood clotting, coagulation disorders, antiplatelets and anticoagulants, 
loss of coagulation factors, cirrhosis of the liver, thrombocytopenia, or protein 
deficiency. Seroma are caused by lymphatic disruption after dissection, partial 
reabsorbed haematoma, and inflammation. 
 
Clinically, these disorders present as pressure pain (ie, tenderness), tenseness, and 
redness. Often secretion extravasates from the wound; in some instances of 
haematoma, coloration of the wound area appears.  
 
Necrosis of Wound Margins or Adjacent Soft Tissue 
Necrosis is typically caused by diminished or absent perfusion of the related area, 
which usually originates from damage of a blood vessel or stasis within it. This can 

2013_09_17_SAWHI_Study Protocol V 8.0 
Page 17 of 90 
be caused by contusion of tissue prior to or during surgery, use of electrocoagulation, 
unfavorable performance of incision, too heavy tension on wound clamps during 
surgery, or a suture placed too tightly. Pre-existing diseases with micro- and 
macroangiopathia, such as diabetes mellitus and arteriosclerosis, have been shown 
to play an important role in this condition. Even seroma and hematoma can lead to 
decreased perfusion of the affected areas within the wound and further enhance 
tissue necrosis.   
 
Soft tissue necrosis that originates from surgical procedures or trauma is often limited 
to small areas or margins of the wound and can become healthy; it is most amenable 
to wound healing after debridement. In contrast, soft tissue necrosis caused by 
angiopathy represents a serious problem. Minimally perfused areas are spread 
diffusely and surrounded by hypoperfused or already necrotic tissue, resulting in 
delayed healing and increasing the risks of developing wound infection. Therefore, 
extensive soft tissue damage is a frequent reason for early infection after surgery. 
When tissue necrosis post-surgery occurs, there is a heightened danger for 
aerogenic bacterial colonization and subsequent tissue infection. 
 
Wound Infections 
The risk for wound infection depends on relative size of the incision, degree of 
contamination of the incision, reason and duration of surgery, nature of surgery 
(emergency or planned intervention), the use of perioperative antibiotics, and various 
patient-related risk factors, such as age, immunosuppression, malnutrition, 
hypalbuminemia, and obesity.  
 
About two-thirds of surgical-site infections (SSIs) of the abdominal wall are 
superficial.[1]  The other one-third is associated with deep tissue wound infections, 
including abscesses, which are most often associated with abdominal wound 
dehiscence. 
The determination of SSI can be made following the criteria outlined in the CDC’s 
guideline for prevention of surgical site infection. [7] 
 
Clinically, if a wound is infected, wound secretions often appear around the third 
postoperative day, typically of predominantly serous or bloody serous character, 
accompanied by recurrent pain, redness, and tenderness in the wound area.  

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Postoperatively, early recognition and optimal treatment of these complications and 
wound-healing disorders may prevent major wound infection, more serious 
complications, and their sequelae. 
 
2.3 Wound Closure after Surgical Wound-Healing Impairment 
Surgical wounds may be closed by primary intention, delayed primary intention, or by 
secondary intention. (Table 2)  
Table 2: Types of wound closure and their definition 
Type of Healing 
Definition 
Primary Closure 
Closure of a wound within hours of its creation 
Secondary Closure 
No formal wound closure; the wound closes spontaneously by 
contraction, granulation, and re-epithelialization 
Delayed Primary 
Closure (Tertiary 
closure) 
Surgical closing of a wound several days after the injury due to an 
inability to close the wound at the time of excision and debridement 
 
Closure by primary intention 
Surgical wounds are usually closed within hours of their creation by primary intention, 
where the wound edges are brought together (apposed) and then held in place by 
mechanical means (adhesive strips, staples, or sutures), allowing the wound time to 
heal and develop enough strength to withstand stress without support.  
 
The goal of surgery is to achieve healing by such means with minimal oedema, no 
serous discharge or infection, without separation of the wound edges, and with 
minimal scar formation. 
 
Closure by delayed primary intention (Tertiary closure) 
If a wound is purposely left open after surgery, has to be reopened because of 
wound healing impairment, or dehisces spontaneously after primary closure was 
performed, this wound can be closed after interim treatment and promotion of 
secondary healing by delayed primary intent. 
 

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This method is often used after traumatic injury or dirty surgery. In cases of wound 
healing impairment, the technique of a delayed primary closure after reopening of the 
irritated wound is an option for achieving healing. A temporal, open-wound treatment 
provides time for optimal preparation of the wound bed and margins. An extensive 
debridement and thorough lavage of the wound to remove necrotic debris and clots 
are essential prior to closure of the wound. 
 
Delayed primary closure, also known as tertiary wound closure, typically involves 
initial debridement of the wound for an extended period and subsequent formal 
closure by direct suturing (secondary suture) or by other closing techniques, after 
successfully apposing of the wound borders. Grafts and flaps also serve as 
alternative tertiary closure techniques to surgically close large, open abdominal 
wounds that are not amenable to direct suturing.   
 
Closure by secondary intention 
During wound closure by secondary intent, wound edges come together naturally by 
means of granulation and contraction. Typically, when open abdominal wounds are 
not amenable to either type of delayed primary closure, small and shallow, or are 
chronically infected, they are left to close by secondary intent. Secondary closure 
involves no formal wound closure; the wound closes spontaneously by contraction, 
granulation, and re-epithelialization. 
 
2.4 Vacuum-assisted wound closure (V.A.C.®) 
V.A.C.® is generally well tolerated and, with few contraindications or complications, is 
fast becoming a mainstay of current wound care.[8] V.A.C.® Therapy has been 
successfully integrated in the management of post-laparotomy wound dehiscence in 
patients with compromised wound healing and has been well documented in the 
peer-reviewed literature. In this setting, V.A.C.® Therapy has been shown to 
successfully provide wound stabilization, followed by accelerated healing and 
resulting in faster wound closure. Although there are reported uses of V.A.C.® 
Therapy in treating these wound types in the acute care setting, there is a consensus 
that there is insufficient clinical data based on the systematic evaluation of V.A.C.® 
Therapy for these wounds in the post-acute environment. 
 

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Healing of these types of wounds often extends beyond the initial hospitalization 
period and frequently requires further wound care treatment outside the hospital 
environment, either in home care or outpatient clinic settings. Therefore, it is 
important to understand the relative effect and benefit of using V.A.C.® Therapy 
versus standard conventional wound therapy (SCWT) in the treatment of these 
wounds across all relevant care settings.  
 
Over 700 peer-reviewed articles (including 22 RCTs, 18 of which involved at least 1 
endpoint associated with wound healing) provide a growing body of evidence 
regarding the clinical results and mechanisms of action of this integrated wound care 
system. The literature provides evidence with regards to V.A.C.® Therapy’s 
effectiveness in diabetic foot wounds, chronic wounds such as pressure ulcers and 
lower extremity ulcers. Additionally to that V.A.C.® Therapy is used in the treatment of 
a variety of acute wounds, including abdominal wounds [9], surgical and dehisced 
wounds [9-11], grafts and flaps [12, 13], deep sternal wounds [14-16] and partial 
thickness burns [17, 18]. In a 2006 study, Yang et al showed that the use of V.A.C.® 
Therapy reduces healing time by 58% in patients with fasciotomy wounds for 
traumatic compartment syndrome (6.7 days vs. 16.1 days, p<0.05). In a 2000 study, 
Avery et al showed the use of V.A.C.® Therapy to manage split thickness skin grafts 
over forearm donor sites had a 100% graft uptake at 5 days. In a 2005 study, Sjogren 
et al showed that V.A.C.® Therapy when compared to conventional treatment, 
significantly reduced the 90-day mortality rate in patients with deep sternal wound 
infections from 15% mortality in the conventional treatment group to 0% mortality in 
the V.A.C.® Therapy group (p<0.01). In a 2005 study, Agarwal et al concluded that 
V.A.C.® Therapy is a safe and effective first-line therapy in the management of 
sternal wound infections due to its efficacy in reducing wound edema, ability to 
decrease time to definitive closure, and ability to reduce wound bacterial colony 
counts. In a 2006 study, Leininger et al demonstrated that U.S. military hospital 
infections decreased from 80% (anecdotal) to 0% (documented) as shown in a 
retrospective analysis of 88 patients when V.A.C.® Therapy was employed. 
 
2.5 Recent History 
When compared to SCWT, most of the published literature confirms the advantage of 
negative pressure wound therapy (NPWT), also called vacuum assisted wound 

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closure, but sufficient proof of effectiveness and efficacy is lacking [19, 20]. The 
Federal Joint Committee (G-BA) of the German Health Care System faced this 
situation by commissioning a report on effectiveness and efficacy of NPWT by the 
Institute for Quality and Efficiency in Health Care (IQWiG). The final IQWiG-Reports 
[21, 22] concluded that, in spite of some indications that NPWT may improve wound 
healing, the methodological quality of the so far performed trials is unsatisfactory and 
thus the body of evidence available is insufficient, more specifically in the post-acute 
care setting.  
 
 

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3 
STUDY OBJECTIVES AND PURPOSE 
3.1 Purpose 
This RCT was designed to collect data that would address areas thought to have 
insufficient evidence. Moreover, this trial seeks to evaluate the use of V.A.C.® 
Therapy in the acute to post-acute environment, particularly because wound healing 
occurs across the continuum of care and often continues after a patient is released 
from hospital to homecare or other community-based care. Thus, there is a need to 
identify the outcomes and benefits of V.A.C.® Therapy when compared to SCWT, 
when used across these care settings.  
This trial is designed to comply with all quality requirements of IQWiG and G-BA as 
well as other European authorities. 
Wounds with healing impairment after abdominal surgery and intact fascia were 
chosen as the target study population because they are considered to be a fair 
representation of open wound types and also are frequently associated with the 
types of comorbidities observed with other types of open wounds. 
 
3.2  Hypothesis 
This study’s hypothesis is that the use of the V.A.C.® Therapy System, when 
compared to SCWT in the management of post-surgical abdominal wound healing 
impairments with intact fascia, will result in a decrease in the time to achieve 
complete wound closure with confirmation after subsequent 14 days. 
 
Using V.A.C.® Therapy is an effective and safe treatment option for hospitals as well 
as for outpatient care for treatment of subcutaneous abdominal wounds with wound 
healing impairment in the postoperative course.  
 
We postulate that V.A.C.® Therapy will demonstrate statistically significant clinical 
and health economics benefits when compared to SCWT in the management of 
human participants with postoperative dehisced abdominal wounds. 
 
3.3  Primary and secondary objectives 
The primary objective of this multicenter, parallel design, prospective, randomized 
clinical trial is to compare the clinical, safety, and economic outcomes of V.A.C.® 

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Therapy and SCWT in postsurgical abdominal wound healing impairments without 
fascial dehiscence.  
The primary outcome to be observed in this study is time to complete abdominal 
wound closure where closure is observed at or before Day 42 and is confirmed to 
have been sustained for a period of at least 14 consecutive days. This study design 
also will allow detailed description of specific covariates to determine their effect on 
response variables (healing).  
 
Secondary endpoints to be analyzed in this study will consider the effect of treatment 
on several quantitative factors for establishing efficacy, safety, quality of life, and 
resource utilization. 
 
 

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4 
STUDY DESIGN 
This study is designed as a multinational, multicentre, randomized controlled, clinical 
superiority trial, with blinded photographic analysis of the primary endpoint. The trial 
will be performed in Austria, Belgium, Germany, the Netherlands and United 
Kingdom. 
 
4.1  Phase and Classification of the Trial 
The trial is classified as an examination of the clinical application of a CE-marked 
medical device with risk category 2 b.  
 
4.2  Treatments 
This study is designed to evaluate treatment effects of a medical device in 
comparison to control therapy. 
 
Trial intervention is wound treatment with V.A.C.® using the basic principle of 
NPWT. 
 
Control therapy is defined as any SCWT according to actual guidelines or local 
clinical standards. Standard therapy is defined as the currently accepted and widely 
used treatment for the respective wound type, based on the results of past research. 
Therapy options for standard wound care are treatments that experts agree to be 
appropriate, accepted, and widely used. Health care providers are obligated to 
provide patients with best practice and standard of care. 
 
For more information about treatments see chapter 6 TRIAL THERAPY. 
 
4.3 Randomisation 
Randomisation to treatment arms will be performed at a 1:1 ratio. Randomisation will 
be performed via a centralized system with an internet-based tool. Every user will 
receive access to register and then later to log into the system in order to receive a 
randomisation number and treatment assignment for a given participant. Participant 
randomisation will be stratified within centre by wound size.  
Patients will be randomised dynamically. The permuted block sizes will randomly 
vary between 2, 4, and 6. 

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4.4  Stratification 
Stratification will take place by study centre and then also subsequently by wound 
size (cm3) within study centre. Wound size categories or strata to be considered will 
be the following: 
 
Wounds 
≤ 60 cm3 
 
Wounds 
> 60 cm3 
 
4.5  Primary Endpoint 
The primary endpoint of this trial is defined as time (number of days) to achieve 
complete wound closure in study participants where closure was observed on or 
before Day 42 and was confirmed to have been sustained for a minimum of 14 
subsequent days.  
 
