A Randomized Open, Controlled Pilot Investigation Comparing Trauma to the Periwound Skin and Pain During Treatment With Avance NPWT System When Using Two Different Fixations
Phase: NA
Conditions: Wounds and Injuries
Sponsor: Molnlycke Health Care AB

Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02
Page 1(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
CLINICAL INVESTIGATION PLAN (CIP) 
INVESTIGATIONAL DEVICE: 
Avance® Negative Pressure Wound Therapy System
INVESTIGATION TITLE: 
A RANDOMIZED, INTRA-PATIENT, OPEN, CONTROLLED PILOT INVESTIGATION 
COMPARING TRAUMA TO THE PERI-WOUND SKIN AFTER TREATMENT WITH 
AVANCE NPWT SYSTEM WHEN USING TWO DIFFERENT FIXATIONS  
CO-ORDINATING INVESTIGATOR: 
MARIANNE BERGSTRÖM 
Sundsvalls sjukhus  
Ljus och sårmottagning 
851 86 Sundsvall 
Phone +46 60 181296 
MÖLNLYCKE CLINICAL STUDY  MANAGER: 
Tina Kjellén 
Mölnlycke Health Care 
P.O Box 130 80 
402 52 Gothenburg, Sweden 
Phone: +46 31 722 3098 
Fax: +46 31 722 34 91

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 2(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
CLINICAL INVESTIGATION PLAN (CIP) SYNOPSIS 
 
INVESTIGATION TITLE: 
 A RANDOMIZED, INTRA-PATIENT, OPEN, CONTROLLED PILOT INVESTIGATION 
COMPARING TRAUMA TO THE PERI-WOUND SKIN AFTER TREATMENT WITH 
AVANCE NPWT SYSTEM WHEN USING TWO DIFFERENT FIXATIONS  
 
Objectives 
Primary objective 
The primary objective of this investigation is to compare trauma and/or other changes to the 
peri-wound skin during treatment with Avance® Negative Pressure Wound Therapy System 
when using two different fixation films. The primary objective will be measured as:  
• 
Changes from baseline in condition of the peri-wound skin defined as skin under the 
dressing, excluding the area were the films are overlapping 
Secondary objectives  
Secondary objectives are to evaluate: 
• 
the ease of use for the subject and care giver when using the NPWT system  
• 
the comfort, conformability and the acceptability of the dressings 
• 
pain before, during and after dressing and foam removal 
• 
SADE, ADE and, DD, i.e. safety data related to the device 
Overall Design   
This investigation is designed as a randomized, intra-patient, controlled open clinical 
investigation . The outcome will be used to guide us to the design and implementation of a 
larger scale randomized study. This pilot study will include 23-30 subjects across 1sites in 
Sweden to yield a total of 7-23 evaluable subjects, all subjects who has not previously been 
treated with NPWT and fulfill all inclusion and none of the exclusion criteria and have signed 
signed a written inform consent will be enrolled. 
This investigation is  comparing trauma and/or other changes to the peri-wound skin during 
treatment with Avance NPWT system when using two different fixation films, Avance film with 
Safetac® Technology and KCI acrylic film (V.A.C.® Drape). Since the investigation is comparing 
films with clear visual differences, it is not possible to blind neither the investigator nor the 
patients.  
Dressing change 
Dressing change will be performed at the investigation site and the frequency of dressing 
change will be depending on the condition of the wound and the peri-wound skin. 
Recommended dressing change frequency according to Avance system is every 48-72 hours. 
A record (dressing log) specifying the type of film and other relevant treatment information will 
be completed for every dressing change 
Investigation Visit frequency and subject participation 
Eligible subjects will be enrolled at the baseline visit (Visit 1), where the first dressing 
applications take place. From Visit 2 and onwards, one dressing application is considered as 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 3(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
one study visit, e.g. the study visits are flexible and depending on the dressing changing 
frequency of the individual subject. The total treatment time for a subject may vary, depending 
on the wound type and condition. Each subject will be followed in the investigation for a 
maximum of five (5) dressing changes or until treatment with NPWT is no longer indicated 
(withdrawal criterion) . After termination from the investigation, subjects will, if necessary, be 
treated according to standard clinical practice at the investigation site. No additional data 
(except for follow up information on ongoing safety events) will be collected after termination.  
Subjects will be recruited at the investigation site, which have experience in managing the 
investigation population with NPWT and have access to a suitable number of subjects (based 
on historic data). 
Following variables should be considered ( Appendix C): 
At visit 1 
 
Informed consent  
 
Subject demographic details 
 
Inclusion and exclusion criteria 
 
Vital signs 
 
Care 
 
Medical and surgical history 
 
Wound history 
 
Skin assessment  
 
Medication  
 
Cleansing 
 
Debridement 
 
Wound status after cleansing and/or debridement 
 
Clinical signs of local infection 
 
Photo 
 
Pain (VAS) 
 
Adverse Event (AE)/ Adverse Device Effect (ADE)/ Serious Adverse Event (SAE) 
/Serious Adverse Device Effect (SADE)/Device Deficiency (DD) 
 
Apply the Investigational Device (ID) and measuring ( proximal cm, distal cm, sinister cm 
and dexter cm) the length between the wound edges and film edges according to the 
Figure 1 
 
Investigator and nurse evaluation 
 
Apply the IP 
 
Randomization 
At visit 2-5 
 
Skin assessment  
 
Medication  
 
Cleansing 
 
Debridement 
 
Wound status after cleansing and/or debridement 
 
Clinical signs of local infection 
 
Apply the IP and measuring ( proximal cm, distal cm, sinister cm and dexter cm) the 
length between the wound edges and film edges according to the Figure 2 
 
Photo 
 
Pain (VAS) 
 
Change and removal of IP 
 
Investigator/Nurse and subject evaluation 
 
AE/ ADE/ SAE/SADE/DD 
Only one target wound per patient will be included in this investigation. 
* Evaluation of the skin se Appendix E 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 4(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Schedule of Assessment 
 
Day 
Visit 1 Visit 2 
Visit 3
Visit 4 Visit 5 
 
Termination 
End of treatment  
Visit (number) 
1 
2 
3 
4 
5 
Termination 
Subject demography 
9 
 
 
 
 
 
Inclusion and Exclusion Criteria 
9 
 
 
 
 
 
Inform Consent 
9 
 
 
 
 
 
Vital Signs 
9 
 
 
 
9 
9 
Medical and surgical history 
9 
 
 
 
 
 
Skin assessment  
9 
9 
9 
9 
9 
9 
Wound History 
9 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization  
9 
 
 
 
 
 
Cleansing and/or Debridment 
9 
9 
9 
9 
9 
 
Signs of symptoms of infection  
9 
9 
9 
9 
9 
9 
Pain ( VAS) 
9 
9 
9 
9 
9 
9 
Wound status after 
( cleansing, debridement ) 
9 
9 
9 
9 
9 
 
Dressing application  
9 
9 
9 
9 
 
 
Dressing removal 
 
9 
9 
9 
9 
9 
Photo  
9 
9 
9 
9 
9 
9 
Investigator/nurse evaluation  
9 
9 
9 
9 
9 
9 
Subject evaluation 
 
9  
9  
9  
9  
9  
Medication log 
9 
9 
9 
9 
9 
 
AE/ADE/DD 
9 
9 
9 
9 
9 
9 
SAE/SADE 
9 
9 
9 
9 
9 
9 
Dressing Log 
9 
9 
9 
9 
9 
9 
 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 5(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Inclusion/Exclusion Criteria 
 
Inclusion Criteria
1. Exuding wound indicated for treatment with NPWT therapy  
2. In case of multiple wounds, target wound must be  10 cm distant from other wounds. 
Selection of target wound is according to the investigator’s preference  
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the wound  
4. Male or female, 18 years of age and above  
5. Signed Informed Consent 
 
Exclusion Criteria 
 
1. Dressing sizes does not fit the target wound  
2. Unexplored blind tunnels or non-enteric fistula 
3. Untreated osteomyelitis 
4. Malignant wounds 
5. Wounds with necrotic tissue or eschar (if not adequately debrided) 
6. Bleeding wounds 
7. Subject not suitable for the investigation according to the investigator’s judgment  
8. Subject included in other ongoing clinical investigation which could interfere with this 
investigation, as judged by the investigator  
9. Known allergy/hypersensitivity to any of the components included into the investigation. 
 
Investigational Device 
Treatment 
System 
All subjects will receive treatment with the Avance® Negative Pressure Wound Therapy System 
consisting of:  
- 
Avance® Pump  
- 
Avance® View Pad  
- 
Avance® Foam  
- 
Film sealant (either the Investigational device, Avance Film® with Safetac®Technology 
or the Comparator, V.A.C. Drape, ) 
Pump settings (pressure and mode intermittent or constant pressure) will be registered in the 
relevant section of the CRF. 
  
Other materials 
Actual use of supporting and/or protecting materials must be registered in the relevant section in 
the CRF.  
 
- 
Skin fixatives 
Mepiseal® will be available for use in combination with the Avance film with Safetac, 
according to investigators preference.  
Mepiseal is a flexible sealant intended to use on the surrounding skin of wounds or 
stomas that are difficult to dress due to uneven skin surfaces, location or mobility. 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 6(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Mepiseal helps prevent leakage and premature loosening of the wound dressing, NPWT 
or ostomy systems. Mepiseal can also be used as a filler uneven surrounding skin.  
 
- 
Wound contact layers  
- 
Non-adherent dressing materials Mepitel can be used to protect fragile tissue such as 
bones, tendons and nerves. It can also be used to cover sharp edged or bones to 
prevent puncture of blood vessels or organs. 
- 
Skin protection  
In this investigation, use of additional film (other transparent film), Cavilon or 
hydrocolloids is not allowed to be used as protection of the peri-wound skin as this 
could potentially interfere with the measurement of the primary objective.  
 
All medical devices are CE marked and used according to intended use, with the exception of 
the overlapping Avance Film® with Safetac with V.A.C. Drape and V.A.C. Drape together with 
Avance System and Avance Foam, which is used outside intended use. Based on product risk 
management for the investigational device, it can be concluded that there are no unacceptable 
risks of harm for subject, the user nor third party involved. 
The investigational device meets all relevant essential requirements except for those being 
investigated in the clinical investigation, as declared separately. 
 
 
Randomization 
Eligible subjects will have the investigated wound randomly divided into two halves. One half of 
the wound will be dressed with Avance Film with Safetac while the other half on top of the 
Avance Film with Safetac will be dressed with V.A.C. Drape. 
 
 
1. The area which is intended to be covered with film will be drawn on the subject’s skin 
with a semi-permanent marker pen: 
 
 
 
2. This skin area will be divided into two approximately equal halves and A or B will be 
written on each half (to allow for correct positioning of new films in connection with 
dressing changes). The intended direction of film application will be according to the 
location of the wound, anatomy of the relevant body part and the investigators best 
judgment for how the best seal can be obtained.  

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 7(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 
 
 
 
3.  Instruction about the film-film overlap and the overlap from wound edge on dry peri-
wound skin to ensure an optimal vacuum is described in the application step-by-step 
guide. 
 
Assignment to treatment group for a given subject will be randomly provided by the electronic 
eCRF system (Viedoc) in as indicated below:  
 
Treatment group 1:  
Film A (subject right side) = Avance Film with Safetac  
Film B (subject left side) = V.A.C. Drape 
 
Treatment group 2:  
Film A (subject right side) = V.A.C. Drape 
Film B (subject left side)  = Avance Film with Safetac  

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 8(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
TABLE OF CONTENTS 
1. OBJECTIVES ......................................................................................................... 13
2. CLINICAL INVESTIGATOR(S) AND INVESTIGATION ADMINISTRATIVE 
STRUCTURE ................................................................................................................ 13
2.1
Staff at Investigation site(s) ................................................................................................................... 13
2.2
Mölnlycke Investigation Personnel ...................................................................................................... 13
2.3
Other Participants ..................................................................................................................................... 13
3. INVESTIGATION PLAN AND PROCEDURES ...................................................... 14
3.1
Overall Design and Flow Chart .............................................................................................................. 14
3.2
Procedures and Assessments ............................................................................................................... 14
3.2.1
Schedule of Assessment ....................................................................................................................... 16
3.3
Selection of Population for Investigation ........................................................................................... 17
3.3.1
Inclusion Criteria ..................................................................................................................................... 17
3.3.2
Exclusion Criteria .................................................................................................................................... 17
3.3.3
Withdrawal of Subjects from Treatment or Assessment ................................................................... 17
3.4
Investigational Device .............................................................................................................................. 18
3.4.1
Summary description of the Investigational Device(s) and Comparator(s) .................................... 18
3.4.2
Labeling .................................................................................................................................................... 18
3.4.3
Accountability .......................................................................................................................................... 19
3.4.4
Storage conditions .................................................................................................................................. 19
3.4.5
Method of Assigning Subjects to Treatment Groups ......................................................................... 19
3.5
Concomitant Treatments......................................................................................................................... 21
3.6
Performance and Safety .......................................................................................................................... 21
3.6.1
Subject Characteristics .......................................................................................................................... 21
3.6.2
Performance and Safety Measurements and Variables ................................................................... 21
3.6.3
Safety Measurements and Variables ................................................................................................... 23
3.6.4
Anticipated ADEs .................................................................................................................................... 23
3.7
Data Quality Assurance ........................................................................................................................... 24
3.7.1
Monitoring, Audits and Inspections ...................................................................................................... 24
3.7.2
Training of Staff ....................................................................................................................................... 24
3.7.3
Data Management .................................................................................................................................. 24
3.8
Statistical Methods and Determination of Sample Size .................................................................. 25
3.8.1
Statistical populations............................................................................................................................. 25
3.8.2
General statistical methodology............................................................................................................ 25
3.8.3
Performance Analyses ........................................................................................................................... 26
3.8.4
Safety analyses ....................................................................................................................................... 26
3.8.5
Baseline analysis .................................................................................................................................... 26
3.8.6
Statistical Analysis Plan (SAP) ............................................................................................................. 27
3.8.7
Determination of Sample Size .............................................................................................................. 27

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 9(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
3.9
Changes to the Clinical Investigation Plan ........................................................................................ 27
4. STATEMENTS OF COMPLIANCE ......................................................................... 27
4.1
Ethics ........................................................................................................................................................... 27
4.1.1
Ethics review............................................................................................................................................ 27
4.1.2
Ethical Conduct of the Investigation ..................................................................................................... 27
4.1.3
Patient Information and Consent Form ................................................................................................ 28
4.2
Regulatory and standards ...................................................................................................................... 28
4.2.1
Regulatory review ................................................................................................................................... 28
4.2.2
Standards and other ............................................................................................................................... 28
4.2.3
Subject Data Protection ......................................................................................................................... 28
4.3
SUBJECT PROTECTION PROCEDURES............................................................................................. 28
4.3.1
Procedures in Case of Medical Emergency ........................................................................................ 28
4.3.2
Insurance ................................................................................................................................................. 28
5. INVESTIGATION TIMETABLE AND TERMINATION ............................................ 29
6. LITERATURE REVIEW AND REFERENCES ........................................................ 30
7. DEFINITIONS AND PROCEDURES FOR REPORTING OF ADVERSE EVENT, 
ADVERSE DEVICE EFFECT, SERIOUS ADVERSE EVENT, SERIOUS ADVERSE 
DEVICE EFFECT AND DEVICE DEFICIENCY ............................................................. 31
 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 10(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
LIST OF APPENDICES 
Appendix A  
F-449 Clinical Investigation Plan Appendix A, Core Signatures 
F-583 Clinical Investigation Plan Principal Investigator Signature 
Appendix B  
F-173 Patient Information and Consent Forms 
Appendix C 
F-542 All variables to be obtained during the Investigation 
Appendix D 
Step-By-Step Guide 
Appendix E 
Evaluation of the skin 
 
