A Randomised Multi-centre Non-inferiority Investigation to Evaluate the Efficacy and Safety of Exufiber Versus Aquacel Extra in Moderately or Strongly Exuding Venous and Mixed Ulcers of Predominantly Venous Origin
Phase: NA
Conditions: Venous Leg Ulcer
Sponsor: Molnlycke Health Care AB

 
NCT02921750 Clinical investigation plan 
 
Title  
A randomised multi-centre non-inferiority investigation to evaluate the efficacy and safety of 
Exufiber versus Aquacel Extra in moderately or strongly exuding venous and mixed ulcers of 
predominantly venous origin  
 
Study code  
CHEXU03  

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 1(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 
 
CLINICAL INVESTIGATION PLAN (CIP) 
INVESTIGATIONAL DEVICE: 
Exufiber 
INVESTIGATION TITLE:  
A randomised multi-centre non-inferiority investigation to evaluate the efficacy 
and safety of Exufiber versus Aquacel Extra in moderately or strongly exuding 
venous and mixed ulcers of predominantly venous origin 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CO-ORDINATING INVESTIGATOR: 
Bo Joergensen 
 
MÖLNLYCKE CLINICAL STUDY  
MANAGER: 
 
Ann-Sofie Svensson 
Mölnlycke Health Care 
P.O Box 130 80 
402 52 Gothenburg, Sweden 
Phone: +46 31 352 37 11 
 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 2(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 
 
CLINICAL INVESTIGATION PLAN (CIP) SYNOPSIS 
 
INVESTIGATION TITLE:  
A randomised multi-centre non-inferiority investigation to evaluate the efficacy 
and safety of Exufiber versus Aquacel Extra in moderately or strongly exuding 
venous and mixed ulcers of predominantly venous origin 
 
Objectives 
The primary objective of this non-inferiority investigation is to compare Exufiber® versus 
Aquacel® Extra™ in terms of efficacy and safety, measured in moderately or strongly exuding 
venous and mixed ulcers of predominantly venous origin during a period of 6 weeks 
investigation period. 
The primary endpoint will be; 
Wound area reduction (%) from baseline until end of investigation (up to 6 weeks). Wound area 
reduction will be centrally measured by one blinded independent review using the validated 
system PictZar®. A second supportive blind review will be done by an independent French 
expert 
Secondary endpoints are to evaluate;  
- 
Relative reduction (%) of fibrin/sloughy tissue 
- 
Wound area reduction (absolute change in cm2) from baseline until end of investigation 
(up to 6 weeks) 
- 
Linear advance of the wound margin according to Gilman’s formula (Cardinal et al, 
2008) based on the digital photos and calculated by PictZar 
- 
Percentage of patients with a debrided wound at end of investigation (at 
least 70% of the wound surface area covered with granulation tissue 
(confirmed using PictZar). Number of additional debridements used during 
the investigation. Pain during the debridement and ease of debridement 
- 
Changes from baseline in the condition of the peri-wound skin measured by 
the following variables; maceration, redness/irritation, blistering, skin 
stripping, trauma to wound edges  
- 
The level of pain in connection to removal of dressing 
- 
Changes in wound status including exudates management 
- 
Clinician’s and subject’s opinion related to the dressing (subject to fill in the 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 3(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
questionnaire him/herself in applicable local language) 
- 
Cost effectiveness and health economics will be measured using EQ-5D-3L and 
wound management related material use 
- 
Tolerance such as adverse events and adverse device effects including those 
reported to be serious 
Ancillary objective 
- 
In order to support that wound area reduction at week 6 is a clinically relevant 
parameter to predict long-term favorable wound healing, a sub-group of at least 
50 subjects will be assessed at 24 weeks post-inclusion. Favorable trajectory will 
be defined by an area regression, compared to baseline, of 80% or more at 
week 24. Additionally, wound closure (100% re-epithelialization confirmed by 
photo) rate will also be evaluated. All these parameters will be centrally 
measured on photos according to previously described procedure. 
Overall Design   
The investigation is designed as an open, randomized, non-inferiority, multi-centre investigation. 
212 subjects will be randomised (subjects lost to follow-up will be replaced). Subjects to be 
included will suffer from an exuding venous or mixed ulcer of predominantly venous origin. Both 
in and out-subjects will be eligible. Each subject will be treated according to the local clinical 
routine and evaluated during a total treatment period of maximum 6 weeks or until the wound is 
healed. At least 50 subjects out of the total 212 subjects will be followed for maximum 24 weeks 
to investigate wound closure. Subjects will either be randomized to Exufiber® or Aquacel® Extra 
using centralized randomization. The secondary dressing will be according to the normal praxis 
at each clinic and preferably one secondary dressing should be chosen by investigational site to 
be used for all subjects at the same site although no active dressings such as anti-microbial 
dressings are allowed. Simple gauzes or polyurethane films are recommended (see schedule of 
assessment for details). Patients should be treated with a recognized efficient compression 
system (e.g. multicomponents such as 2-, 3- or 4-LB (two-, three- or four-layer bandage) or SSB 
(short stretch bandage)). The nature of applied bandages will be captured in the eCRF. 
Visits are planned for baseline followed by 1, 2, 3, 4 and 6 weeks post treatment. The 
sub-group of at least 50 subjects will also be followed at week 8, 12, 16, 20, and 24 post 
treatment or until wound is healed if earlier. Dressing changes in-between visits are 
allowed and should be carried out according to normal praxis/intended use eg when the 
dressing is saturated. These can be performed at the subject’s home according to normal 
routine. At each dressing change, the wound is to be inspected and cleaned 
exclusively with normal saline or warm water (or Actimaris Rinsing Solution). When the 
wound is dry, Exufiber® is no longer applicable. The treatment should then continue 
with the secondary dressing or other suitable dressing according to local guidelines 
and compression followed until end of investigation (6 weeks or earlier if the wound 
heals). Aquacel® Extra is also intended for dry wounds but should be used in the same 
way as Exufiber® for consistency. 
A record (dressing log) for Exufiber® or Aquacel® Extra will be filled in to capture all 
dressing changes at the scheduled visits including secondary dressing and compression 
applied. The number of dressing changes in-between scheduled visits will be asked for at 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 4(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
each visit as well as number of dispensed and returned dressings. A nurse book can be 
used to collect the data related to the dressing change (number of dressings, reason for 
dressing change) between scheduled visits. 
Subjects will be screened on a daily basis and if they seem evaluable they will be given a 
patient information. 
At the baseline visit the following will be registered for all enrolled subjects;  
- 
Subjects characteristics including vital signs, informed and photograph consent, 
medical and surgical history, ulcer duration, size, location and ABPI (ankle 
brachial pressure index using hospital routine and most recent value obtained), 
current dressing and compression type and duration (if applicable) 
- 
Cleansing/debridement according to details in schedule of assessment 4.2.1 
- 
Level of pain before dressing assessment measured by validated Visual 
Analogue Scale (VAS) 0-100mm  
- 
Wound status using colorimetric scale = Percentage of fibrin/sloughy tissue, 
granulation tissue, epithelialization etc. Total should be 100%. Evaluated before 
and after cleansing/debridement. 
- 
Photos will be taken according to guidelines in Appendix D and details in 
Appendix C. Photos from before and after debridement will be analysed using 
PictZar by a blinded reviewer 
- 
Signs of local infection such as pain between dressing changes, perilesional skin 
erythema, oedema, foul odour and high levels of exudates 
- 
Dressing application including secondary dressing and compression according to details 
in schedule of assessment and in Appendix C 
- 
Clinician’s evaluation according to details in Appendix C 
At each follow-up visit until week 6 the following should be registered;  
- 
Cleansing/debridement according to details in schedule of assessment 4.2.1 
- 
Wound status using colorimetric scale = Percentage of fibrin/sloughy tissue, 
granulation tissue, epithelialization etc. Total should be 100%. Evaluated before 
and after cleansing/debridement. 
- 
Dressing application including secondary dressing and compression according to details 
in schedule of assessment and in appendix C 
- 
Photos will be taken according to guidelines in Appendix D and details in 
Appendix C. At week 4 and 6 or final visit the photos before and after 
debridement will be analysed using PictZar by a blinded reviewer. Other photos 
taken after debridement can be analysed using PictZar if deemed necessary for 
primary endpoint 
- 
Level of pain during dressing removal measured by validated Visual Analogue 
Scale (VAS) 0-100mm and analgetics used within 3 hours 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 5(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
- 
Signs of local infection such as pain between dressing changes, perilesional skin 
erythema, oedema, foul odour and high levels of exudates 
- 
Technical performance according to details in Appendix C 
- 
Subject evaluation according to details in Appendix C 
- 
Clinician’s evaluation according to details in Appendix C 
- 
All relevant concomitant medications during the investigation period will also be 
collected including antibiotics and analgesics. Adverse events will be collected 
according to details in section 8. 
- 
Debridement is allowed during the treatment period but should be specified as well as 
ease of debridement and pain during the debridement (VAS). 
Variables to be collected at week 8-24 for the sub-group of at least 50 subjects are specified in 
schedule of assessment 4.2.1 and in appendix C. 
 
