A Prospective, Randomized, Controlled Study Using Cross-Over Design to Evaluate and Compare 3 Multi-Layered Foam Dressings for the Management of Chronic Wounds
Phase: NA
Conditions: Chronic Wound, Venous Leg Ulcer, Diabetic Foot Ulcer
Sponsor: Molnlycke Health Care AB

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 1(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
CLINICAL INVESTIGATION PLAN (CIP) 
INVESTIGATIONAL DEVICE:  
MEPILEX® BORDER FLEX 
INVESTIGATION TITLE:  
A PROSPECTIVE, RANDOMIZED, CONTROLLED, STUDY USING CROSS-OVER 
DESIGN TO EVALUATE AND COMPARE 3 MULTI-LAYERED FOAM DRESSINGS 
FOR THE MANAGEMENT OF CHRONIC WOUNDS  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CO-ORDINATING INVESTIGATOR: 
Dr Oscar M. Alvarez PhD, CCT, FPWCA 
 
SPONSOR 
MÖLNLYCKE CLINICAL STUDY  
MANAGER: 
 
David Pham 
Mölnlycke Health Care 
P.O Box 130 80 
402 52 Gothenburg, Sweden 
Phone: +46 31 722 30 xx 
Fax: +46 31 722 34 91 
 
IRB Approved at the 
Protocol Level 
Mar 15, 2019
20182500

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 2(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 3(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
PROTOCOL SYNOPSIS 
 
PROTOCOL TITLE:  
A PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY USING CROSS-OVER DESIGN 
TO EVALUATE AND COMPARE 3 MULTI-LAYERED FOAM DRESSINGS FOR THE 
MANAGEMENT OF CHRONIC WOUNDS 
 
Clinical Study Site: 
Multiple Sites 
Investigational Device (test dressings): 
Mepilex® Border Flex, Mölnlycke Health Care; Optifoam Gentle EX Wound Dressing, Medline 
Industries Inc.; Allevyn Life Wound Dressing, Smith and Nephew Inc. 
 
Study Objectives 
 
Primary Objective 
To demonstrate superiority in efficacy of Mepilex® Border Flex versus Optifoam Gentle EX 
and Allevyn Life in the management of venous leg ulcers (VLUs) and diabetic foot ulcers 
(DFUs) in an outpatient setting, as determined by dressing durability (i.e. wear time). 
 
Secondary Objectives 
• 
To compare clinical wound characteristics during wound management with each of the 
test dressings (in combination with standard care), including the rate of wound healing, 
peri-wound skin condition, and local pain levels. 
 
• 
To evaluate the safety of the three test dressings in terms of occurrence of device 
related adverse events (AEs). 
 
• 
To study subject-centric outcomes associated with each of the test dressings. 
 
Health Economics Objective 
• 
To retrospectively compare the cost-effectiveness of the three wound dressings. 
 
Primary Endpoint:  
Wound dressing durability, as defined as the interval of time to dressing strike-through and 
need for dressing change (dressing wear time [days]).  

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 4(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
Secondary Endpoints: 
• 
Clinical wound characteristics: wound healing status, condition of surrounding skin, signs 
of infection, and local pain levels. 
 
 
• 
The number of device related (AEs) associated with each of the test dressings. 
 
• 
Subject-centric outcomes between three treatment groups. 
 
Health Economics Endpoint 
 
To retrospectively compare resource-use as related to: 
• 
 Quantity of dressing changes per week (stratified by wound type) 
 
• 
Time required per dressing change (in minutes) 
a. Start time: Initiation of old dressing removal 
b. End time: New dressing is securely in place 
 
• 
Staff cost associated with dressing change 
a. Identification of those involved with dressing change (e.g., MD, Nurse, Assistant, 
etc.) 
b. Average hourly rate for those individuals directly involved with dressing change 
(this can be market data if individuals do not want to provide actual salary 
information) 
 
• 
Material Cost 
a. Quantity of each product (dressing) used per week 
b. Size of dressings used 
c. Cost of each dressing used per week 
d. Other material cost used in dressing change 
i. Identification of products used per week 
ii. Quantity of each product used per week 
iii. Cost of each product used per week 
 
Additional Safety Measures 
• 
The incidence of AEs and serious adverse events (SAEs)associated with each of the 
test dressings. 
 
Study Design   

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 5(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
Prospective, randomized, controlled clinical trial (RCT) using a cross-over (repeated measures) 
design to evaluate safety and efficacy. The study will be conducted at multiple sites in an 
outpatient setting.    
 
Each subject will be randomly assigned to one of four treatment groups. The treatments and 
treatment schedule are detailed in the table below:  
 
 
Treatment Group 1 
Treatment Group 2 
Treatment Group 3 
Treatment Group 4 
Week 1 
Tr. B 
Tr. A 
Tr. C 
Tr. A 
Week 2 
Tr. B 
Tr. A 
Tr. C 
Tr. A 
Week 3 
Tr. A  
Tr. B 
Tr. A 
Tr. C 
Week 4 
Tr. A  
Tr. B 
Tr. A 
Tr. C 
 
*A=Study Product, B=Comparator Product 1, C=Comparator Product 2 
 
Approximately 40 subjects will be enrolled to have 32 subjects for the evaluation. There will be 
two subject groups: those with VLU and those with DFU. Approximately 50% of the subjects will 
be in the VLU group and 50% of the subjects in the DFU group. Treatment sequence will be 
randomized so that a fair distribution is achieved. The total duration of the study will be 
approximately 4 weeks or 28 ± 2 days. 
 
Visit Schedule 
Potential study subjects will be screened for eligibility. Inclusion and exclusion criteria, vital 
signs, medical record reviews, subject demographics and informed consent will be performed 
and obtained at the Screening Visit (Day 0). If the patient meets the eligibility criteria, he or she 
will be enrolled and randomized into one of four treatment groups. The test wound dressing will 
be applied on the screening day (Day-0) and evaluations will take place twice weekly 
throughout the 4-week Treatment Period. The dressing will only be changed at Day 7 of each 
treatment week (e.g. Visit Days 7, 14, 21 and 28) or as needed at the discretion of the study 
doctor or investigator. There will be a total of 8 visits to the Vascular and Wound Care Center 
during the Treatment Period.  During those visits, evaluations will be performed to assess the 
condition of the wound dressing, the wound, wound pain and patient comfort.   
All study evaluations will be performed by a study doctor or nurse during the follow-up visit at 
the Vascular and Wound Care Center. 
All subjects in the VLU group will receive the same compression therapy and all subjects in the 
DFU group will receive the same off-loading footwear throughout the entire study period.      
Study Methods 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 6(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
 
Wound dressings will be evaluated twice weekly by the study doctor or study nurse. All 
other evaluations will be performed once weekly before dressing change.     
 