LIST OF ABBREVIATIONS 
 Abbreviation or 
special term 
Explanation 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
CA 
Competent Authorities 
CDM 
Clinical Data Manager 
CIP 
Clinical Investigation Plan 
CIR 
Clinical Investigation Report 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRM 
Clinical Research Manager 
DCF 
Data Clarification Forms 
DD 
Device Deficiency 
FSI 
First subject in 
GCP 
Good Clinical Practice 
IEC 
Independent Ethics Committee 
ID 
Investigational Device 
ITT 
Intention to Treat 
LSO 
Last subject out 
MHC 
Mölnlycke Health Care AB 
PI 
Principal Investigator, a person responsible for the conduct of the clinical investigation at the 
investigational investigation site. Every investigational investigation site has a principal 
investigator. 
PIC 
Patient Information and Consent Form 
RA 
Regulatory Authority 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SDV 
Source Data Verification 
 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 11(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
INTRODUCTION 
Negative pressure wound therapy (NPWT), also referred to as topical negative pressure (TNP), 
negative pressure therapy (NPT), sub-atmospheric pressure wound therapy, and sealed surface 
wound suction, is a modality that has found significant use in complex acute surgical, delayed 
healing surgical and hard to heal chronic wounds, including those with elevated bacterial 
contamination.  Negative pressure wound therapy manages exudate, combats peri-wound 
oedema, increases blood flow to the wound, maintains optimal moist wound conditions and 
encourages the formation of wound bed granulation tissue. A meta-analysis reported a 
significant reduction in time to healing for wounds treated with NPWT when compared to those 
treated with standard care (1). The Avance NPWT System comprises a range of CE marked 
products which are used collectively as a NPWT system. The Avance NPWT System has been 
marketed by Mölnlycke Health Care AB since May 2010. 
 
Despite the research support for its effectiveness in wound healing, fewer studies have 
considered the impact of NPWT on the patient in terms of the pain that can be experienced. 
Wound care and dressing changes can be very painful for patients, and this pain can also 
cause patients to feel stressed or anxious, thus impacting negatively on both their physical and 
psychological well-being. Such factors need to be considered in any evaluation of NPWT or 
other treatment (2).  
 
Trauma and pain caused by the removal and reapplication of the NPWT dressings and/or 
removal of the foam has been identified as a major contributor to wound pain (2). Film-based 
dressings with adhesive skin contact layers are used to keep NPWT system in place and skin 
stripping may occur because the film can adhere to aggressively to the peri-wound skin, 
resulting in trauma and pain (2). Trauma may also occur when tissue grows into the foam on the 
dressing and this tissue becomes torn during dressing change (3). Damage to the wound and 
surrounding skin can involve bleeding, blisters, skin stripping and other skin damage, leading to 
a higher frequency of dressing changes, a greater level of pain and a longer time taken for the 
wound to heal (3). Despite the importance of minimizing trauma during NPWT and other wound 
care, few researchers have focused on this area (3)  
 
Although not focusing on NPWT specifically, a study by Upton and Solowiej also demonstrated 
how dressing type can affect the level of pain experienced during dressing change. In 49 
patients with chronic wounds, the authors explored differences in pain and stress levels 
between those who received conventional dressings ( n = 39) and those who were given 
atraumatic dressings with Safetac technology. Physiological and psychological measures of 
pain and stress were taken. It was found that self-reported pain and stress were significantly 
lower in those who were given atraumatic dressings as part of their care routine (2).  
In the literature there are numerous supporting articles reporting effectiveness of NPWT 
treatment. However, information regarding choice of dressing materials are lacking. Should for 
example the adhesive material of the dressing have a protecting effect on the surrounding skin 
around the NPWT treated wound?   
What is known from other studies in other stages of the wound healing is that skin trauma such 
as bleeding, redness, irritation, skin stripping and blisters might occur when a film dressing is 
removed. Such trauma can lead to delayed healing and prolonged treatment of the patient. 
In a study made by Upton in 2013, half of the participating patients reported skin trauma or 
irritation. 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 12(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
The purpose of this study is to compare with two different types of film dressings one with silicon 
adhesive ( Avance Film with Safetac) and one with acrylic adhesive( V.A.C drape) to see if there 
is a difference in skin damage.  
 
 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 13(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 
1. OBJECTIVES 
Primary objective 
The primary objective of this investigation is to compare trauma and/or other changes to the 
peri-wound skin during treatment with Avance® Negative Pressure Wound Therapy System 
when using two different fixation films. The primary objective will be measured as:  
• 
Changes from baseline in condition of the peri-wound skin defined as skin under the 
dressing, excluding the area were the films are overlapping 
Secondary objectives  
Secondary objectives are to evaluate: 
• 
the ease of use for the subject and care giver when using the NPWT system  
• 
the comfort, conformability and the acceptability of the dressings 
• 
pain before, during and after dressing and foam removal 
 
2. CLINICAL INVESTIGATOR(S) AND INVESTIGATION 
ADMINISTRATIVE STRUCTURE 
 
2.1 Staff at Investigation site(s) 
Name and addresses of principal investigator (s) are listed in Appendix A. 
 
2.2 Mölnlycke Investigation Personnel 
Tina Kjellén, Clinical Study Manager 
Roland Frösing, Medical Doctor 
Lennart Wäne, Clinical Data Manager 
 
2.3 Other Participants 
Pharma Consulting Group 
Kungsängsvägen 19, 1 tr 
753 23 Uppsala, Sweden 
Statistiska Konsultgruppen 
Nils-Gunnar Pehrsson, Biostatistician 
Stigbergsliden 5 
SE-414 63 Göteborg 
 
 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 14(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
3. INVESTIGATION PLAN AND PROCEDURES 
3.1 Overall Design and Flow Chart 
This investigation is designed as a randomized, intra-patient controlled open clinical 
investigation comparing trauma and/or other changes to the peri-wound skin during treatment 
with Avance NPWT system when two different fixation films are used. Avance film with Safetac 
Technology and V.A.C. Drape (KCI Film). Since the investigation is comparing films with clear 
visual differences, it is not practically possible to blind neither the investigator nor the patients. 
The outcome will guide in to the design of a larger scale randomized study. This pilot study will 
include 23-30 subjects across 1 sites in Sweden to yield a total of 7-23 evaluable subjects, all 
subjects who fulfill all inclusion and none of the exclusion criteria and have by them signed a 
written inform consent will be enrolled. An evaluable subject is defined as a subject that is 
enrolled and has data for at least one visit after baseline visit 
  
The target populations are male or female, 18 years and above, which have exuding wounds 
indicated for treatment with NPWT therapy. The subject should not previously been treated with 
NPWT, previous treatment, may have an bias on the skin evaluation. 
 The study visits are flexible and depending on the dressing changing frequency of the 
individual subject. The total treatment time for each subject may vary depending on the wound 
type and condition of the wound. Each subject will be followed for a maximum of five (5) 
dressing changes or until treatment with NPWT is no longer indicated (withdrawal criterion). 
After termination from the investigation, subjects will, if necessary, be treated according to 
standard clinical practice at the investigation site. No additional data (except for follow up 
information on ongoing safety events) will be collected after termination.  
 
3.2 Procedures and Assessments 
 
Following variables should be considered ( Appendix C): 
At visit 1 
 
Informed consent  
 
Subject demographic details 
 
Inclusion and exclusion criteria 
 
Vital signs 
 
Care 
 
Medical and surgical history 
 
Wound history 
 
Skin assessment  
 
Medication  
 
Cleansing 
 
Debridement 
 
Wound status after cleansing and/or debridement 
 
Clinical signs of local infection 
 
Photo 
 
Pain (VAS) 
 
Adverse Event (AE)/ Adverse Device Effect (ADE)/ Serious Adverse Event (SAE) 
/Serious Adverse Device Effect (SADE)/Device Deficiency (DD) 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 15(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 
Apply the Investigational Device (ID) and measuring ( proximal cm, distal cm, sinister cm 
and dexter cm) the length between the wound edges and film edges according to the 
Figure 1 
 
Investigator and nurse evaluation 
 
Apply the IP 
 
Randomization 
 
At visit 2-5 
 
Skin assessment  
 
Medication  
 
Cleansing 
 
Debridement 
 
Wound status after cleansing and/or debridement 
 
Clinical signs of local infection 
 
Apply the IP and measuring ( proximal cm, distal cm, sinister cm and dexter cm) the 
length between the wound edges and film edges according to the Figure 2 
 
Photo 
 
Pain (VAS) 
 
Change and removal of the IP 
 
Investigator/Nurse and subject evaluation 
 
AE/ ADE/ SAE/SADE/DD 
Only one target wound per patient will be included in this investigation. 
* Evaluation of the skin se Appendix E 
 
Figure: 2 
 
 
 
 
 
 
 
 
 
 
 
Only one target wound per patient will be included in this investigation. 
 
Additional wound care material used will be documented on the dressing log. 
Photos will also be taken if extra dressing changes are required. AE´s/ADE´s/unexpected 
events with the device may be documented by relevant photos at time. All photos shall include a 
sticker marked with subject code, visit number/date and time. All photos will be checked by 
monitor.  
 
 

 
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3.2.1 Schedule of Assessment 
Day 
Visit 1 Visit 2 
Visit 3
Visit 4 Visit 5 
 
Termination 
End of treatment  
Visit (number) 
1 
2 
3 
4 
5 
Termination 
Subject demography 
9 
 
 
 
 
 
Inclusion and Exclusion Criteria 
9 
 
 
 
 
 
Inform Consent 
9 
 
 
 
 
 
Vital Signs 
9 
 
 
 
9 
9 
Medical and surgical history 
9 
 
 
 
 
 
Skin assessment  
9 
9 
9 
9 
9 
9 
Wound History 
9 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization  
9 
 
 
 
 
 
Cleansing and/or Debridement 
9 
9 
9 
9 
9 
 
Signs of symptoms of infection  
9 
9 
9 
9 
9 
9 
Pain ( VAS) 
9 
9 
9 
9 
9 
9 
Wound status after 
( cleansing, debridement ) 
9 
9 
9 
9 
9 
 
Dressing application  
9 
9 
9 
9 
 
 
Dressing removal 
 
9 
9 
9 
9 
9 
Photo  
9 
9 
9 
9 
9 
9 
Investigator/nurse evaluation  
9 
9 
9 
9 
9 
9 
Subject evaluation 
 
9  
9  
9  
9  
9  
Medication log 
9 
9 
9 
9 
9 
 
AE/ADE/DD 
9 
9 
9 
9 
9 
9 
SAE/SADE 
9 
9 
9 
9 
9 
9 
Dressing Log 
9 
9 
9 
9 
9 
9 
 
 
 
 
 
 

 
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3.3 Selection of Population for Investigation 
 
3.3.1 Inclusion Criteria 
Inclusion Criteria
1. Exuding wound indicated for treatment with NPWT therapy  
2. In case of multiple wounds, target wound must be  10 cm distant from other wounds. 
Selection of target wound is according to the investigator’s preference  
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the wound  
4. Male or female, 18 years of age and above  
5. Signed Informed Consent 
 
3.3.2 Exclusion Criteria 
 
1. Dressing sizes does not fit the target wound  
2. Unexplored blind tunnels or non-enteric fistula 
3. Untreated osteomyelitis 
4. Malignant wounds 
5. Wounds with necrotic tissue or eschar (if not adequately debrided) 
6. Bleeding wounds 
7. Subject not suitable for the investigation according to the investigator’s judgment  
8. Subject included in other ongoing clinical investigation which could interfere with this 
investigation, as judged by the investigator  
9. Known allergy/hypersensitivity to any of the components included into the investigation. 
 
3.3.3 Withdrawal of Subjects from Treatment or Assessment 
Subjects are free to discontinue participation in the investigation at any time, and without 
prejudice to further treatment. Subjects who discontinue the investigation should always be 
asked about the reason(s) for their discontinuation and about the presence of any AE/ADE or 
DD and, if possible, be assessed by an investigator. AE/ADE should be followed up.  
Subjects may be withdrawn from investigation treatment and assessments at any time, at the 
discretion of the investigator. 
Incorrectly enrolled or randomized subjects will be withdrawn from further investigation 
treatment and assessments. A subject may, however, continue the investigation under special 
circumstances (i.e. if continuation of investigation treatment or follow-up actions are necessary 
for the subject’s safety and well-being, or if only a follow-up period remains, and the 
continuation of the investigation is not expected to be associated with any risk or discomfort for 
the subject). 
 
 
 

 
Clinical Investigation Plan 
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3.4 Investigational Device 
3.4.1 Summary description of the Investigational Device(s) and Comparator(s) 
Treatment 
System 
All subjects will receive treatment with the Avance® Negative Pressure Wound Therapy System 
consisting of:  
- 
Avance® Pump  
- 
Avance® View Pad  
- 
Avance® Foam  
- 
Film sealant (either the Investigational device, Avance Film® with Safetac®Technology 
or the Comparator, V.A.C. Drape, ) 
Pump settings (pressure and mode (intermittent or constant pressure) and size of the foam and 
the film must be registered in the relevant section of the CRF. 
  
Other materials 
Actual use of supporting and/or protecting materials must be registered in the relevant section in 
the CRF.  
 
- 
Skin fixatives 
Mepiseal®  will be available for use in combination with the Avance film with Safetac, 
according to investigators preference.  
Mepiseal is a flexible sealant intended to use on the surrounding skin of wounds or 
stomas that are difficult to dress due to uneven skin surfaces, location or mobility. 
Mepiseal helps prevent leakage and premature loosening of the wound dressing, NPWT 
or ostomy systems. Mepieseal can also be used as a filler uneven surrounding skin.  
 
- 
Wound contact layers  
Non-adherent dressing materials Mepitel can be used to protect fragile tissue such as 
bones, tendons and nerves. It can also be used to cover sharp edged or bones to 
prevent puncture of blood vessels or organs..  
 
- 
Skin protection  
In this investigation, use of additional film (other transparent film), Cavilon or 
hydrocolloids is not allowed to be used as protection of the peri-wound skin as this 
could potentially interfere with the measurement of the primary objective.  
 
All medical devices are CE marked and used according to intended use, with the exception of 
the overlapping Avance Film® with Safetac with V.A.C. Drape and V.A.C. Drape together with 
Avance System and Avance Foam, which is used outside intended use. Based on product risk 
management for the investigational device, it can be concluded that there are no unacceptable 
risks of harm for subject, the user nor third party involved. 
The investigational device meets all relevant essential requirements except for those being 
investigated in the clinical investigation, as declared separately. 
 