Complete wound closure is defined as: 
 100% Epithelialization  
 No drainage from the wound 
 No need for adjuvant therapy or dressing  
 No presence of sutures 
Complete wound closure has to be confirmed after a minimum of 14 consecutive 
days (14 days -0 / + 3). 
 
The clinically determined closure of the wound has to be documented by photos.  
 
Wound closure can be achieved by delayed primary intention (secondary suture, skin 
flap, skin graft) or secondary intention according to requirements of the participant 
and wound in the estimation of the attending physician. Optimal care for the 
participant has to be ensured. 
Independent from type of closure, criteria for wound closure have to be reached 
within a maximum time frame of 42 days and wound closure has to be confirmed for 
a minimum of 14 consecutive days (14 days -0 / + 3). 
 
 
 

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4.6  Secondary Endpoints 
Incidence of wound closures within 42 days  
The incidence of wound closure achieved within each treatment arm will be 
evaluated after a maximum study observation/treatment period of 42 days. These 
wound closures have to be confirmed to sustain for a minimum of 14 subsequent 
days. This will be conducted via blinded photographic analysis. 
 
Recurrence 
Recurrence of wound opening after initial closure and confirmed wound closure will 
be assessed and compared between the treatment groups. 
 
Reduction of wound size over time 
Reduction of wound size over time will be evaluated using the following methods:  
reduction in wound volume over time and reduction in wound surface area over time. 
 
4.7 Verification of wound closure and wound size  
For the purposes of this trial a web-based photo documentation platform for wound 
photographs of study participants will be established. Wound photographs will be 
uploaded by study sites for each trial visit. The Wound Healing Analyzing Tool 
(W.H.A.T.) will be integrated within the platform. A centralized wound analysis of 
anonymized photographs (blinded assessment of wound photos) will be performed, 
which facilitates the objective evaluation of wound healing processes. 
The clinically determined primary endpoint will be verified through blinded 
assessment of wound photos by observers that are independent from the clinical 
trial. 
Secondary endpoints (numerical parameters) like circumference (mm), area (mm2), 
maximum length (mm), and height (mm) will be calculated from the wound image 
using W.H.A.T., whereas the application of the system also will be performed by 
blinded independent assessors. 
 
4.8 Safety Endpoints 
Incidence of serious adverse events (SAEs) including mortality of any cause within 
132 days from the time ofrandomisation, incidence of device-related events (ADEs), 

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wound-related adverse events (AEs) and incidence of unsustained closure within the 
study treatment time of 42 days are considered to be safety endpoints of this trial. 
 
4.9 Patient Reported Outcome  
Patient-reported outcome (PRO) is an umbrella term that covers different types of 
measurements to record unbiased self-reports by the participant. Instruments and 
assessments used for measurement of PRO of the SAWHI-V.A.C.®trial focus on the 
constructs “Quality of life” (QoL) and “Reports and Ratings of health care” (Patient 
Satisfaction).  
 
Quality of Life 
Healing of the wound is directly associated with patient well-being. QoL is an 
adequate measurement for a comparison of the treatment options. QoL is measured 
by using a multidimensional questionnaire assessing a combination of aspects of 
impairments and disability and reflects a patient’s health status.  
QoL questionnaires are multidimensional, generic instruments for the measurement 
of health related QoL that consider health effects and physical restrictions as well as 
background information about daily activities and emotional response to restrictions. 
An innovative treatment option has the ability to cause earlier return to daily activities, 
improvement of functioning, direct or indirect reduction of emotional distress, and 
social reintegration. QoL will be measured using the SF-36v2 questionnaire at day 42 
(end of maximum treatment time) or at wound closure visit, hospital discharge, and at 
the general follow-up visit. 
 
Pain 
In evaluating pain associated with wound healing and wound healing treatments, the 
total burden of pain must be considered. Therefore, during study visits, participants 
will be asked to provide their assessments of pain with an 11-point Likert Scale 
(Visual Analogue Scale). Participants will be asked to provide an estimate of their 
wound-associated pain of the last 24 hours.  
The holistic treatment of patients with wound healing disorders calls for adequate 
pain therapy according to existing guidelines during disease-specific treatment time. 
Therefore, the documentation of therapy-caused pain medication is considered. 

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Wound related AEs, ADEs and SAEs are part of the safety assessment and will be 
documented.  
 
Patient Satisfaction 
This item covers a structured participant self-report and a valuation of the disease-
specific healthcare [23]. Furthermore, this point includes participants’ valuation of the 
treatment result with regard to scarring and the cosmetic result. The Participant 
should be asked about the general estimation of therapy progression and detailed 
treatment satisfaction.  
 
This item will be evaluated by using a self-constructed questionnaire on the basis of 
specific scales of the Cologne Patient Questionnaire [24]. The Cologne Patient 
Questionnaire has formerly been used to develop a theory-based and empirically 
tested instrument for measuring patient-reported “psychosocial care by physicians” 
[25] and represents an ideal basis for development of a specific questionnaire for 
participant satisfaction of this trial. 
 
Patient Satisfaction will be evaluated during General Follow Up Visit. 
 
4.10 Health Economic Endpoints 
Additionally to the evaluation of clinical treatment effectiveness, a prospective 
assessment of health economic issues will be performed. 
 
This evaluation includes the assessment of parameters relevant for inpatient and 
outpatient resource use (resource utilization). A detailed baseline data acquisition 
regarding underlying disease and intervention will create the basis for further 
assessments of health development and resource use. Participants’ co-morbidities 
will be documented using a separate, standardized case report form (CRF) sheet. 
 
Direct medical resource use 
Resource use that results directly from wound treatment or disease-specific therapy 
is considered as direct resource use.  
The category direct medical resource use (direct medical costs) includes the 
resource use that is an immediate consequence of the disease pattern: 

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 general and specific clinical diagnostics 
 medication (in particular analgesics and antibiotics) 
 specific wound therapy 
 number and type of debridements 
 residential treatment and medical attendance  
 outpatient treatment and medical attendance 
 reinterventions 
 rehospitalizations 
Surgical reinterventions and rehospitalizations are especially a burden for health care 
and will be evaluated during the study. Reasons for these resource utilization 
parameters of particular interest will be documented explicitly within the CRF. 
 
Indirect resource use 
Resource use (cost) that is not directly associated with disease treatment is 
considered as indirect resource use (cost):  
 restrictions of productivity besides absence from the workplace (activities of 
daily living) 
 nonproductive time for those who are gainfully employed 
 
4.11 Blinding 
Due to the physical differences between the treatment regimens (eg, V.A.C.® 
Therapy versus SCWT), it is not possible to blind either Participant or physician to the 
treatment. Nevertheless, the Federal Joint Committee of the German Health Care 
System and International Conference on Harmonisation (ICH) GCP guidelines 
demand blinding procedures within RCTs whenever possible.  
To address issues of blinding, wound photo documentation will be obtained during 
the trial and confirmation of wound closure will be assessed via blinded assessment 
of photos by independent observers, which will serve as the method of primary 
endpoint analysis.  
 
4.12 Cross-sectoral patient treatment 
Due to the scope of the trial to evaluate outcomes and benefits of V.A.C.® Therapy 
when compared to SCWT, when used across these care settings, all patients at the 
time point of randomization or during the active treatment period of 42 days that are 
eligible for outpatient care and have reasonable access to it, have to be transferred 

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to outpatient care.The transfer of appropriate patients to outpatient care will be 
monitored and a missing transition that is not due to medical condition of the patient 
or is due to provide the optimal treatment will be considered to be a protocol 
violation.

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5 
PATIENT SELECTION AND RECRUITMENT 
This multicentre study will be conducted in hospital departments with the required 
manpower as well as structural and scientific qualifications. Study therapy will be 
started in ambulatory care or in-hospital and may be continued in ambulatory care. 
Study sites and investigators will be listed in a separate document.  
Only patients meeting all Inclusion Criteria and no Exclusion Criteria should be 
included in the study. No deviation will be granted for waiver of Inclusion Criteria 
and/or Exclusion Criteria.   
 
5.1  Diagnosis 
There are 2 categories of wound patients with distinct post-surgical open abdominal 
wound diagnoses that will qualify for this study:  
 Patients with primarily closed post-surgical abdominal wounds without fascial 
dehiscence that develop a spontaneous wound dehiscence or require an active 
reopening of the wound by the treating physician 
 Patients with open post-surgical abdominal wounds without fascial dehiscence 
that cannot be closed by primary intention and require further treatment to 
achieve permanent closure 
 
5.2  Inclusion Criteria 
Only patients meeting all of the following characteristics will be eligible for clinical 
trial enrolment. 
 Written informed consent 
Participant is willing and able to provide written informed consent.  
 Diagnosis 
of 
post-surgical 
subcutaneous 
abdominal 
wound 
healing 
impairment 
Participant must have post-surgical abdominal wound with intact fascia (see 
definition of diagnosis).  
 Minimum wound size eligible for the application of the randomized treatment 
Minimum wound size must be eligible for both possible study treatment 
options according to the therapeutical requirements of the respective 
randomized treatment arm. 

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 Inclusion, randomisation, and start of therapy  
Inclusion, randomization, adequate wound pre-treatment (debridement) and 
start of therapy must be completed within 48 hours after reopening of the 
wound, diagnosis for non-closable wound or in case of spontaneous wound 
dehiscence 
 
5.3  Exclusion Criteria 
Patients with any of the following characteristics are not eligible for clinical trial 
enrollment. 
 
 Age <18 years 
Patients younger than 18 years are not allowed to be included in the trial. 
 Noncompliance with study procedures, visit schedule, or follow-up  
A patient unable or unwilling to comply with the protocol and study-related 
requirements, to sign the Informed Consent Form, or to have their legally 
authorized representative act as a surrogate will be excluded from study 
participation. If a potential study patient, in the estimation of the Clinical 
Investigator, is unable to comply, the patient must be excluded from 
participation.  
 Pregnancy 
Female candidates have to be asked about pregnancy. If a pregnancy is 
present, the patient must be excluded from participation. 
 Present or nonclosable defect of the abdominal fascia 
If the defect of the abdominal fascia is present at the timepoint of initial 
diagnosis or reopening of the wound but can be closed before randomization 
but within the timeframe of 48 hours, participants may be included in the 
study. 
 Any pre-existing or ongoing organ system failure, that cannot be stabilized or 
solved by appropriate medical treatment 
 Necrotic tissue with eschar present 

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 Non-enteric and unexplored fistulas 
 Malignancy of the wound 
 Use of any other device based on the principle of negative pressure wound 
therapy on the study wound within ≤ 8 days prior to screening  
 Competing therapy and procedures 
Any concomitant therapies or procedures deviating from the clinical standard 
wound treatment or with investigational character (eg, use of hyperbaric 
oxygen therapy [HBO]) are not allowed ≤ 30 days prior to screening or during 
the course of the trial. 
The need for concomitant therapies or procedures that, in the opinion of the 
treating physician, would directly affect wound healing or the ability to observe 
wound healing is an exclusion criterion for trial participation. 
 Other clinical trials 
Concurrent participation in another trial that interferes directly or in the 
foreseeable future with study procedures, patient’s compliance, wound 
healing or targeted endpoints is not allowed for participants of this trial.  

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5.4  Enrolment 
A non-enrolled/ineligible potential-participant log (including reasons for non-
enrolment/ineligibility) will be monitored for any potential selection bias of enrolled 
participants that may occur.   
 
5.5 Description and justification for duration of treatment 
For both treatment arms, a maximum treatment time of 42 days to achieve complete 
wound closure shall be provided to cover 80% of participants whether healing occurs 
by secondary or delayed primary closure [4].  
 
5.6 Description and justification for follow-up 
All participants will be followed up for 90 days (3 months) after the maximum 
treatment time of 42 days, independent from whether a wound closure was achieved 
or not or at which time point within the maximum time frame for active treatment the 
wound closure was achieved. Thus, a general follow-up date for all study participants 
will be at day 132. 
A follow-up period of 3 months after the active treatment period allows for an 
assessment of recurrence of the wound dehiscence or impairment as well as an 
adequate assessment of health economic relevant issues. 
 
Participants who have not achieved wound closure after 42 days will be seen at 45 
days (6 weeks) after the end of active treatment time (Day 87). This timeframe 
allows for a complete assessment of wound progression after study treatment and 
an assessment of wound closure that is achieved later than day 42.

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6 
TRIAL THERAPY 
6.1  Description of Intervention 
6.1.1   General information 
The V.A.C.® Therapy System is a non-invasive wound therapy system that uses 
controlled, localized negative (ie, subatmospheric) pressure to create an 
environment that promotes wound healing in chronic and acute wounds. 
Picture 1: Vacuum Assisted Closure (V.A.C. ®) 
 
 
 
The V.A.C.® Therapy System label is on the market since 1995 and bears the CE 
mark and includes the trade name and address of the manufacturer, the batch code, 
and all other essential information according to European Union (EU) Directive 
1993/42/EEC.  
 