Health related quality of life (HRQoL); 
Patient reported HRQoL will be measured by using the standardized generic EQ-5D-3L 
instrument (EuroQol, 1990). 
The EQ-5D-3L consists of two parts: a descriptive system and a visual analogue scale (VAS). 
The descriptive system records HRQoL in five dimensions (mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression), each of which dimensions has three levels of possible 
responses indicating (1) no problems, (2) some problems or (3) extreme problems. The 
responses of the patient results in a 5-digit code (e.g. 21223) defining his/her health state. 
These health states can be converted to a single index value representing how a particular 
health state is valued by the general population. 
Using the second part of the instrument, the VAS, patients rate their health state on a 0-100 
vertical scale. 
Subjects will be provided with the paper version of the EQ-5D-3L three times during the 
investigation: (1) at baseline (2) at four weeks and (3) at six weeks (final visit). 
Subjects followed for up to 24 weeks will however be provided with the EQ-5D-3L a fourth time 
i.e. at week 24 (final visit). 
All outputs of the EQ-5D-3L instrument, the descriptive health states, the single index value and 
the VAS scores will be analysed. 
 
Inclusion Criteria 
1. Provision of informed consent i.e. subject must be able to understand and sign the 
Patient Information and Consent Form 
2. Both gender ≥18 years old 
3. Ulcer moderately or strongly exudative justifying the use of an absorbent dressing 
6. 0.7 ≤ ABPI < 1.3 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 6(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
7. Ulcer duration 6 weeks to 60 months 
8. Ulcer size 3 cm2 -100 cm2  
9. Target ulcer at least 3 cm away from any other lesion 
 
The subject can have multiple wounds but only the largest eligible wound per subject is to be 
included in the investigation. The remaining ulcers should be treated according to normal 
praxis. 
 
Exclusion Criteria 
 
1. Known allergy/hypersensitivity to the dressings 
2. Pregnant or breastfeeding 
3. Circumferential wounds (the entire wound should be able to be captured on a single 
image/photo)  
4. Subjects who will have problems following the protocol 
5. Subjects included in other ongoing clinical investigation evaluating wound dressings at 
present or during the past 30 days 
6. Patient with a systemic infection not controlled by suitable antibiotic treatment 
7. Clinically infected wound according to the judgement of the investigator (heat, pain, 
swelling, redness or purulent secretion) 
8. Wound covered with black necrosis  
9. Dry wounds 
10. Malignant wound degeneration 
11. Current treatment with radiotherapy, chemotherapy, immunosuppressant drugs or high 
doses of oral corticosteroids if any  
12. Subject with deep vein thrombosis within 3 months prior to inclusion 
 
Investigational Device - Exufiber® 
Gelling Fibre Dressing 
Product Description 
Exufiber® is a sterile nonwoven dressing made from highly absorbent polyvinyl alcohol fibres. In 
contact with wound exudate, Exufiber® transforms into a gel that facilitates moist wound healing 
and ease of removal during dressing change. Exufiber® absorbs and retains wound exudate. 
Exufiber® is available both as sheet and ribbon dressings. 
 
Intended use  
Exufiber® wound dressing is intended to be used on a wide range of exuding wounds:  
• 
Leg and foot ulcers 
• 
Pressure ulcers 
• 
Partial thickness burns 
• 
Surgical wounds 
• 
Donor sites 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 7(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
• 
Malignant wounds 
 
Precautions 
• 
All wounds should be inspected frequently. In case of signs of clinical infection, consult a 
health care professional for adequate infection treatment. 
• 
Exufiber® is not intended for dry wounds, full thickness burns. 
• 
If the dressing dries out and is difficult to remove, it should be moistened according to 
local policies (e.g. with sterile saline or sterile water) and allowed to soak until it lifts 
easily. It may take several minutes for Exufiber® to transform into a gel. Remove the 
dressing by gently cleansing/flushing. 
 
Other Information 
• 
Exufiber® is for single-use only and should not be re-used. Re-use may lead to product 
deterioration or cross contamination may occur. 
• 
Sterility is guaranteed unless pouch is opened or damaged prior to use. Do not re-
sterilise. 
• 
Exufiber® can be left in place for up to 7 days depending on wound condition or as 
indicated by clinical practice. 
 
See also Appendix E, Instructions For Use. 
 
Comparator - Aquacel® Extra™ 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre is a soft, sterile, non- woven 
pad dressing composed of sodium carboxymethylcellulose and regenerated cellulose fibre for 
strengthening. This conformable and highly absorbent dressing absorbs wound fluid and 
transforms into a soft gel, which maintains a moist environment to support the body’s healing 
process and aid in the removal of nonviable tissue from the wound (autolytic debridement), 
without damaging newly formed tissue. 
 
Intended use 
Under medical supervision Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre 
may be used for the management of: 
• 
leg ulcers, pressure ulcers (Stage II-IV) and diabetic ulcers. 
• 
surgical wounds (e.g., post-operative, wounds left to heal by secondary intent and donor 
sites). 
• 
partial thickness burns 
• 
traumatic wounds (e.g. abrasions and lacerations). 
• 
exudates absorption in oncology wounds (eg., fungating cutaneous tumours, cutaneous 
metastases and Kaposi’s sarcomas). 
 
Contraindications 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 8(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre should not be used on 
individuals who are sensitive to or who have had an allergic reaction to the dressing or its 
components. 
 
Precautions and observations 
 
• 
Caution: Sterility is guaranteed unless pouch is damaged or opened prior to use. 
• 
This device is for single-use only and should not be re-used. Re-use may lead to increased 
risk for infection or cross contamination. Physical properties of the device may no longer be 
optimal for intended use. 
• 
Appropriate supportive measures should be taken where indicated (e.g. use of graduated 
compression in the management of venous leg ulcers or pressure relief measures in the 
management of pressure ulcers/sores). 
• 
The control of blood glucose, as well as appropriate supportive measures, should be 
provided with diabetic foot ulcers. 
• 
Infection is not a contraindication to the use of Aquacel® Extra™ Hydrofiber® Dressing with 
Strengthening Fibre. Should infection develop during the use of the dressing antibiotic 
therapy should be initiated, as clinically indicated, by a health care professional. 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre can facilitate the control of 
minor bleeding. 
• 
If removing the dressing is difficult, the dressing should be fully saturated with sterile saline 
or water and removed slowly. 
• 
Because Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre provides a moist 
environment that supports the growth of new blood vessels, occasionally the delicate newly 
formed blood vessels may produce a blood stained wound fluid. 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre is not intended for use as a 
surgical sponge. 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre is not intended for use 
within internal body cavities or within closed wounds. 
 
Other Information 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre can be left in place for 
up to 7 days, where clinically indicated. 
• 
Discard any unused portion of the dressing. 
• 
If the immediate product packaging is damaged, do not use. 
 
See also Appendix F, Instructions For Use. 
 