3.4.2 Labeling 
MHC will provide the investigational medical devices to the investigation sites for free. Labelling 
of the investigational medical device will be performed in accordance with Good Manufacturing 
Practice (GMP). The labels will be produced in the local language and in accordance with local 
regulations for each participating country. 

 
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3.4.3 Accountability 
The Principal Investigator is responsible for establishing routines for correct handling of 
investigational medical device, to ensure that: 
 
- 
The Principal Investigator or his/she’s designee correctly receives deliveries of such 
device from MHC. 
- 
Accurate records are maintained, accounting for the receipt of the investigational 
medical device (a delivery note for this purpose will be provided) and for the disposition 
of the device 
- 
Investigational medical device is to be handled and stored safely, properly and in 
agreement with the given storage instructions. 
- 
The investigational medical device is to be prescribed only by the investigator or by a 
person authorized to do so by the Principal Investigator 
- 
Under no circumstances will the investigator allow the investigational device to be used 
for other purposes than as directed by the CIP. 
- 
When dispensing investigational medical device to subjects, this must be noted in the 
accountability form investigation device per subject. Recorded information includes 
identification of the subject to whom the investigational medical device is dispensed, the 
investigational medical device and quantity dispensed, date of dispensing, and 
documentation of returned device (if any) from the subject. This record must be kept in 
the Central Site File (CSF). 
- 
Returned and unused devices is accounted for and returned to MHC for destruction, or 
destroyed locally upon agreement with, and approval from MHC.  All returned devices 
should be documented for on a specific form supplied by MHC. 
 
3.4.4 Storage conditions 
The device should be stored under normal condition. 
 
3.4.5 Method of Assigning Subjects to Treatment Groups 
The investigation is randomized, open, controlled pilot study. All subjects who fulfil all inclusion 
and none of the exclusion criteria and have signed a written inform consent form will be 
randomly assigned in a 1:1 ratio, within each arm on day 1, to one of the two treatment groups 
provided by the electronic eCRF system (Viedoc)  as indicated below:  
 
Treatment group 1:  
Film A (subject right side) = Avance Film with Safetac  
Film B (subject left side) = V.A.C. Drape 
 
Treatment group 2:  
Film A (subject right side)  = V.A.C. Drape 
Film B (subject left side) = Avance Film with Safetac 
 
The investigation center will be numbered 01 and the subject will be consecutively allocated to 
the treatment and given a subject code e.g. 0101,0102 etc 
 
 

 
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Randomization 
Eligible subjects will have the investigated wound randomly divided into two halves. One half of 
the wound will be dressed with Avance Film with Safetac while the other half on top of the 
Avance Film with Safetac will be dressed with V.A.C. Drape. 
 
 
1. The area which is intended to be covered with film will be drawn on the subject’s skin 
with a semi-permanent marker pen: 
 
 
 
2. This skin area will be divided into two approximately equal halves and A or B will be 
written on each half (to allow for correct positioning of new films in connection with 
dressing changes). The intended direction of film application will be according to the 
location of the wound, anatomy of the relevant body part and the investigators best 
judgment for how the best seal can be obtained.  
 
 
 
 
3. Instruction about the film-film overlap and the overlap from wound edge on dry peri-
wound skin to ensure an optimal vacuum is described in the application step-by-step 
guide. 

 
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3.5 Concomitant Treatments 
Medication, which is considered necessary for the subject’s safety and well-being, may be given 
at the discretion of the investigator. All concomitant medication and relevant treatment must be 
recorded in the appropriate section of the Case Report Form (CRF).  
 
3.6 Performance and Safety 
3.6.1 Subject Characteristics 
See Appendix C 
3.6.2 Performance and Safety Measurements and Variables 
Primary outcome variable: 
Primary performance variable will be change in total score of Condition of peri-wound skin, the 
sum of scores (0-3) of redness/irritation, rash, peri-wound dermatitis or eczema, maceration, 
blistering and skin tear from baseline to last visit 
 
Secondary outcome variables: 
Secondary performance variables will be change in the following variables from baseline to last 
visit: 
- 
Redness/irritation 
- 
Rash, periwound dermatitis or eczema 
- 
Maceration 
- 
Blistering 

 
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- 
Skin tear  
- 
Damage to peri-wound skin caused by Avance Film 
- 
Damage to peri-wound skin caused by KCI Film 
- 
Overall peri-wound condition changes by the Avance Film  
- 
Overall peri-wound condition changes by the KCI film  
 
Investigator/Nurse evaluation 
Film 
- 
Overall ease of application 
- 
Overall ease of removal 
- 
Adherence to healthy, intact skin 
- 
Conformability 
- 
Overall satisfaction 
- 
Sticking to the wound bed 
- 
Sticking to the surrounding skin 
- 
Retention of dressing pieces in the wound 
 
Foam  
- 
Overall ease of application 
- 
Overall ease of removal 
- 
Conformability 
- 
Overall satisfaction 
- 
Sticking to the wound bed 
- 
Foam adhering to tissues  
- 
Foam imbedded in the wound  
- 
Foam fragmentation  
- 
Disintegration of the foam  
- 
Foam retention, needing for sharp debridement 
Patient reported outcome (PRO) 
- 
VAS before removal of the covering film 
- 
VAS before removal of the foam filler, 
- 
VAS during removal of the covering film, 

 
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- 
VAS during removal of the foam filler 
- 
VAS after removal of the covering film, 
- 
VAS after removal of the foam filler 
 
Saftey 
- 
Incidence of AE, ADE, DD and SAE 
- 
Incidence of AE:s,ADE:s, DD:s and SAE:s leading to withdrawal 
For details see Appendix C 
 
3.6.3 Safety Measurements and Variables 
 
AE/ADE, SAE/SADE and DD. The definition of AE, ADE, SAE, SADE and DD and procedures 
for reporting, SAE and SADE and DD that could have led to a SADE are presented in section 8 
of this CIP. All AE, ADE, SAE, SADE and DD must also be recorded in the appropriate section 
of the CRF. It is of utmost importance that all staff involved in the investigation is familiar with 
the content of section 8. It is the responsibility of the Principal Investigator to ensure this. 
 
3.6.4 Anticipated ADEs  
The following events have been identified as anticipated effects in the Product Risk 
Management Record: 
• 
Wound dry out 
• 
Maceration 
• 
Infection 
• 
Pain and discomfort 
• 
Skin irritation 
• 
Skin stripping 
• 
Skin tears 
 
The conclusion of the Product Risk Management Record is as following: 
Based on this risk management record it can be concluded that for the investigational devices 
there are no unacceptable risks of harm for subject, the user nor third party involved in this 
investigation when used under normal condition. 
 
 
 
 
 
 
 

 
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3.7 Data Quality Assurance 
 
3.7.1 Monitoring, Audits and Inspections 
During the investigation, the monitor will have regular contacts with the investigation site. These 
contacts will include visits to confirm that the facilities remain adequate to specified standards 
and that the investigation site team is carrying out the procedure stated in the clinical 
investigation plan and supports the investigator. All data must be accurately recorded in the 
CRF. Source data verification (a comparison of data in the CRF with the subject’s 
hospital/practice and other records at the investigation site) with direct access to records will 
also be performed. 
The monitor or other Mölnlycke Health Care (MHC) personnel will be available between visits if 
the investigator or other staff at the site needs information and/or advice. 
Authorised representatives of MHC and/or a Competent Authority (CA) and/or the Ethics 
Committee (EC) may visit the investigation site to perform audits/inspections, including source 
data verification. 
 
3.7.2 Training of Staff 
The Principal Investigator will ensure that appropriate training relevant to the investigation is 
given to the medical, nursing and other staff at the site involved and that new information of 
relevance to the performance of this investigation is forwarded to the staff involved. 
 
3.7.3 Data Management 
The Data Management process includes all activities related to data handling regarding: 
• 
Randomization 
• 
Set-up of eCRF and database 
• 
Specification of on-line checks 
• 
Data entry / Data editing 
• 
Export of data from Viedoc to SAS 
• 
Creation of post-entry checks and listings 
• 
Reconciliation of Serious Adverse Event  (SAE), Serious Adverse Device Effect 
(SADE), Adverse Devise Effect (ADE) and Device Deficiency (DD) 
• 
Clean-file process including execution of post-entry checks and listings 
• 
Post clean-file tasks 
Viedoc, a web based electronic CRF system, will be used to capture data in this investigation. 
The eCRF system complies with FDA Title 21 CRF part 11 (ER/ES) requirement. 
eCRF training will be given to appropriate personnel before/at initiation of the investigation 
site(s).  
Data entry will be done by investigators and other authorized personnel at the site(s). When 
entering data, on-line checks are incorporated in Viedoc help for consistency and validation of 
the data. 

 
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Pharma Consulting Group will support with a helpdesk function taking care of system user 
questions regarding Viedoc. 
When data has been entered authorized personnel at MHC can immediately view the data, 
send queries if necessary and lock eCRF pages when they have been validated.  
Photos will be uploaded in Viedoc and are marked with the subject code. Uploaded photos shall 
not contain any information that can reveal the identity of the subject. All uploaded photos will 
be reviewed by personnel at MHC and stored in the company database. All data entered in 
Viedoc will be encrypted. The physical database will be stored in Sweden. 
Programs for post-entry checks and data listings will be created and executed for validation of 
data.  
Completeness will be checked by authorized personnel at MHC so that there are no 
unexplainable empty fields in Viedoc. This is done in order to prevent that data have been 
overlooked by personnel entering the data. 
A clean-file meeting will be held prior to database lock. All decisions on the evaluability of the 
data from each individual subject for the statistical analysis must be made and documented 
before locking the database.  
 
3.8 Statistical Methods and Determination of Sample Size 
3.8.1 Statistical populations 
 
ITT Population  
The Intention to Treat (ITT) population will include all randomised subjects with at least one 
post-randomisation performance measurement. The final definition of the ITT population will be 
made at the clean-file meeting. 
 
Per Protocol Population 
The Per Protocol (PP)-Population will include all subjects in the ITT-population without 
significant protocol violations. Subjects identified as protocol violators will be documented and 
agreed between MHC and the principal investigator at the clean-file meeting before the 
database lock.  
 
Safety Population 
The safety population will include all subjects with at least one treatment with at least one of the 
study films. 
 
 
3.8.2 General statistical methodology 
 The design of the study is paired since both treatments are applied on each side of the same 
wound. This implies that all statistical analyses will be paired. 
For comparison of change in continuous variables (e.g. total score) between the two treatments 
Wilcoxon Signed Rank test will be applied on the differences of the changes from baseline to 
last visit between the two treatments. 
For comparison of change in ordered categorical variables (e.g. each of the conditions of peri-

 
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wound skin) between the two treatments Wilcoxon Signed Rank test will be applied on the 
differences of the changes from baseline to last visit classified as worse (-1), equal (0) and 
better(1) between the two treatments. 
For comparison of change over time within groups Wilcoxon Signed Rank will be used for 
continuous variables and sign test for ordered categorical variables. 
 
Continuous variables will be described with mean, SD, median and minimum and maximum and 
categorical variables will be described with number and percentage. 
All variables will be described per treatment film and with distributions of the differences 
between the two treatment films.

All the main performance analyses will be performed on the ITT-population. Complementary 
performance analyses will be performed on the PP-population. 
All safety analyses will be performed on the safety population. 
 
All significance tests will be two-sided and conducted at the 5% significance level.
 
3.8.3 Performance Analyses
 
Primary Performance Analysis
Primary performance analysis will be the analysis of the difference in primary performance 
variable, change in total score, the sum of scores (0-3) of redness/irritation, rash peri-wound 
dermatitis or eczema, maceration, blistering and skin tear on the skin from baseline to last visit 
between the Avance Film with Safetac and V.A.C Drape with two-sided Wilcoxon Signed Rank 
on the ITT-population at the 5% significance level. 
 
Secondary Performance Analyses 
Secondary performance analyses will be the analyses between the Avance Film with Safetac 
and V.A.C Drape film of all the secondary performance variables given above in section 3.6.2 
according to the statistical methods given above in section 3.8.2 General statistical 
methodology on both the ITT population and PP population. 
 
3.8.4 Safety analyses 
All safety variables given above in section 3.6.2 will be analyzed descriptively by treatment film 
on the safety population. 
 
3.8.5 Baseline analysis 
All variables measured at baseline will be summarized for the ITT population and for the PP 
population using appropriate descriptive statistics. 
 

 
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3.8.6 Statistical Analysis Plan (SAP) 
Before the database is locked a statistical analysis plan (SAP) will be written and signed with all 
details in the statistical analyses given, together with a listing of all Tables, Figures and Listings 
to be produced. 
 
3.8.7 Determination of Sample Size 
In order to find a mean difference in change of primary performance variable, total sum score 
(0-15) of 1 unit between Avance Film with Safetac and V.A.C Drape with Wilcoxon Signed Rank 
test with power 80% at 5% significance level 7-23 evaluable subjects are needed. From a pilot 
study the SD of the change in corresponding score (0-5) was 0.647. The SD for change in total 
sum score (0-15) was then estimated to be 1.94. In the sample size analysis it is assumed a 
correlation of 0.70 between the change in Avance Film with Safetac and change in V.A.C 
Drape.  
 
3.9 Changes to the Clinical Investigation Plan 
No change in the investigation procedure will be effected without the mutual agreement of the 
Principal Investigator and MHC. 
An amendment to the Investigation Plan may require notification or approval from EC and, in 
many countries, also the CA before implementation. Local requirements must be followed. 
MHC will distribute clinical investigation plan amendments to the Principal Investigator who is 
responsible for the distribution of these documents to the EC and staff concerned at his/her site. 
The distribution of these documents to the CA will be handled according to local practice. 
  
4. STATEMENTS OF COMPLIANCE 
4.1 Ethics 
4.1.1 Ethics review  
The final clinical investigation plan, including the final version of the Patient Information and 
Consent Form, must be approved or given a favorable opinion in writing by an EC/IRB before 
enrolment of any subject into the investigation. The Principal Investigator is responsible for 
informing the EC/IRB of any amendment to the investigation plan as per local requirements. 
 
4.1.2 Ethical Conduct of the Investigation 
The investigation will be performed in accordance with the ethical principles that have their 
origin in the most recent version of the Declaration of Helsinki, and with applicable regulatory 
requirements. 
 

 
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4.1.3 Patient Information and Consent Form 
The Principal Investigator will ensure that the subject is given full and adequate oral and written 
information about the nature, purpose, possible risks and benefits of the investigation. Subjects 
must also be notified that they are free to discontinue participation in the investigation at any 
time. The subject should be given the opportunity to ask questions and time for consideration. 
The subject’s signed informed consent has to be obtained before conducting any procedure 
specifically for the investigation. The original must be filed by the Principal Investigator. A copy 
of the Patient Information including the signed Consent Form should be given to the subject. 
 
A sample of the Patient Information and Consent Form is enclosed (Appendix B). If 
modifications are made according to local requirements, the new version must be approved by 
MHC. 
 