The V.A.C.® Therapy System promotes wound healing through optimization of blood 
flow, decreasing local tissue edema, and removing excessive fluid from the wound 
bed. These physiologic changes facilitate the removal of bacteria from the wound. 
Additionally, the cyclical application of subatmospheric pressure alters the 
cytoskeleton of the cells in the wound bed through microstrain, triggering a cascade 
of intracellular signals that increases the rate of cell division and subsequent 
formation of granulation tissue. Moreover, this system has been shown to also cause 
macrostrain, bringing the edges of the wound closer and also stimulating wound bed 
granulation. Further, V.A.C.® Therapy has proven beneficial in reconstruction of 
wounds by allowing elective planning of the definitive reconstructive surgery without 
significantly jeopardizing the wound or outcome. It has been shown to significantly 

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increase the success rate of skin graft uptake when used as a bolster over the 
freshly grafted wound. V.A.C.® Therapy is generally well tolerated and, with few well-
known contraindications and a limited number of AEs, is fast becoming a mainstay of 
current open-wound care. 
 
6.1.2 Composition and functionality 
The V.A.C.® Therapy System employs medical grade polyurethane or polyvinyl 
alcohol foam dressing that is fitted at the bedside to the appropriate size for each 
Participant wound and then covered with an adhesive drape to create an occlusive 
dressing seal. 
The V.A.C.® Therapy devices that will be used in this study include the ActiV.A.C.®, 
InfoV.A.C.®, V.A.C. Freedom®, V.A.C. Via® and V.A.C Ulta®. 
There are 3 types of wound dressings, available in different sizes, typically used in 
the treatment of open wounds with the V.A.C.® Therapy System.  
The V.A.C.® GranuFoam™ Dressing has reticulated or open pores and is considered 
effective at stimulating granulation tissue while aiding in wound contraction. It is 
hydrophobic (or moisture repelling), which enhances exudate removal.  
The V.A.C.® WhiteFoam Dressing is dense foam with a higher tensile strength. It is 
hydrophilic (or moisture maintaining) and is premoistened with sterile water. The 
dressing possesses overall nonadherent properties and is generally recommended 
for situations where the growth of granulation tissue into the foam needs to be more 
controlled or when the Participant cannot tolerate the V.A.C.® GranuFoam™ 
dressing due to pain. Due to the higher density of the V.A.C.® WhiteFoam Dressing, 
higher negative pressures (–125 mm Hg to –175 mm Hg) must be utilized in order to 
provide adequate NPWT distribution throughout the wound.   
The V.A.C. GranuFoam Silver® Dressing has reticulated or open pores with 
microbonded metallic silver uniformly distributed throughout the dressing, providing 
continuous delivery of silver. The silver is an effective barrier to bacterial penetration 
and may help reduce infection. The V.A.C. GranuFoam Silver® Dressing is 
considered effective at stimulating granulation tissue while aiding in wound 
contraction. The dressing is hydrophobic, which enhances exudate removal.  

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A hole is cut in the adhesive drape and the T.R.A.C.™ Pad or SensaT.R.A.C.™ 
opening is placed directly over the hole. The tubing attached to the T.R.A.C.™ Pad 
or SensaT.R.A.C.™ Pad is then connected to a fluid collection canister contained 
within a portable computer-controlled vacuum pump. V.A.C.® Therapy devices create 
controlled subatmospheric (negative) pressure. The SensaT.R.A.C.™ Pad (used 
with ActiV.A.C.®, InfoV.A.C.®, V.A.C. Freedom® , V.A.C. Via® and V.A.C Ulta®.) 
reliably maintain the target pressure at the wound site to help provide safe, 
controlled therapy.  
V.A.C.® Therapy delivers continuous or intermittent negative pressure, providing a 
range of negative pressure options to optimize fluid removal, tissue tension, capillary 
flow, and enhanced vascular perfusion through vessels previously compressed by 
excess fluid pressure. Negative pressure settings may range from –50 mm Hg and  
–200 mm Hg, where –125 mm Hg is typically used for wound healing. Dressing 
changes are recommended to be performed no less than 3 times per week. Dressing 
changes for infected wounds may need to be performed more frequently (every 12–
24 hours). 
 
6.1.3  Contraindications and Precautions for Use of V.A.C.® Therapy 
There are several contraindications and precautions for the use of V.A.C.® Therapy. 
These are shown in Table 3. 
Table 3: V.A.C.® -Therapy Contraindications and Precautions 
V.A.C.® Therapy Contraindications and Precautions 
Contraindications for 
patients with: 
 
Malignancy in the wound  
 
Non-enteric and unexplored fistula 
 
Untreated osteomyelitis 
 
Necrotic tissue with eschar present 
 
Exposed blood vessels or organs  

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6.1.4  Use within the trial 
The V.A.C.® Therapy devices that will be used in this study include the ActiV.A.C.® 
Therapy System, InfoV.A.C.® Therapy System, V.A.C. Freedom® ,V.A.C. Via® and 
V.A.C Ulta® Therapy Systems. All V.A.C.® Therapy devices to be utilized in this study 
bear the CE mark and will be operated within normal conditions of use. In addition, 
all dressings to be used in the treatment group (V.A.C.® Therapy) bear the CE mark 
and will be used according to clinical guidelines. The use of the allocated V.A.C.® 
Therapy System should be performed according to the clinical guidelines released 
by KCI. Instructions for use (User Manuals) will be provided for every study centre. 
The standard patient labelling will be provided with products. Product labelling will be 
indemnified by the manufacturer (KCI) according to local requirements. 
In this trial, V.A.C.® Therapy should be used with any of the following dressings: 
black GranuFoam™ Dressing, V.A.C. GranuFoam Silver® Dressing, or V.A.C.® 
WhiteFoam Dressing as indicated by the treating physician.  
Dressing changes have to be performed every 48–72 hours, no fewer than 3 times 
per week, with frequency adjusted by the clinician as appropriate. In particular, the 
first dressing change should be performed carefully and with moistened dressing to 
ensure that the foam can be removed easily. During dressing changes, if any 
analgesics or local anesthetics are used to provide an optimal pain management, 
their amounts and types should be recorded in the CRF. At each visit, the wound will 
be examined. In case of formation of excess granulation tissue and necrotic areas, a 
repeated debridement may be necessary to assure optimal conditions for wound 
healing and surgical closure.  
Precautions for patients 
with: 
 
Active bleeding 
 
Difficult wound hemostasis 
 
Anticoagulants 
 
When placing a V.A.C.® Dressing in close proximity to blood vessels or 
organs, take care to ensure that all vessels are adequately protected 
with overlying fascia, tissue, or other protective barriers 
 
Greater care should be taken with respect to weakened, irradiated, or 
sutured blood vessels or organs 
 
Bone fragments or sharp edges could puncture protective barriers, 
vessels, or organs 
 
Wounds with enteric fistula require special precautions to optimize 
V.A.C.® Therapy  
 
Follow universal precautions 

2013_09_17_SAWHI_Study Protocol V 8.0 
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Infected wounds detected by the wound contamination measurements post-op or 
during the follow-up visits must be monitored often and very closely. For these 
wounds, dressings may need to be changed more often than 48–72 hours; the 
dressing change intervals should be based on a continuing evaluation of wound 
condition and the Participant’s clinical presentation. 
Participants randomized to receive V.A.C.® Therapy may receive only V.A.C.® 
Therapy or V.A.C.® Therapy plus SCWT when the treating physician prescribes it in 
order to achieve wound closure by secondary intent; epithelialization may only occur 
with SCWT. V.A.C.® Therapy is indicated for granulation and preparation of an 
abdominal wound bed. In general, all participants receiving V.A.C.® Therapy should 
receive it only to the point where the treating physician believes the Participant has 
achieved maximum benefits from it. After that point, participants should be treated 
with SCWT to achieve final closure. 
These are important fundamentals of V.A.C.® Therapy, as it is intended to promote 
granulation and wound bed preparation but not epithelialization. 
 
Table 4: V.A.C. ® Treatment Recommendation   
Treatment 
cycle 
Target negative pressure 
Dressing change 
interval 
V.A.C.® 
Granufoam® 
(black) 
V.A.C.® 
Granufoam® 
Silver® 
V.A.C.® 
WhiteFoam® 
Continuous 
125 mmHg 
125 mmHg 
125-175 
mmHg 
Titrate up for 
more drainage 
Every 48-72 hours 
Or more frequent if 
clinically indicated 
(no less than 3 
times a week) 
 
 
 
 
 

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6.1.5 Operating Conditions of V.A.C.® Therapy Systems and disposables 
within the trial 
The V.A.C.® Therapy System carries the CE mark and is a commercially available 
product. All V.A.C.® Therapy units and disposables will be used in clinical routine 
according to local regulations.  
Purchasing, storage and dispense of the devices will follow the usual practices of the 
institutions performing the study and applicable regulatory requirements. The therapy 
unit and dressing are to be stored in a dry location at controlled room temperature 
away from direct sun exposure. If significant temperature deviations are noted, the 
study site should ensure that storage conditions be brought into compliance. 
It is the CI’s responsibility to ensure that an accurate record of each Participant’s 
exposure to the device is maintained. The clear assignment of the medical device to 
the trial participant will be recorded in the medical device log. The CRA shall ensure 
that a copy of the medical device form is kept in each Investigator Study File and is 
to review by the CRA during routine monitoring visits. 
The CRA shall document inadequate device-using practices, discuss them with the 
CI, and report them to IFOM. A pattern of deviation from the manufacturer's 
specifications is considered grounds for terminating the site’s participation in the 
study.   
 
6.2 Description of Control Therapy: Standard Conventional Wound Therapy  
Given the objective to determine the superiority of V.A.C.® Therapy to standard of 
care practices, it is important to ensure that the comparator arm of this study reflects 
optimal outcomes (wound closure) achievable without the use of V.A.C.® Therapy. 
As wounds have different barriers to healing, and various clinical presentations that 
will evolve over time, this study allows the use of all commonly used wound care 
dressings such that the physician can, based upon the wound and the Participant’s 
needs, deliver optimum wound care. 
For the purposes of this study, SCWT is the control therapy. It will be considered 
standard of care in the current healthcare system and will be performed within the 
context of the clinical wounds delineated within this protocol. SCWT constitutes a 
range of simple (i.e. gauze) to advanced dressings and other pertinent products that 

2013_09_17_SAWHI_Study Protocol V 8.0 
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demonstrate benefit through the facilitation of a moist wound environment, which is 
known to promote faster relative wound healing compared to wounds exposed to air. 
SCWT constitutes a myriad of products that are used alone or in combination to 
achieve wound healing.  
SCWT in treatment of open abdominal wounds without fascial dehiscence includes a 
multitude of products and may be performed according to the clinical standards 
determined by the treating physician.  
The choice of dressing type, rinsing solution, and topical treatments used should be 
determined based on the wound type and the best expected clinical outcome and 
should be applied as often as necessary. The therapy used will be recorded in the 
CRF. 
At each visit, the wound will be examined, and in case of formation of excess 
granulation tissue and necrotic debris, the open areas will be curetted and debrided 
to remove this tissue and debris. All such processes should be documented in the 
CRF. 
Most of the products discussed above have been reported as being used in 
conjunction with either V.A.C.® Therapy or SCWT. For the purpose of this study, 
SCWT includes non-V.A.C.® Therapy moist/advanced wound care dressings that are 
appropriate and applicable for treating the wounds according to the physician’s 
treatment intent. Further, their use with either therapy and between dressing 
changes will be allowed at the discretion of the treating physician.  
 
6.2.1 Operating Conditions of SCWT-material within the trial 
All SCWT supplies will be used in clinical routine according to local regulations. 
Logging, storage and dispense is the responsibility of the study site and is based on 
the manufacturers guidance as well as in accordance with applicable regulatory 
requirements. 

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6.3  Wound Care Principles and Practices 
The challenges associated with the management of wound healing, especially in 
light of complications, are multifactorial and thus effective therapy is multifaceted. 
Given that the goal of this study is to compare V.A.C.® Therapy with SCWT, it is 
important to apply key non-wound-dressing-related interventions such as 
debridement, infection management, and nutritional support consistently and in 
alignment with established clinical standards. For the purposes of this study, the 
following principles and practices should be applied as medically indicated in the 
judgment of the treating physician, irrespective of randomized treatment assignment 
within the clinical trial.    
 
6.3.1 Wound Debridement 
Effective wound debridement is a foundation for timely healing of complex abdominal 
wounds. All participants will have undergone appropriate debridement of necrotic 
and nonviable tissue from the wound (if medically indicated) before randomisation 
and treatment start. The CI will assess the need for debridement during each 
subsequent visit and perform such wound debridement as medically indicated, 
irrespective of randomized treatment assignment. Debridement may occur by 
surgical or sharps debridement, pulsatile lavage, or enzymatic means. Given the 
impact of debridement on the size, appearance, and state of the wound, wound 
examination will be performed both pre- and post-debridement. Microorganisms 
identified within laboratory cultures from samples taken during debridement should 
be documented and, if indicated, the wound should undergo appropriate infection 
management. 
 
6.3.2  Wound Cleansing 
Wound cleansing, as a premise of good wound care, should occur within this study 
as is clinically indicated by the general appearance of the wound, irrespective of 
randomized treatment assignment. Established standards of wound care indicate 
that washing of the wound with a nontoxic agent (such as normal saline) is 
acceptable for all wounds to remove debris and infectious materials. It is expected 
that the use of other antiseptic/antimicrobial skin cleansers or wound irrigants will be 
reserved for situations where there is a clinical indication to address wound 
bioburden or infection.  