 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 9(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
TABLE OF CONTENTS 
1. INTRODUCTION .................................................................................................... 12 
2. OBJECTIVES ......................................................................................................... 15 
3. CLINICAL INVESTIGATOR(S) AND INVESTIGATION ADMINISTRATIVE 
STRUCTURE ................................................................................................................ 16 
3.1 
PI at Investigation site(s)......................................................................................................................... 16 
3.2 
Mölnlycke Investigation Personnel ...................................................................................................... 16 
3.3 
Other Participants ..................................................................................................................................... 16 
4. INVESTIGATION PLAN AND PROCEDURES ...................................................... 18 
4.1 
Overall Design and Flow Chart .............................................................................................................. 18 
4.2 
Procedures and Assessments ............................................................................................................... 21 
4.2.1 
Schedule of Assessment ....................................................................................................................... 21 
4.3 
Selection of Population for Investigation ........................................................................................... 22 
4.3.1 
Inclusion Criteria ..................................................................................................................................... 22 
4.3.2 
Exclusion Criteria .................................................................................................................................... 23 
4.3.3 
Withdrawal of Subjects from Treatment or Assessment ................................................................... 23 
4.4 
Investigational Device .............................................................................................................................. 24 
4.4.1 
Summary description of the Investigational Device(s) and Comparator(s) .................................... 24 
4.4.2 
Labelling ................................................................................................................................................... 26 
4.4.3 
Accountability .......................................................................................................................................... 26 
4.4.4 
Storage conditions .................................................................................................................................. 27 
4.4.5 
Method of Assigning Subjects to Treatment Groups ......................................................................... 27 
4.5 
Concomitant Treatments......................................................................................................................... 27 
4.6 
Efficacy and Safety ................................................................................................................................... 27 
4.6.1 
Subject Characteristics .......................................................................................................................... 27 
4.6.2 
Medical condition .................................................................................................................................... 28 
4.6.3 
Surgical history ........................................................................................................................................ 28 
4.6.4 
Efficacy Measurements and Variables ................................................................................................ 28 
4.6.5 
Safety Measurements and Variables ................................................................................................... 30 
4.6.6 
Anticipated ADEs .................................................................................................................................... 31 
4.7 
Data Quality Assurance ........................................................................................................................... 31 
4.7.1 
Monitoring, Audits and Inspections ...................................................................................................... 31 
4.7.2 
Training of Staff ....................................................................................................................................... 32 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 10(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
4.7.3 
Data Management .................................................................................................................................. 32 
4.8 
Statistical Methods and Determination of Sample Size .................................................................. 33 
4.8.1 
Statistical Evaluation .............................................................................................................................. 33 
4.8.2 
Determination of Sample Size .............................................................................................................. 34 
4.9 
Changes to the Clinical Investigation Plan ........................................................................................ 34 
5. STATEMENTS OF COMPLIANCE ......................................................................... 35 
5.1 
Ethics ........................................................................................................................................................... 35 
5.1.1 
Ethics review............................................................................................................................................ 35 
5.1.2 
Ethical Conduct of the Investigation ..................................................................................................... 35 
5.1.3 
Patient Information and Consent Form ................................................................................................ 35 
5.2 
Regulatory and standards ...................................................................................................................... 35 
5.2.1 
Regulatory review ................................................................................................................................... 36 
5.2.2 
Standards and other ............................................................................................................................... 36 
5.2.3 
Subject Data Protection ......................................................................................................................... 36 
5.3 
SUBJECT PROTECTION PROCEDURES............................................................................................. 36 
5.3.1 
Procedures in Case of Medical Emergency ........................................................................................ 36 
5.3.2 
Insurance ................................................................................................................................................. 36 
5.4 Publication of results ..................................................................................................................................... 36 
6. INVESTIGATION TIMETABLE AND TERMINATION ............................................ 36 
7. LITERATURE REVIEW AND REFERENCES ........................................................ 38 
8. DEFINITIONS AND PROCEDURES FOR REPORTING OF ADVERSE EVENT, 
ADVERSE DEVICE EFFECT, SERIOUS ADVERSE EVENT, SERIOUS ADVERSE 
DEVICE EFFECT AND DEVICE DEFICIENCY ............................................................. 40 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 11(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
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  Guide for Digital Photography 
Appendix E Instructions For Use, Exufiber® 
Appendix F Instructions For Use, Aquacel® Extra™ 
 
LIST OF ABBREVIATIONS  
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CA 
Competent Authority 
CRF 
Case Report Form 
DD 
Device Deficiency 
EC 
Ethics Committee 
HAS 
French Health Authority 
IRB 
Institutional Review Board 
MHC 
Mölnlycke Health Care 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
VAS  
Visual Analogue Scale 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 12(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
1. INTRODUCTION 
It is often misunderstood that wound exudate is ‘bad’ (WUWHS, 2007). In fact, wound exudate 
has a number of beneficial properties for the healing wound. These include the maintenance of 
a moist wound bed, preventing the wound from drying out, aiding the migration of skin cells, 
providing essential nutrients to the wound for cell metabolism, as well as encouraging autolysis 
(WUWHS, 2007). However, when the volume of exudate becomes excessive and when the 
composition of the exudate changes (e.g. when the exudate becomes thick), steps must be 
taken to manage the exudate to prevent wound deterioration, peri-wound skin damage and 
wound infection. Poor management of exudate in chronic wounds can lead to a number of 
problems, including wound and peri-wound breakdown of maceration due to leakage and a 
delay in healing. Excess levels of exudate within the wound bed can also lead to elevated 
proteolytic activity due to an imbalance in the levels of certain matrix metalloproteinases, 
resulting in tissue destruction and a delay in healing (WUWHS, 2007; EWMA, 2004; Romanelli, 
Vowden & Weir, 2010). 
Changes in the type and volume of exudate can be indicators of a number of underlying factors, 
such as infection, and should alert the clinician that the wound is not following the normal 
phases of healing. Wounds which produce this type of exudate or slough not only impact on the 
clinical outcome of the wound (i.e. prevention or delay in wound healing) and health care 
resources, but can also have a huge impact on physical and psychosocial morbidity and patient 
quality of life (WUWHS; 2007). Other patient-related problems concerning the management of 
wound exudate include leakage and malodour (Vowden, Bond & Stryja, 2015). Production of 
high levels of thick exudate in venous leg ulcer patients may indicate inflammation and infection, 
longer periods spent with the legs in a dependent position reduced compliance to compression 
therapy or the development or deterioration of congestive cardiac failure and peripheral oedema 
(WUWHS, 2007). Robson et al (2006) presented evidence to verify wound management 
guidelines, including the selection of dressings that will manage wound exudate and protect the 
peri-wound skin around venous leg ulcers. This is based on the principle that peri-wound 
maceration and continuous contact with wound exudate can enlarge the wound and impede 
healing (ROBSON et al, 2006). Whilst the primary dressing is not usually considered the most 
important factor in the healing of leg ulcers, it does have a significant bearing on the cost of 
wound management, particularly in those ulcers which are heavily exuding (Harding, Price, 
Robinson et al, 2001). Problems associated with poor exudate management in patients with 
venous leg ulcers can result in a multitude of physical, psychological and psychosocial issues 
(Maddox, 2012). 
Whilst the initial cost of the dressing is one consideration in terms of the impact on health care 
costs, it is certainly not the only factor. It is difficult to evaluate the true costs of wound 
management since the process involves more than just material costs. They so-called ‘hidden 
costs’ of wound care must be appreciated (Vowden, Bond & Stryja, 2015; Tickle, 2012). These 
include increased demands on the clinicians’ time and resources as a result of poor 
management (Tickle, 2012; Department of Health, 2009). This is a particular concern when 
treating wounds with high levels of thick or sloughy exudate which, if not managed effectively, 
can result in iatrogenic complications including peri-wound skin maceration and pain during the 
process of dressing changes. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 13(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Dressing selection is a fundamental aspect of effective wound management, particularly in 
those wounds with high levels of viscous exudate or slough. A dressing that is able to adapt to a 
changing wound environment is important, particularly in chronic wounds which do not follow 
the usual steps of healing. The chosen dressing, therefore, needs to not only generate and 
maintain an optimal wound environment conducive to healing but also to respond and adapt to 
the changing demands of the wound (Walker & Parson, 2010). Matching the characteristics of 
the dressing to the exudate profile of the wound is important in the maintenance of a moist 
wound environment (Bishop et al, 2003). The absorption capacity, ability to retain exudate, loss 
of fluid by evaporation and how the dressing can modify the rate of exudate production are 
important considerations when choosing the optimal dressing. Again, it is about creating an 
optimal moisture balance (EWMA, 2004; Romanelli, Vowden & Weir, 2010; Wounds UK Best 
Practice Statement, 2013). Insufficient absorption will result in leakage and maceration (thus 
requiring more frequent dressing changes), whilst excessive absorption will effect patient 
comfort and will dry the wound out (Walker & Parsons, 2010). 
Debridement is a vital stage of the healing process and can be defined as the removal of all 
material that forms a barrier to wound healing, including necrotic and devitalised tissue, slough 
or any other type of bioburden from a wound (Meaume et al, 2014). Autolytic debridement is 
one type of non-surgical debridement that allows the removal of unwanted slough from the 
wound via the release of the body’s endogenous proteolytic enzymes (Meaume et al, 2014). 
This method is often chosen as a first line treatment, providing a moist environment whilst 
sparing healthy tissue (Meaume et al, 2014). Hydrofiber dressings have been shown to aid this 
type of debridement (Meaume et al, 2014). 
Hydrofiber wound dressings are recommended for their ability to maintain a moist wound 
healing environment by absorbing wound fluid to form a cohesive gel. The gelling action of this 
type of dressing also helps to debride the wound of sloughy tissue by autolysis (Tickle, 2012; 
Barnea et al, 2004, Kogan et al, 2004) which, if unmanaged, can delay the healing process. 
Hydrofibers also act by protecting the delicate peri-wound skin from maceration and pain 
associated with dressing changes (Tickle, 2012). These dressings are recognized for their 
ability to manage exudate throughout the healing process, adapting to the changing 
environment of the wound. Hydrofibre dressing is a sterile dressing nonwovens 
carboxymethylcellulose fiber with a high absorbency. In the French list of products and benefits, 
the support is provided for managing exuding wounds associated with a secondary dressing to 
keep the wound moist. The recommandations from the consensus conference “Prévention et 
traitement des escarres de l’adulte et du sujet âgé” organised by French Health Authority (HAS) 
suggest a dressing type depending on the condition of the wound. So, for exuding wound, they 
recommend to use hydrofibre dressing, alginate or hydrocellular dressing. 
A wealth of evidence is available to support the use of Aquacel® in wounds with elevated levels 
of exudate in terms of aiding wound progression towards healing (Brunner & Euberlein, 2000; 
Barnea et al, 2004; Ravenscroft, 2006). Tickle et al (2012), demonstrated the clinical 
effectiveness of Aquacel® Extra (a hydrofiber dressing designed to provide additional properties 
relating to extra dressing strength and absorbency) in the management of wet, sloughy wounds. 
This case study series concluded that Aquacel® Extra can effectively manage moderate to high 
levels of exudate, resulting in reduced dressing changes and reduced nursing time/resources, a 
reduction in cost and improved patient comfort and a reduction in patient distress.  Therefore, 
this dressing was chosen as a comparative dressing in the present non-inferiority study, given 
that it is one of the most frequently used dressings for wet or sloughy chronic wounds. It is well 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 14(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
documented that venous leg ulcers (VLUs) are difficult to manage, not least due to patient 
intolerance of certain therapies due to associated pain (Reyzelman & Vartivarian, 2015). VLUs 
are often associated with pain and increased exudate production, which can lead to a reduction 
in patient quality of life (Do, Edwards & Finlayson, 2015). As such, VLUs were chosen as a 
model wound type for the present study. 
Exufiber® is a highly absorbent primary dressing indicated for the management of moderately-
to-highly exuding wounds. The dressing absorbs and retains wound exudate, blood and 
bacteria by forming a gel. In a recent publication by Chadwick and McArdle (2015), the 
effectiveness of Exufiber® was demonstrated in diabetic foot ulcers. Ease of use, patient 
satisfaction and exudate management were all rated highly. The potential of Exufiber® to 
provide an effective alternative dressing in the management of exuding wounds will be 
investigated throughout the entire healing process as well as its ability to adapt to a changing 
wound environment.  
The primary objective of the current non-inferiority investigation is to compare Exufiber® versus 
Aquacel Extra in terms of efficacy, measured in exuding venous and mixed ulcers of 
predominantly venous origin during a period of 6 weeks. The primary endpoint will be wound 
area reduction (%) from baseline until the end of investigation (up to 6 weeks). Secondary 
endpoints will relate to reduction of sloughy tissue, autolytic debridement capability, pain at 
debridement and during dressing removal, condition of the peri-wound skin, dressing tolerance, 
health status, cost-effectiveness and wound closure from baseline up to maximum 24 weeks for 
a sub-group of at least 50 subjects. The assumptions of the sample size calculation have been 
based on previous pilot investigations on Exufiber® and especially the EARTH investigation 
(Meaume el al 2014). 
This investigation supports the renewal application reimbursement of Exufiber®, to the French 
Health Authority, on the list of products and benefits mentioned in the article L165-1 of the 
National Health Service Code. 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 15(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
2. OBJECTIVES 
The primary objective of this non-inferiority investigation is to compare Exufiber® versus Aquacel 
Extra in terms of efficacy and safety, measured in moderately or strongly exuding venous and 
mixed ulcers of predominantly venous origin during a period of 6 weeks investigation period. 
The primary endpoint will be; 
Wound area reduction (%) from baseline until end of investigation (up to 6 weeks). Wound area 
reduction will be centrally measured by one blinded independent review using the validated 
system PictZar®. A second supportive blind review will be done by an independent French 
expert 
Secondary endpoints are to evaluate;  
- 
Relative reduction (%) of fibrin/sloughy tissue 
- 
Wound area reduction (absolute change in cm2) from baseline until end of investigation 
(up to 6 weeks) 
- 
Linear advance of the wound margin according to Gilman’s formula (Cardinal et al, 
2008) based on the digital photos and calculated by PictZar 
- 
Percentage of patients with a debrided wound at end of investigation (at 
least 70% of the wound surface area covered with granulation tissue 
(confirmed using PictZar). Number of additional debridements used during 
the investigation. Pain during the debridement and ease of debridement 
- 
Changes from baseline in the condition of the peri-wound skin measured by 
the following variables; maceration, redness/irritation, blistering, skin 
stripping, trauma to wound edges  
- 
The level of pain in connection to removal of dressing 
- 
Changes in wound status including exudates management 
- 
Clinician’s and subject’s opinion related to the dressing (subject to fill in the 
questionnaire him/herself in applicable local language) 
- 
Cost effectiveness and health economics will be measured using EQ-5D-3L and 
wound management related material use 
- 
Tolerance such as adverse events and adverse device effects including those 
reported to be serious 
Ancillary objective 
- 
In order to support that wound area reduction at week 6 is a clinically relevant 
parameter to predict long-term favorable wound healing, a sub-group of at least 
50 subjects will be assessed at 24 weeks post-inclusion. Favorable trajectory will 
be defined by an area regression, compared to baseline, of 80% or more at 
week 24. Additionally, wound closure (100% re-epithelialization confirmed by 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 16(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
photo) rate will also be evaluated. All these parameters will be centrally 
measured on photos according to previously described procedure. 
 