4.2 Regulatory and standards 
4.2.1 Regulatory review 
The final clinical investigation plan, including the final version of the Patient Information and 
Consent Form, must be approved or given a favorable opinion in writing by a CA before 
enrolment of any subject into the investigation. MHC is responsible for informing the CA of any 
amendment to the investigation plan as per local requirements. 
 
4.2.2 Standards and other 
 
The most recent version of ISO 14155 is followed in addition to national regulations.  
 
4.2.3 Subject Data Protection 
The written Patient Information explains that the data will be stored in a computer database, 
maintaining confidentiality in accordance with national data legislation and that authorised 
representatives of MHC and/or a CA and/or EC/IRB, require direct access to those parts of the 
hospital/practice records relevant to the investigation, including medical history, for verification 
of data. All data computerized by MHC will be identified by subject number only. 
 
4.3 SUBJECT PROTECTION PROCEDURES 
4.3.1 Procedures in Case of Medical Emergency 
The Principal Investigator is responsible for ensuring that procedures and expertise are 
available to cope with medical emergencies during the investigation. 
 
4.3.2 Insurance 
Mölnlycke Health Care AB has product liability insurance, which also covers test products.  

 
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5. INVESTIGATION TIMETABLE AND TERMINATION 
 
Investigation start: Q4 2015 
Inclusion completed:Q2 2016 
Last subject out:Q2 2016 
 
The investigation could be prematurely discontinued if the dropout rate is high and/or the 
investigation site is unable to fulfil the inclusion period according to the Clinical Investigation 
Agreement. 
The Sponsor, Ethics Committee or Regulatory Authority may prematurely terminate or suspend 
the Clinical Investigation as a whole or at an individual investigation site for significant and 
documented reasons. The Principal Investigator may also prematurely terminate or suspend the 
Clinical Investigation at his/her site, for significant and documented reasons. Reasons for 
premature termination or suspension by any party include, but are not limited to safety, 
inadequate recruitment, Principal Investigator issues, and device related problems, alignment 
with business strategy or administrative issues.  
If suspicion of an unacceptable risk to subjects arises during the Clinical Investigation, or when 
instructed by an Ethics Committee or Regulatory Authority, the Sponsor shall suspend the 
Clinical Investigation at all active sites while the risk is assessed. The Sponsor shall terminate 
the Clinical Investigation if an unacceptable risk is confirmed, or resume the Clinical 
Investigation following appropriate communication and approval from the Ethics Committee and 
Regulatory Authority as required.  
In terminating the clinical investigation, the Sponsor and the Principal Investigator will assure 
that adequate consideration is given to the protection of the subject’s interests. 
After the clinical investigation has been successfully completed the participating subject will 
continue to receive standard care according the institute’s routine practice. 

 
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6. LITERATURE REVIEW AND REFERENCES 
In order to determine the scientific background for this clinical investigation as well as to assess 
risks/benefits of the device, a literature review was conducted. The literature listed below was 
critically evaluated before serving as background information. 
 
1. Sussia, D., Danino, A., & Nikolis, A. (2011). Negative-pressure therapy versus standard 
wound care: a meta-analysis of randomized trials. Plastic and reconstructive surgery, 128 
(5) 498 e-503e doi:10.1097/PRS.2b013e31822b675c 
2. Rafter, L., Use of soft silicon based film dressing in negative pressure wound therapy. 
Wounds UK (2013), Volume 9; Number 4 :107-113 
3. Upton, D., Andrew, A., Pain and trauma in negative wound therapy: a review. International 
Wound Journal 2013, March, doi:10.1111/iwj.12059 
 
 
 
 
 
 
 

 
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7. DEFINITIONS AND PROCEDURES FOR REPORTING OF 
ADVERSE EVENT, ADVERSE DEVICE EFFECT, SERIOUS 
ADVERSE EVENT, SERIOUS ADVERSE DEVICE EFFECT 
AND DEVICE DEFICIENCY  
Definitions: 
 
Device Deficiency (DD) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, 
safety or performance. 
 
Note:  
• 
Device Deficiencies include malfunctions, use errors, and inadequate labeling. 
 
All Device Deficiencies that could have lead to a Serious Adverse Device Effect shall be 
reported in accordance with Serious Adverse Event reporting procedures, as specified 
below. 
Adverse Event (AE) 
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 
Note:  
• 
This definition includes events related to the investigational medical device or 
the comparator. 
• 
This definition includes events related to the procedures involved. 
• 
For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
 
 
Adverse Device Effect (ADE) 
 
Adverse Event related to the use of an investigational medical device  
 
 
Note:  
• 
This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, or operation, or any malfunction 
of the investigational medical device. 
• 
This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device. 
 
Serious Adverse Event (SAE) 
 
Adverse Event that: 
 
a) led to death, 
b) led to a serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 32(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
3) in-patient or prolonged hospitalization or,  
4)  medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.     
 
c) led to foetal distress, foetal death or a congenital abnormality or birth defect. 
 
 
Note: 
Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
 
 
Serious Adverse Device Effect (SADE) 
 
Adverse Device Effect that has resulted in any of the consequences characteristic of a 
Serious Adverse Event.   
 
 
PROCEDURES FOR SAE AND/OR SADE REPORTING OR REPORTING OF 
DD THAT COULD HAVE LEAD TO A SADE 
 
The investigator must inform Mölnlycke Health Care (MHC), within 1 day of awareness of 
the event by sending the Serious Adverse Event/Serious Adverse Device Effect form by 
email to: Clinical_Investigations_Event_Reporting@molnlycke.com, of any SAE that 
occurs in the course of the investigation. All SAE have to be reported, whether or not they 
are considered causally related to the investigation product. When a SAE has been 
entered into the eCRF by the investigator /authorised site staff, the eCRF system will 
automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com and a separate report are 
therefore not required when eCRF is used. 
 
Device Deficiencies that could have lead to SADE if either a) suitable action had not been 
taken, b) if intervention had not been made, or c) if circumstances had been less fortunate 
must be reported as a SADE. 
 
The investigator is responsible for informing the EC and/or the Competent Authority of the 
SAE/SADE as per local requirements. 
 
 
PROCEDURES FOR DD REPORTING  
 
All DD needs to be reported to MHC as soon as possible, without unjustified delay. If the 
DD could have lead to a SADE the reporting requirements for SADE described above 
must be followed. DDs can be either subject related or non subject related depending on if 
the investigational device was used by a subject or not. Separate forms are used for 
subject related and non subject related DDs. The completed DD report form must be sent 
by email to Clinical_Investigations_Event_Reporting@molnlycke.com  
 

 
Clinical Investigation Plan 
Document ID: PD-485250 Rev: 01 
Title: Avance 02 
Page 33(33) 
Investigation Code Avance 02 
Final Version 
Approval date 2015-09-11 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
When a subject related DD has been entered into the eCRF by the investigator 
/authorised site staff, the eCRF system will automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com. 
 
Causality Assessment 
The investigator is required to assess the causal relationship to the investigation product 
for each AE/SAE according to the following classifications: 
1. Definite:  
Event with plausible time relationship to device application 
No other explanation - current disease, concomitant drugs and/or other devices 
Response to withdrawal plausible 
Event definitive - localized, specific 
Rechallenge positive 
 
2. Probable:  
Event with reasonable time relationship to device application 
No other explanation current disease, concomitant drugs and/or other devices 
Response to withdrawal clinically reasonable 
No rechallenge 
 
3. Possible:  
Event with reasonable time relationship to device application 
Could also be explained by disease or other drugs and/or devices 
Information on device withdrawal lacking or unclear 
No rechallenge 
 
4. Unlikely: 
Event with duration to onset that makes a relationship improbable (but not 
impossible) 
Diseases other drugs or devices provide plausible explanations 
Symptoms do not resolve on withdrawal 
Nature of event unrelated to action or properties of device 
No rechallenge 
 
5. Unable to determine 
Event occurred but there is insufficient information 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 1(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
CLINICAL INVESTIGATION PLAN (CIP) Central AMENDMENT no 01 
Substantial 
  
INVESTIGATIONAL DEVICE:  
Avance® Negative Pressure Wound Therapy System 
INVESTIGATION TITLE:  
A randomized open, controlled pilot investigation comparing trauma to the peri-
wound skin and Pain during treatment with Avance NPWT system when using two 
different fixations  
 
 
SITES AFFECTED BY THE AMENDMENT: 
The amendment affect all in the study 
 
 
 
 
 
 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 2(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
THE CLINICAL INVESTIGATION PLAN (CIP) IS TO BE AMENDED AS FOLLOWS: 
 
FROM: 
1. Title: Randomized, Intra-patient, Open Controlled Pilot Investigation  
2. Comparing trauma to the peri-wound skin 
3. Patient included 7-23 evaluable subjects 
4. Eligible subjects will have the investigated wound randomly divided into two halves. One half of 
the wound will be dressed with Avance Film with Safetac while the other half on top of the Avance 
Film with Safetac will be dressed with V.A.C. Drape. 
5. Each subject will be followed in the investigation for a maximum of five (5) dressing changes or 
until treatment with NPWT is no longer indicated 
6. Investigational Device 
Treatment 
System 
All subjects will receive treatment with the Avance® Negative Pressure Wound Therapy System 
consisting of: 
- 
Avance® Pump 
- 
Avance® View Pad 
- 
Avance® Foam 
- 
Film sealant (either the Investigational device, Avance Film® with
 Safetac®Technology or the Comparator, V.A.C. Drape) 
7. Inclusion/Exclusion Criteria 
Inclusion Criteria 
1. Exuding wound indicated for treatment with NPWT therapy 
2. In case of multiple wounds, target wound must be _ 10 cm distant from other wounds. 
Selection of target wound is according to the investigator’s preference 
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the wound 
4. Male or female, 18 years of age and above 
5. Signed Informed Consent 
Exclusion Criteria 
1. Dressing sizes does not fit the target wound 
2. Unexplored blind tunnels or non-enteric fistula 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 3(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
3. Untreated osteomyelitis 
4. Malignant wounds 
5. Wounds with necrotic tissue or eschar (if not adequately debrided) 
6. Bleeding wounds 
7. Subject not suitable for the investigation according to the investigator’s judgment 
8. Subject included in other ongoing clinical investigation which could interfere with this 
investigation, as judged by the investigator 
9. Known allergy/hypersensitivity to any of the components included into the investigation 
 
TO: 
1. Title: Randomize, Open Controlled Pilot Investigation. 
2. Comparing trauma to the peri-wound skin and pain during treatment with Avance NPTW system. 
3. Patient included 32 evaluable subjects. 
4. Subjects will be randomized using optimal allocation (minimization) balancing baseline variables 
age and type of skin (normal/dry/flaky/oily/moist). Eligible subjects will be randomized to receive 
Avance® Film with Safetac® Technology or Avance® Transparent film in a ratio of 1:1 provided by 
the electronic eCRF system (Viedoc). 
5. Each subject will be followed in the investigation for a maximum of six (6) dressing changes or 
until treatment with NPWT is no longer indicated 
6. Investigational Device 
Treatment 
System 
All subjects will receive treatment with the Avance® Negative Pressure Wound Therapy 
System consisting of:  
- 
Avance® Pump  
- 
Avance® View Pad  
- 
Avance® Foam  
- 
Film sealant (either the Investigational device, Avance ® Film with 
Safetac®Technology or the Comparator, Avance® Transparent film. ) 
7. Inclusion/Exclusion Criteria 
 
Inclusion Criteria 
1. Traumatic, surgical or dehisced wounds, Venous Leg Ulcer or Pressure Ulcer 
indicated for treatment with NPWT therapy  
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 4(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
2. In case of multiple wounds the target wound must be  10 cm distant from other 
wounds. Selection of the target wound is according to the investigator’s preference  
 
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the 
wound  
 
4. Male or female, 18 years of age and above  
 
5. Signed Informed Consent 
 
Exclusion Criteria 
1. Dressing sizes does not fit the target wound 
 
2. Unexplored blind tunnels or non-enteric fistula 
 
3. Untreated osteomyelitis 
 
4. Malignant wounds 
 
5. Wounds which needed extra skin protection such as Cavilon, Zink pasta, 
ointment, or other type of skin protections. 
 
6. Subjects treated with systemic immunosuppressive or glucocorticosteroids, 
except subjects taking occasional doses or doses less than 10mg 
prednisolone/day or equivalent.  
 
7. Subjects with decreased sensation, as judged by the investigator 
 
8. Wounds with exposed blood vessels, anastomotic sites, organs or nerves. 
 
9. Previous NPWT treatment on the target wound  3 months at inclusion 
 
10. Wounds with necrotic tissue or eschar  
 
11. Significantly bleeding wounds, as judged by the investigator 
 
12. Subject not suitable for the investigation according to the investigator’s 
judgment  
 
13. Subject included in other ongoing clinical investigation which could interfere 
with this investigation, as judged by the investigator  
 
14. Known allergy/hypersensitivity to any of the components included into the 
investigation. 
 
15. Previous treatment of the target wound with acrylic film  1 week at inclusion 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 5(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
 
REASON FOR MAKING THE AMENDMENT: 
The Medical Products Agency (MPA) recommendation was to do the study on a CE approved 
design. The purpose of the previous design was neither CE mark V.A.C Drape  for use in 
combination with the Avance NPWT system nor to CE mark V.A.C Drape overlapping Avance Film.  
 