2013_09_17_SAWHI_Study Protocol V 8.0 
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6.3.3 Wound Infection Management 
As a premise of good wound care, sources of wound infection must be readily 
identified and appropriately treated to facilitate wound healing. It is assumed that all 
participants included in the study will have undergone appropriate debridement and 
removal of nonviable tissue as an initial step to addressing wound infection (where 
indicated). All participants having clinical signs and symptoms of infection at any 
point during the study should receive medically indicated antibiotic and topical wound 
therapies consistent with standard of care within the respective treatment facility, 
irrespective of randomized treatment assignment. All antibiotics and topical therapies 
administered for the treatment of infection should be documented under the study’s 
concomitant medications. 
Some participants enrolled in this study will have an active diagnosis of wound 
infection that resulted in the wound dehiscence or inability to primarily close the 
wound. This information is relevant and should be captured on the initial wound 
assessment (examination) and medical history in the CRF. In such participants, the 
initial infection would not be considered an AE unless that infection worsened or 
deteriorated after initiation of randomized study treatment. Infections that occur after 
the initiation of study-randomized treatment will be considered an AE and should be 
documented and reported as such. 
 
6.3.4 Wound Pain Management 
Each person's experience of wound pain is complex and is influenced by a wide 
range of factors specific to the individual. Wound pain can be persistent, greatly 
affecting individuals' quality of life and having a significant impact on the lives of 
those around them. For others, the pain experienced is specifically related to, and 
often exacerbated by, wound dressing-related procedures. It is also important to 
recognise that emotional components, including anxiety and previous experience, 
can compound a person's perception of pain and may negatively affect the 
patient/practitioner relationship. Thus, a sufficient pain treatment concept is required 
for study participants, regardless of the randomised treatment arm. Pain 
management for study participants should be performed according to clinical 

2013_09_17_SAWHI_Study Protocol V 8.0 
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standards and will be documented during treatment time (pain medication and 
assessment). Pain treatment is recommended to be performed in a sufficient manner 
according to local guidelines [26-28].  
 
6.3.5 Treatment Compliance 
Monitoring will be performed to ensure compliance by the CIs to the protocol. The 
Steering Committee or its designees, CRAs, IFOM representatives, and KCI 
representatives may visit participating centres to control adherence to the protocol. 
Wound healing documentation may be evaluated by the Steering Committee, the 
IDMC, qualified personnel (assigned by either of these committees), CRAs, IFOM 
representatives, and KCI representatives by visit or by using photographs. 
Compliance to follow-up will be enforced by reminders. 
 
6.4 
Training on Study Products and Procedures 
The CI and site staff will be trained on the study as a whole, the investigational 
device, if applicable, and any specialized procedures prior to and/or during the site 
initiation visit. 
IFOM and KCI will ensure that clinical support to site staff is provided for any 
questions or concerns related to treatment plans; however, IFOM and KCI will not 
have any influence on participants’ care. 
  
 
 

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7 
STUDY PLAN 
7.1 Study Flow Chart 
Picture 2: Study Flow Chart 
Diagnosis: Subcutaneous Abdominal Wound Healing Impairment after Surgery 
 Wound reopening 
 Spontaneous dehiscence 
 Wound left open after surgery 
DAY 132 (-0 / +3 days): GENERAL FOLLOW UP  
FOLLOW UP Day 87 (-0 / +3 days)  
(for non-closed wounds only) 
SCREENING 
RANDOMISATION 
STUDY SITE 
WEEKLY 
VISITS + 
WOUND 
ASSESSMENT 
& 
PHOTOGRAPHS 
INITIATION OF THERAPY 
DAY 42:  
END OF MAXIMUM STUDY TREATMENT TIME 
ACTIVE STUDY TREATMENT 
NO 
YES 
WOUND 
CLOSURE 
WOUND CLOSURE 
CONFIRMATION 
(14 -0/+3 Days) 
V.A.C. 
SCWT 
Within 48 
hours after 
diagnosis 
or initial 
procedure! 
Within 48 
hours after 
diagnosis or 
initial 
procedure! 
END 
OF 
TREATMENT 

2013_09_17_SAWHI_Study Protocol V 8.0 
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7.2 Description of Study Visits 
The following section describes the planned visits and information to be collected. 
The following procedures and assessments are to be performed and documented. 
An overview of study visits can be found in APPENDIX Schedule of Visits. 
 
7.2.1 Screening 
 Written informed consent (to be performed before other procedures start) 
 Review of Inclusion Criteria and Exclusion Criteria 
 Demographics 
 Relevant medical and surgical history 
 Concomitant medications taken routinely and within the last 3 days before 
screening. Medications given during anaesthesia should not be collected. 
 Baseline health economic parameters 
 Working status and standard job 
 Location prior to hospitalization 
 Hospitalization time prior to screening 
 Reason for hospitalization 
 Date of, location of, and reason for initial surgery 
 Type of surgical procedure performed 
 Wound examination: Location, status of wound and surrounding area 
 Wound measurement, including depth, wound surface area,  
 Digital wound photographs (pre- or post-debridement, as applicable) 
(Appendix)  
 Wound pain assessment 
 Laboratory parameters (Blood count, C-Reactive Protein [CRP], Coagulation: 
Quick, Partial Thromboplastin Time [PTT]): to be completed if collected as 
part of standard of care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 

2013_09_17_SAWHI_Study Protocol V 8.0 
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7.2.2 Randomisation and Initiation of Therapy  
Randomisation, wound pre-treatment, and initiation of therapy have to be performed 
within 48 hours after wound reopening, spontaneous dehiscence, or decision for 
wound to be left open. 
 Randomisation of participant to either the treatment group (V.A.C.® Therapy) 
or control group (SCWT)  
 Time point of post-surgery initiation of wound care (V.A.C.® Therapy or 
SCWT)  
 Performance and documentation of wound pre-treatment 
 Wound examination: Status of wound and surrounding area  
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximum width and length, maximum 
depth) 
 Digital wound photographs 
 Documentation of wound treatment (V.A.C.® Therapy or SCWT) 
 Concomitant medications wound pain assessment  
 Laboratory parameters (Blood count, CRP, Coagulation: Quick, PTT): to be 
completed if collected as part of standard of care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 
7.2.3 Weekly wound visits until wound closure or end of active treatment 
period 
Beginning at Day 6-8 (Week 1), weekly wound visits will be performed until wound 
closure or end of maximum treatment time. A maximum of 6 visits will be performed 
within the maximum treatment time of 42 days. 
Weekly visits should be planned and scheduled to take place during dressing 
changes in the V.A.C. Therapy® arm. 
 Treatment continuation 
 Wound examination: Status of wound and surrounding area  
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximum width and length, maximum 
depth) 
 Digital wound photographs  
 Wound pain assessment  

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 Concomitant medication  
 Wound related procedures (localization, time, quality, person) 
 Dressing changes/applications between study visits  
 Rehospitalisation (reason, time, procedures, length of hospital stay) 
 Length of hospital stay 
 Resource utilization 
 Discharge documentation, if applicable (see visit: Hospital Discharge) 
 Wound closure documentation, if applicable (see visit: Wound Closure) 
 Laboratory parameters (Blood count, CRP, Coagulation: Quick, PTT): to be 
completed if collected as part of standard of care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 
7.2.4 Hospital Discharge 
 Date of discharge 
 Disposition 
 Wound examination: Status of wound and surrounding area 
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximum width and length, maximum 
depth) 
 Digital wound photographs  
 Concomitant medication  
 Wound pain assessment  
 SF-36® 
 Description of procedures 
 Status of treatment 
 Resource utilization  
 Laboratory parameters (Blood count, CRP, Coagulation: Quick, PTT): to be 
completed if collected as part of standard of care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 

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7.2.5 End of treatment 
End of Treatment (EOT) will be reached if an optimal preparation of the wound bed 
is achieved as determined by the treating physician. 
In case of wound closure by secondary suture, skin graft, or flap, the surgical 
procedure is required to be performed not longer than 72 hours after end of 
treatment. If the intended surgical procedure cannot be performed within 72 hours 
after end of therapy, randomised therapy has to be continued until surgery. 
 Wound examination: Status of wound and surrounding area 
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximum width and length, maximum depth) 
 Digital wound photographs  
 Concomitant medication  
 Wound pain assessment  
 Dressing changes/applications between study visits and surgical or local wound 
treatment procedures 
 Description of procedures 
 Resource utilization 
 Laboratory parameters (Blood count, CRP, Coagulation: Quick, PTT): to be 
completed if collected as part of standard of care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 
7.2.6 Wound closure 
Wound closure visit will be performed at any time complete wound closure according 
to wound closure definitions is achieved within the maximum treatment time of 42 
days.  
Independent from type of closure, it should be the primary intent of therapy to 
achieve wound closure in a prompt fashion! 
The following procedures and assessments are to be performed and documented: 
 Wound examination: Status of wound and surrounding area 
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximum width and length, maximum 
depth) 
 Digital wound photographs  
 Concomitant medication 
 Wound pain assessment  

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 SF 36® 
 Dressing changes/applications between study visits and surgical or local 
wound treatment procedures 
 Description of procedures 
 Resource utilization 
 Laboratory parameters (Blood count, CRP, Coagulation: Quick, PTT): to be 
completed if collected as part of standard of care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 
7.2.7 Wound Closure Confirmation  
This visit takes place after a minimum of 14 and a maximum of 17 days after clinical 
diagnosis of complete wound closure according to wound closure criteria defined in 
chapter 4.5. 
The wound closure has to sustain constantly for a minimum of 14 days after wound 
closure visit. 
If wound closure cannot be confirmed during this visit, wound therapy has to be 
continued as randomised.  
 Wound examination: Status of wound and surrounding area 
 Wound status: determination of wound closure  
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximum width and length, maximum 
depth)  
 Digital wound photographs  
 Concomitant medication  
 Wound pain assessment  
 Description of procedures  
 Dressing changes/applications between study visits and surgical or local 
wound treatment procedures 
 Collection of resource utilization Laboratory parameters (Blood count, CRP, 
Coagulation: Quick, PTT): to be completed if collected as part of standard of 
care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 

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7.2.8 End of maximum treatment period 
End of Maximum Treatment Time (EOMT) (Day 42) or early termination 
In case of a non-closed wound at day 42 an additional follow-up will be performed at 
day 87. 
 Wound examination: Status of wound and surrounding area  
 Wound measurement, including wound area and volume (size: area of wound 
opening, largest distance of wound margins, maximum width and length, 
maximum depth) 
 Digital wound photographs  
 Concomitant medication  
 Wound pain assessment  
 SF 36® 
 Description of procedures 
 Dressing changes/applications between study visits and surgical or local 
wound treatment procedures 
 Collection of resource utilization Laboratory parameters (Blood count, CRP, 
Coagulation: Quick, PTT): to be completed if collected as part of standard of 
care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 
7.2.9 Follow-up Visit at Day 87 for non-closed wound at Day 42 (EOMT) 
 Wound closures (date and number) 
 Recurrences 
 Wound examination: Status of wound and surrounding area 
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximal width and length, maximum 
depth)  
 Wound pain assessment 
 Digital wound photographs  
 Type, length and care setting of wound treatment after Day 42 
 Collection of resource utilization Laboratory parameters (Blood count, CRP, 
Coagulation: Quick, PTT): to be completed if collected as part of standard of 
care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 

2013_09_17_SAWHI_Study Protocol V 8.0 
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 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 
7.2.10 General Follow-up Visit at Day 132 
 Wound closures (date and number) and recurrences, if applicable 
 Wound examination: Status of wound and surrounding area 
 Wound measurement, including wound area (size: area of wound opening, 
largest distance of wound margins, maximum width and length, maximum 
depth)  
 Digital wound photographs  
 Type, length and care setting of wound treatment after Day 42 
 Wound pain assessment 
 SF36® 
 Patient satisfaction 
 Collection of resource utilization  
 Laboratory parameters (Blood count, CRP, Coagulation: Quick, PTT): to be 
completed if collected as part of standard of care 
 Local wound swab and blood culture, if signs and symptoms of infection are 
present: to be completed if collected as part of standard of care 
 Safety: Wound related adverse events and device-related adverse events 
(ADEs); all SAEs (including Serious Adverse Device Events (SADEs)) 
 
 

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7.3  All Interim Dressing Changes 
Wounds being treated with the V.A.C.® Therapy System and with SCWT should be 
monitored on a regular basis. In a monitored, non-infected wound, V.A.C.® foams 
should be changed every 48 to 72 hours but no less than 3 times per week, with 
frequency adjusted by the clinician as appropriate.  
If a dressing change is required between scheduled visits, the participant can go to 
the ambulant department of the study centre (if on V.A.C.® Therapy arm) or to a 
certified and appropriately trained resident physician or certified, appropriately 
trained home health care professional. For the SCWT arm, the participant dressing 
changes will be performed according to standard of care.  
If the dressing changes are performed elsewhere than in the study centres, the 
participant will be given an informational sheet instructing the physician or nurse to 
refer the participant to the study centre for any AEs and observations of wound 
closure. The visit documentation will be done at every visit. If a dressing change is 
required between study visits, the details will be documented in the next regular visit 
form.  
For all dressing changes special data collection forms for participants’ bedside or to 
put into source document like participants’ health records will be offered to ensure 
that all data that need to be collected for the study visits can be filled in properly and 
completely. 
 