There may be an initial debridement (at the investigator’s discretion prior to enrollment).  
 
 Additional debridement is not allowed.   
 
Wound dressing wear time and durability will be determined by study doctors’ judgement 
and by photography. 
 
Exudate absorption and exudate dispersion will be determined clinically and by 
photodigital planimetry.  
 
Wound surface area will be measured serially using photo-digital planimetric software.  
 
Wound and surrounding skin characteristics will be evaluated by the study doctor at 
dressing change. 
 
Dressing comfort and subject-centric outcomes will be captured at the end of weeks 2 
and 4. 
 
SF12 will be captured at the on Day 0 Screening & Baseline Visit and bi-weekly 
thereafter. Please see Appendix E for sampling of questions. 
 
Local wound pain will be evaluated using the Baker-Wong (Faces) Scale before and 
after each dressing change.   
Inclusion Criteria 
1. Male and female subjects 18-85 years of age with leg and foot ulcers (i.e. VLU, DFU). 
2. Subject’s Ankle-Brachial Index (ABI) by Doppler is ≥ 0.7. 
3. The subject has adequate circulation to the foot to allow for healing. This must be 
demonstrated by methods described in Section 4.3.3 
4. Signed informed consent. 
5. Subject and/or caregiver must be willing and able to tolerate multi-layered compression 
bandages when applicable and offloading footwear. 
6. Study subject must be available and able to visit the clinic twice weekly for the full 4-
week period.  
Exclusion Criteria 
1. Pressure injury (as defined by the National Pressure Ulcer Advisory Panel [NPUAP]) in 
any anatomical location 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 7(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
2. Presence of local wound infection as determined by study doctor based on clinical signs 
and symptoms 
3. Subject’s ABI is <0.7 or has any evidence of peripheral arterial disease (PAD). 
4. Subject diagnosed with malignancy other than cutaneous basal cell carcinoma. 
5. Subject has received growth factor therapy (e.g. autologous platelet-rich plasma gel, 
becaplermin, bilayered cell therapy, dermal substitute, extracellular matrix) within 2 
weeks of screening date. 
6. Pregnancy or lactation at time of study participation. 
7. Subject is currently receiving or has received radiation or chemotherapy within 3 months 
of randomization. 
8. Subject is currently enrolled or participated in another investigational device, drug or 
biological trial within 30 days of baseline of this study.  
9. Present history of alcohol or drug abuse.  
10. Known allergy/hypersensitivity to any of the components of the dressing. 
11. Subject not suitable for the investigation according to the investigator’s judgment. 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 8(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
TABLE OF CONTENTS 
1. INTRODUCTION ...................................................................................................... 12 
2. OBJECTIVES ........................................................................................................... 13 
3. CLINICAL INVESTIGATOR(S) AND INVESTIGATION ADMINISTRATIVE 
STRUCTURE ................................................................................................................... 15 
3.1 
Staff at Investigation site ........................................................................................................................... 15 
3.2 
Mölnlycke Investigation Personnel ......................................................................................................... 15 
3.3 
Other Participants ........................................................................................................................................ 15 
4. INVESTIGATION PLAN AND PROCEDURES ........................................................ 16 
4.1 
Overall Design and Flow Chart ................................................................................................................ 16 
4.2 
Procedures and Assessments ................................................................................................................. 18 
4.2.1 
Schedule of Assessment .......................................................................................................................... 18 
4.3 
Study subject selection .............................................................................................................................. 19 
4.3.1 
Inclusion Criteria ......................................................................................................................................... 19 
4.3.2 
Exclusion Criteria ....................................................................................................................................... 19 
4.3.3 
Withdrawal of Subjects from Treatment or Assessment ..................................................................... 20 
4.4 
Investigational Device ................................................................................................................................. 22 
4.4.1 
Summary description of the Investigational Device and Comparators ............................................ 22 
4.4.2 
Labelling ....................................................................................................................................................... 22 
4.4.3 
Accountability .............................................................................................................................................. 22 
4.4.4 
Storage conditions ..................................................................................................................................... 23 
4.4.5 
Returns and Destruction ........................................................................................................................... 23 
4.4.6 
Method of Assigning Subjects to Device Groups ................................................................................. 23 
4.4.7 
Sizes to be used of Investigational Devices.......................................................................................... 23 
4.5 
Concomitant Treatments ........................................................................................................................... 23 
4.6 
Efficacy and Safety ...................................................................................................................................... 24 
4.6.1 
Subject Baseline Characteristics ............................................................................................................. 24 
4.6.2 
Efficacy Measurements and Variables ................................................................................................... 26 
4.6.3 
Safety Measurements and Variables ..................................................................................................... 31 
4.6.4 
Anticipated ADEs ....................................................................................................................................... 31 
4.7 
Data Quality Assurance .............................................................................................................................. 32 
4.7.1 
Monitoring, Audits and Inspections ......................................................................................................... 32 
4.7.2 
Training of Staff .......................................................................................................................................... 33 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 9(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
4.7.3 
Data Management ..................................................................................................................................... 33 
4.8 
Statistical Methods and Determination of Sample Size .................................................................... 34 
4.8.1 
Statistical Evaluation ................................................................................................................................. 34 
4.8.2 
Primary Efficacy Analysis ......................................................................................................................... 35 
4.8.3 
Determination of Sample Size ................................................................................................................. 35 
4.9 
Changes to the Clinical Investigation Plan .......................................................................................... 36 
5. STATEMENTS OF COMPLIANCE .......................................................................... 36 
5.1 
Ethics ............................................................................................................................................................... 36 
5.1.1 
Ethics review ............................................................................................................................................... 36 
5.1.2 
Ethical Conduct of the Investigation ....................................................................................................... 36 
5.1.3 
Patient Information and Consent Form .................................................................................................. 36 