 
ACTIONS TO BE TAKEN: 
Investigator at the site will be provided with the amendment and signature will be collected. 
The Amendment will be sent to the Ethic committee for approval according to local procedures. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 6(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
CLINICAL INVESTIGATION PLAN (CIP) SYNOPSIS 
 
Investigation title: 
 A randomized open, controlled pilot investigation comparing trauma to the peri-
wound skin and Pain during treatment with Avance NPWT system when using two 
different fixations  
 
Objectives 
Primary objective 
• 
Changes on Peri-Wound* Skin from baseline to termination during treatment with  Avance 
System and Avance Foam.  
* Redness/Irritation, Flaky, Maceration, Blistering, Skin tears ( None, Mild/Moderate/Severe) 
Secondary objectives  
• 
Changes in Pain measured by the Visuell analog scale (VAS) from baseline to termination 
 
• 
AE,SAE,SADE, ADE and DD 
Overall Design 
This investigation is designed as a randomized controlled open clinical investigation. The outcome 
will be used to guide the manufacture to the design and implementation of a larger scale 
randomized study. In order to compensate for a drop-out rate of 5 %, this clinical investigation will 
include 17 subjects per group across one (1) site in Sweden to yield a total of 32 evaluable 
subjects. 
All subjects who has not previously been treated with NPWT and fulfill all inclusion, none of the 
exclusion criteria and have signed a written inform consent will be enrolled. Subjects will be 
randomized using optimal allocation (minimization) balancing baseline variables age and type of 
skin (normal/dry/flaky/oily/moist). Eligible subjects will be randomized to receive Avance® Film with 
Safetac® Technology or Avance® Transparent film in a ratio of 1:1 provided by the electronic eCRF 
system (Viedoc). 
This investigation is comparing pain at dressing change and trauma and/or other changes to the 
peri-wound skin during treatment with Avance NPWT system when using two different fixation 
films, Avance® Film with Safetac® Technology or  Avance® Transparent film. Since the investigation 
is comparing films with clear visual differences, it is not possible to blind neither the investigator nor 
the subject.  
Dressing change 
Dressing change will be performed at the investigation site and the frequency of dressing change 
will be depending on the condition of the wound and the peri-wound skin. Recommended dressing 
change frequency is every 48-72 hours. 
A record (dressing log) will be completed for every dressing change. 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 7(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Investigation Visit frequency and subject participation 
Eligible subjects will be enrolled at the baseline visit (Visit 1), where the first dressing applications 
take place. From Visit 2 and onwards, one dressing application is considered as one study visit, 
e.g. the study visits are flexible and depending on the dressing changing frequency of the 
individual subject. The total treatment time for a subject may vary, depending on the wound type 
and condition. Each subject will be followed in the investigation for a maximum of six (6) dressing 
changes or until treatment with NPWT is no longer indicated. After termination from the 
investigation, subjects will be treated according to standard clinical practice at the investigation 
site. No additional data (except follow up information on ongoing safety events) will be collected 
after termination.  
Subjects will be recruited at the investigation site, which have experience in managing the 
investigation population with NPWT and have access to a suitable number of subjects (based on 
historic data). 
Following variables should be considered ( Appendix C): 
At visit 1 
 
Informed consent 
 
Subject demographic details 
 
Inclusion and exclusion criteria 
 
Vital signs 
 
Care (Inpatient/ Outpatient) 
 
Medical and surgical history 
 
Wound history 
 
Skin assessment* 
 
Concomitant medication  
 
Photo 
 
Pain (VAS) 
 
Adverse Event (AE)/ Adverse Device Effect (ADE)/ Serious Adverse Event (SAE) /Serious 
Adverse Device Effect (SADE)/Device Deficiency (DD) 
 
Apply the Investigational Product (IP) 
 
Randomization 
 
At visit 2-6 
 
Skin assessment*  
 
Concomitant medication  
 
Photo 
 
Pain (VAS) 
 
Change and removal of IP 
 
AE/ ADE/ SAE/SADE/DD 
Only one target wound per patient will be included in this investigation. 
 
* Evaluation of the skin se Appendix D 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 8(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Schedule of Assessment 
 
Day 
Visit 1 Visit 2 
Visit 3 
Visit 4 Visit 5 
 
Visit 6 
Termination 
End of treatment 
Visit (number) 
1 
2 
3 
4 
5 
6 
Termination 
Subject demography 
9 
 
 
 
 
 
 
Inclusion and Exclusion Criteria 
9 
 
 
 
 
 
 
Inform Consent 
9 
 
 
 
 
 
 
Vital Signs 
9 
 
 
 
 
9 
9 
Medical and surgical history 
9 
 
 
 
 
 
 
Skin assessment  
9 
9 
9 
9 
9 
9 
9 
Wound History 
9 
 
 
 
 
 
 
Randomization  
9 
 
 
 
 
 
 
Pain ( VAS) 
9 
9 
9 
9 
9 
9 
9 
Dressing application  
9 
9 
9 
9 
9 
 
 
Dressing removal 
 
9 
9 
9 
9 
9 
9 
Photo  
9 
9 
9 
9 
9 
9 
9 
Medication log 
9 
9 
9 
9 
9 
9 
9 
AE/ADE/DD 
9 
9 
9 
9 
9 
9 
9 
SAE/SADE 
9 
9 
9 
9 
9 
9 
9 
 
Inclusion/Exclusion Criteria 
 
Inclusion Criteria
1. Traumatic, surgical or dehisced wounds, Venous Leg Ulcer or Pressure Ulcer indicated for 
treatment with NPWT therapy  
 
2. In case of multiple wounds the target wound must be  10 cm distant from other wounds. 
Selection of the target wound is according to the investigator’s preference  
 
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the wound  
 
4. Male or female, 18 years of age and above  
 
5. Signed Informed Consent 
 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 9(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Exclusion Criteria 
 
1. Dressing sizes does not fit the target wound 
 
2. Unexplored blind tunnels or non-enteric fistula 
 
3. Untreated osteomyelitis 
 
4. Malignant wounds 
 
5. Wounds which needed extra skin protection such as Cavilon, Zink pasta, ointment, or 
other type of skin protections. 
 
6. Subjects treated with systemic immunosuppressive or glucocorticosteroids, except 
subjects taking occasional doses or doses less than 10mg prednisolone /day or 
equivalent.  
 
7. Subjects with decreased sensation, as judged by the investigator 
 
8. Wounds with exposed blood vessels, anastomotic sites, organs or nerves 
 
9. Previous NPWT treatment on the target wound  3 months at inclusion 
 
10. Wounds with necrotic tissue or eschar (if not adequately debrided) 
 
11. Significantly bleeding wounds, as judged by the investigator 
 
12. Subject not suitable for the investigation according to the investigator’s judgment  
 
13. Subject included in other ongoing clinical investigation which could interfere with this 
investigation, as judged by the investigator  
 
14. Known allergy/hypersensitivity to any of the components included into the investigation. 
 
15. Previous treatment of the target wound with acrylic film  1 week at inclusion 
 
Investigational Device 
Treatment 
System 
All subjects will receive treatment with the Avance® Negative Pressure Wound Therapy System 
consisting of:  
- 
Avance® Pump  
- 
Avance® View Pad  
- 
Avance® Foam  
- 
Film sealant (either the Investigational device, Avance ® Film with Safetac®Technology or 
the Comparator, Avance® Transparent film. ) 
 
All medical devices are CE marked.  

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 10(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
TABLE OF CONTENTS 
1.
OBJECTIVES 
14
2.
CLINICAL INVESTIGATOR(S) AND INVESTIGATION ADMINISTRATIVE 
STRUCTURE 
14
2.1
Staff at Investigation site(s) 
14
2.2
Mölnlycke Investigation Personnel 
14
2.3
Other Participants 
14
3.
INVESTIGATION PLAN AND PROCEDURES 
15
3.1
Overall Design and Flow Chart 
15
3.2
Procedures and Assessments 
15
3.2.1
Schedule of Assessment 
16
3.3
Selection of Population for Investigation 
17
3.3.1
Inclusion Criteria 
17
3.3.2
Exclusion Criteria 
17
3.3.3
Withdrawal of Subjects from Treatment or Assessment 
18
3.4
Investigational Device 
18
3.4.1
Summary description of the Investigational Device(s) and Comparator(s) 
18
3.4.2
Labeling 
18
3.4.3
Accountability 
18
3.4.4
Storage conditions 
19
3.4.5
Method of Assigning Subjects to Treatment Groups 
19
3.5
Concomitant Treatments 
19
3.6
Performance and Safety 
19
3.6.1
Subject Characteristics 
19
3.6.2
Performance and Safety Measurements and Variables 
20
3.6.3
Safety Measurements and Variables 
20
3.6.4
Anticipated ADEs 
21
3.7
Data Quality Assurance 
21
3.7.1
Monitoring, Audits and Inspections 
21
3.7.2
Training of Staff 
21
3.7.3
Data Management 
22

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 11(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
3.8
Statistical Methods and Determination of Sample Size 
23
3.8.1
Statistical populations 
23
3.8.2
General statistical methodology 
23
3.8.3
Performance Analyses 
23
3.8.4
Safety analyses 
24
3.8.5
Baseline analysis 
24
3.8.6
Statistical Analysis Plan (SAP) 
24
3.8.7
Determination of Sample Size 
24
3.9
Changes to the Clinical Investigation Plan 
24
4.
STATEMENTS OF COMPLIANCE 
25
4.1
Ethics 
25
4.1.1
Ethics review 
25
4.1.2
Ethical Conduct of the Investigation 
25
4.1.3
Patient Information and Consent Form 
25
4.2
Regulatory and standards 
25
4.2.1
Regulatory review 
25
4.2.2
Standards and other 
25
4.2.3
Subject Data Protection 
26
4.3
SUBJECT PROTECTION PROCEDURES 
26
4.3.1
Procedures in Case of Medical Emergency 
26
4.3.2
Insurance 
26
5.
INVESTIGATION TIMETABLE AND TERMINATION 
26
6.
LITERATURE REVIEW AND REFERENCES 
27
7.
DEFINITIONS AND PROCEDURES FOR REPORTING OF ADVERSE EVENT, 
ADVERSE DEVICE EFFECT, SERIOUS ADVERSE EVENT, SERIOUS ADVERSE 
DEVICE EFFECT AND DEVICE DEFICIENCY 
28
 
LIST OF APPENDICES 
Appendix A  
F-449 Clinical Investigation Plan Appendix A, Core Signatures 
F-583 Clinical Investigation Plan Principal Investigator Signature 
Appendix B  
F-173 Patient Information and Consent Forms 
Appendix C 
F-542 All variables to be obtained during the Investigation 
Appendix D 
Evaluation of the skin 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 12(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
 
LIST OF ABBREVIATIONS 
 Abbreviation or 
special term 
Explanation 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
CA 
Competent Authorities 
CDM 
Clinical Data Manager 
CIP 
Clinical Investigation Plan 
CIR 
Clinical Investigation Report 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRM 
Clinical Research Manager 
DCF 
Data Clarification Forms 
DD 
Device Deficiency 
FSI 
First subject in 
GCP 
Good Clinical Practice 
IEC 
Independent Ethics Committee 
ID 
Investigational Device 
ITT 
Intention to Treat 
LSO 
Last subject out 
MHC 
Mölnlycke Health Care AB 
PI 
Principal Investigator, a person responsible for the conduct of the clinical investigation at the 
investigational investigation site. Every investigational investigation site has a principal 
investigator. 
PIC 
Patient Information and Consent Form 
RA 
Regulatory Authority 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SDV 
Source Data Verification 
 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 13(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
INTRODUCTION 
Negative pressure wound therapy (NPWT) also referred to as topical negative pressure (TNP), 
negative pressure therapy (NPT), sub-atmospheric pressure wound therapy, and sealed surface 
wound suction is a modality that has found significant use in complex acute surgical, delayed healing 
surgical and hard to heal chronic wounds, including those with elevated bacterial contamination. 
Negative pressure wound therapy manages exudate, combats peri-wound oedema, increases blood 
flow to the wound, maintains optimal moist wound conditions and encourages the formation of wound 
bed granulation tissue. A meta-analysis reported a significant reduction in time to healing for wounds 
treated with NPWT when compared to those treated with standard care (1). The Avance NPWT 
System comprises a range of CE marked products which are used collectively as a NPWT system. 
The Avance NPWT System has been marketed by Mölnlycke Health Care AB since May 2010. 
Despite the research support for its effectiveness in wound healing, fewer studies have considered 
the impact of NPWT on the patient in terms of the pain that can be experienced. Wound care and 
dressing changes can be very painful for patients, and this pain can also cause patients to feel 
stressed or anxious, thus impacting negatively on both their physical and psychological well-being. 
Such factors need to be considered in any evaluation of NPWT or other treatment (2).  
Trauma and pain caused by the removal and reapplication of the NPWT dressings and/or removal 
of the foam has been identified as a major contributor to wound pain (2). Film-based dressings with 
adhesive skin contact layers are used to keep NPWT system in place and skin stripping may occur 
because the film can adhere to aggressively to the peri-wound skin, resulting in trauma and pain 
(2). Trauma may also occur when tissue grows into the foam on the dressing and this tissue 
becomes torn during dressing change (3). Damage to the wound and surrounding skin can involve 
bleeding, blisters, skin stripping and other skin damage, leading to a higher frequency of dressing 
changes, a greater level of pain and a longer time taken for the wound to heal (3). Despite the 
importance of minimizing trauma during NPWT and other wound care, few researchers have 
focused on this area (3)  
Although not focusing on NPWT specifically, a study by Upton and Solowiej also demonstrated 
how dressing type can affect the level of pain experienced during dressing change. In 49 patients 
with chronic wounds, the authors explored differences in pain and stress levels between those who 
received conventional dressings ( n = 39) and those who were given atraumatic dressings with 
Safetac technology. Physiological and psychological measures of pain and stress were taken. It 
was found that self-reported pain and stress were significantly lower in those who were given 
atraumatic dressings as part of their care routine (2).  
In the literature there are numerous supporting articles reporting effectiveness of NPWT treatment. 
However, information regarding choice of dressing materials are lacking. Should for example the 
adhesive material of the dressing have a protecting effect on the surrounding skin around the 
NPWT treated wound?   
What is known from other studies in other stages of the wound healing is that skin trauma such as 
bleeding, redness, irritation, skin stripping and blisters might occur when a film dressing is 
removed. Such trauma can lead to delayed healing and prolonged treatment of the patient. 
In a study made by Upton in 2013, half of the participating patients reported skin trauma or 
irritation.The purpose of this study is to compare with two different types of film dressings one with 
silicon adhesive (Avance® Film with Safetac®Technology) and one with acrylic adhesive (Avance® 
Transparent film) to see if there is a difference in peri-wound skin damage and pain at dressing 
removal.  

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Amendment Final Version 
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Rev: 04 
 
 
1. 2%-(&7,9(6 
Primary objective 
• 
Changes on Peri-Wound* Skin from baseline to termination during treatment with  Avance 
System and Avance Foam.  
* Redness/Irritation, Flaky, Maceration, Blistering, Skin tears ( None, Mild/Moderate/Severe) 
 
Secondary objectives  
• 
Changes in Pain measured by the Visuell analog scale (VAS) from baseline to termination 
 
• 
AE,SAE,SADE, ADE and DD 
2. &/,1,&$/,19(67,*$7256$1',19(67,*$7,21
$'0,1,675$7,9(6758&785( 
 
2.1 Staff at Investigation site(s) 
Name and addresses of principal investigator (s) are listed in Appendix A. 
 
2.2 Mölnlycke Investigation Personnel 
Tina Kjellén, Clinical Study Manager 
Lennart Wäne, Clinical Data Manager 
 
2.3 Other Participants 
Pharma Consulting Group 
Kungsängsvägen 19, 1 tr 
753 23 Uppsala, Sweden 
Statistiska Konsultgruppen 
Nils-Gunnar Pehrsson, Biostatistician 
Stigbergsliden 5 
SE-414 63 Göteborg 
 
 
 
 
 

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Amendment Final Version 
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Document template: F-168 CIP Amendment 
Rev: 04 
 
 
3. ,19(67,*$7,213/$1$1'352&('85(6 
3.1 Overall Design and Flow Chart 
This investigation is designed as a prospective, randomized controlled open clinical investigation. 
The outcome will be used to guide the manufacture to the design and implementation of a larger 
scale randomized study. In order to compensate for a drop-out rate of 5 %, this clinical 
investigation will include 17 subjects per group across one (1) site in Sweden to yield a total of 32 
evaluable subjects.  
All subjects who has not previously been treated with NPWT and fulfill all inclusion and none of the 
exclusion criteria and have signed a written inform consent will be enrolled. Subjects will be 
randomized using optimal allocation (minimization) balancing for baseline variables age and type 
of skin (normal/dry/flaky/oily/moist). Eligible subjects will be randomized to receive Avance® Film 
with Safetac® Technology or Avance® Transparent film in a ratio of 1:1 provided by the electronic 
eCRF system (Viedoc). 
An evaluable subject is defined as a subject that is enrolled and has data for at least one visit after 
baseline visit.  
The target populations are male or female, 18 years and above, which have exuding wounds 
indicated for treatment with NPWT therapy. The subject should not previously been treated with 
NPWT, previous treatment, may have an bias on the skin evaluation. 
The study visits are flexible and depending on the dressing changing frequency of the individual 
subject. The total treatment time for each subject may vary depending on the wound type and 
condition of the wound. Each subject will be followed for a maximum of six (6) dressing changes or 
until treatment with NPWT is no longer indicated (withdrawal criterion). After termination from the 
investigation, subjects will, if necessary, be treated according to standard clinical practice at the 
investigation site. No additional data (except for follow up information on ongoing safety events) 
will be collected after termination.  
 