3. CLINICAL INVESTIGATOR(S) AND INVESTIGATION 
ADMINISTRATIVE STRUCTURE 
 
3.1 PI at Investigation site(s) 
Name and addresses of principal investigator(s) are listed in Appendix A. 
 
3.2 Mölnlycke Investigation Personnel 
 
Viktoria Ahlenius Körner, Senior Clinical Research Manager, Author of the CIP  
Caroline Gröndahl, Clinical Research Manager, Author of the CIP 
Wassila Drareni, Project Leader Clinical Research, France  
Henrik Ahlbom, Clinical Data Manager  
Karin Rylander, Clinical Evaluation Manager 
Anand Chandarana, Global Marketing Manager 
Viktor Gergely, Health Economist 
Sarah McCarthy, Information Systems Manager 
Roland Sobenius, Regulatory Affairs Manager 
Annika Rydström, Clinical Research Administrator 
Markus Wittebo, Director of Clinical Research 
Ann-Sofie Svensson, Clinical Project Manager/Clinical Data Manager 
3.3 Other Participants 
Supplier of the eCRF system  
Pharma Consulting Group  
Kungsängsvägen 19, 1 tr 
753 23 Uppsala, Sweden 
Supplier of the PictZar program 
Martin E. Wendelken, DPM, RN, 
FAPWCA President - Director Of R&D 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 17(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
646-220-1745 
Advanced Planimetric Services, L.L.C. 
Elmwood Park, NJ 07407 
DrMarty@AdvancedPlanimetricServices.com 
 
Supplier of full service CRO for Clinical Research 
NAMSA/Medvance 
Medvance House, Burn Grange 
Doncaster Road, Burn, Selby, YO8 8LA, 
United Kingdom 
 
Supplier of CRO for Clinical Research 
Devicia AB 
Energigatan 10B 
434 37 Kungsbacka 
Sweden 
 
Statistician 
Nils-Gunnar Pehrsson 
CEO / Senior Biostatistician 
Statistiska Konsultgruppen 
Thorild Wulffsgatan 1  
413 19 Gothenburg 
Sweden  
 