5.2 
Regulatory and standards ......................................................................................................................... 37 
5.2.1 
Regulatory review ...................................................................................................................................... 37 
5.2.2 
Standards and other .................................................................................................................................. 37 
5.2.3 
Subject Data Protection ............................................................................................................................ 37 
5.3 
SUBJECT PROTECTION PROCEDURES ............................................................................................... 37 
5.3.1 
Procedures in Case of Medical Emergency .......................................................................................... 37 
5.3.2 
Insurance ..................................................................................................................................................... 38 
6. INVESTIGATION TIMETABLE AND TERMINATION ............................................. 38 
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 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 10(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
LIST OF APPENDICES 
Appendix A  Signatures of Clinical Investigation Plan 
Appendix B  Package inserts of all study dressings 
Appendix C  Case Report Forms template (CRF) 
Appendix D  Patient Informed Consent Form (ICF) 
Appendix E SF12 questionnaire, Questionnaire for the subjects 
LIST OF ABBREVIATIONS  
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CA 
Competent Authority 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
CTA 
Clinical Trial Agreement 
DD 
Device Deficiency 
DFU 
Diabetic Foot Ulcer 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
FAS 
Full Analysis Set 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
NPUAP 
National Pressure Ulcer Advisory Panel 
PAD 
Peripheral Arterial Disease 
PCG 
Pharma Consulting Group 
PP 
Per Protocol 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SD 
Standard Deviation 
UADE 
Unanticipated Adverse Device Effect 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 11(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
VLU 
Venous Leg Ulcer 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 12(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
1. INTRODUCTION 
The impact of living with a wound is multifactorial and chronic wounds are associated with a 
range of morbidities; these wounds and their associated complications can have a significant 
effect upon a patient’s quality of life (QoL) (1, 2). Ineffective wound assessment and 
management can exacerbate this negative impact upon the patient (3). Wound management 
strategies should be optimized not only to effectively manage the wound, but also to avoid 
further wound complications. Frequently reported patient issues associated with chronic wounds 
include discomfort, pain, malodor, leakage and restriction to daily activities (2). 
Whilst dressings are an essential part of wound management, dressing-associated 
complications can hinder wound healing progression and cause unnecessary distress to the 
patient. Potential disturbances to the wound can occur as a result of suboptimal dressing 
choice. There are many potential ways in which a wound dressing, in close contact with the 
wound bed and surrounding skin, can damage or disturb the wound. These include: sub-optimal 
moisture balance, adherence, mechanical stress, presence of foreign bodies, sub-optimal 
temperature, chemical imbalance, and chemical stress (4). Of particular focus in the literature in 
recent years is the trauma and pain that wound dressing may cause, with the repeated 
application and removal of dressings that adhere to the wound bed causing trauma and 
epidermal stripping (5). Frequent application and removal of wound dressings can cause 
damage to the fragile wound or surrounding skin; this can cause considerable suffering for the 
patient (4). Ultimately, this trauma to the wound can lead to an increase in wound size, 
exacerbated pain and delay healing (5). 
Pain is an important issue for clinicians to consider when managing chronic wounds. Wound 
pain can occur from many sources, with wound management procedures (including dressing 
changes) contributing to this pain (5). When compared to dressings with traditional adhesives, 
the use of wound dressings incorporating soft silicone can minimize traumatic injuries to the 
wound/peri-wound skin, as well as minimizing dressing-associated pain (6-8). Research has 
demonstrated the potential of these atraumatic wound dressings in overcoming these issues. 
Whilst optimal dressing choice is important in achieving good healing progression, it is also 
important to minimize the frequency of dressing changes to enable healing to occur undisturbed 
(9). Frequent removal and reapplication of wound dressings may delay wound healing through 
mechanical disturbance to the healing process, temperature loss at the wound site (affecting the 
cellular healing process) and potential increase in the ingress of harmful bacteria to the wound 
site (9). Wound healing may be further hindered as a result of psychological stress and pain 
during dressing changes (9). 
A dressing’s ability to absorb and retain wound exudate is a key influential factor in terms of 
dressing wear time (9). Whilst exudate production is a part of the normal wound healing 
trajectory and an essential component to healing, when excessive exudate is not managed 
effectively it can have a negative impact on the patient (3). Wound exudate is associated with 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 13(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
several complications. These include: leakage, maceration, pain and discomfort, malodor, and 
psychological and psychosocial implications, all of which can impede patient QoL (3, 10-13). 
Chronic wounds may produce high levels of exudate as a result of a prolonged inflammatory 
response. Both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) are often associated 
with high levels of wound exudate (14-16). 
In terms of exudate management, the ideal wound dressing has several key functions: to 
optimally handle fluid (absorption and retention of exudate and its components, even under 
pressure); to reduce the risk of leakage; to reduce the spread of exudate onto the peri-wound 
area (thus reducing the risk of maceration); and to act as a bacterial barrier. The dressing 
should also ensure conformability, provide patient comfort, be easy to use, provide optimal 
dressing change frequency, minimize wound disturbance, and should be cost-effective (14). 
Previous research has demonstrated the ability of a layered foam dressing with siliconized 
adhesive to effectively manage wound exudate in exuding wounds, whilst maintaining a moist 
wound healing environment (6, 8, 17, 18). The adhesion of the dressing to the wound or 
surrounding skin is a further contributory factor that affects dressing wear time. The ability of the 
dressing to conform to body contours helps to ensure dressing adhesion (9).  
Extended dressing wear may add value not only to the patient, but also to the health care 
provider. Frequent dressing changes are a huge cost driver and can impact greatly on 
resources (9). Minimizing the number of dressing changes (depending on the condition of the 
wound), may help to minimize unnecessary disturbance to the wound, minimize pain and stress 
for the patient, limit exposure of the wound to contamination and help to limit wound care costs 
(associated with nursing time, materials, pain medication, and medication for dressing-related 
trauma). 
The aim of this clinical investigation is to evaluate and compare three different foam dressings in 
the local management of chronic wounds (i.e. VLUs and DFUs) in an outpatient setting. 
Mepilex® Border Flex will be evaluated versus Optifoam (Medline) and Allevyn Life 
(Smith&Nephew) within three focus areas; efficacy and safety of the dressings, subject-centric 
outcomes and health economic evaluation.  
2. OBJECTIVES 
Primary Objective 
To demonstrate superiority in efficacy of Mepilex® Border Flex versus Optifoam Gentle EX 
and Allevyn Life in the management of venous leg ulcers (VLUs) and diabetic foot ulcers 
(DFUs) in an outpatient setting, as determined by dressing durability (i.e. wear time). 
 Secondary Objectives 
• 
To compare clinical wound characteristics during wound management with each of the 
test dressings (in combination with standard care), including the rate of wound healing, 
peri-wound skin condition, and local pain levels. 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 14(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
• 
To evaluate the safety of the three test dressings in terms of occurrence of device 
related adverse events (AEs). 
• 
To study patient-centric outcomes associated with each of the test dressings. 
Health Economics Objective 
• 
To retrospectively compare the cost-effectiveness of the three wound dressings. 
 