3.2 Procedures and Assessments 
 
Following variables should be considered ( Appendix C): 
At visit 1 
 
Informed consent  
 
Subject demographic details 
 
Inclusion and exclusion criteria 
 
Vital signs 
 
Care (Inpatient/ Outpatient) 
 
Medical and surgical history 
 
Wound history 
 
Skin assessment* 
 
Concomitant medication  
 
Photo 
 
Pain (VAS) 
 
Adverse Event (AE)/ Adverse Device Effect (ADE)/ Serious Adverse Event (SAE) /Serious 
Adverse Device Effect (SADE)/Device Deficiency (DD) 
 
Apply the Investigational Device (ID) Apply the IP 
 
Randomization 

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At visit 2-6 
 
Skin assessment* 
 
Medication  
 
Photo 
 
Pain (VAS) 
 
Change and removal of the IP 
 
AE/ ADE/ SAE/SADE/DD 
Only one target wound per patient will be included in this investigation. 
* Evaluation of the skin se Appendix D 
Photos will be taken before and after application of the film fixations and also if extra dressing 
changes are required. All unexpected events with the device may be documented by relevant 
photos at time. All photos shall include a sticker marked with subject code, visit number/date and 
time. All photos will be checked by monitor.  
 
 
3.2.1 Schedule of Assessment 
 
Day 
Visit 1 Visit 2 
Visit 3 
Visit 4 Visit 5 
 
Visit 6 
Termination 
End of treatment 
Visit (number) 
1 
2 
3 
4 
5 
6 
Termination 
Subject demography 
9 
 
 
 
 
 
 
Inclusion and Exclusion Criteria 
9 
 
 
 
 
 
 
Inform Consent 
9 
 
 
 
 
 
 
Vital Signs 
9 
 
 
 
 
9 
9 
Medical and surgical history 
9 
 
 
 
 
 
 
Skin assessment  
9 
9 
9 
9 
9 
9 
9 
Wound History 
9 
 
 
 
 
 
 
Randomization  
9 
 
 
 
 
 
 
Pain ( VAS) 
9 
9 
9 
9 
9 
9 
9 
Dressing application  
9 
9 
9 
9 
9 
 
 
Dressing removal 
 
9 
9 
9 
9 
9 
9 
Photo  
9 
9 
9 
9 
9 
9 
9 
Medication log 
9 
9 
9 
9 
9 
9 
9 
AE/ADE/DD 
9 
9 
9 
9 
9 
9 
9 
SAE/SADE 
9 
9 
9 
9 
9 
9 
9 
 

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Amendment Final Version 
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Rev: 04 
 
 
3.3 Selection of Population for Investigation 
3.3.1 Inclusion Criteria 
1. Traumatic, surgical or dehisced wounds, Venous Leg Ulcer or Pressure Ulcer indicated for 
treatment with NPWT therapy  
 
2. In case of multiple wounds the target wound must be  10 cm distant from other wounds. 
Selection of the target wound is according to the investigator’s preference  
 
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the wound  
 
4. Male or female, 18 years of age and above  
 
5. Signed Informed Consent 
3.3.2 Exclusion Criteria 
1. Dressing sizes does not fit the target wound 
 
2. Unexplored blind tunnels or non-enteric fistula 
 
3. Untreated osteomyelitis 
 
4. Malignant wounds 
 
5. Wounds which needed extra skin protection such as Cavilon, Zink pasta, ointment, or 
other type of skin protections. 
 
6. Subjects treated with systemic immunosuppressive or glucocorticosteroids, except 
subjects taking occasional doses or doses less than 10mg prednisolone /day or 
equivalent.  
 
7. Subjects with decreased sensation, as judged by the investigator 
 
8. Wounds with exposed blood vessels, anastomotic sites, organs or nerves 
 
9. Previous NPWT treatment on the target wound  3 months at inclusion 
 
10. Wounds with necrotic tissue or eschar  
 
11. Significantly bleeding wounds, as judged by the investigator 
 
12. Subject not suitable for the investigation according to the investigator’s judgment  
 
13. Subject included in other ongoing clinical investigation which could interfere with this 
investigation, as judged by the investigator  
 
14. Known allergy/hypersensitivity to any of the components included into the investigation. 
 
15. Previous treatment of the target wound with acrylic film  1 week at inclusion 

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Rev: 04 
 
 
3.3.3 Withdrawal of Subjects from Treatment or Assessment 
Subjects are free to discontinue participation in the investigation at any time, and without prejudice 
to further treatment. Subjects who discontinue the investigation should always be asked about the 
reason(s) for their discontinuation and about the presence of any AE/ADE or DD and, if possible, 
be assessed by an investigator. AE/ADE should be followed up.  
Subjects may be withdrawn from investigation treatment and assessments at any time, at the 
discretion of the investigator. 
Incorrectly enrolled or randomized subjects will be withdrawn from further investigation treatment 
and assessments. A subject may, however, continue the investigation under special circumstances 
(i.e. if continuation of investigation treatment or follow-up actions are necessary for the subject’s 
safety and well-being, or if only a follow-up period remains, and the continuation of the 
investigation is not expected to be associated with any risk or discomfort for the subject). 
 
3.4 Investigational Device 
3.4.1 Summary description of the Investigational Device(s) and Comparator(s) 
Treatment 
System 
All subjects will receive treatment with the Avance® Negative Pressure Wound Therapy System 
consisting of:  
- 
Avance® Pump  
- 
Avance® View Pad  
- 
Avance® Foam  
- 
Film sealant (either the Investigational device, Avance® Film with Safetac®Technology or 
the Comparator, Avance® Transparent film ) 
 
All medical devices are CE marked.  
 
3.4.2 Labeling 
MHC will provide the investigational medical devices to the investigation sites for free. Labelling of 
the investigational medical device will be performed in accordance with Good Manufacturing 
Practice (GMP). The labels will be produced in the local language.  
 
3.4.3 Accountability 
The Principal Investigator is responsible for establishing routines for correct handling of 
investigational medical device, to ensure that: 
 
- 
The Principal Investigator or his/she’s designee correctly receives deliveries of such device 
from MHC. 
- 
Accurate records are maintained, accounting for the receipt of the investigational medical 
device (a delivery note for this purpose will be provided) and for the disposition of the 
device. 

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- 
Investigational medical device is to be handled and stored safely, properly and in 
agreement with the given storage instructions. 
- 
The investigational medical device is to be prescribed only by the investigator or by a 
person authorized to do so by the Principal Investigator. 
- 
Under no circumstances will the investigator allow the investigational device to be used for 
other purposes than as directed by the CIP. 
- 
When dispensing investigational medical device to subjects, this must be noted in the 
accountability form investigation device per subject. Recorded information includes 
identification of the subject to whom the investigational medical device is dispensed, the 
investigational medical device and quantity dispensed, date of dispensing, and 
documentation of returned device (if any) from the subject. This record must be kept in the 
Central Site File (CSF). 
- 
Returned and unused devices is accounted for and returned to MHC for destruction, or 
destroyed locally upon agreement with, and approval from MHC.  All returned devices 
should be documented for on a specific form supplied by MHC. 
 
3.4.4 Storage conditions 
The device should be stored according to instruction for use (IFU:n).  
 
3.4.5 Method of Assigning Subjects to Treatment Groups 
The investigation is a prospective randomized, controlled open clinical investigation .All subjects 
who fulfil all inclusion and none of the exclusion criteria and have signed a written inform consent 
form  will be randomized using optimal allocation (minimization) balancing for baseline variables 
age and type of skin (normal/dry/flaky/oily/moist). Eligible subjects will be randomized to receive 
Avance® Film with Safetac® Technology or Avance® Transparent film in a ratio of 1:1 provided by 
the electronic eCRF system (Viedoc). 
 
The investigation center will be numbered 01 and the subject will be consecutively allocated to the 
treatment and given a subject code e.g. 0101,0102 etc. 
 
3.5 Concomitant Treatments 
Medication, which is considered necessary for the subject’s safety and well-being, may be given at 
the discretion of the investigator. All concomitant medication and relevant treatment must be 
recorded in the appropriate section of the Case Report Form (CRF).  
 
3.6 Performance and Safety 
3.6.1 Subject Characteristics 
See Appendix C 
 

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3.6.2 Performance and Safety Measurements and Variables 
Primary outcome variable: 
Primary performance variable will be change in total score of Condition of peri-wound skin, the sum 
of scores (0-3) of redness/irritation, flaky, maceration, blistering and skin tear from baseline to last 
visit. 
Secondary outcome variables: 
Secondary performance variables will be change in the following variables from baseline to last 
visit: 
- 
Redness/irritation 
- 
Flaky 
- 
Maceration 
- 
Blistering 
- 
Skin tear  
 
Patient reported outcome (PRO) 
- 
Pain before application 
- 
Pain before removal of the covering film 
- 
Pain  before removal of the foam filler, 
- 
Pain during removal of the covering film, 
- 
Pain during removal of the foam filler 
- 
Pain direct after removal of the covering film, 
- 
Pain direct after removal of the foam filler 
 
Safety 
- 
Incidence of AE, ADE, DD, SADE and SAE 
- 
Incidence of AE:s, ADE:s, DD:s, SADE and SAE:s leading to withdrawal 
For details see Appendix C 
 
3.6.3 Safety Measurements and Variables 
 
AE/ADE, SAE/SADE and DD. The definition of AE, ADE, SAE, SADE and DD and procedures for 
reporting, SAE and SADE and DD that could have led to a SADE are presented in section 7 of this 
CIP. All AE, ADE, SAE, SADE and DD must also be recorded in the appropriate section of the 
CRF. It is of utmost importance that all staff involved in the investigation is familiar with the content 
of section 7. It is the responsibility of the Principal Investigator to ensure this. 

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Amendment Final Version 
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Document template: F-168 CIP Amendment 
Rev: 04 
 
 
3.6.4 Anticipated ADEs  
The following events have been identified as anticipated effects in the Product Risk Management 
Record: 
• 
Wound dry out 
• 
Maceration 
• 
Infection 
• 
Pain and discomfort 
• 
Skin irritation 
• 
Skin stripping 
• 
Skin tears 
 
The conclusion of the Product Risk Management Record is as following: 
Based on this risk management record it can be concluded that for the investigational devices 
there are no unacceptable risks of harm for subject, the user nor third party involved in this 
investigation when used under normal condition. 
 
 
3.7 Data Quality Assurance 
 
3.7.1 Monitoring, Audits and Inspections 
During the investigation, the monitor will have regular contacts with the investigation site. These 
contacts will include visits to confirm that the facilities remain adequate to specified standards and 
that the investigation site team is carrying out the procedure stated in the clinical investigation plan 
and supports the investigator. All data must be accurately recorded in the CRF. Source data 
verification (a comparison of data in the CRF with the subject’s hospital/practice and other records 
at the investigation site) with direct access to records will also be performed. 
The monitor or other Mölnlycke Health Care (MHC) personnel will be available between visits if the 
investigator or other staff at the site needs information and/or advice. 
Authorised representatives of MHC and/or a Competent Authority (CA) and/or the Ethics 
Committee (EC) may visit the investigation site to perform audits/inspections, including source data 
verification. 
 
3.7.2 Training of Staff 
The Principal Investigator will ensure that appropriate training relevant to the investigation is given 
to the medical, nursing and other staff at the site involved and that new information of relevance to 
the performance of this investigation is forwarded to the staff involved. 
 

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Document template: F-168 CIP Amendment 
Rev: 04 
 
 
3.7.3 Data Management 
The Data Management process includes all activities related to data handling regarding: 
• 
Randomization 
• 
Set-up of eCRF and database 
• 
Specification of on-line checks 
• 
Data entry / Data editing 
• 
Export of data from Viedoc to SAS 
• 
Creation of post-entry checks and listings 
• 
Reconciliation of Serious Adverse Event  (SAE), Serious Adverse Device Effect (SADE), 
Adverse Devise Effect (ADE) and Device Deficiency (DD) 
• 
Clean-file process including execution of post-entry checks and listings 
• 
Post clean-file tasks 
Viedoc, a web based electronic CRF system, will be used to capture data in this investigation. The 
eCRF system complies with FDA Title 21 CRF part 11 (ER/ES) and the Swedish requirement. 
eCRF training will be given to appropriate personnel before/at initiation of the investigation site(s).  
Data entry will be done by investigators and other authorized personnel at the site(s). When 
entering data, on-line checks are incorporated in Viedoc help for consistency and validation of the 
data. 
Pharma Consulting Group will support with a helpdesk function taking care of system user 
questions regarding Viedoc. 
When data has been entered authorized personnel at MHC can immediately view the data, send 
queries if necessary and lock eCRF pages when they have been validated.  
Photos will be uploaded in Viedoc and are marked with the subject code. Uploaded photos shall 
not contain any information that can reveal the identity of the subject. All uploaded photos will be 
reviewed by personnel at MHC and stored in the company database. All data entered in Viedoc will 
be encrypted. The physical database will be stored in Sweden. 
Programs for post-entry checks and data listings will be created and executed for validation of 
data.  
Completeness will be checked by authorized personnel at MHC so that there are no unexplainable 
empty fields in Viedoc. This is done in order to prevent that data have been overlooked by 
personnel entering the data. 
A clean-file meeting will be held prior to database lock. All decisions on the evaluability of the data 
from each individual subject for the statistical analysis must be made and documented before 
locking the database.  
 
 
 
 
 
 

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Title: CIP Amendment 01 
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Rev: 04 
 
 
3.8 Statistical Methods and Determination of Sample Size 
3.8.1 Statistical populations 
 
ITT Population  
The Intention to Treat (ITT) population will include all randomized subjects with at least one post-
randomization performance measurement. The final definition of the ITT population will be made at 
the clean-file meeting. 
 
Per Protocol Population 
The Per Protocol (PP)-Population will include all subjects in the ITT-population without significant 
protocol violations. Subjects identified as protocol violators will be documented and agreed 
between MHC and the principal investigator at the clean-file meeting before the database lock.  
 
Safety Population 
The safety population will include all subjects with at least one treatment with at least one of the 
study films. 
 