 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 18(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
4. INVESTIGATION PLAN AND PROCEDURES 
4.1 
Overall Design and Flow Chart 
Overall Design 
The investigation is designed as an open, randomized, non-inferiority, multi-centre investigation. 
A total of 212 subjects will be randomised. Subjects to be included will suffer from a moderately 
or strongly exuding venous or mixed ulcer of predominantly venous origin. Both in and out-
subjects will be eligible. Each subject will be treated according to the local clinical routine and 
evaluated during a total treatment period of maximum 6 weeks or until the wound is healed. At 
least 50 subjects out of the total 212 subjects will be followed for maximum 24 weeks to 
investigate wound closure. Subjects will either be randomized to Exufiber® or Aquacel Extra 
using a centralized randomization. The secondary dressing will be according to the normal praxis 
at each clinic and preferably one secondary dressing should be chosen to be used for all 
subjects although no active dressings such as anti-microbial dressings are allowed. Simple 
gauzes or polyurethane (PU) films are recommended (see schedule of assessment for details). 
Patients should be treated with a recognized efficient compression system (e.g. multicomponents 
such as 2-, 3- or 4-LB (two-, three- or four-layer bandage) or SSB (short stretch bandage)). The 
nature of applied bandages will be captured in the eCRF. 
Visits are planned for baseline followed by 1, 2, 3, 4 and 6 weeks post treatment. The 
sub-group of at least 50 subjects will also be followed at week 8, 12, 16, 20, and 24 post 
treatment or until wound is healed if earlier. Dressing changes in-between visits are 
allowed and should be carried out according to normal praxis/intended use eg when the 
dressing is saturated. These can be performed at the subject’s home according to normal 
routine. At each dressing change, the wound is to be inspected and cleaned 
exclusively with normal saline or warm water (or Actimaris Rinsing Solution). When the 
wound is dry, Exufiber® is no longer applicable. The treatment should then continue 
with the secondary dressing or other suitable dressing according to local guidelines 
and compression followed until end of investigation at 6 or 24 weeks or earlier if the 
wound heals. Aquacel Extra is also intended for dry wounds but should be used in the 
same way as Exufiber® for consistency.  
A record (dressing log) for Exufiber® or Aquacel Extra will be filled in to capture all 
dressing changes at the scheduled visits including secondary dressing and compression 
applied. The number of dressing changes in-between scheduled visits will be asked for at 
each visit as well as number of dispensed and returned dressings. A nurse book can be 
used to collect the data related to the dressing change (number of dressings, reason for 
dressing change) between scheduled visits. 
Subjects will be screened on a daily basis and if they seem evaluable they will be given a 
patient information. 
At the baseline visit the following will be registered for all enrolled subjects;  
- 
Subjects characteristics including vital signs, informed and photograph consent, 
medical and surgical history, ulcer duration, size, location and ABPI (ankle 
brachial pressure index using hospital routine and most recent value obtained), 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 19(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
current dressing and compression type and duration (if applicable) 
- 
Cleansing/debridement according to details in schedule of assessment 4.2.1 
- 
Level of pain before dressing assessment, measured by validated visual 
analogue scale (VAS) 0-100mm 
- 
Wound status using colorimetric scale; Percentage of fibrin/sloughy tissue, 
granulation tissue, epithelialization etc. Total should be 100%. Evaluated before 
and after cleansing/debridement. 
- 
Photos will be taken according to guidelines in Appendix D and details in 
appendix C. Photos from before and after debridement will be analyzed using 
PictZar and by a blinded reviewer 
- 
Signs of local infection such as pain between dressing changes, perilesional skin 
erythema, oedema, foul odour and high levels of exudates 
- 
Dressing application including secondary dressing and compression according to details 
in schedule of assessment and in appendix C 
- 
Clinician’s evaluation according to details in appendix C 
At each follow-up visit until week 6 the following should be registered;  
- 
Cleansing/debridement according to details in schedule of assessment 4.2.1 
- 
Wound status using colorimetric scale = Percentage of fibrin/sloughy tissue, 
granulation tissue, epithelialization etc. Total should be 100%. Evaluated before 
and after cleansing/debridement. 
- 
Dressing application including secondary dressing and compression according to details 
in schedule of assessment and in appendix C 
- 
Photos will be taken according to guidelines in Appendix D and details in 
appendix C. At week 4 and 6 or final visit, the photos before and after 
debridement will be analyzed using PictZar by a blinded reviewer. Other photos 
taken after debridement can be analysed using Pictar if deemed necessary for 
primary endpoint 
- 
Level of pain during dressing removal measured by validated Visual Analogue 
Scale (VAS) 0-100mm and analgetics used within 3 hours 
- 
Signs of local infection such as pain between dressing changes, perilesional skin 
erythema, oedema, foul odour and high levels of exudates 
- 
Technical performance according to details in appendix C 
- 
Subject evaluation according to details in appendix C 
- 
Clinician’s evaluation according to details in appendix C 
- 
All relevant concomitant medications during the investigation period will also be 
collected including antibiotics and analgesics. Adverse events will be collected 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 20(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
according to details in section 8. 
- 
Debridement is allowed during the treatment period but should be specified as well as 
ease of debridement and pain during the debridement (VAS). 
Variables to be collected at week 8-24 for the sub-group of at least 50 subjects are specified in 
schedule of assessment 4.2.1 and in appendix C. 
Health related quality of life (HRQoL); 
Patient reported HRQoL will be measured by using the standardized generic EQ-5D-3L 
instrument (EuroQol, 1990). 
The EQ-5D-3L consists of two parts: a descriptive system and a visual analogue scale (VAS). 
The descriptive system records HRQoL in five dimensions (mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression), each of which dimensions has three levels of possible 
responses indicating (1) no problems, (2) some problems or (3) extreme problems. The 
responses of the patient results in a 5-digit code (e.g. 21223) defining his/her health state. 
These health states can be converted to a single index value representing how a particular 
health state is valued by the general population. 
Using the second part of the instrument, the VAS, patients rate their health state on a 0-100 
vertical scale. 
Subjects will be provided with the paper version of the EQ-5D-3L three times during the 
investigation: (1) at baseline, (2) at four weeks and (3) at six weeks (or final visit). 
Subjects followed for up to 24 weeks will however be provided with the EQ-5D-3L a fourth time 
i.e. at week 24 (or final visit). 
All outputs of the EQ-5D-3L instrument, the descriptive health states, the single index value and 
the VAS scores will be analyzed. 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 21(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
4.2 Procedures and Assessments 
4.2.1 Schedule of Assessment 
Week number 
Week 0 
(Baseline) 
Week 1,2,3,4 
and 6 
Unscheduled 
visits* 
Week 8-24** 
Visit window 
NA 
± 2 days 
NA 
± 3 days 
Informed Consent 
√ 
 
 
 
Inclusion and Exclusion 
Criteria 
√ 
 
 
 
Subject Demographics 
including vital signs 
√ 
 
 
 
Relevant medical condition 
and surgical procedure 
√ 
 
 
 
Current treatment 
√ 
 
 
 
History of Leg ulcer 
  √ 
 
 
 
Wound status (colorimetric 
scale) 
√ 
√ 
 
√ 
Condition of peri-wound 
skin 
√ 
√ 
 
√ 
Signs and symptoms of 
local infection 
√ 
√ 
 
 
Pain assessment (VAS)a 
√ 
√ 
 
 
Wound preparation 
(cleansing/debridement) b 
√ 
√ 
√ 
√ 
Dressing applicationc 
√ 
√ d 
√ 
√ d 
Dressing removale 
 
√ 
√ 
√ 
EQ-5D-3L 
√ 
√ f 
 
√ f 
Photographg 
√ 
√ 
 
√ 
Clinician’s evaluation 
√ 
√ 
 
 
Subject’s evaluation 
 
√ 
 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 22(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Week number 
Week 0 
(Baseline) 
Week 1,2,3,4 
and 6 
Unscheduled 
visits* 
Week 8-24** 
Technical performance 
 
√ 
 
 
Medicine log 
√ 
√ 
√ 
√ 
Adverse Events 
√ 
√ 
√ 
√ 
*: Unscheduled visits can be performed at the clinic if/when deemed necessary for dressing changes. Cleansing should be 
performed according to intended use. Only saline and warm water or Actimaris Rinsing Solution are allowed on the wound. 
Debridement is not allowed at unscheduled visits. The dressing log should only be filled in at scheduled visits. 
**: At least 50 subjects out of the total 212 subjects, will be followed for 24 weeks or until wound is healed if earlier. Visits will be 
performed once a month e.g. at week 8, 12, 16, 20 and 24. 
a: Document any analgesics used under Medicine Log. 
b: Only saline and warm water or Actimaris Rinsing Solution is allowed on the wound. Local applications such as pastes and 
corticosteroids are allowed outside the lesions. Any type of mechanical debridement is allowed in the investigation and it will 
be up each site to decide what mechanical debridement includes. Surgical debridement is not allowed. Debridement is not 
allowed at unscheduled visits. 
c: Exufiber® or Aquacel Extra should be applied after cleaning/debridement and according to the randomisation schedule. 
Secondary dressing should be applied according to hospital praxis, simple gauzes of PU films are preferred and active 
dressings such as anti-microbial dressings are not allowed. Details to be recorded in the eCRF. The ulcer should be treated 
with a recognized efficient compression system (e.g. multicomponents such as 2-,3- or 4-LB or SSB). Record the nature of 
applied bandages in the eCRF. 
d: Not at week 6/24 (i.e. final visit). 
e: The number of dressing changes in-between visits should be captured at each scheduled visit, only changes in the 
dressing routine will be captured at each scheduled visit. 
f: Only at week 4, 6 and 24. 
g: Please see Appendix C for a detailed instruction of when photos should be taken. 
 Please include measuring scale (ruler) with date, subject number and visit number and please respect the confidentiality of 
the subject by not including any personal numbers or identifying characteristics. A digital camera will be distributed by 
Mölnlycke Health Care at or before the initiation. The ruler is used for calibration of the photograph for objective 
measurements in the PictZar program. The PictZar analysis including wound size measurement will be performed on the 
photos taken after debridement at week 0, 4 and 6 or the final visit if sooner. For subjects that are followed up to 24 weeks, an 
additional PictZar analysis including wound size measurement will be performed on photos taken at week 24 (or last visit). 
The PictZar analysis including tissue type measurement will be performed on the photos taken before debridement at week 0, 
4 and 6 or the final visit if sooner. 
Please refer to Appendix D for a complete digital photography guideline. 
 