 
Primary Endpoint:  
Wound dressing durability, as defined as the interval of time to dressing strikethrough and 
need for dressing change (dressing wear time [days]).  
Secondary Endpoints: 
• 
Clinical wound characteristics: wound healing status, condition of surrounding skin, signs 
of infection, and local pain levels. 
• 
Number of device related (AEs) associated with each of the test dressings. 
• 
Patient-centric outcomes between three treatment groups. 
Additional Safety Measures 
• 
The incidence of AEs and SAEs associated with each of the test dressings. 
  
Health Economics Endpoint 
To retrospectively compare resource-use as related to: 
• 
Quantity of dressing changes per week (stratified by wound type) 
 
• 
Time required per dressing change (in minutes) 
a. Start time: Initiation of old dressing removal 
b. End time: New dressing is securely in place 
 
• 
Staff cost associated with dressing change 
a. Identification of those involved with dressing change (e.g., MD, Nurse, Assistant, 
etc.) 
b. Average hourly rate for those individuals directly involved with dressing change 
(This can be market data if individuals do not want to provide actual salary 
information) 
 
• 
Material Cost 
a. Quantity of each product (dressing) used per week 
b. Size of dressings used 
c. Cost of each dressing used per week 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 15(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
d. Other material cost used in dressing change 
i. Identification of products used per week 
ii. Quantity of each product used per week 
iii. Cost of each product used per week 
3. CLINICAL INVESTIGATOR(S) AND INVESTIGATION 
ADMINISTRATIVE STRUCTURE 
3.1 Staff at Investigation site 
 
Investigators 
 
Oscar M. Alvarez, PhD (Coordinating Principal Investigator – Study wide) 
 
Mark S. Granick, MD (Principal Investigator) 
Oscar M. Alvarez, PhD (Co-Investigator, Medical Officer) 
Sonia Mvuemba, DPM (Sub-Investigator) 
Evelyn Obando, BSN, WOCN Study Nurse   
 
 
Site 02 – TBD 
Site 03 – TBD 
 
3.2 Mölnlycke Investigation Personnel 
David Pham, Clinical Project Manager, Mölnlycke Health Care 
 
3.3 Other Participants 
Supplier of the eCRF system 
Pharma Consulting Group 
Kungsängsvägen 19, 1tr 
753 23 Uppsala, Sweden 
 
Supplier of SF12 Questionnaire Database 
Optum 
1301 Atwood Ave, Suite 311N 
Johnston, RI  02919 
 
Statistician 
Statistiska Konsultgruppen 
Nils-Gunnar Pehrsson 
CEO / Senior Biostatiscian 
Thorild Wulffsgatan 1 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 16(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
413 19 Gothenburg 
Sweden 
4. INVESTIGATION PLAN AND PROCEDURES 
4.1 Overall Design and Flow Chart 
Study Design   
 
Prospective, randomized, controlled clinical trial (RCT) using a 2x2 cross-over (repeated 
measures) design to evaluate safety and efficacy. The study will be conducted in an outpatient 
setting of an academic clinical center.    
 
Each subject will be randomly assigned to one of four treatment groups. The treatments and 
treatment schedule are detailed in the table below:  
 
Table 1. Treatment Groups 
 
Treatment Group 1 
Treatment Group 2 
Treatment Group 3 
Treatment Group 4 
Week 1 
Tr. B 
Tr. A 
Tr. C 
Tr. A 
Week 2 
Tr. B 
Tr. A 
Tr. C 
Tr. A 
Week 3 
Tr. A  
Tr. B 
Tr. A 
Tr. C 
Week 4 
Tr. A  
Tr. B 
Tr. A 
Tr. C 
 
*A=Study Product, B=Comparator Product 1, C=Comparator Product 2 
 
Approximately 40 subjects will be enrolled to have 32 subjects for the evaluation. Approximately 
50% of the subjects will be in the VLU group and 50% of the subjects in the DFU group. 
Treatment sequence will be randomized so that a fair distribution is achieved. The total duration 
of the study will be approximately 4 weeks or 28 ± 2 days. 
Visit Schedule 
Potential study subjects will be screened for eligibility. Inclusion and exclusion criteria, vital 
signs, medical record reviews, subject demographics and informed consent will be performed 
and obtained at the Screening Visit (Day 0). If the patient meets the study eligibility criteria, he 
or she will be asked to sign consent.  Study subjects will be randomized into one of four 
treatment groups. The test wound dressing will be applied at screening (Day-0) and evaluations 
will take place twice weekly throughout the Treatment Period. The scheduled dressing change 
will be on Day 7 of each treatment week (e.g. Visit Days 7, 14, 21 and 28), unless a dressing 
change is necessary because of strikethrough loss of adherence or discomfort. There will be a 
total of 8 visits to the Wound Care Center during the Treatment Period.  During those visits, 
evaluations will be performed to assess the condition of the wound dressing, the wound, wound 
pain and patient comfort.   

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 17(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
All study evaluations will be performed by a study doctor or nurse during the follow-up visit at 
the Wound Care Center. 
 