 
3.8.2 General statistical methodology 
 The design of the study is a two parallel group design. The main analyses will be  a comparison 
between the two randomized treatments regarding change from baseline to last visit.  
For comparison between the two groups Mann-Whitney U-test will be used for continuous 
variables, Mantel-Haenszel chi-square test for ordered categorical variables, Fisher’s exact test for 
dichotomous variables and chi-square test for non-ordered categorical variables. For comparison 
of changes within groups Wilcoxon Signed Rank test will be used for continuous variables and sign 
test for dichotomous variables and ordered categorical variables. 
Continuous variables will be described with mean, SD, median and minimum and maximum and 
categorical variables will be described with number and percentage. 
All variables will be described per randomized treatment.
All the main performance analyses will be performed on the ITT-population. Complementary 
performance analyses will be performed on the PP-population. 
All safety analyses will be performed on the safety population. 
In the main analysis missing values will be replaced using last observation carried forward (LOCF). 
 
All significance tests will be two-sided and conducted at the 5% significance level.
 
3.8.3 Performance Analyses
 
Primary Performance Analysis
Primary performance analysis will be the analysis of the difference in primary performance 
variable, change in total score, the sum of scores (0-3) of redness/irritation, flaky, maceration, 
blistering and skin tear on the skin from baseline to last visit between the Avance® Film with 

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Title: CIP Amendment 01 
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Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Safetac®Technology and Avance® Transparent film with Mann-Whitney U-test on the ITT-
population at the 5% significance level. 
 
Secondary Performance Analyses 
Secondary performance analyses will be the analyses between the Avance® Film with Safetac® 
Technology and Avance® Transparent film of all the secondary performance variables given above 
in section 3.6.2 according to the statistical methods given above in section 3.8.2 General statistical 
methodology on both the ITT population and PP population. 
 
3.8.4 Safety analyses 
All safety variables given above in section 3.6.2 will be analyzed descriptively by treatment film on 
the safety population. 
 
3.8.5 Baseline analysis 
All variables measured at baseline will be summarized for the ITT population and for the PP 
population using appropriate descriptive statistics by randomized treatment and analyzed by 
treatment group according statistical methods given above in section 3.8.2 General statistical 
methodology 
 
3.8.6 Statistical Analysis Plan (SAP) 
Before the database is locked a statistical analysis plan (SAP) will be written and signed with all 
details in the statistical analyses given, together with a listing of all Tables, Figures and Listings to 
be produced. 
 
3.8.7 Determination of Sample Size 
In order to find a mean difference in change of primary performance variable, total sum score (0-
15) of 1 unit between Avance® Film with Safetac® Technology and Avance® Transparent film with 
Mann-Whitney U-test test with power 80% at 5% significance level 16 evaluable subjects are 
needed in each group. From a pilot study the SD of the change in corresponding score (0-5) was 
0.647. The SD for change in total sum score (0-15) was then estimated to be 1.94. In the sample 
size analysis it is assumed a correlation of 0.70 between the baseline values and last observation. 
In order to compensate for a drop-out rate of 5% we need to randomize 17 to each group.
 
3.9 Changes to the Clinical Investigation Plan 
No change in the investigation procedure will be effected without the mutual agreement of the 
Principal Investigator and MHC. 
An amendment to the Investigation Plan may require notification or approval from EC and, in many 
countries, also the CA before implementation. Local requirements must be followed. 

CIP Amendment 
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Title: CIP Amendment 01 
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Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
MHC will distribute clinical investigation plan amendments to the Principal Investigator who is 
responsible for the distribution of these documents to the EC and staff concerned at his/her site. 
The distribution of these documents to the CA will be handled according to local practice. 
  
4. 67$7(0(1762)&203/,$1&( 
4.1 Ethics 
4.1.1 Ethics review  
The final clinical investigation plan, including the final version of the Patient Information and 
Consent Form, must be approved or given a favorable opinion in writing by an EC before 
enrolment of any subject into the investigation. The Principal Investigator is responsible for 
informing the EC of any amendment to the investigation plan as per local requirements. 
 
4.1.2 Ethical Conduct of the Investigation 
The investigation will be performed in accordance with the ethical principles that have their origin in 
the most recent version of the Declaration of Helsinki, and with applicable regulatory requirements. 
 
4.1.3 Patient Information and Consent Form 
The Principal Investigator will ensure that the subject is given full and adequate oral and written 
information about the nature, purpose, possible risks and benefits of the investigation. Subjects 
must also be notified that they are free to discontinue participation in the investigation at any time. 
The subject should be given the opportunity to ask questions and time for consideration. The 
subject’s signed informed consent has to be obtained before conducting any procedure specifically 
for the investigation. The original must be filed by the Principal Investigator. A copy of the Patient 
Information including the signed Consent Form should be given to the subject. 
 
A sample of the Patient Information and Consent Form is enclosed (Appendix B). If modifications 
are made according to local requirements, the new version must be approved by MHC. 
 
4.2 Regulatory and standards 
4.2.1 Regulatory review 
Not applicable.  
 
4.2.2 Standards and other 
 
The most recent version of ISO 14155 is followed in addition to national regulations.  
 

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4.2.3 Subject Data Protection 
The written Patient Information explains that the data will be stored in a computer database, 
maintaining confidentiality in accordance with national data legislation and that authorized 
representatives of MHC and/or a CA and/or EC/IRB, require direct access to those parts of the 
hospital/practice records relevant to the investigation, including medical history, for verification of 
data. All data computerized by MHC will be identified by subject number only. 
 
4.3 SUBJECT PROTECTION PROCEDURES 
4.3.1 Procedures in Case of Medical Emergency 
The Principal Investigator is responsible for ensuring that procedures and expertise are available to 
cope with medical emergencies during the investigation. 
 
4.3.2 Insurance 
Mölnlycke Health Care AB has product liability insurance, which also covers test products.  
5. ,19(67,*$7,217,0(7$%/($1'7(50,1$7,21 
 
Investigation start: Q2 2016 
Inclusion completed:Q4 2016 
Last subject out:Q42016 
The investigation could be prematurely discontinued if the dropout rate is high and/or the 
investigation site is unable to fulfil the inclusion period according to the Clinical Investigation 
Agreement. 
The Sponsor, Ethics Committee or Regulatory Authority may prematurely terminate or suspend the 
Clinical Investigation as a whole or at an individual investigation site for significant and 
documented reasons. The Principal Investigator may also prematurely terminate or suspend the 
Clinical Investigation at his/her site, for significant and documented reasons. Reasons for 
premature termination or suspension by any party include, but are not limited to safety, inadequate 
recruitment, Principal Investigator issues, and device related problems, alignment with business 
strategy or administrative issues.  
If suspicion of an unacceptable risk to subjects arises during the Clinical Investigation, or when 
instructed by an Ethics Committee or Regulatory Authority, the Sponsor shall suspend the Clinical 
Investigation at all active sites while the risk is assessed. The Sponsor shall terminate the Clinical 
Investigation if an unacceptable risk is confirmed, or resume the Clinical Investigation following 
appropriate communication and approval from the Ethics Committee and Regulatory Authority as 
required.  
In terminating the clinical investigation, the Sponsor and the Principal Investigator will assure that 
adequate consideration is given to the protection of the subject’s interests. 
After the clinical investigation has been successfully completed the participating subject will 
continue to receive standard care according the institute’s routine practice. 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
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Investigation Code Avance 02 
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CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
  
6. /,7(5$785(5(9,(:$1'5()(5(1&(6 
In order to determine the scientific background for this clinical investigation as well as to assess 
risks/benefits of the device, a literature review was conducted. The literature listed below was 
critically evaluated before serving as background information. 
 
1. Sussia, D., Danino, A., & Nikolis, A. (2011). Negative-pressure therapy versus standard wound 
care: a meta-analysis of randomized trials. Plastic and reconstructive surgery, 128 (5) 498 e-
503e doi:10.1097/PRS.2b013e31822b675c 
2. Rafter, L., Use of soft silicon based film dressing in negative pressure wound therapy. Wounds 
UK (2013), Volume 9; Number 4 :107-113 
3. Upton, D., Andrew, A., Pain and trauma in negative wound therapy: a review. International 
Wound Journal 2013, March, doi:10.1111/iwj.12059 
 
 
 
 
 
 
 
 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 28(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
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$1''(9,&('(),&,(1&< 
Definitions: 
 
Device Deficiency (DD) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety 
or performance. 
 
Note:  
• 
Device Deficiencies include malfunctions, use errors, and inadequate labeling. 
 
All Device Deficiencies that could have lead to a Serious Adverse Device Effect shall be 
reported in accordance with Serious Adverse Event reporting procedures, as specified 
below. 
Adverse Event (AE) 
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 
Note:  
• 
This definition includes events related to the investigational medical device or the 
comparator. 
• 
This definition includes events related to the procedures involved. 
• 
For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
 
 
Adverse Device Effect (ADE) 
 
Adverse Event related to the use of an investigational medical device  
 
 
Note:  
• 
This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, or operation, or any malfunction of 
the investigational medical device. 
• 
This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device. 
 
Serious Adverse Event (SAE) 
 
Adverse Event that: 
 
a) led to death, 
b) led to a serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 29(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
3) in-patient or prolonged hospitalization or,  
4)  medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.     
 
c) led to foetal distress, foetal death or a congenital abnormality or birth defect. 
 
 
Note: 
Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
 
 
Serious Adverse Device Effect (SADE) 
 
Adverse Device Effect that has resulted in any of the consequences characteristic of a 
Serious Adverse Event.   
 
 
PROCEDURES FOR SAE AND/OR SADE REPORTING OR REPORTING OF DD 
THAT COULD HAVE LEAD TO A SADE 
The investigator must inform Mölnlycke Health Care (MHC), within 1 day of awareness of the 
event by sending the Serious Adverse Event/Serious Adverse Device Effect form by email to: 
Clinical_Investigations_Event_Reporting@molnlycke.com, of any SAE that occurs in the 
course of the investigation. All SAE have to be reported, whether or not they are considered 
causally related to the investigation product. When a SAE has been entered into the eCRF 
by the investigator /authorised site staff, the eCRF system will automatically generate a 
report to: Clinical_Investigations_Event_Reporting@molnlycke.com and a separate report 
are therefore not required when eCRF is used. 
 
Device Deficiencies that could have lead to SADE if either a) suitable action had not been 
taken, b) if intervention had not been made, or c) if circumstances had been less fortunate 
must be reported as a SADE. 
 
The investigator is responsible for informing the EC and/or the Competent Authority of the 
SAE/SADE as per local requirements. 
 
PROCEDURES FOR DD REPORTING  
All DD needs to be reported to MHC as soon as possible, without unjustified delay. If the DD 
could have lead to a SADE the reporting requirements for SADE described above must be 
followed. DDs can be either subject related or non subject related depending on if the 
investigational device was used by a subject or not. Separate forms are used for subject 
related and non subject related DDs. The completed DD report form must be sent by email to 
Clinical_Investigations_Event_Reporting@molnlycke.com  
 
When a subject related DD has been entered into the eCRF by the investigator /authorised 
site staff, the eCRF system will automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com. 
 
 

CIP Amendment 
Document ID:  PD-508478 Rev: 01 
Title: CIP Amendment 01 
Page 30(30) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-03-07 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Causality Assessment 
The investigator is required to assess the causal relationship to the investigation product for 
each AE/SAE according to the following classifications: 
1. Definite:  
Event with plausible time relationship to device application 
No other explanation - current disease, concomitant drugs and/or other devices 
Response to withdrawal plausible 
Event definitive - localized, specific 
Rechallenge positive 
 
2. Probable:  
Event with reasonable time relationship to device application 
No other explanation current disease, concomitant drugs and/or other devices 
Response to withdrawal clinically reasonable 
No rechallenge 
 
3. Possible:  
Event with reasonable time relationship to device application 
Could also be explained by disease or other drugs and/or devices 
Information on device withdrawal lacking or unclear 
No rechallenge 
 
4. Unlikely: 
Event with duration to onset that makes a relationship improbable (but not 
impossible) 
Diseases other drugs or devices provide plausible explanations 
Symptoms do not resolve on withdrawal 
Nature of event unrelated to action or properties of device 
No rechallenge 
 
5. Unable to determine 
Event occurred but there is insufficient information 
 

CIP Amendment 
Document ID:  PD-514016 Rev: 00 
Title: CIP Amendment 02 
Page 1(2) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-05-31 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
CLINICAL INVESTIGATION PLAN (CIP) Central AMENDMENT no 2 
Substantial 
  
INVESTIGATIONAL DEVICE:  
Avance® Negative Pressure Wound Therapy System 
INVESTIGATION TITLE:  
A randomized open, controlled pilot investigation comparing trauma to the 
periwound skin and Pain during treatment with Avance NPWT system when using 
two different fixation 
 
SITES AFFECTED BY THE AMENDMENT: 
ALL 
 
 
 
 

CIP Amendment 
Document ID:  PD-514016 Rev: 00 
Title: CIP Amendment 02 
Page 2(2) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-05-31 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
THE CLINICAL INVESTIGATION PLAN (CIP) IS TO BE AMENDED AS FOLLOWS: 
 
Section and page in the Clinical Investigation Plan: 
SYNOPSIS, Section : Overall Design, Page:2 
Section 3.1 Overall design and Flow Chart, page 14 
From:  
This pilot study will include 23-30 subjects across 1sites in Sweden to yield a total of 7-23 
evaluable subjects, all subjects who has not previously been treated with NPWT and fulfill all 
inclusion and none of the exclusion criteria and have signed signed a written inform consent will be 
enrolled. 
To: 
This pilot study will include 23-30 subjects across 2 sites in Sweden to yield a total of 7-23 
evaluable subjects, all subjects who has not previously been treated with NPWT and fulfill all 
inclusion and none of the exclusion criteria and have signed signed a written inform consent will be 
enrolled 
Information och samtycke, Section: Bakgrund och syfte, Page 1 
From:  
Totalt kommer 32 patienter med sår som kräver vakuumassisterad sårbehandling att ingå i studien 
som genomförs på en klinik i Sverige och omfattar både män och kvinnor över 18 år. 
To: 
Totalt kommer 32 patienter med sår som kräver vakuumassisterad sårbehandling att ingå i studien 
som genomförs på två kliniker i Sverige och omfattar både män och kvinnor över 18 år. 
 
REASON FOR MAKING THE AMENDMENT: 
Add an additional center. 
 
ACTIONS TO BE TAKEN: 
Investigators at all centres will be provided with the amendment and their signatures will be 
collected. 
This Amendment will be sent to the Ethic committee for approval, according to local procedures.  
 