4.3 Selection of Population for Investigation 
4.3.1 Inclusion Criteria 
1. Provision of informed consent i.e. subject must be able to understand and sign the 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 23(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Patient Information and Consent Form 
2. Both gender ≥18 years old 
3. Ulcer moderately or strongly exudative justifying the use of an absorbent dressing 
6. 0.7 ≤ ABPI < 1.3 
7. Ulcer duration 6 weeks to 60 months 
8. Ulcer size 3 cm2 -100 cm2  
9. Target ulcer at least 3 cm away from any other lesion 
 
The subject can have multiple wounds but only the largest eligible wound per subject is to be 
included in the investigation. The remaining ulcers should be treated according to normal praxis. 
 
4.3.2 Exclusion Criteria 
1. Known allergy/hypersensitivity to the dressings 
2. Pregnant or breastfeeding 
3. Circumferential wounds (the entire wound should be able to be captured on a single 
image/photo) 
4. Subjects who will have problems following the protocol 
5. Subjects included in other ongoing clinical investigation evaluating wound dressings at 
present or during the past 30 days 
6. Patient with a systemic infection not controlled by suitable antibiotic treatment 
7. Clinically infected wound according to the judgement of the investigator (heat, pain, 
swelling, redness or purulent secretion) 
8. Wound covered with black necrosis  
9. Dry wounds 
10. Malignant wound degeneration 
11. Current treatment with radiotherapy, chemotherapy, immunosuppressant drugs or high 
doses of oral corticosteroids if any  
12. Subject with deep vein thrombosis within 3 months prior to inclusion 
 
4.3.3 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 Adverse 
Event/Adverse Device Effect or Device Deficiency and, if possible, be assessed by an 
investigator. It is however up to the subject to provide a reason or not. Adverse Event/Adverse 
Device Effect 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 randomised 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 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 24(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
continuation of the investigation is not expected to be associated with any risk or discomfort for 
the subject). 
 
4.4 Investigational Device 
4.4.1 Summary description of the Investigational Device(s) and Comparator(s) 
Investigational Device - Exufiber® 
Gelling Fibre Dressing 
 
Product Description 
Exufiber® is a sterile nonwoven dressing made from highly absorbent polyvinyl alcohol fibres. In 
contact with wound exudate, Exufiber® transforms into a gel that facilitates moist wound healing 
and ease of removal during dressing change. Exufiber® absorbs and retains wound exudate. 
Exufiber® is available both as sheet and ribbon dressings. 
 
Intended use  
Exufiber® wound dressing is intended to be used on a wide range of exuding wounds:  
• 
Leg and foot ulcers 
• 
Pressure ulcers 
• 
Partial thickness burns 
• 
Surgical wounds 
• 
Donor sites 
• 
Malignant wounds 
 
Precautions 
• 
All wounds should be inspected frequently. In case of signs of clinical infection, consult a 
health care professional for adequate infection treatment. 
• 
Exufiber® is not intended for dry wounds, full thickness burns. 
• 
If the dressing dries out and is difficult to remove, it should be moistened according to 
local policies (e.g. with sterile saline or sterile water) and allowed to soak until it lifts 
easily. It may take several minutes for Exufiber® to transform into a gel. Remove the 
dressing by gently cleansing/flushing. 
 
Other Information 
• 
Exufiber® is for single-use only and should not be re-used. Re-use may lead to product 
deterioration or cross contamination may occur. 
• 
Sterility is guaranteed unless pouch is opened or damaged prior to use. Do not re-
sterilise. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 25(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
• 
Exufiber® can be left in place for up to 7 days depending on wound condition or as 
indicated by clinical practice. 
 
See also Appendix E, Instructions For Use. 
 
Comparator - Aquacel® Extra™ 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre is a soft, sterile, non- woven 
pad dressing composed of sodium carboxymethylcellulose and regenerated cellulose fibre for 
strengthening. This conformable and highly absorbent dressing absorbs wound fluid and 
transforms into a soft gel, which maintains a moist environment to support the body’s healing 
process and aid in the removal of nonviable tissue from the wound (autolytic debridement), 
without damaging newly formed tissue. 
Intended use 
Under medical supervision Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre 
may be used for the management of: 
• 
leg ulcers, pressure ulcers (Stage II-IV) and diabetic ulcers. 
• 
surgical wounds (e.g., post-operative, wounds left to heal by secondary intent and donor 
sites). 
• 
partial thickness burns 
• 
traumatic wounds (e.g. abrasions and lacerations). 
• 
exudates absorption in oncology wounds (eg., fungating cutaneous tumours, cutaneous 
metastases and Kaposi’s sarcomas). 
 
Contraindications 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre should not be used on 
individuals who are sensitive to or who have had an allergic reaction to the dressing or its 
components. 
Precautions and observations 
 
• 
Caution: Sterility is guaranteed unless pouch is damaged or opened prior to use. 
• 
This device is for single-use only and should not be re-used. Re-use may lead to increased 
risk for infection or cross contamination. Physical properties of the device may no longer be 
optimal for intended use. 
• 
Appropriate supportive measures should be taken where indicated (e.g. use of graduated 
compression in the management of venous leg ulcers or pressure relief measures in the 
management of pressure ulcers/sores). 
• 
The control of blood glucose, as well as appropriate supportive measures, should be 
provided with diabetic foot ulcers. 
• 
Infection is not a contraindication to the use of Aquacel® Extra™ Hydrofiber® Dressing with 
Strengthening Fibre. Should infection develop during the use of the dressing antibiotic 
therapy should be initiated, as clinically indicated, by a health care professional. 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre can facilitate the control of 
minor bleeding. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 26(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
• 
If removing the dressing is difficult, the dressing should be fully saturated with sterile saline 
or water and removed slowly. 
• 
Because Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre provides a moist 
environment that supports the growth of new blood vessels, occasionally the delicate newly 
formed blood vessels may produce a blood stained wound fluid. 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre is not intended for use as a 
surgical sponge. 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre is not intended for use 
within internal body cavities or within closed wounds. 
Other Information 
• 
Aquacel® Extra™ Hydrofiber® Dressing with Strengthening Fibre can be left in place for 
up to 7 days, where clinically indicated. 
• 
Discard any unused portion of the dressing. 
• 
If the immediate product packaging is damaged, do not use. 
 
See also Appendix F, Instructions For Use. 
 
4.4.2 Labelling 
Labeling of the Investigational Devices will be in accordance with ISO 14155, the 
Medical Devices Directive (MDD) and Mölnlycke Health Care’s Quality Management 
System. 
 
The labels will be produced in accordance with local regulations for each participating 
country. 
 
4.4.3 Accountability 
Accountability will be performed on the Investigational Device (Exufiber®) and the 
comparator (Aquacel® Extra) provided to the investigation site by Mölnlycke Health Care 
free of charge. 
 
The sites will be provided with the size 10x10 cm free of charge for both Exufiber® and 
Aquacel® Extra. More than one dressing can be used on a wound when deemed 
necessary. 
The Principal Investigator is responsible for establishing routines for correct handling of 
the Investigational Devices to ensure that: 
- 
Deliveries of products from Mölnlycke Health Care are correctly received 
- 
Accurate records are maintained, accounting for the receipt of the investigational 
device (a delivery note will be provided with the shipments) and for the return or 
destruction of the products. 
- 
Investigational Devices are handled and stored safely, properly and in agreement 
with the provided storage conditions. 
- 
The Investigational Devices are prescribed only by the Principal Investigator or by 
a person authorized to do so by the Principal Investigator. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 27(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
- 
The Principal Investigator will under no circumstances allow the Investigational 
Devices to be used for other purposes than directed by this Clinical Investigation 
Plan. 
- 
Use of Investigational Devices must be documented on a subject specific level in 
the eCRF. Information to be documented includes identification of the subject using 
the device, identification and quantity of the medical device dispensed, date of 
dispensing and documentation of returned devices (if any) from the subject 
Returned and unused products are accounted for and returned to Mölnlycke Health Care for 
destruction. All returned or destroyed products should be documented on a specific form 
provided by Mölnlycke Health Care. 
4.4.4 Storage conditions 
Exufiber® should be stored below 25°C (77°F) in dry conditions and protected from direct 
sunlight. 
Aquacel® Extra should be stored in a cool dry place. (10°C - 25°C/50°F - 77°F). 
4.4.5 Method of Assigning Subjects to Treatment Groups 
Subjects will be randomized to either Exufiber® (6w) or to Aquacel® Extra (6w). At least 50 out of 
the total 212 subjects will be randomized to Exufiber® (24w) or to Aquacel® Extra (24w). The 
randomization will be centralized performed after cleansing/debridement using an electronic 
system using the minimization technique and with the following strata; Wound duration (6w-
12m,>12m), wound area (<10cm2,≥10cm2), ABPI (0.7-0.9,>0.9), Compression at inclusion (No, 
Yes) ( Margolis, 2004 (2)). 
 