All subjects in the VLU group will receive the same compression therapy and all subjects in the 
DFU group will receive the same off-loading footwear throughout the entire study period.      
 
Study Methods 
 
 
Wound dressings will be evaluated twice weekly by the study doctor or study nurse. All 
other evaluations will be performed once weekly before dressing change.     
 
There may be an initial debridement (at the investigator’s discretion prior to enrollment).  
 
 
Additional debridement is not allowed.   
 
Wound dressing wear time and durability will be determined by study doctors’ judgement 
and by photography. 
 
Exudate absorption and exudate dispersion will be determined clinically and by 
photodigital planimetry.  
 
Wound surface area will be measured serially using photo-digital planimetric software.  
 
Wound and surrounding skin characteristics will be evaluated by the study doctor at 
dressing change. 
 
Dressing comfort and subject-centric outcomes will be captured at the end of weeks 2 
and 4. 
 
SF12 will be captured at the initial visit and then bi-weekly 
 
Local wound pain will be evaluated using the Baker-Wong (Faces) Scale before and 
after each dressing change.   
 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 18(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
4.2 Procedures and Assessments 
4.2.1 Schedule of Assessment 
Table 2. Schedule of Assessment 
 
Assessments 
 
 
 
 
 
Screening 
& Baseline 
Visit 
(Day 0) 
 
Treatment Phase 
Week  
1  
Day 3 
(-1/+2) 
Week  
1  
Day 7 
(-1/+2) 
 
Week  
2  
Day 10 
(-1/+2) 
 
Week  
2  
Day 14 
(-1/+2) 
 
Week  
3  
Day 17 
(-1/+2) 
 
Week  
3  
Day 21 
(-1/+2) 
Week  
4  
Day 24 
(-1/+2) 
Week  
4  
Day 28 
(-1/+2) 
Inclusion/ 
Exclusion 
Criteria 
√ 
 
 
 
 
 
 
 
 
 
Informed Consent 
√ 
 
 
 
 
 
 
 
 
 
Subject 
ID 
√ 
 
 
 
 
 
 
 
 
 
Subject 
Randomization 
√ 
 
 
 
 
 
 
 
 
 
Subject 
Demography 
√ 
 
 
 
 
 
 
 
 
 
Medical/ 
Surgical History 
√ 
 
 
 
 
 
 
 
 
 
Vascular Studies 
ABI, Duplex, PVR, 
Toe Pressures 
√ 
 
 
 
 
 
 
 
 
 
Wound Assessment 
√ 
 
 
√ 
 
√ 
 
√ 
 
√ 
Performance of the 
Dressing 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Dressing 
Application 
√ 
 
 
√ 
 
√ 
 
√ 
 
 
Application of 
Compression 
Bandages or Off-
Loading Footwear 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Dressing Removal 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
Dressing change (if 
needed)2 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Concomitant 
medication 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pain Assessment 
√ 
 
 
√ 
 
√ 
 
√ 
 
√ 
Photo of the wound 
√ 
 
√5 
√ 
√5 
√ 
√5 
√ 
√5 
√ 
Photo of dressing in 
situ  
√ 
 
√4 
√4 
√4 
√4 
√4 
√4 
√4 
√4 
Photo of dressing 
√ 
 
√5 
√ 
√5 
√ 
√5 
√ 
√5 
√ 
Subject-Centric 
Outcomes 
 
 
 
 
 
√ 
 
 
 
√ 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 19(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
Health related 
quality of life SF12 
√ 
 
 
 
 
√ 
 
 
 
√ 
Reason for 
Termination 
 
 
√6 
√6 
√6 
√6 
√6 
√6 
√6 
√6 
AE/ADE/SAE/SADE
/DD 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
1 make sure subject is still eligible 
2 dressing change to be performed if there is strikethrough of exudate, i.e. loss of edge seal or adherence, leakage, 
dislodgement, etc. 
3 after dressing is applied 
4 after outer dressing/compression is removed and before investigational dressing is removed (i.e. 2 photos where 
applicable) 
5 if dressing is changed only 
6 if subject is terminated for reasons other than study completion 
In case of an unscheduled study visit, safety parameters will be assessed as well as parameters 
related to the wound status and dressing change.  
 
4.3 Study subject selection 
4.3.1 Inclusion Criteria 
1. Male and female subjects 18-85 years of age with leg and foot ulcers (i.e. VLU, DFU). 
 
2. Subject’s Ankle-Brachial Index (ABI) by Doppler is ≥ 0.7. 
3. The subject has adequate circulation to the foot to allow for healing. This must be 
demonstrated by methods described in Section 4.3.3 
 
4. Signed informed consent. 
 
5. Subject and/or caregiver must be willing and able to tolerate multi-layered compression 
bandages when applicable and offloading footwear. 
 
6. Study subject must be available and able to visit the clinic weekly for the full 4-week 
period. 
4.3.2 Exclusion Criteria 
1. Pressure ulcers should not be included. Pressure injury as defined by the National 
Pressure Ulcer Advisory Panel (NPUAP). 
2. Presence of local wound infection as determined by study doctor based on clinical signs 
and symptoms 
 
3. Subject’s ABI <0.7 or has any evidence of peripheral arterial disease (PAD). 
 
4. Subject diagnosed with malignancy other than cutaneous basal cell carcinoma. 
 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 20(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
5. Subject has received growth factor therapy (e.g. autologous platelet-rich plasma gel, 
becaplermin, bilayered cell therapy, dermal substitute, extracellular matrix e.g. amnion, 
amniotic tissue) within 2 weeks of screening date. 
 
6. Pregnancy or lactation at time of study participation. 
 
7. Subject is currently receiving or has received radiation or chemotherapy within 3 months 
of randomization. 
 
8. Subject is currently enrolled or participated in another investigational device, drug or 
biological trial within 30 days of baseline of this study.  
 