7.4 Wound Assessment (Examination) 
A wound assessment (examination) will include: 
 Observatory confirmation of wound closure 
 Epithelialization and granulation on wound base 
 Skin Condition: wound edge, periwound condition, wound appearance and 
wound base color, presence of necrotic tissue, signs and symptoms of 
infection, peripheral tissue edema  
 Wound drainage: amount, appearance 

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 Wound measurements will be recorded according to the Schedule of Study 
Visits (Appendix A). Wound measurements will include: 
o 
(Volume = Maximum Length × Maximum Width × Maximum Depth) 
o 
Reduction in wound surface area over time (Area = Maximum Length × 
Maximum Width) 
Photographs will be taken during study visits to document reduction of wound size 
over time, wound closure and confirmation of closure.  
 
7.5 Wound pain assessment 
Wound pain assessment during active treatment time will be performed during study 
visits. Participants should record an estimation of their average pain of the last 24 
hours in the CRF. 
 
7.6 Prior and Concomitant Medication  
Medication will be documented for the following categories:  
 Anti-diabetics 
 Anticancer agents 
 Immunomodulators 
 Corticosteroids 
 Antiinfectives for systemic use 
 Antiinflammatories 
 Antirheumatics 
 Antithrombotics 
 Antihemorrhagics 
 Analgesics 
Medication taken within 3 days prior to randomisation and taken or administered until 
EOMT will be recorded in the CRF. Concomitant medications will be recorded as per 
the Schedule of Study Visits. 
 
7.7 Early Termination of Treatment and Trial Participation 
If a participant prematurely terminates trial participation, he/she will be offered 
adequate medical treatment, as necessary. Unless requested by the participant, all 

2013_09_17_SAWHI_Study Protocol V 8.0 
Page 55 of 90 
data collected up to termination will be available for database entry and analysis. 
Participants who terminate the study early will be offered to be followed for safety 
monitoring for up to 42 days post-intervention.  
 
7.8 Early Study Termination 
The IDMC may decide in the interest of healthcare to terminate the study before 
completion of participant recruitment (eg, if an unacceptably high rate of ADEs is 
seen in participants or if issues arise that prevent successful completion of the 
study). 
Noncompliance due to unfulfilled contractual and/or financial agreements between 
KCI and the PCI may lead to early termination of the study, after consultation with 
the Steering Committee, IDMC, KCI, and IFOM.  
Also, unfeasibility for successful completion of the study may lead to premature 
termination after consulting with the Steering Committee, IDMC, KCI, and IFOM. 
Early termination of the study should be based on mutual agreement among the 
Steering Committee, IDMC, KCI, and IFOM. 
 
7.9 
Removal of Participants from Therapy or Assessment 
The participating CIs are responsible for adequate treatment of participants following 
the study protocol. A CI may decide to remove a participant from the therapy or the 
trial for these reasons: 
 Deterioration of the wound that cannot be solved within a temporarily therapy 
intermission and that medically precludes or contraindicates continuation of 
randomized study therapy. In such case, the participant may be withdrawn 
from the active treatment phase of the study and considered to be a treatment 
failure but followed in the study’s follow-up phase for safety, quality of life, and 
healthcare economics resource utilization.  
 New information becomes known that changes the risks and benefits for the 
participant (this includes conditions of the participant). 
 Best medical interest, including safety, of the participant. 

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Regardless of the underlying reasons, participants have the right to withdraw at any 
time. Likewise, any relevant medical event as judged by a PCI may lead to the 
decision to withdraw a participant from the study. All reasons for drop-out of a 
participant will be documented. 
 
7.10 Closure of Study Centers and Exclusion of Investigators 
The Steering Committee or KCI may decide to exclude participating centres and/or 
CIs from further participation on the basis of fraud or noncompliance with the study 
protocol (eg, international guidelines for Good Clinical Practice [GCP]) by the 
participating center or CI. If the Steering Committee makes the decision, this 
determination can be made only after consulting with the IDMC, KCI, and IFOM. If 
KCI makes the decision, this determination can be made only after consulting with 
the IDMC, Steering Committee, and IFOM.  
Study centres or CIs may stop recruiting Participants for this study when the CI finds 
that inclusion of participants into this trial presents problems for ethical, medical, or 
organizational reasons. If this occurs, the study centre or CI must provide a detailed 
explanation to the Steering Committee and IDMC for the decision to cease 
recruitment. 

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8 
DATA 
8.1  Data Quality Assurance 
Steps to be taken to ensure the accuracy and reliability of data include the selection 
of qualified CIs and appropriate study centres, review of protocol procedures with the 
CI and associated personnel before the study commences, periodic onsite monitoring 
visits, and any other procedures as deemed appropriate by IFOM and KCI. IFOM and 
KCI will confirm that the clinical trial will meet International Organization for 
Standardization (ISO) 14155 guidelines and all applicable regulatory requirements, 
including ICH-GCP. All evaluation methods used are standard according to current 
scientific literature. 
 
Guidance for CRF completion will be provided and reviewed with the study personnel 
before the start of the study.  
 
In order to guarantee the high quality of the study data and data retrieval, all 
participating centres will be visited on a regular basis onsite by the CRAs according 
to a predefined monitoring plan. Data protection rights will be respected. Participant 
files will be monitored on a 100 % basis to control original data and to verify accurate 
data registration and management (100 % source data verification). The presence of 
a written Informed Consent Form (ICF) and the correct interpretation of Inclusion 
Criteria and Exclusion Criteria will be controlled. The IFOM CRAs will review CRFs 
for accuracy and completeness during on-site monitoring visits and any 
discrepancies will be resolved with the CI or designee, as appropriate. The CRA also 
will have regular contact in person, by phone, and/or by email with all participating 
centres as specified in a predefined monitoring plan. The purpose of the contacts is 
to monitor the study progression, verify adherence to the study protocol, and discuss 
problems related to the study. The CRA will particularly concentrate on AEs, the 
number of drop-outs, and excluded participants. The CIs in the participating centres 
will support the CRA in his/her activities. 
 
8.2  Data Collection and Documentation 
The study CRF is the primary data collection instrument for this study. A paper CRF 
will be used throughout this study. All data fields on the CRF or on the documentation 
sheets (for wound assessment, wound related procedures and medical history) which 

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is supposed to be archived as source data in the patient file should be completed 
within 24 hours of the Participant’s visit. All missing data should be explained in an 
appropriate comment section. A detailed guideline document for completion of CRFs 
will be provided to all study sites. 
 
All Participant data, excluding photographs of wounds, are to be considered source 
data and must be retained in a secure place and made available for review during 
routine monitoring/audits or on request of IFOM and KCI. The CI must document in 
the Participant’s clinical file that the Participant participated in this study. 
 
The CRF includes all necessary forms, separated according to the anticipated 
investigation time points. The CI will be responsible for the maintenance of every 
CRF in an up-to-date manner. The CI is responsible for the quality of all data 
documented in the CRF. The CI is responsible for the documentation of the study 
data in the source-data documents and the quality and correct entry of all data 
documented in the CRF. 
 
Only the CI or qualified personnel authorized by him/her are entitled to enter data into 
the CRF. All authorized personnel must be identified in the delegation of authority 
log, which specifies the delegation of responsibilities for the study. Corrections and 
additions must be signed with initials and dated by qualified study personnel.  
 
Remaining questions or missing data posed either by the monitor or by the data 
manager (appearing during data entry or additional consistency checks on the data 
base) will be noted using data clarification forms (DCFs). These queries will be sent 
to the CI. It is the CI’s obligation to complete and return the forms to the data 
management group within five working days or within 24 hours of database lock. The 
data management will do the bookkeeping of the queries, ie, requery in case the 
answer is not sufficient or keep track of the data entry into the database.  
 
Original copies of the CRFs will be sent to IFOM’s data management department for 
data entry into the study database. Copies of the CRFs designated for the CI must be 
stored together with the study documentation. 
 

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CRFs and source data are to be retained and stored in accordance with local 
applicable regulations or in accordance with the ICH-GCP regulations in effect for the 
jurisdiction where the clinical trial site is located whichever period is greater. The CI 
will ensure that a correct assignment of the CRFs to the corresponding Participant 
files, including all relevant source data, is possible at any time. A separate Participant 
identification list must be recorded by the CI. Participants’ ID lists and medical 
records will be kept separately at the individual study sites by the CI. 
 
The Participant ICFs designated for the CI are to be kept in the study documentation 
files at each CI’s site. All information on which the entries in the CRF are based must 
be available in the Participant files (ie, source documentation). 
 
After termination of the study, the CI will enter all relevant information obtained 
subsequent to the study in a Participant’s medical records. 
 
8.3  Data Handling and Management 
The infrastructure and personnel for data management will be provided by the Center 
for Clinical Studies and Innovation (ZKSI) at the University of Witten/Herdecke. The 
ZKSI will assign qualified personnel for the implementation of data management 
activities. 
IFOM and KCI are responsible for compilation and verification of the study data, 
retention of the clinical study database, performance of statistical analysis, and 
preparation of the trial reports. IFOM will perform data management activities in 
accordance with the study Data Management Plan (DMP).   
The setup of the database will be done by IFOM. The design of the database is given 
by the structure of the study, here a multicentre investigation. The content of the 
tables and variables in the database is determined by the paper CRF (pCRF) and 
refers to the study schedule. The pCRF serves as a reference to setup a Meta 
database describing the structure of the CRF and the variables. This Meta database 
will be validated against the pCRF. The Meta database serves as a basis to generate 
the study database. The study database itself will be validated against the Meta 
database and the pCRF. 

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The data validation plan contained within the DMP describes the edit and 
consistency checks for the entered data. The checks are implemented into the study 
database. The checks will be tested during the validation procedure.  
A data management program will be used that is FDA compliant. All protocol-
specified data documented on the CRFs will be dually entered into the study 
database utilizing appropriate data management procedures. After the data have 
been entered and verified, various edit checks will be performed for the purpose of 
ensuring the accuracy, integrity, and validity of the database. Queries generated from 
these edit checks will be sent to the study site for resolution, and the database will be 
updated to reflect query resolutions as appropriate. All activities associated with entry 
or alteration of any data will be traceable. 
All incoming CRFs and DCFs will be registered by data management. All registration 
forms will be checked for completeness, plausibility, and correctness.  
Participant ID lists and medical records will be kept separately at the individual study 
sites. 
Further details on implementation of the data management structure can be found in 
the DMP. 
 
8.4 Record Storage and Retention 
Investigator 
In accordance with the Investigator Agreement, the CI shall maintain all study 
documentation in his/her possession and/or control and institute measures to prevent 
accidental or premature destruction of any data and/or documents related to the 
study. 
 
After formal discontinuation of the clinical trial, the CI shall retain the clinical trial 
documentation produced by the CI in accordance with local applicable regulations or 
in accordance with the ICH-GCP regulations in effect for the jurisdiction where the 
clinical trial site is located, whichever period is greater. 
In accordance with the Investigator Agreement, the CI shall allow KCI and IFOM to 
have access to the clinical trial documents as defined in the Investigator Agreement. 
 
 

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KCI and IFOM 
KCI and IFOM shall maintain all study documentation in their possession and/or 
control and shall institute measures to prevent accidental or premature destruction of 
any data and/or documents related to the clinical trial. 
Study records will be stored for a minimum of 10 years after trial completion. 
 
After formal discontinuation of the clinical trial, the PCI shall retain the clinical trial 
documentation produced by the PCI for a minimum of three (3) years or in 
accordance with the ICH-GCP regulations in effect for the jurisdiction where the 
clinical trial site is located, whichever period is greater. 
 
8.5  Data Ownership 
Rights, duties, and obligations regarding ownership of any ideas, concepts, 
inventions, or results, whether patentable or not, shall be in accordance with the 
terms and conditions set forth in the Investigator Agreement by and between the 
Institution and IFOM. KCI retains exclusive ownership of all data, results, reports, 
findings, discoveries, and any other information collected during this clinical trial, 
including information set forth in and derived from the CRFs.  
 
In accordance with the Investigator Agreement, all materials, information (oral or 
written), 
and 
unpublished 
documentation 
provided 
to 
the 
CIs 
(or 
any 
company/institution acting on their behalf), inclusive of this protocol and the CRFs, 
are exclusive property of KCI and IFOM and may not be given or disclosed, either in 
part or in whole, by the CI or by any person under his/her authority to any third party 
without the prior express consent of KCI. 
 
The CI shall consider all information, results, discoveries, records accumulated, 
acquired, or deduced in the course of the study, other than that information to be 
disclosed by law, as confidential and shall not disclose any such results, discoveries, 
or records to any third party without IFOM’s and KCI’s prior written consent, without 
comments and with or without analysis, in order to submit data to the health 
authorities of any country for purposes of regulatory filing and/or submissions.