4.5 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 relevant medication and treatment must be 
recorded in the appropriate section of the Case Report Form (CRF).  
 
4.6 Efficacy and Safety 
 
4.6.1 Subject Characteristics 
See appendix C for details. 
• 
Date of birth 
• 
Gender 
• 
Race (where applicable) 
• 
Mobility 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 28(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
• 
Height, weight and BMI (calculated) 
• 
Duration of leg ulcer and wound location 
• 
Latest ABPI value 
• 
Recurrent ulcer  
• 
Current dressing and current compression type and duration (if applicable) 
 
4.6.2 Medical condition 
All ongoing relevant medical conditions must be recorded in the appropriate section 
of the eCRF. 
Relevant medical condition is defined as an existing condition that may potentially affect 
the performance of the primary dressing according to the best judgement of the 
investigator. 
4.6.3 Surgical history 
All relevant surgical history must be recorded in the appropriate section of the eCRF. 
Relevant surgical history is defined as previous surgery that may potentially affect 
the performance of the primary dressing according to the best judgement of the 
investigator. 
 
4.6.4 Efficacy Measurements and Variables 
See appendix C for details. 
The primary endpoint will be 
• 
Relative reduction of wound area (%) from baseline to end of investigation (up to 6 
weeks) measured by the validated system PictZar on the photos taken after debridement 
at week 0, week 4 and week 6 (or final visit). 
Secondary endpoints are to evaluate;  
• 
Wound area reduction (absolute change in cm2) from baseline to end of investigation (up 
to 6 weeks). Also measured by PictZar. 
• 
Linear advance of the wound margin according to Gilman’s formula (Cardinal et al, 
2008) based on the digital photos and calculated by PictZar 
• 
Relative reduction of fibrin/sloughy tissue after the 6-week treatment period or when the 
wound is dry/healed. (Measured with PictZar and according to the judgment of the 
clinician) 
• 
Debrided wound at end of investigation 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 29(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 at least 70% of the wound surface area covered with granulation tissue 
confirmed using PictZar 
• 
Changes from baseline in the condition of the peri-wound skin measured by 
the following variables; maceration, redness/irritation, blistering, skin 
stripping, trauma to wound edges 
•  The level of pain in connection to dressing changes and during debridement 
(measured by visual analog scale 0-100mm)  
 Any intake/application of analgesics within 3 hours?  
 Pain before dressing assessment 
 Pain DURING dressing removal 
 Pain during debridement 
• 
Cost effectiveness and health economics will be measured using EQ-5D-3L and 
dressing material used 
• 
No of dressing changes per week and during the total treatment period 
• 
Wound status 
o Exudate amount and nature 
o Wound bed aspect before and after debridement/cleansing 
 % of fibrin/sloughy tissue 
 % of granulation tissue 
 % of epithelialization  
 % other 
• 
Clinician’s opinion in relation to the dressing 
 Ease of application of the dressing 
 Ease of removal of the dressing 
 Non-adherence to wound bed at removal of primary dressing 
 Non-adherence to peri-wound skin at removal of primary dressing 
 Flexibility of dressing 
 Overall experience of the dressing 
 Conformability to the wound 
• 
Subject’s opinion in relation to the dressing 
 Experience anxiety during study product change 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 30(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 Ease of movement while wearing study product 
 Study product remained in place while wearing it 
 Sting or burning while wearing study product 
 Comfortable to wear 
 Would you use this product again (only at last visit) 
• 
Technical performance in relation to the dressing 
 Presence of residual in the wound after dressing removal 
 Ability to absorb exudate 
 Ability to retain exudate within the study product 
 Ability to absorb blood 
 Ability to keep slough and blood within study product 
Ancillary endpoint is to evaluate; 
 Wound area reduction (compared to baseline) of 80% or more at week 24 
 Wound closure (100% epithelialization confirmed by photo) rate 
 
4.6.5 Safety Measurements and Variables 
 
Adverse Event (AE)/Adverse Device Effect (ADE), Serious Adverse Event (SAE)/Serious 
Adverse Device Effect (SADE), and Device Deficiencies (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. 
Signs of local infection will be judged by the investigator; 
 Pain since last dressing change 
 Perilesional skin erythema 
 Oedema 
 Foul odour 
 High levels of exudates 
 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 31(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
4.6.6 Anticipated ADEs  
The conclusion of the Product Risk Management Record (PD-411100) and the Clinical 
Evaluation Report (PD- 474698) of Exufiber® is that the benefits of using the investigational 
device outweigh the residual risks and that there are no unacceptable risks of harm for the 
patient, the user nor third part involved in this device when used under normal conditions and 
within its intended use. 
Before reaching the above conclusion, the identified risks of the investigational device, which 
had been ranked for severity, occurrence and detectability according to Mölnlycke Health Care 
risk management process,  were mitigated as far as possible in the risk management process 
(following ISO 14971, Application of Risk Management to Medical Devices). 
The following possible clinical outcomes are connected to the risks evaluated in the Product 
Risk Management Record: 
• 
Maceration 
• 
Prolonged wound healing 
• 
Dressing related pain and/or trauma to the wound bed and edges 
• 
Infection 
The Principal Investigator or designee is responsible for judging whether the appearance of any 
of the above mentioned events are considered to be adverse events or adverse device effects. 
If this is the case, the event must be reported in the applicable section of the eCRF according to 
the timelines and definitions mentioned in section 8. Furthermore, worsening of an existing 
medical history during the intervention group may also be relevant to report as an adverse event 
or adverse device effect and the Principal Investigator or designee is responsible for making this 
judgment. 
Concomitant treatments that are known to potentially affect the performance of the 
investigational device are mentioned in section 4.5 and any such medication must be registered 
in the eCRF. 
There are no additional risks to the subjects by participating in this clinical investigation than 
there would be if the subject was treated with the investigational device (or standard care) under 
non-investigational settings. An additional benefit of participation may be more frequent and/or 
thorough wound assessments as part of this Clinical Investigation Plan.  
 
4.7 Data Quality Assurance 
4.7.1 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 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 32(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
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 according to the monitoring plan. 
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)/Institutional Review Board (IRB) may visit the investigation site to perform 
audits/inspections, including source data verification. 
 
4.7.2 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. 
 
4.7.3 Data Management 
The Data Management process includes all activities related to data handling regarding: 
• Randomisation 
• 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 CFR 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 for consistency and validation. 
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.  

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 33(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
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 and final definition of ITT, PP and 
safety populations must be made and documented before locking the database. 
A blinded observer will do the measurements (from the validated tool PictZar which complies 
with FDA cleared under CFR part 11 (ER/ES) requirement) of the primary endpoint based on 
digital photos uploaded in the electronic CRF. The blinded observer will not know the treatment 
that each subject received.  
  
4.8 Statistical Methods and Determination of Sample Size 
4.8.1 Statistical Evaluation 
The intent-to-treat (ITT) population is defined as all randomised patients with at least one follow 
up planimetry value (from the validated tool PictZar) and the per-protocol (PP) population as all 
patients with a wound area measurement till the fourth week of follow-up, at least. Subjects with 
significant protocol deviations will be excluded from the PP population.  
 