9. Present history of alcohol or drug abuse.  
 
10. Known allergy/hypersensitivity to any of the components of the dressing. 
 
11. Subject not suitable for the investigation according to the investigator’s judgment. 
4.3.3 Evaluations 
 
1. Vascular testing (ABI or PVR or other non-invasive vascular examination) by one of the 
following methods: 
• 
The subject has a palpable pulse on the study foot (either dorsalis pedis or posterior 
tibial artery) and has clinical signs of adequate circulation in the foot (e.g., toes are 
warm and pink). 
• 
If there are either no palpable pulses or clinical signs of adequate circulation are 
lacking, the Principal Investigator must perform an additional assessment to assure 
that there is adequate circulation to the leg and foot: Transcutaneous oxygen tension 
(TcPo2), photoplethysmography (PPG), Toe-Arm Index, Doppler wave form, 
Cardiosynchronous Limb Compression (CSC), Pulse Volume Recording (PVR) or 
exercise Ankle-Brachial Index (ABI).  Determination of adequate circulation must be 
according to generally accepted criteria for the particular test employed. The 
additional assessments must be documented in the subject’s source document and 
Case Report Form. 
2. Abbreviated physical exam, medical/surgical history, demographic information, 
concomitant medications and history of non-healing, weight for Body Mass Index (BMI) 
3. High resolution ultrasonography (Duplex) to confirm CVI diagnosis and rule out DVT 
4. Pre-debridement photos, wound measurements including surface area 
5. Informed Consent Process, Inclusion/Exclusion Criteria 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 21(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
4.3.4 Withdrawal of Subjects from Treatment or Assessment  
A subject may be discontinued from the study at any time if the subject, the Investigator, or the 
Sponsor feels that it is not in the subject’s best interest to continue.  The following is a list of 
possible reasons for study treatment discontinuation:  
• Screen failure 
• Subject withdrawal of consent  
• Subject is not compliant with study procedures 
• AE that in the opinion of the Investigator would be in the best interest of the subject to 
discontinue study participation 
• Protocol violation requiring discontinuation  
• Lost to follow-up 
• Sponsor request for early termination of study 
• Subject death 
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. Reasonable attempts will be made by the Investigator to 
provide a reason for subject withdrawals. The reason for the subject’s withdrawal from the study 
will be specified in the subject’s source documents and the Case Report Form (CRF).   
If a subject is withdrawn from treatment due to an AE, the subject will be followed and treated by 
the Investigator until the abnormal parameter or symptom has resolved or stabilized. 
The Investigator must make every effort to contact subjects who are lost to follow-up.  Three (3) 
attempted telephone contacts should be documented by key research personnel in order to 
consider the participant lost to follow-up. Furthermore, a certified letter will be mailed to the 
participant’s address. If the participant does not respond, the certified letter receipt should be 
filed in the individual’s research record with a copy of the letter sent. Attempts to contact such 
subjects must be documented in the patients’ records (e.g., times and dates of attempted 
telephone contact, receipt for sending a registered letter, etc.). 
 
Handling of Participant Withdrawals or Termination 
Although subjects may withdraw from the study at any time and for any reason, (or may be 
withdrawn at the Investigator’s discretion), subject withdrawal should be avoided as much as 
reasonably possible.  In any case, appropriate follow-up for endpoints should be continued.  
The reason for study discontinuation will be recorded on the subject’s source document and 
CRF. 
Subjects who prematurely discontinue are not to be replaced.  For subjects considered lost to 
follow-up, the CRF must be completed up to the last visit performed. 
Premature Termination or Suspension of Study 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 22(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to the Investigator, the 
Sponsor and the Institutional Review Board (IRB), as appropriate.  If the study is prematurely 
terminated or suspended, the Investigator will promptly inform the IRB and will provide the 
reason(s) for the termination or suspension.  
Circumstances that may warrant termination or suspension include, but are not limited to:  
• Determination of unexpected, significant, or unacceptable risk to participants  
• Demonstration of efficacy that would warrant stopping  
• Insufficient compliance to protocol requirements  
• Data that are not sufficiently complete and/or evaluable  
• Determination of futility  
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed and satisfy the Sponsor and/or the IRB. 
4.4 Investigational Device 
4.4.1 Summary description of the Investigational Device and Comparators 
For full package inserts of all study dressings see Appendix B 
Investigational Device 
Study dressing 1 (T1) 
Bordered, five-layer, flexible foam dressing with soft silicone adhesive technology 
(Mepilex® Border Flex, Mölnlycke Health Care) 
 
Study dressing 2 (T2) 
Hydropolymer, adhesive foam island dressing 
(Optifoam Gentle EX, Medline Industries) 
 
Study dressing 3 (T3) 
Multi-layered, hydrocellular foam dressing with silicone adhesive 
(Allevyn Life, Smith and Nephew, Inc.)  
4.4.2 Labelling 
All devices under investigation in this study have a market authorization in US.  They will be 
supplied with their standard product labelling, and no study-specific labelling will be applied. 
4.4.3 Accountability 
Full device accountability will be performed on all the Investigational Devices: Mepilex® Border 
Flex, Allevyn Life and Optifoam. Mepilex® Border Flex will be provided to the investigation site 
by Mölnlycke Health Care free of charge.  Allevyn Life and Optifoam dressings will be shipped 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 23(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
directly to site via an independent distributor and the costs of these dressing will be reimbursed 
to the site by Mölnlycke Health Care. 
4.4.4 Storage conditions 
All study dressings should be stored in dry conditions, below 35°C, and be protected from direct 
sunlight. All study dressings will be stored in a locked and secured space with restricted access. 
The study dressings will be kept separately from normal hospital inventory. 
 
4.4.5 Returns and Destruction 
According to instructions specified in the Clinical Trial Agreement with the hospital. 
4.4.6 Method of Assigning Subjects to Device Groups 
Each subject will be randomized to one of four treatment groups as follows: 1) Mepilex® Border 
Flex, Allevyn Life cross-over group; 2) Allevyn Life, Mepilex® Border Flex crossover group; 3) 
Mepilex® Border Flex, Optifoam cross-over group and; 4) Optifoam, Mepilex® crossover group. 
A computer-generated randomization schedule will be provided by Pharma Consulting Group 
(PCG). 
 