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9 
STATISTICAL CONSIDERATIONS 
The primary outcome to be observed in this multicentre, parallel design, prospective, 
randomized clinical trial is time to complete open abdominal wound closure by day 42 
which is confirmed after 14 (-0 / +3) consecutive days. Secondary endpoints to be 
analyzed in this study with repeated observations over time will consider the effect of 
treatment on several quantitative factors for establishing efficacy, safety, Patient-
reported outcome, and economic parameters.  
 
The Statistical Analysis Plan (SAP) will include a detailed description of specific 
covariates that will be evaluated to determine their effect on response variables. 
 
9.1 Determination of Sample Size 
The primary efficacy endpoint is the time to achieve confirmed wound closure within 
42 days of surgery (ie, wound confirmed closed after 14 consecutive days). Time to 
confirmed wound closure will be compared between the 2 treatment groups using 
log-rank test. Sample size estimation has been performed using the expected 
difference in wound closure rates rather than hazard ratios. Assuming a complete 
wound closure rate of 50% in the control group, and a minimum difference of 12.5% 
after a treatment time of 42 days, a number of 246 participants per group would be 
needed (chi-square test) to achieve 80% power with α = 0.05. If α = 0.048 due to one 
interim analysis (see below) sample size per group would increase only marginally 
(n=249 per group, or n=498 in total). Assuming a maximum loss-to-follow-up rate of 
10% for both treatment groups, a total of 550 participants will be required. Up to 600 
participants will be enrolled in this study. 
The computer program of Dupont and Plummer was used for sample size calculation 
[29]. 
One interim analysis will be performed when 250 participants complete the first 
phase of the study, and type I error rate will be adjusted using O’Brien-Fleming 
method (α = 0.005 for the interim analysis and α = 0.048 for the final analysis). 
The final analysis is planned to be performed with time-to-event data (survival curves; 
log-rank test) rather than wound closure rates. However, since this more detailed 

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approach is able to detect differences more sensitive than event rates, the calculated 
sample size is considered to be sufficiently large. 
 
9.2 Analysis Populations 
The following Participant populations will be considered for analyses for this study: 
 Intention-to-Treat Population (ITT) – The ITT analysis population will include 
all randomized participants who have a valid baseline and at least 1 valid post 
baseline wound assessment (examination). For the ITT analysis population, 
participants will be assigned to treatment group based on the randomisation 
schedule, regardless of the treatment actually received.  
 Per-Protocol Population (PP) – The PP analysis population will include 
participants in the ITT analysis population set who do not have disqualifying 
important protocol deviations such as participants who did not satisfy the 
inclusion/exclusion criteria, participants who received the wrong treatment, or 
participants who were not compliant with the protocol.  
 Safety Population – The Safety Population will consist of all enrolled and 
randomized participants who receive any study-related treatment procedure. 
Safety analysis will be analyzed as treated. All safety results will be presented 
based on the Safety Population.  
 
9.3  General Considerations and Baseline Parameters 
Unless otherwise stated, all statistical tests will be performed using 2-sided tests at 
the 5% significance level. Baseline is defined as the last observation before the 
intervention. Continuous demographic parameters, such as the Participant’s age at 
the time of enrollment, will be summarized for the ITT population using descriptive 
statistics (N, mean, median, standard deviation, minimum and maximum value, and 
95% 2-sided confidence limits). Categorical demographic parameters, such as 
gender, will be summarized as a proportion of the ITT population. Comorbid risk 
factors will be summarized for the ITT population by treatment assignment and 
according to the type of variable (categorical, continuous). Kaplan-Meier estimates 
for the individual time-to-event analyses will be prepared based on the ITT 
population. The number and proportion of participants who achieve complete closure 
will be tabulated and summarized using 95% binomial confidence intervals and 
compared between treatment groups using a Chi-square test.  

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Separate tables containing Participant counts, percentages, and 95% binomial 
confidence limits will be prepared based on individual risk factors.  
 
9.4  Efficacy Analysis 
9.4.1 Primary Efficacy Analysis (Time to Confirmed Wound Closure) 
The primary efficacy variable for this clinical study is time to achieve confirmed 
wound closure, defined as the number of days from onset of wound reopening, 
spontaneous dehiscence, or diagnosis for not closable wound until the wound meets 
the wound closure definition. All participants in the trial should be observed 14 (–0 / 
+3 days) post first observation of wound closure to determine if the closure has been 
sustained. Wound closure is defined as 100% epithelialization with no need for 
drainage or adjuvant therapy or presence of sutures. Wound closure has to be 
confirmed after a minimum of 14 days. 
If a wound was closed but was reopened prior to Day 14 post wound closure, this 
wound would be considered to not have achieved closure (unsustained closure).  
Participants who fail to close during the acute study phase (Baseline to Day 42) will 
be censored at Day 42.  
For the purposes of analyzing time to confirmed wound closure, the time to confirmed 
wound closure will be derived as: (date of first confirmed wound closure – date of 
onset of wound dehiscence) + 1 day. 
For participants who fail to achieve confirmed wound closure until Day 42, time to 
confirmed wound closure will be derived as the smallest of: (date of discharge/ 
discontinuation – date of onset of wound dehiscence) + 1 day, and Day 42; this 
derived time will be censored.  
The time to confirmed wound closure will be compared between treatment groups 
using a log rank test, and the supportive Kaplan-Meier curves will be generated and 
presented as well. As supportive analysis, a Cox proportional hazards regression will 
be performed. Covariates in the Cox regression model will be treatment assignment, 
study centre, wound size, and other baseline parameters, such as medical history 
(infection, diabetes, and cardiovascular disease), aetiology of wound, and wound 
closure method used. 

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9.4.2 Secondary Efficacy Analysis 
Incidence of Confirmed Wound Closure 
Confirmed wound closure is defined as in the primary efficacy section. Participants 
who discontinue the study prior to having achieved confirmed wound closure will be 
treated as a failure.  
 
Incidence of confirmed wound closure at Day 42 will be analyzed using a Chi-square 
test comparing the 2 randomized treatment groups. 
 
An additional supportive statistical analysis will include a logistic regression with 
factors and covariates in the model to include treatment assignment, study centre, 
and wound size, as well as appropriate baseline parameters, such as medical history 
(infection, diabetes, and cardiovascular disease), aetiology of wound, and wound 
closure method used.  
 
Reduction in Wound Volume (cm3) 
The wound volume will be derived from the wound measurements (Length, Width, 
and Depth) recorded at every visit or time point of interest. 
The actual wound volume will be assessed. The actual wound volume reduced at 
each respective visit will be derived as: actual wound volume – baseline wound 
volume.  
The percentage wound volume reduced also will be assessed. Percentage wound 
volume reduced at each respective visit will be derived as: (actual wound volume – 
baseline wound volume) / baseline wound volume × 100. 
A 3-factor (treatment group, site, and time) repeated measures (time) analysis of 
covariance, using the intra-Participant wound volume recorded at baseline as the 
covariate, will be used to assess the actual reduction, and a similar analysis will be 
performed for the percentage reduction in wound volume. 
 
Reduction in Wound Surface Area (cm2) 
The wound area will be derived from the wound measurements (Length and Width) 
recorded at every visit or time point of interest.  

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The actual wound area reduced at each respective visit will be derived as: wound 
area – baseline wound area.  
The percentage wound area reduced also will be assessed. Percentage wound area 
reduced at each respective visit will be derived as: (wound area – baseline wound 
area)/baseline wound area × 100. 
A 3-factor (treatment group, site, and time) repeated measures (time) analysis of 
covariance, using the intra-Participant wound area recorded at baseline as the 
covariate will be used to assess the actual reduction, and a similar analysis will be 
performed for the percentage reduction in wound area.  
 
Wound Recurrence 
Wound recurrence will have occurred if a wound that had achieved confirmed wound 
closure is subsequently determined to be reopened at any time during the follow-up 
phase.  
Wound recurrence will be analyzed using a Chi-square test comparing the 
randomized treatment groups. An additional supportive analysis will be performed 
using logistic regression analysis. 
The population for this endpoint will consist of those participants who achieved 
confirmed wound closure during the study. 
 
9.4.3 Patient-Reported Outcome 
Wound-related Pain 
Participants will provide an assessment of pain using an 11-point Likert Scale (Visual 
Analogue Scale). An estimate of the Participant’s wound-associated pain and their 
worst wound-associated pain of the last 24 hours will be recorded at each study visit. 
Comparison between treatment groups will be performed using a Wilcoxon’s rank 
sum test. Changes over time within each study group will be assessed with 
Wilcoxon’s signed rank test.  
 
Quality of Life 
For each Participant, health-related quality of life (HR-QoL) will be assessed at 
hospital discharge, at wound closure, or Day 42 (end of study period) in case of non-
closed wounds and at general follow up (Day 132). HR-QoL will be assessed using 

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the self-assessment instrument Medical Outcomes Study 36 Item Short Form Health 
Survey (SF-36) with 36 items. 
The SF-36 will be analysed according to the user manual with 8 subscales and 2 
summary scales (physical; psychological). QoL score will be calculated using the 
scoring manual. Differences in QoL scores between the treatment groups will be 
assessed using non-parametric rank statistics (Mann-Whitney U). Changes over time 
within each study group will be assessed with Wilcoxon’s Signed Rank test. 
 
Patient satisfaction 
Patient satisfaction will include the Participant’s evaluation of treatment result in 
regards to scarring and cosmetic aspects. These data or results will be obtained 
using specific scales from the Cologne Patient Questionnaire.  
Differences between the treatment groups will be assessed using non-parametric 
rank statistics (Mann-Whitney U). 
 
9.4.4 Health economic parameters 
Economic-based outcome measures will include the assessment of parameters 
relevant for inpatient and outpatient resource use or utilization. This will involve direct 
medical resource use, and indirect resource use. Differences between the treatment 
groups will be assessed using non-parametric rank statistics (Mann-Whitney U). 
Changes over time within each study group will be assessed with Wilcoxon’s Signed 
Rank test. 
 
9.5 Safety Analysis 
Safety analyses will be carried out using the Safety population to allow a benefit/risk 
assessment within the same study population. Safety parameters will include 
adverse device events (ADEs), serious adverse events (SAEs), and mortality during 
the duration of the study. 
An event will be considered as treatment emergent if the onset is any time on or after 
randomisation through 30 days after the end of study device treatment. Any event 
with an onset on the day of randomisation where the time of onset is missing will be 
assumed to be treatment emergent. 
The primary presentation of AE data will be prepared without regard to causality or 
relationship to study treatment.  

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Serious AEs and events leading to death will be summarized overall and by body 
system and preferred term. A life table or other similar analyses to show the relation 
to time on treatment and assess risk over time may be used. 
Unsustained wound closure will be defined as a wound that was closed within the 
maximum treatment time of 42 days according to the respective criteria, but then 
subsequently wound closure was not confirmed after a minimum of 14 consecutive 
days. Incidence of unsustained wound closure will be analyzed using a Chi-square 
test comparing the randomized treatment groups. An additional supportive analysis 
will be performed using logistic regression analysis. 
 
9.6  Interim Assessment 
One interim analysis will be performed when 250 participants complete the first 
phase of the study. Both efficacy and safety parameters will be presented in the 
interim analysis, and the overall type I error rate will be adjusted using the O’Brien-
Fleming method Interim data will be used to validate the assumptions made for the 
sample size calculation, and sample size re-estimation may be performed if 
warranted. 
The trial will be stopped if interim results are able to show a positive effect for 
V.A.C.®-therapy in comparison with standard therapy at a p-value of <0.001 or if 
interim data analysis shows a negative effect for V.A.C.®-therapy at a p-value of 
<0.05. 
 
9.7 Handling of Missing and Spurious Data  
Specific algorithms for imputing missing or partially missing data will be discussed in 
the SAP. Imputed or derived data will be identified in the individual Participant data 
listings. Imputed data will not be incorporated into the CRF datasets. Imputed data 
will be used in the preparation of the derived datasets. 

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10 ETHICAL AND LEGAL ASPECTS 
10.1 Ethics Committee 
The principle coordinating investigator or in other countries than Germany the CI of 
every participating study center must submit this protocol to the appropriate EC if 
requested. As allowed by the EC, submission also may be done by IFOM on behalf 
of the CI. The CI is required to forward to University Sponsor (IFOM) a copy of the 
written and dated approval/favourable opinion signed by the Chair, or designee with 
EC composition. IFOM is required to forward to the KCI a copy of the written and 
dated approval/favourable opinion signed by the Chair with EC composition. 
The study (study number, protocol title, and version number), the documents 
reviewed, and the date of the review should be clearly stated on the written EC 
approval/favourable opinion. This approval/favourable opinion will be provided to the 
ECs of all participating centers together with the CV of the responsible CI to get 
professional legal advice before enrolment of participants.  
Enrolment of participants at a site will not start until a copy of the written and dated 
approval/favourable opinion has been received by IFOM.  
During the clinical trial, any substantial amendment or modification to the protocol 
must be approved by the EC of the principal coordinating investigator but should also 
be sent to the participating ECs. The EC also should be informed of any event likely 
to affect the safety of participants or the conduct of the clinical trial as per local 
requirements. (see section SAE reporting)  
A master ICF will be generated and will be adapted for every participating country as 
requested by the respective EC and according to local requirements. The ICF used 
by each CI in local language (as required from the ECs in every country for obtaining 
the Participant’s informed consent) must be reviewed and approved by IFOM prior to 
submission to the appropriate EC for approval/favourable opinion.  
A progress report will be sent to the EC as per local requirements and a summary of 
the trial’s outcome will be reported at the end of the clinical trial. 
The final study protocol, including the final version of the written ICF, must be 
approved or given a favourable opinion by the EC responsible for the CI before 
commencement of the study. The CI is responsible for informing the EC of any 
substantial amendment to the protocol in accordance with local requirements. 