 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 1(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
CLINICAL INVESTIGATION PLAN (CIP) Central AMENDMENT no 3 
Substantial 
  
INVESTIGATIONAL DEVICE:  
Avance® Negative Pressure Wound Therapy System 
INVESTIGATION TITLE:  
 
A randomized, intra-patient, open, controlled pilot investigation comparing trauma 
to the peri-wound skin after treatment with Avance NPWT system when using two 
different fixations 
 
SITES AFFECTED BY THE AMENDMENT: 
The amendment affect all in the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 2(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
THE CLINICAL INVESTIGATION PLAN (CIP) IS TO BE AMENDED AS FOLLOWS: 
 
Section and page in the Clinical Investigation Plan: 
 
Page 6, Synopsis, Overall Design 
From:  
This investigation is designed as a randomized controlled open clinical investigation. The outcome 
will be used to guide the manufacture to the design and implementation of a larger scale 
randomized study. In order to compensate for a drop-out rate of 5 %, this clinical investigation will 
include 17 subjects per group across two (2) sites in Sweden to yield a total of 32 evaluable 
subjects. 
All subjects who has not previously been treated with NPWT and fulfill all inclusion, none of the 
exclusion criteria and have signed a written inform consent will be enrolled. Subjects will be 
randomized using optimal allocation (minimization) balancing baseline variables age and type of 
skin (normal/dry/flaky/oily/moist). Eligible subjects will be randomized to receive Avance® Film with 
Safetac® Technology or Avance® Transparent film in a ratio of 1:1 provided by the electronic eCRF 
system (Viedoc). 
This investigation is comparing pain at dressing change and trauma and/or other changes to the 
peri-wound skin during treatment with Avance NPWT system when using two different fixation 
films, Avance® Film with Safetac® Technology or  Avance® Transparent film. Since the investigation 
is comparing films with clear visual differences, it is not possible to blind neither the investigator nor 
the subject.  
Dressing change 
Dressing change will be performed at the investigation site and the frequency of dressing change 
will be depending on the condition of the wound and the peri-wound skin. Recommended dressing 
change frequency is every 48-72 hours. 
A record (dressing log) will be completed for every dressing change. 
Investigation Visit frequency and subject participation 
Eligible subjects will be enrolled at the baseline visit (Visit 1), where the first dressing applications 
take place. From Visit 2 and onwards, one dressing application is considered as one study visit, 
e.g. the study visits are flexible and depending on the dressing changing frequency of the 
individual subject. The total treatment time for a subject may vary, depending on the wound type 
and condition. Each subject will be followed in the investigation for a maximum of six (6) dressing 
changes or until treatment with NPWT is no longer indicated. After termination from the 
investigation, subjects will be treated according to standard clinical practice at the investigation 
site. No additional data (except follow up information on ongoing safety events) will be collected 
after termination.  
Subjects will be recruited at the investigation site, which have experience in managing the 
investigation population with NPWT and have access to a suitable number of subjects (based on 
historic data). 
 
 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 3(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
To: 
This investigation is designed as a randomized controlled open clinical investigation. The outcome 
will be used to guide the manufacture to the design and implementation of a larger scale 
randomized study. In order to compensate for a drop-out rate of 5 %, this clinical investigation will 
include 17 subjects per group across two (2) sites in Sweden to yield a total of 32 evaluable 
subjects. 
All subjects who fulfill all inclusion, none of the exclusion criteria and have signed a written inform 
consent will be enrolled. Subjects will be randomized using optimal allocation (minimization) 
balancing baseline variables age and type of skin (normal/dry/flaky/oily/moist). Eligible subjects will 
be randomized to receive Avance® Film with Safetac® Technology or Avance® Transparent film in a 
ratio of 1:1 provided by the electronic eCRF system (Viedoc). 
This investigation is comparing pain at dressing change and trauma and/or other changes to the 
peri-wound skin during treatment with Avance NPWT system when using two different fixation 
films, Avance® Film with Safetac® Technology or  Avance® Transparent film. Since the investigation 
is comparing films with clear visual differences, it is not possible to blind neither the investigator nor 
the subject.  
Dressing change 
Dressing change will be performed at the investigation site and the frequency of dressing change 
will be depending on the condition of the wound and the peri-wound skin. Recommended dressing 
change frequency is every 48-72 hours. 
A record (dressing log) will be completed for every dressing change. 
Investigation Visit frequency and subject participation 
Eligible subjects will be enrolled at the baseline visit (Visit 1), where the first dressing applications 
take place. From Visit 2 and onwards, one dressing application is considered as one study visit, 
e.g. the study visits are flexible and depending on the dressing changing frequency of the 
individual subject. The total treatment time for a subject may vary, depending on the wound type 
and condition. Each subject will be followed in the investigation for a maximum of four (4) dressing 
changes or until treatment with NPWT is no longer indicated. After termination from the 
investigation, subjects will be treated according to standard clinical practice at the investigation 
site. No additional data (except follow up information on ongoing safety events) will be collected 
after termination.  
Subjects will be recruited at the investigation site, which have experience in managing the 
investigation population with NPWT and have access to a suitable number of subjects (based on 
historic data). 
 
 
 
 
 
 
 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 4(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Page 7, Synopsis, Overall Design &  
Page 16, Section:3.2, Procedures and Assessments 
From: 
Following variables should be considered ( Appendix C): 
 
At visit 2-6 
To: 
Following variables should be considered ( Appendix C): 
At visit 2- 4 
 
Page 8, Synopsis, Schedule of Assessment &  
Page 16, Section: 3.2.2, Scheduled of Assessment 
From: 
Day 
Visit 1 Visit 2 
Visit 3 
Visit 4 Visit 5 
 
Visit 6 
Termination 
End of treatment 
Visit (number) 
1 
2 
3 
4 
5 
6 
Termination 
Subject demography 
9 
 
 
 
 
 
 
Inclusion and Exclusion Criteria 
9 
 
 
 
 
 
 
Inform Consent 
9 
 
 
 
 
 
 
Vital Signs 
9 
 
 
 
 
9 
9 
Medical and surgical history 
9 
 
 
 
 
 
 
Skin assessment  
9 
9 
9 
9 
9 
9 
9 
Wound History 
9 
 
 
 
 
 
 
Randomization  
9 
 
 
 
 
 
 
Pain ( VAS) 
9 
9 
9 
9 
9 
9 
9 
Dressing application  
9 
9 
9 
9 
9 
 
 
Dressing removal 
 
9 
9 
9 
9 
9 
9 
Photo  
9 
9 
9 
9 
9 
9 
9 
Medication log 
9 
9 
9 
9 
9 
9 
9 
AE/ADE/DD 
9 
9 
9 
9 
9 
9 
9 
SAE/SADE 
9 
9 
9 
9 
9 
9 
9 
 
 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 5(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
To: 
Day 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Termination 
End of treatment 
Visit (number) 
1 
2 
3 
4 
Termination 
Subject demography 
9 
 
 
 
 
Inclusion and Exclusion Criteria 
9 
 
 
 
 
Inform Consent 
9 
 
 
 
 
Vital Signs 
9 
 
 
 
9 
Medical and surgical history 
9 
 
 
 
 
Skin assessment  
9 
9 
9 
9 
9 
Wound History 
9 
 
 
 
 
Randomization  
9 
 
 
 
 
Pain ( VAS) 
9 
9 
9 
9 
9 
Dressing application  
9 
9 
9 
 
 
Dressing removal 
 
9 
9 
9 
9 
Photo  
9 
9 
9 
9 
9 
Medication log 
9 
9 
9 
9 
9 
AE/ADE/DD 
9 
9 
9 
9 
9 
SAE/SADE 
9 
9 
9 
9 
9 
 
Page 8, Synopsis, Inclusion and Exclusion Criteria &  
Page 17, Section: 3.3.1, 3.3.2, Inclusion and Exclusion criteria.  
 
From:  
Inclusion Criteria
1. Traumatic, surgical or dehisced wounds, Venous Leg Ulcer or Pressure Ulcer indicated for 
treatment with NPWT therapy  
 
2. In case of multiple wounds the target wound must be  10 cm distant from other wounds. 
Selection of the target wound is according to the investigator’s preference  
 
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the wound  
 
4. Male or female, 18 years of age and above  
 
5. Signed Informed Consent 
 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 6(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Exclusion Criteria 
 
1. Dressing sizes does not fit the target wound 
 
2. Unexplored blind tunnels or non-enteric fistula 
 
3. Untreated osteomyelitis 
 
4. Malignant wounds 
 
5. Wounds which needed extra skin protection such as Cavilon, Zink pasta, ointment, or 
other type of skin protections. 
 
6. Subjects treated with systemic immunosuppressive or glucocorticosteroids, except 
subjects taking occasional doses or doses less than 10mg prednisolon/day or 
equivalent.  
 
7. Subjects with decreased sensation, as judged by the investigator 
 
8. Wounds needed, wound contact layer to protect veins and nerves 
 
9. Previous NPWT treatment on the target wound  3 months at inclusion 
 
10. Wounds with necrotic tissue or eschar (if not adequately debrided) 
 
11. Significantly bleeding wounds, as judged by the investigator 
 
12. Subject not suitable for the investigation according to the investigator’s judgment  
 
13. Subject included in other ongoing clinical investigation which could interfere with this 
investigation, as judged by the investigator  
 
14. Known allergy/hypersensitivity to any of the components included into the investigation. 
 
15. Previous treatment on the target wound with acrylic film  1 week at inclusion 
To: 
Inclusion Criteria
1. Traumatic, surgical or dehisced wounds, Venous Leg Ulcer, Diabetic Foot Ulcer or Pressure 
Ulcer indicated for treatment with NPWT therapy  
 
2. In case of multiple wounds the target wound must be  10 cm distant from other wounds. 
Selection of the target wound is according to the investigator’s preference  
 
3. Peri-wound skin assessable and 5 cm of peri-wound skin present around the wound  
 
4. Male or female, 18 years of age and above  
 
5. Signed Informed Consent 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 7(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Exclusion Criteria 
 
1. Dressing sizes does not fit the target wound 
 
2. Unexplored blind tunnels or non-enteric fistula 
 
3. Untreated osteomyelitis 
 
4. Malignant wounds 
 
5. Subjects treated with systemic immunosuppressive or glucocorticosteroids, except 
subjects taking occasional doses or doses less than 10mg prednisolon/day or 
equivalent.  
 
6. Wounds with necrotic tissue or eschar (if not adequately debrided) 
 
7. Significantly bleeding wounds, as judged by the investigator 
 
8. Subject not suitable for the investigation according to the investigator’s judgment  
 
9. Subject included in other ongoing clinical investigation which could interfere with this 
investigation, as judged by the investigator  
 
10. Known allergy/hypersensitivity to any of the components included into the investigation. 
 
 
 
Page 14, Section 2.2 Mölnlycke Investigation Personnel 
From: 
Tina Kjellén, Clinical Study Manager 
Lennart Wäne, Clinical Data Manager 
 
To: 
Tina Kjellén, Clinical Study Manager 
Henrik Ahlbom, Clinical Data Manager 
Sven Anders Benjegård, Clinical Operation Manager 
 
 
 
 
 
 

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 8(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Page 15, Section 3.1 Overall Design and Flow Chart Synopsis 
From:  
This investigation is designed as a prospective, randomized controlled open clinical investigation. 
The outcome will be used to guide the manufacture to the design and implementation of a larger 
scale randomized study. In order to compensate for a drop-out rate of 5 %, this clinical 
investigation will include 17 subjects per group across two (2) sites in Sweden to yield a total of 32 
evaluable subjects.  
All subjects who has not previously been treated with NPWT and fulfill all inclusion and none of the 
exclusion criteria and have signed a written inform consent will be enrolled. Subjects will be 
randomized using optimal allocation (minimization) balancing for baseline variables age and type 
of skin (normal/dry/flaky/oily/moist). Eligible subjects will be randomized to receive Avance® Film 
with Safetac® Technology or Avance® Transparent film in a ratio of 1:1 provided by the electronic 
eCRF system (Viedoc). 
An evaluable subject is defined as a subject that is enrolled and has data for at least one visit after 
baseline visit.  
The target populations are male or female, 18 years and above, which have exuding wounds 
indicated for treatment with NPWT therapy. The subject should not previously been treated with 
NPWT, previous treatment, may have an bias on the skin evaluation. 
The study visits are flexible and depending on the dressing changing frequency of the individual 
subject. The total treatment time for each subject may vary depending on the wound type and 
condition of the wound. Each subject will be followed for a maximum of six (6) dressing changes or 
until treatment with NPWT is no longer indicated (withdrawal criterion). After termination from the 
investigation, subjects will, if necessary, be treated according to standard clinical practice at the 
investigation site. No additional data (except for follow up information on ongoing safety events) 
will be collected after termination.  
To: 
This investigation is designed as a prospective, randomized controlled open clinical investigation. 
The outcome will be used to guide the manufacture to the design and implementation of a larger 
scale randomized study. In order to compensate for a drop-out rate of 5 %, this clinical 
investigation will include 17 subjects per group across two (2) sites in Sweden to yield a total of 32 
evaluable subjects.  
All subjects who has fulfill all inclusion and none of the exclusion criteria and have signed a written 
inform consent will be enrolled. Subjects will be randomized using optimal allocation (minimization) 
balancing for baseline variables age and type of skin (normal/dry/flaky/oily/moist). Eligible subjects 
will be randomized to receive Avance® Film with Safetac® Technology or Avance® Transparent film 
in a ratio of 1:1 provided by the electronic eCRF system (Viedoc). 
An evaluable subject is defined as a subject that is enrolled and has data for at least one visit after 
baseline visit.  
The target populations are male or female, 18 years and above, which have exuding wounds 
indicated for treatment with NPWT therapy.  
The study visits are flexible and depending on the dressing changing frequency of the individual 
subject. The total treatment time for each subject may vary depending on the wound type and 
condition of the wound. Each subject will be followed for a maximum of four (4) dressing changes 
or until treatment with NPWT is no longer indicated (withdrawal criterion). After termination from 
the investigation, subjects will, if necessary, be treated according to standard clinical practice at the 
investigation site. No additional data (except for follow up information on ongoing safety events) 
will be collected after termination.  

CIP Amendment 
Document ID:  PD-522687 Rev: 00 
Title: CIP Amendment 03 
Page 9(9) 
Investigation Code Avance 02 
Final Version 
CIP Approval date 2015-09-11 
Amendment Final Version 
Amendment Approval date 2016-12-16 
 
Document template: F-168 CIP Amendment 
Rev: 04 
 
 
Page 26, Section 5, Investigation Timetable and Termination 
From: 
Investigation start: Q2 2016 
Inclusion completed: Q4 2016 
Last subject out:       Q4 2016 
 
To: 
Investigation start: Q3 2016 
Inclusion completed: Q3 2017 
Last subject out:       Q3 2017 
 
 
 
 
REASON FOR MAKING THE AMENDMENT: 
The reason to add one inclusion criteria, and removing five exclusion criteria’s are to be more align 
with the majority of the patients group, who are visiting the two participated sites. Participated sites 
are located in the northern region of Sweden with a large, patient uptake area. The majority of the 
patients are elderly and have long way to travel to the hospital by decreasing the number of visits 
from 6 to 4, will this lead to a decreased traveling for the potential study patients. This will hopefully 
do it easier for the clinics to include patients to the study. We have considered that the update will 
not lead to any bias. 
 
ACTIONS TO BE TAKEN: 
Investigator at the sites will be provided with the amendment and signatures will be collected. 
The Amendment will be sent to the Ethic committee for approval according to local procedures.