4.4.7 Sizes to be used of Investigational Devices 
Test dressing pad size should be >60% of the surface area of the wound. The following 
dressing sizes will be used: 
 
Sizes for VLU 
Mepilex® Border Flex: 10x10cm (6.5x6.5cm pad) and 15x15cm (11x11cm pad) 
Optifoam Gentle EX: 10.2x10.2cm (6.3x6.3cm pad) and 15.2x15.2cm (11.4x11.4cm pad) 
Allevyn Life: 10.3x10.3cm (5.1x5.1cm pad) and 15x15cm (10.2x10.2cm pad) 
 
Sizes for DFU 
Mepilex® Border Flex: 15x15cm (11x11cm pad) 
Optifoam Gentle EX: 15.2x15.2cm (11.4x11.4cm pad) 
Allevyn Life: 15x15cm (10.2x10.2cm pad) 
 
4.5 Concomitant Treatments 
Standard Static Compression Therapy:  
All subjects with VLU will have their affected leg treated with one of two static compression 
bandage systems:  
1. Modified Unna’s Boot (Unna’s paste bandage plus cohesive bandage)   
2. 4-Layer Compression Bandage System     

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 24(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
The Compression bandages are removed and reapplied at each dressing evaluation/change.  
Off-Loading Footwear:  
All subjects with DFU will have their affected foot treated with the following off-loading footwear: 
1. OPTIMA® Diabetic boot with the appropriate insole kit based on subject weight and 
wound size and make the boot non-removable by using the locking system. 
Any additional post-operative medication which is considered necessary for the subject’s safety 
and well-being is permitted, However, topical medication applied to the wound is not allowed. All 
concomitant medication and relevant treatment must be recorded in the appropriate section of 
the (CRF).  
4.6 Efficacy and Safety 
4.6.1 Subject Baseline Characteristics 
 
Date of birth 
DD/MMM/YYYY
Gender  
Male/Female/other
Vital signs  
 
Height (cm/ft and in) 
Weight (kg/pounds) 
BMI (kg/m2)
Relevant current medical 
history 
Relevant such as diabetes, 
arterial disease lower leg, 
anemia, cardio-vascular 
disease, thrombosis, that 
may affect the evaluation of 
dressings performance 
Medical condition 
Date of initial diagnosis/procedure 
Past/current 
Ongoing medication 
Relevant surgical 
history 
Relevant such as varicose 
vein, amputation defined as 
surgery that may affect the 
evaluation of dressings 
performance. 
Surgical procedure 
Date of surgical procedure 
Ongoing medication 
Type of wound 
Venous leg ulcer 
Diabetic foot ulcer 
Wound location 
VLU 
Right lower leg 
Left lower leg 
Medial/Lateral 
Below Malleolus 
Above Malleolus 
DFU 
Right foot 
Left foot 
Plantar surface (Y/N) 
Toe (specify)  
Forefoot 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 25(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
Midfoot 
Heel 
Other (specify) 
Wound history 
Responded to previous treatment (Y/N) 
Debridement procedure (type and 
instrument) 
Number of wounds  
Duration of target wound  
<1week 
≥1 week to <6 weeks 
≥6 weeks to <12 months 
≥12 months 
Wound status 
Type of Wound Drainage 
(Serous, Sanguineous, Serosanguinous, 
Purulent) 
 
Exudate amount 
(None, Scant/minimal, Moderate, Heavy) 
 
Wound size (from pictzar) 
Previous dressing 
Number of days 
Brand name of dressing 
Reason for dressing change 
Compression type 
Duration of compression 
Off-loading 
Condition of surrounding skin 
and wound bed 
Condition of surrounding skin 
(Healthy/not healthy) 
 
Inflammatory signs (Y/N) 
 
Skin irritation at dressing site (Y/N) 
 
Allergic rash/eczema (Y/N) 
 
Blistering (Y/N) 
 
Skin maceration 
(None, Slight, Moderate, Severe) 
 
Dressing application  
Dressing size  
Type of compression 
Off-loading (Y/N) (if yes, specify) 
Photo of the wound  
Y/N 
Photo of the dressing in situ after 
first initial application 
Y/N 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 26(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
 
4.6.2 Efficacy Measurements and Variables 
 
Primary Endpoint 
Outcome variable 
The Mepilex® Border 
Flex versus Optifoam 
and Allevyn Life 
dressings. 
 
Interval of time (measured in days) to strikethrough, i.e. loss 
of edge seal/adherence, leaks, dislodgement. 
 
Secondary Endpoints 
Outcome variable 
Dressing evaluation 
Unchanged - Dressing looks the same as when put on the 
wound. 
Partly Saturated - Dressing is <50% saturated with exudate 
but remains intact. 
Mostly Saturated – Dressing is >50% saturated with 
exudates 
Strike-through – Dressing is completely saturated and 
exudates have leaked outside the bandage.  
 
Clinical wound 
characteristics during 
wound management 
with each of the test 
dressings (in 
combination with 
standard care). 
 
Wound status 
 
Type of Wound Drainage 
(Serous, Sanguineous, Serosanguinous, Purulent) 
 
Exudate amount 
(None, Scant/minimal, Moderate, Heavy) 
 
Exudate Absorption 
(Very Poor/Poor/Good/Very Good/NA) 
 
Exudate Dispersion 
1. wound exudate dispersed 1-25% of pad 
2. wound exudate dispersed 26-50% of pad 
3. wound exudate dispersed 51-75% of pad 
4. wound exudate dispersed 76-100% 
5. Is wound dressing completely saturated with no strike 
through 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 27(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
6. Is wound dressing completely saturated with strike 
through 
 
Wound granulation 
None 
Trace islands of granulation tissue, less than 25%  
25% - 49% Wound base is covered with granulation tissue 
50% - 74% Wound base is covered with granulation tissue 
75% - 99% Wound base is covered with granulation tissue 
100% - Wound base completely filled with granulation tissue 
 
(%, captured via photodigital planimetry and visual 
judgement by research doctor/nurse) 
 
Non-viable tissue  
(eschar, fibrin slough, both) 
None  
Less than 25%  
25% - 49%  
50% - 74%  
75% - 100% 
 
(captured via photodigital planimetry and visual judgement 
by research doctor/nurse as above) 
 
Wound size 
(captured via photodigital planimetry) 
 
Rate of wound healing 
(%, captured via photodigital planimetry) 
 
 
Condition of surrounding skin (Healthy/not healthy) 
 
Signs of inflammation (erythema, edema, induration) (Y/N) 
 