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Changes and local modifications in accordance with local requirements have to be 
approved by IFOM and KCI.  
The CI must provide the EC or other authorities with any reports of SAEs from the 
study as local regulations require. This also may be done by IFOM on behalf of the 
CI. 
 
10.2  Ethical Conduct of the Study 
This study is to be conducted in accordance with the following directives and 
guidelines: 
 ICH Harmonised Tripartite Guidelines for Good Clinical Practice 1996 
 EU Directive 95/46/EC on the protection of individuals with regard to the 
processing of personal data and on the free movement of such data as 
transposed into national law 
 EU Medical Device Directive 93/42/EC as amended by Directive 2007/47/EC 
as amended into national law 
 ISO 14155 related to AE definitions 
 In the spirit of the Declaration of Helsinki concerning medical research in 
humans (latest edition) 
The CI agrees by signing the protocol to adhere to the instructions and procedures 
described and to adhere to the above regulatory requirements.   
 
10.3  Regulatory Authority Approvals/Authorizations 
Regulatory authority approvals, authorizations, or notifications, where required, will 
be in place and fully documented in accordance with European and national 
legislation. 
 
10.4   Participant Information and Consent 
Before inclusion (ie, before randomisation or any other study-specific procedure is 
undertaken) participants will be given written informed consent after receiving full, 
adequate oral and written information about the nature, purpose, and possible risks 
and benefits of the study. Participants also must be notified that they are free to 
discontinue their participation in this study at any time without any disadvantages. 
Participants will be informed that ICH-GCP practices will be maintained throughout 

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the trial. Participants also will be informed about and agree to having their data 
captured, monitored, and inspected by qualified personnel or regulatory authorities 
from inside and outside of the country. Participants will be informed that they may be 
contacted by phone, fax, mail, or email during the follow-up portion of the study.  
 
Within each center, the CI will be responsible for obtaining written informed consent. 
The CI can delegate Participant information to a qualified sub-investigator who is 
informed in full detail about the study. Participants will be given the opportunity to ask 
questions and allowed time to consider the information provided. 
 
Participant information will be updated if new relevant information becomes available 
that changes the risk-benefit assessment. Participants already enrolled in the study 
will be informed by the CI, especially if the Participant’s safety is a concern. 
 
The original of the ICF will be kept with the study documentation at the individual 
study site. Every participating Participant will receive a copy of the Participant 
information guide and the signed ICF.  
 
During monitoring, ICFs will be checked for each participating Participant by the 
IFOM CRAs. 
 
The CI will inform a potential Participant of the intention of this clinical trial. The 
potential Participant and the CI or his/her designated research staff member must 
sign and date the ICF before the potential Participant can participate in any clinical 
trial-related activities. The potential Participant will provide a written and signed ICF 
prior to participating in any clinical trial-related activities using the EC-approved ICF. 
The Participant will proceed through clinical trial participation as outlined in this 
section. A clinical trial calendar summarizing the assessments and procedures for 
this clinical trial is provided in Table 7. 
 
 
Informed consent will be obtained under the conditions set forth in ICH-GCP 
guidelines. 

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 Potential participants 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 as described in the ICF. 
 Potential participants shall have sufficient opportunity to ask questions and 
consider participation in the clinical trial. 
 Consent forms shall be written in local language that is non technical and 
understandable to potential participants or a potential Participant’s LAR. 
 Potential participants cannot be led to believe that they are waiving their legal 
rights to release the PCIs, CCI, KCI, institution, IFOM, or any of their agents from 
liability from negligence. 
 Potential participants will be asked to sign and date the informed consent, 
indicating their permission for enrolment in the clinical trial. 
 The PCI’s responsibilities related to the ICF process include: 
o Screening out potential clinical trial participants who may not be able or willing 
to comply with the protocol. 
o Assuring that only potential participants fully meeting the Inclusion Criteria and 
not meeting any Exclusion Criteria are included in the clinical trial. 
o Assuring that participants have signed the ICF prior to being enrolled in the 
clinical trial.   
o Documenting how informed consent was obtained, including any question(s) 
asked by the potential Participant or potential Participant’s LAR prior to signing 
the ICF and the corresponding responses. If no questions are asked, this 
should be recorded.   
The case history for each Participant shall document that informed consent was 
obtained prior to participation in the study. 
 
10.5 Insurance 
According to transposition of the (amended) Medical Devices Directive, local 
insurance shall be applied for. The insurance policy will be referenced in the 
Participant Information documents.  
 
10.6  Confidentiality 
The written ICF will explain that the study data will be stored in a computer database, 
maintaining confidentiality in accordance with local data legislation and the EU 

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directive 95/46/EG. Participants in this database will be identified by Participant 
identifier only. The Participant identifier format will be in accordance with local 
requirements. The Participant information also will explain that for data verification 
purposes, authorized representatives of the CIs, a regulatory authority, an EC, IFOM, 
or KCI may require direct access to parts of the medical records relevant to the study, 
including participants’ medical history. 
 
Anonymity of participants will be assured when presenting the data at scientific 
meetings or publishing in scientific journals. 
 
In accordance with the Investigator Agreement, all materials, information (oral or 
written), and unpublished documentation provided to the CIs (or any company/ 
institution acting on their behalf), including this protocol and the Participant CRFs, are 
exclusive property of KCI and may not be given or disclosed, either in part or in 
whole, by the CI or by any person under his/her authority to any third party without 
the prior express consent of KCI. 
 
The submission of this protocol and other necessary documentation to the EC is 
expressly permitted. The EC members have the same obligation of confidentiality. 
 
The CI shall consider all information, results, discoveries, and records accumulated, 
acquired, or deduced in the course of the study, other than that information to be 
disclosed by law, as confidential and shall not disclose any such results, discoveries, 
and records to any third party without the KCI’s prior written consent.

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11 SAFETY 
Device- and wound-related AEs and all SAEs will be captured after the Participant 
has signed the ICF. Device- and wound-related AEs will be captured at each study 
visit during treatment period. All SAEs will be captured at each study visit including 
all follow-up visits regardless of causality or severity.  
 
11.1  Warnings/Precautions 
All described surgical techniques are currently used in general surgical practice. All 
wound care materials to be used in this trial, in both the V.A.C.® Therapy and SCWT 
arms, are CE approved or marketed. When any study materials are used in 
combination with drugs, the drugs must be marked as approved in the country in 
which they are used. 
 
11.2  Expected Adverse Events 
Known risks of V.A.C.® Therapy and SCWT include the following: 
 Pain during therapy or dressing changes (especially if tissue grows into 
wound-dressing material) 
 Maceration of the surrounding skin (periwound maceration) 
 Desiccation of wound 
 Local infection with signs of inflammation 
 Dehiscence 
 Serious or fatal bleeding from the wound or adjacent blood vessels in 
participants with weakened or sutured vessels 
 Irritation or sensitivity to the drape used to secure dressings (eg, skin rash) 
 Pieces of dressing material accidentally left behind in the wound that become 
embedded in the wound tissue  
 Technical problems (eg, leaks, blockage of tubes, breakage of seals)  
 Minor bleeding 
 Cellulitis 
 
 
 

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11.3  Potential Risks Associated with Study Participation 
Participation in this clinical trial presents risks and benefits to participants in both 
V.A.C.® Therapy and SCWT treatment arms. Some risks and benefits to participants 
are generalized, regardless of the treatment arm, while others are specific to the 
assigned therapy. General risks and benefits are outlined in Table 5. 
Table 5: Potential Risks and Benefits Associated with Study Participation 
Potential Risks and Benefits Associated with Study Treatment Participation 
Potential 
Risks 
 
Wound may not heal by the end of the clinical trial 
 
Pain during debridement 
 
Stinging/burning/pain associated with wound dressing changes 
Potential 
Benefits 
 
Participants will receive frequent and comprehensive medical treatment 
for and monitoring of their wounds from a research team comprised of 
physicians and other health care professionals.   
 
11.4  Potential Risks and Benefits Associated with V.A.C.® Therapy and SCWT 
Incidents, complications or adverse reactions have been reported only sporadically 
while using V.A.C. ® Therapy for treating acute and chronic wounds. (Table 6) 
Table 6: Potential Risks and Benefits Associated with V.A.C.® Therapy 
V.A.C.® Therapy 
Potential 
Risks 
 
Pain during therapy or dressing changes 
 
Maceration 
 
Desiccation 
 
Infection 
 
Rash 
 
Cellulitis 
 
Osteomyelitis 
 
Wound dehiscence 
 
Serious or fatal bleeding from the wound or adjacent blood vessels in 
participants with weakened or sutured blood vessels 
 
Tissue may attach to the foam if it is left in for too long or if the wound 
grows aggressively 
 
Irritation or sensitivity to the drape used to secure the dressing 
 
Minor bleeding 

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Potential 
Benefits 
 
Creates an environment that promotes wound healing by secondary or 
tertiary (delayed primary) intention by preparing wound bed for closure  
 
Reducing edema  
 
Promoting granulation tissue formation and perfusion 
 
Removing exudate and infectious material 
 
The below potential AEs can usually be avoided by complying with the basic rules of 
vacuum therapy (as detailed in the manufacturer’s instructions for use and 
Guidelines for the use of V.A.C.® Therapy) as well as by the use of specific designed 
vacuum device systems or can be significantly reduced [30-32]. 
 
 Ingrowth of granulation tissue into the sponge 
The pull caused by granulation stimulus may lead to an ingrowth of tissue 
into the sponge, especially if the system was not changed for a long period 
of time. Descriptive literature on the use of the V.A.C.® Therapy System 
reported this event almost exclusively if the recommended time course of 
2-3 days between 2 dressing changes was exceeded.  
The ingrowth of the sponge into underlying and surrounding tissue was 
predominantly observed in well vascularized, soft tissue with a high 
tendency for granulation tissue growth [30, 33, 34]. Removal of foam with 
tissue ingrowth can result in minor tissue trauma or bleeding. 
 
 Pain caused by pull or dressing changes 
Wound patients generally suffer from pain, especially during wound 
dressing changes.  
Clinical practitioners should make arrangements for an optimal pain 
treatment. 
An increased pain perception during therapy or during dressing changes 
was shown to appear in about 2% of the V.A.C.® treated patients [34].  
Pain caused by suction on the wound may be reduced by using lower 
negative pressures between 50-100 mmHg, which still was to be shown to 
have adequate effects on wound healing. In standard practice, a suction 
fortitude of 125 mmHg is tolerated by the patients and viewed as painless 
[35, 36]. 

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 Maceration and pressure damage 
Maceration caused by the occlusive foil and the applied pull appear in 
about 20% of the V.A.C.® treated patients with chronic wounds. Mostly this 
effect is caused by a fragile surrounding area of the wound or a decreased 
perfusion in patients suffering from chronic wound healing impairments. 
Establishing adequate counteractive measures like exact fitting of the 
sponge, protection of wound margins with foils or dressings, and 
elimination of leakages can avoid the appearance of maceration of wound 
margins or surrounding area [34, 37].  
Pressure damages are rarely possible if the T.R.A.C.™ Pad is larger than 
the wound itself. In this case, wound margins should be protected by a 
second sponge prior to application of the system [38, 39]. 
 
Table7 lists the potential risks and benefits associated with Standard Conventional 
Wound Therapy (SCWT). 
 
Table 7: Potential Risks and Benefits Associated with SCWT 
Standard Conventional Wound Therapy (SCWT) 
Potential 
Risks 
 
Risk of bleeding from the wound 
 
Pain during therapy or dressing changes 
 
Maceration 
 
Desiccation 
 
Infection 
 
Rash 
 
Cellulitis 
 
Osteomyelitis 
 
Wound dehiscence 
 
A piece of dressing material may be accidentally left in the wound 
 
Tissue may attach to the foam if it is left in for too long or if the wound 
grows aggressively 
 
Irritation or sensitivity to the tape used to secure dressing 
 
Minor bleeding 

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Potential 
Benefits 
 
Promotes a moist wound environment 
 
May remove necrotic tissue 
 
Controls exudates 
 
May control infection 
 
Insulates the wound 
 
Minimizes pain 
 
Ease of use 
 
Multiple and versatile dressings available to meet the needs of the wound 
or wound environment 
 
11.5  Other Study-related Risks 
The trial protocol does not include any invasive procedures, such as wound biopsies 
or additional blood testing beyond routine clinical care. Furthermore, no radiographic 
examinations are demanded by the study protocol. All wounds will be redressed in 
certain intervals, but the frequency of wound care visits is not different from routine 
clinical care. 
 