PictZar has received 510k notification and is compliant with CFR Part 11. 
In this non-inferiority study the primary efficacy analysis will be constructing a two sided 95% 
confidence interval, using Fisher’s non-parametric permutation test, for between-treatment 
differences (Exufiber® - Aquacel® Extra) in the mean percentage area change from baseline to 6 
weeks. This means that if the lower limit of this confidence interval is greater than 12% non-
inferiority will be established. 
All the main efficacy analyses will be performed on the PP population. Complementary efficacy 
analyses will be performed on the ITT-population for further confirmation. The ITT and PP 
analyses will have to provide the same results to establish the non-inferiority. All safety analysis 
will be performed on the safety population. 
Superiority can be concluded if the lower bound of a two sided 95% confidence interval for 
between-treatment differences (Exufiber® - Aquacel® Extra) in the mean percentage area 
change from baseline to 6 weeks does not overpass zero. 
There will also be a second blinded assessment carried out (not using the PictZar system) that 
will support the main analysis done by PictZar. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 34(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
For secondary variables Fishers exact test for dichotomous variables, Mantel-Haenszel chi-
square test for ordered categorical variables and Pearson Chi-square test for non-ordered 
categorical variables and Fisher’s non-parametric permutation will be used for continuous 
variables. 
If necessary adjustment for baseline variables will be done with multiple logistic regression for 
dichotomous variables and with covariance analysis for continuous variables.  
All statistical tests will be two-sided and conducted at the 5% significance level. 
A sub-group analysis by country will be performed. 
For the primary endpoint last observation carried forward will be applied for the final 
measurement. No other imputation methods will be used. 
For all secondary endpoints differences between Exufiber® and  Aquacel® Extra will be analyzed 
with the statistical methods given above and 95% confidence interval for the differences 
between the two groups will be given when appropriate. 
The distribution of continuous variables as for changes in continuous variables will be given as 
mean, SD, median, minimum and maximum and as number and percentages for categorical 
variables. 
Other endpoints will be summarized using descriptive statistics only. 
A complete statistical analysis plan (SAP) with the details for all analyses for the whole study 
will be finalized before first patient in. 
A blinded observer will do the measurements of the primary endpoint based on digital photos 
uploaded in the electronic CRF. The blinded observer will not know the treatment that each 
subject received. 
 
4.8.2 Determination of Sample Size 
This investigation was designed to document the non-inferiority of the test dressing, Exufiber®, 
compared with the control dressing, Aquacel® Extra, on the relative reduction/change in wound 
size from baseline to end of investigation (6w). Applying a non-inferiority margin of 12% (same 
as EARTH investigation, Meaume el al 2014) and a standard deviation of 35%, 106 subjects 
were necessary in each group (i.e. 212 subjects in total) with a power level at 80%. Two 
investigations have been conducted on Exufiber®, one on DFU (diabetic foot ulcer) and one on 
PU (pressure ulcer). The SD are a little higher than 35% but since those investigations were 
quite small (21 subjects) it is reasonable to expect a smaller SD which justifies the calculation 
above. 
 
4.9 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. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 35(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
An amendment to the Investigation Plan may require notification or approval from EC/IRB 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/IRB and staff concerned at his/her 
site. In France it is the sponsor who is responsible for this distribution. The distribution of these 
documents to the CA will be handled according to local practice. 
  
5. STATEMENTS OF COMPLIANCE 
5.1 Ethics 
5.1.1 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 (in France the 
Sponsor) is responsible for informing the EC of any amendment to the investigation plan as per 
local requirements. 
 
5.1.2 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. 
 
5.1.3 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. 
 
5.2 Regulatory and standards 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 36(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
5.2.1 Regulatory review 
If applicable, 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. 
 
5.2.2 Standards and other 
The most recent version of ISO 14155 is followed in addition to national regulations. 
 
5.2.3 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. 
 
5.3 SUBJECT PROTECTION PROCEDURES 
5.3.1 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. 
 
5.3.2 Insurance 
Mölnlycke Health Care AB has product liability insurance, which also covers test products. 
 
5.4 Publication of results  
The results from this investigation are intended to be published.  
The investigation will be registered on a web site for free access (ClinicalTrials.gov) before the 
inclusion of the first subject. 
  
6. INVESTIGATION TIMETABLE AND TERMINATION 
 
Investigation start: Q2/Q3 2016 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 37(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
Inclusion completed: Estimated Q1/Q2 2019 
Last subject out: Estimated Q3 2019 
 
The investigation could be prematurely discontinued if the dropout rate is higher than 20% 
and/or the investigation site is unable to fulfill the inclusion period according to the Clinical 
Investigation Agreement. 
  

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 38(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
7. 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. Barnea, Y. Amir, A., Lesham, D et al.  Clinical comparative study of Aquacel and 
paraffin gauze dressings for Split-skin donor site treatment. Ann Plast Surg. 2004 
Aug; 53(2):132-136. 
2. Bishop, SM., Walker, M., Rogers, AA., Chen WY. Importance of moisture balance at 
the wound-dressing interface. J Wound Care 2003; 12(4):125-128. 
3. Brunner, U., Eberlein, T. Experiences with hydrofibres in the moist treatment of 
chronic wounds, in particular of diabetic foot. Vasa 2000; 29(4):253-257. 
4. Chadwick, P., McCardle, J. Exudate management using a gelling fibre dressing. The 
Diabetic Foot J 2015; 18(1):43-48. 
5. Department of Health (2009) NHS 2010–2015 from Good to Great: Preventative, 
People-centred, Productive. http://tinyurl.com/9lnwdmh (accessed 24 August 2012). 
6. European Wound Management Association (EWMA). Position document: Wound 
bed preparation in practice. London: MEP Ltd, 2004.  
7. EuroQol G. EuroQol--a new facility for the measurement of health-related quality of 
life. Health policy. 1990;16(3):199-208. PubMed ID: 10109801. 
8. Harding, KG., Price, P., Robinson, S et al. Cost and dressing evaluation of hydrofiber 
and alginate dressings in the management of community-based patients with chronic 
leg ulceration. Wounds 2001; 13(6):229-236.  
9. Maddox, D. Effects of venous leg ulceration on patients’ quality of life. Nursing 
Standard 2012; 26(38):42-49. 
10. Margolis, D. et al. The accuracy of venous leg ulcer prognostic models in a wound 
care system, Wound Repair Regen 2004; 12(2): 163-168. 
11. Meaume, S. Evaluation of two fibrous wound dressings for the management of leg 
ulcers: Results of a European randomized controlled trial, J Wound Care 2014; 23(3).  
12. Ravenscroft, MJ., Harker, J., Buch, KA. A prospective randomised controlled trial 
comparing wound dressings used in hip and knee surgery: Aquacel and Tegaderm 
versus Cutiplast. Ann R. Coll Surg Engl. 2006; 88(1):18-22.  

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 39(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
13. Robson, MC., Cooper, DM., Aslam, R et al. Guidelines for the treatment of venous 
ulcers. Wound Repair Regen. 2006; 14:649-662.  
14. Romanelli, M., Vowden, K., Weir, D. Exudate management made easy. Wounds 
International 2010; 1(2) 
15. Tickle, J. Effective management of exudate with Aquacel Extra. Br J Community 
Nurs. 2012 (Supplement); S38:S40-S46.  
16. Walker, M., Parsons, D. Hydrofiber® technology: its role in exudate management. 
Wounds UK 2010; 6(2):31-38.  
17. World Union of Wound Healing Societies (WUWHS). Principles of best practice: 
Wound exudate and the role of dressings. A consensus document. London: MEP Ltd, 
2007.  
18. Wounds UK Best Practice Statement. Effective exudate management. London: 
Wounds UK, 2013. 
19. Vowden, P., Bond, E., Stryja, J. Meeting report: Changing the way we look at viscous 
exudate. Wounds International 2015; 6(3):35-41.  
20. Cardinal M, Eisenbud DE, Phillips T, Harding K. Early healing rates and wound area 
measurements are reliable predictors of later complete wound closure. Wound 
Repair Regen. 2008;16(1):19–22. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 40(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
8. 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 labelling.  
 
All Device Deficiencies that might have led 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 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 41(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization 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 LED TO A SADE 
The investigator must inform Mölnlycke Health Care (MHC), within 1 calender day of awareness 
of the event. When a SAE/SADE 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. 
 
In case of problem with  the eCRF, a paper based version of the SAE/SADE report form 
(available in the Investigator Site File) shall be used and sent by email to: 
Clinical_Investigations_Event_Reporting@molnlycke.com. 
 
All SAEs/SADEs that occurs during the Clinical Investigation shall be reported, whether or not 
they are considered causally related to the investigational device. 
 
Device Deficiencies that might have led 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/IRB and/or the Competent Authority of the 
SAE/SADE as per local requirements. 

Clinical Investigation Plan 
 
Title: CIP with integrated Central Amendment 1, 2, 3 and 4 
Page 42(42) 
Investigation Code Chexu03 
Final Version CIP Approval date 2016-04-19 
Amendment 1 Approval date 2016-10-17 
Amendment 2 Approval date 2016-12-19 
Amendment 3 Approval date 2017-09-12 
Amendment 4 Approval date 2017-12-28 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 09 
 
 
 
PROCEDURES FOR DD REPORTING  
All DD shall be reported to MHC as soon as possible, without unjustified delay . If the DD might 
have led 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. 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.  
Non-subject related DDs are reported using  the  paper based report form located in the 
Investigator Site File. The completed form shall be sent by email to 
Clinical_Investigations_Event_Reporting@molnlycke.com  
 
Causality Assessment 
The relationship between the use of the investigational device and the occurrence of each 
AE/SAE shall be assessed by the investigator and the sponsor and classified as investigational 
device related or not related to investigational device.