11.6  Risk-Benefit Analysis 
Participation in this trial presents risks and benefits in both V.A.C.® Therapy and 
SCWT treatment arms. Some risks are generalized regardless of the treatment arm, 
while others are specific to assigned therapy. 
 
Possible risks that are not related to the treatment arm are wound healing 
disturbances, pain caused by debridement, pain associated with dressing changes, 
wound infection, and minor bleeding. 
It can be argued that for an individual with an open abdominal wound with intact 
fascia, trial participation entails only minimal risk because the probability and 
magnitude of harm or discomfort anticipated in this trial are not greater than those 
ordinarily encountered in routine clinical care. Patients with an open abdominal 
wound with intact fascia routinely receive a variety of dressings, including V.A.C.® 
Therapy and SCWT. To some extent, the choice of dressing depends on medical 
variables, such as size of wound, but institutional aspects also play a very important 
role. Therefore, randomisation within this trial only mimics everyday clinical practice, 
where V.A.C.® Therapy is being tried on some but not all patients. The medical risk 

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of wound therapy in this trial is not different compared to routine clinical care. 
Patients with a potentially higher risk (eg, impaired blood coagulation) and vulnerable 
populations (eg, pregnant women) are identified during the screening process and 
will not be included in the trial.  
 
Trial participation involves additional follow-up visits and assessment of participative 
parameters, such as quality-of-life and pain. Nevertheless, this imposes only minimal 
risk and inconvenience for trial participants.  
 
Trial-related procedures (eg, wound documentation and photograph) do not delay 
wound therapy in an unduly way. The confidentiality of all documentation is 
protected. Furthermore, participants will not have to pay any costs related to the trial.  
 
In accordance with national and international clinical trial regulations such as ICH-
GCP, ISO 14155, and general ethical principles, no patient will be randomized or 
receive any trial-related procedure before written informed consent has been 
obtained and the screening process has been successfully completed. The trial will 
only be started in a center if the EC responsible for the CI has approved the study. 
By continuous monitoring of trial safety data and published evidence on wound 
therapy, the IDMC, CCI, KCI, and IFOM will be responsible for Participant safety 
issues during the ongoing trial. Based on the incidence of SAEs, the IDMC may 
recommend terminating the trial or changing the protocol.  
 
Some potential benefits of trial participation may be assumed for individuals who 
take part in the trial. Most importantly, participants may receive a wound therapy that 
is better than that when compared to the usual clinical care. This may be the case 
because V.A.C.® Therapy is not applied routinely to open abdominal wounds with 
intact fascia, especially on an ambulatory basis. Preliminary evidence suggests 
beneficial effects of V.A.C.® Therapy on open abdominal wounds with intact fascia.  
 
From a societal perspective, the trial will be able to answer the important question of 
which of the 2 therapies studied is superior to the other. In addition, because the 
design of the trial is in accordance with the highest scientific standards, this ensures 
the likelihood of obtaining the quality of results necessary to answer the hypothesis 

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that V.A.C.® Therapy is more effective than SCWT on open abdominal wounds with 
intact fascia. The number of trial participants is based on a sample size calculation. 
Therefore, trial results are likely to improve medical care of a large group of patients 
around the globe. In summary, it can be stated that the benefits and risks of this trial 
are, on balance, favorable, both on an individual level and on a societal level. 
 
11.7 Adverse Event Monitoring 
Participants will be monitored regularly during visits for development of AEs, and 
data on AEs will be collected in both the V.A.C.® Therapy arm and the SCWT arm. 
The CI or his/her delegate must report to IFOM any SAEs as soon as possible and at 
the latest within 24 hours of knowledge of occurrence. KCI will be notified by IFOM 
within 24 hours after knowledge of occurrence of a SAE. IFOM will take care that all 
SAEs/SADEs will be notified to the authorities as requested by local law and the 
ECs. IFOM will advise the Clinical Investigator on the applicable reporting 
requirements. All SAEs will be followed by the CI up to 30 days after last follow-up 
visit or until resolution/stabilization. After the end of the trial, the CI will be informed 
about trial participation and responsibilities by a letter of the PCI. IFOM will inform 
KCI, the ECs and the IDMC according to agreements and law about incidence of 
SAE/SADEs during and after the trial as per local regulations. 
 
11.8 Safety Monitoring 
Participant safety is of the utmost importance in this clinical trial. IFOM and KCI will 
ensure that all research sites are trained and consequently monitored for adequate 
safety reporting. The IFOM CRA will review all Participant data to confirm that all 
SAEs and SADEs are reported accurately and promptly to IFOM. Each participating 
CI has the responsibility for the safety of the participants under his/her care. 
 
Wound related AEs, SAEs, ADEs, and SADEs in the V.A.C.® Therapy group will be 
monitored and processed by IFOM until their resolution or stabilization; ADEs and 
SADEs will be processed in KCI’s complaint system and will be reviewed for 
reporting according to EU vigilance guidelines. Wound related AEs, SAEs, ADEs, 
and SADEs in the SCWT group will be logged and monitored by IFOM until their 
resolution or stabilization; resolution for ADEs and SADEs will be the responsibility of 
the subsequent manufacturer per their vigilance requirements. The specific guidance 

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on safety reporting responsibilities between IFOM and KCI can be found within the 
respective safety plan for the trial. 
 
11.9  Adverse Event Definitions 
Adverse Event 
According to ISO 14155-11, an adverse event is any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, whether or not related to the 
investigational medical device. 
 
Serious Adverse Event 
According to ISO 14155-11, ICH GCP and MEDDEV2.7/3, a serious adverse event 
is an adverse event that  
a. led to a death,  
b. led to a serious deterioration in the health of the Participant that  
1 resulted in a life-threatening illness or injury,  
2 resulted in a permanent impairment of a body structure or a body 
function,  
3 required 
inpatient 
hospitalization 
or 
prolongation 
of 
existing 
hospitalization,  
4 resulted in medical or surgical intervention to prevent permanent 
impairment to body structure or a body function.  
c. led to fetal distress, fetal death, or a congenital abnormality or birth defect.  
A planned hospitalisation for pre-existing condition, or a procedure required by the 
study protocol, without a serious deterioration in health, is not considered to be a 
serious adverse event. 
All SAEs should be reported to IFOM as soon as possible and at the latest within 24 
hours of knowledge of their occurrence; these will be followed by the CI until 
stabilization or resolution. 
 
Adverse Device Effect 
According to ISO 14155-11,  

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An adverse device effect is an adverse event related to the use of an investigational 
medical device 
 
Serious Adverse Device Effect 
According to ISO 14155-11, a serious adverse device effect is an adverse device 
effect that has resulted in any of the consequences characteristic of a serious 
adverse event or that might have led to any of these consequences if suitable action 
had not been taken or intervention had not been made or if circumstances had been 
less opportune. 
 
Unanticipated (Unexpected) Adverse Event 
 All AEs not consistent with those listed as in section 11.2: “Expected Adverse 
Events” of the SAWHI study protocol or in the product instructions of the devices 
used within the study are regarded as unanticipated / unexpected. Adverse Events 
related to a procedure will be regarded as expected if the event is mentioned in the 
literature. 
 
11.10 Documentation of Adverse Events 
Wound related AEs, ADEs, and all SAEs including a separate documentation of 
SADEs will be documented in the CRF.  
 
11.11 Reporting of Serious Adverse Events and Incidents 
CIs will inform IFOM as soon as possible and at the latest within 24 hours about any 
SAE or incident. 
 
The PCI will inform IFOM and KCI, IDMC, EC, CIs, and competent authorities about 
any relevant changes to the risk-benefit ratio. 
 
11.12 Reporting Requirements 
The CI has the primary responsibility for safety of individual participants under his or 
her care. In this function, the CI should routinely monitor each Participant for the 
occurrence of any AE.   
 

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Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE 
occurs, expedited reporting will follow local and international regulations, as 
appropriate. CIs will inform IFOM as soon as possible and at the latest within 24 
hours about any SAE or incident. 
 
For every SAE and wound and device related AE that occurs, a full description of the 
event should be recorded including the date of onset, time course, severity, causal 
relationship to study treatment, and alternate causality if not related to the study 
treatment, action taken regarding the study treatment, outcome, and the treatment 
applied if any. Relevant procedures are all measurements to prepare the wound (e.g. 
debridement), V.A.C.®-installation, V.A.C.®-treatment and dressing changes.   
 
As the event term, the CI should list the specific diagnosis, disease, or syndrome 
rather than associated signs and symptoms. However, if the CI does not consider an 
observed or reported sign or symptom a component of a specific disease or 
syndrome, it should be recorded as a separate AE.   
 
The CI is also responsible for reporting all device malfunctions whether or not they 
resulted in an AE for the Participant. If a device failure resulted in an SAE/SADE for 
the Participant, this SAE/SADE must be reported as previously noted.   
 
Reporting of Pregnancies 
If a Participant becomes pregnant during the course of the study, she must notify her 
study doctor immediately. If the Participant becomes pregnant during the study, the 
Participant can no longer continue in the study. CIs will inform IFOM as soon as 
possible and at the latest within 24 hours after knowledge about the pregnancy of a 
Participant and the pregnancy’s outcome. 
 

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12 REPORTING AND PUBLICATION 
12.1 Study Report 
Interim Report 
An interim assessment report will be done after 250 participants have either 
completed the study or withdrawn prematurely, as described in section: 
Determination of Sample Size.  
 
Annual Study Report 
The purpose of the Annual Study Report is to meet reporting obligations to the EC. 
The Annual Study Report will be completed annually and submitted to the EC and 
other competent authorities, as required. 
 
Final Study Report 
The Final Study Report will present the results of the trial, including appropriate 
tables and figures in the spirit of unbiased objectivity. The PCIs will provide the EC 
with a summary of the trial’s outcome, and if applicable, the regulatory authorities 
with any reports required. The report or parts of it may be submitted in the form of a 
summary, a synopsis, published article, or similar document. 
 
Clinical Study Report 
The Clinical Study Report (CSR) will be finalized within 1 year of the study’s 
completion. 
 
12.2 Publication 
Both positive and negative results of the trial will be disclosed. The results of the trial 
will be submitted for publication to peer-reviewed scientific journals and/or presented 
at international scientific congresses. The trial will be registered at a national German 
as well as at an international WHO approved register. 
The Principal Coordinating Investigator and the Steering Committee are responsible 
for the primary and secondary publications and/or presentations arising from the 
study. No other publication or presentations of the results of the study are allowed 
before the primary publication and/or presentation is released. All publications and/or 
presentations are part of additional requirement more specifically addressed within 
each institution’s clinical trial agreement.  

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KCI is entitled to examine the manuscript prior to publication and to make comments 
on it. KCI may delay publication for up to three months after analyzing the research 
results if it is applying for a patent or other important reasons. 
All publications will maintain data protection of Participant data as well as data of the 
participating Investigators. 
 
The publishing of data from a single study center is permitted after analysis and 
primary publication of the final results only. Publication of study results or data, 
including data of a single study center, has to be reviewed and approved by the 
Steering Committee, IFOM, and KCI. 
 
KCI guarantees IFOM the publication rights for study results. Study results will be 
prepared for publication according to CONSORT statement. CONSORT, which 
stands for Consolidated Standards of Reporting Trials, encompasses various 
initiatives developed by the CONSORT Group to alleviate the problems arising from 
inadequate reporting of randomized controlled trials (RCTs) [40]. 
 
Every CI who enrolled more than 15 patients into the trial will be offered a Co-
authorship for the primary publication. In addition the CI may nominate one of his 
subinvestigators to be included in the authorlist. 
 
The Steering Committee and IFOM will furnish KCI with a written copy of any 
proposed publication or presentation of material related to the trial at least 30 days in 
advance of the submission of any proposed publication (eg, abstract, manuscript) or 
presentation (eg, poster, seminar) for inclusion at an event (eg, scientific meeting, 
annual conference). 
 

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13 
CHANGES IN TRIAL CONDUCT OR PLANNED ANALYSIS 
In order to maintain comparable conditions in all study centres and to obtain an 
objective data analysis, changes to the protocol are not intended. If changes become 
necessary, they are to be reported as an amendment. The amendment will be 
agreed upon by the IDMC, Steering Committee, IFOM, and KCI. The amendment will 
be approved and signed by the same individuals who signed the protocol. The 
amendment then becomes part of the protocol. An amendment must be approved by 
each responsible EC and must be submitted to regulatory authorities when 
appropriate. 
 

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TABLES AND PICTURES 
 
Table 1: Factors that affect surgical wound healing 
Table 2: Types of wound closure and their definition 
Table 3: V.A.C.® -Therapy Contraindications and Precautions 
Table 4: V.A.C. ® Treatment Recommendation   
Table 5: Potential Risks and Benefits Associated with Study Participation 
Table 6: Potential Risks and Benefits Associated with V.A.C.® Therapy 
Table 7: Potential Risks and Benefits Associated with SCWT 
 
Picture 1: Vacuum Assisted Closure (V.A.C.®)

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APPENDICES 
A 
Schedule of Visits 
B 
Guideline for Photo Documentation 
C 
Patient Satisfaction Questionnaire 
D 
Documentation sheet for wound assessment 
E 
Documentation sheet for wound-related procedures 
F 
Documentation Sheet for medical history 
G 
SF-36®