Signs of skin irritation at dressing site (Y/N) 
 
Skin rash/skin erosion, eczema (Y/N) 
 
Stasis dermatitis (Y/N)

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 28(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
 
Vesicular erosion (blistering) (Y/N) 
 
Skin maceration (None, Slight, Moderate, Severe) 
 
 
Clinical signs/symptoms of acute infection 
 
Increased pain and tenderness (Y/N) 
Increased warmth (Y/N) 
Sudden increase in ulcer size (Y/N) 
Is there localized Erythema (Y/N) 
Foul smelling exudates (Y/N) 
Does the wound bleed easily (Y/N) 
 
Wound odor (before and after cleansing) 
(None, Minimal, barely noticeable, Moderate, noticeable but 
not offensive, Moderate, offensive, Putrid) 
 
Safety Evaluation 
 
Number of device related safety events associated with 
each of the wound dressings (ADEs/SADEs/DDs) 
 
 
Patient-centric 
outcomes. 
 
Patient Reported outcomes 
 
Pain 
 
Local wound and skin pain before dressing removal 
(Baker-Wong) 
 
Pain at removal 
(Baker-Wong) 
 
Pre-procedural or intra-procedural pain medication 
administration at the time of dressing removal 
(Concomitant Medical) 
 
Local wound and skin pain immediately after dressing 
removal 
(Baker-Wong) 
 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 29(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
12-item Short Form Survey (SF12) 
 
Comfort and conformability 
 
Comfort during wear of the dressing 
(Very Poor/Poor/Good/Very Good/NA) 
 
Overall impression of the dressing 
(Very Poor/Poor/Good/Very Good/NA) 
 
Bulkiness of the dressing 
(Very Poor/Poor/Good/Very Good/NA) 
 
Friction of the dressing 
(Very Poor/Poor/Good/Very Good/NA) 
 
Appearance of dressing is discreet 
(Very Poor/Poor/Good/Very Good/NA) 
 
The stay-on-ability of the dressing 
(Very Poor/Poor/Good/Very Good/NA) 
 
Dressing stick to “hairy” skin 
(Very Poor/Poor/Good/Very Good/NA) 
 
Showerablility of the dressing 
(Very Poor/Poor/Good/Very Good/NA) 
 
 
Investigator Reported outcomes 
 
Ease of handling 
(Very Poor/Poor/Good/Very Good/NA) 
 
Ability to maintain its integrity 
(Very Poor/Poor/Good/Very Good/NA) 
 
Ease of application 
(Very Poor/Poor/Good/Very Good/NA) 
 
Ability to be repositioned 
(Very Poor/Poor/Good/Very Good/NA) 
 
Conformability 
(Very Poor/Poor/Good/Very Good/NA) 
 
Ability to stay in place 
(Very Poor/Poor/Good/Very Good/NA) 

 
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Ease of removal 
(Very Poor/Poor/Good/Very Good/NA) 
 
Does the dressing cause skin stripping (Y/N) 
 
Presence of material remnant (None, Some) 
 
Is dressing adherent to the wound bed? 
(No/Yes, mild adhesion without bleeding/Yes, 
severe adhesion with bleeding) 
 
Wound re-injury or trauma to skin upon removal  
  (Y/N) 
 
Exudate absorption even under compression (Y/N) 
 
Trauma to wound edges (Y/N) 
 
Additional Endpoint 
Outcome variable 
 
Safety Evaluation 
 
Number of safety events, not device related, associated with 
each of the wound dressings (AEs/SAEs) 
 
Health Economics 
Endpoint 
Outcome variable 
 
To retrospectively 
compare cost 
effectiveness 
parameters of each of 
the study dressings 
 
Health Economics  
 
To retrospectively compare resource-use as related to: 
  
• 
Quantity of dressing changes per week (stratified 
by wound type) 
 
• 
Time required per dressing change (in minutes) 
a. Start time: Initiation of old dressing removal 
b. End time: New dressing is securely in place 
 
• 
Staff cost associated with dressing change 
a. Identification of those involved with dressing 
change (e.g., MD, Nurse, Assistant, etc.) 
b. Average hourly rate for those individuals 
directly involved with dressing change (This 
can be market data if individuals do not want 
to provide actual salary information) 
 
•
Material Cost

 
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a. Quantity of each product (dressing) used per 
week 
b. Size of dressings used 
c. Cost of each dressing used per week 
d. Other material cost used in dressing change 
i. Identification of products used per 
week 
ii. Quantity of each product used per 
week 
iii. Cost of each product used per week 
 
• 
Additional medication or management to 
address pain or injury during dressing removal  
 
 
 
4.6.3 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 clinical 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 and/or trauma since last dressing change 
• 
Foul odor 
• 
High levels of exudates 
4.6.4 Anticipated ADEs  
The conclusion of the Product Risk Management Record (PD-518122 rev 05) and the Clinical 
Evaluation Report (PD-511948 rev 3) of Mepilex® Border® is: Mepilex® Border has substantial 
support for both performance and safety given the substantial amount of clinical investigations 
performed on the device, together with the low risk and long term performance and safety of the 
device. Before reaching the above conclusion, the identified risks of the investigational device 
were mitigated to an acceptable level in the risks analysis process (following ISO 14971, 
Application of Risk Management to Medical Devices). 
The following events have been identified as anticipated effects in the Clinical Evaluation Report 
based on the Product Risk Management Record:   
• 
Pain at dressing removal 
• 
Trauma to the wound bed or surrounding skin 
• 
Skin stripping/irritation 

 
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• 
Skin irritation or local allergic reactions 
• 
Maceration 
• 
Infection 
All identified risks have been assessed. It is concluded that all applicable risk mitigation actions 
have been performed and verified to be effective. No unacceptable risks remain. Thus, the 
benefit of using the products outweighs the remaining risks. 
The Principal Investigator or designee is responsible for judging whether the appearance of any 
of the above mentioned events are considered to be AEs or adverse device effects (ADEs). If 
this is the case, the event must be reported in the applicable section of the electronic Case 
Report Forms (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 AE or ADE 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 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 
CRF. Source data verification (a comparison of data in the CRF with the subject’s 
hospital/practice and other records at the investigation site) with direct access to records will 
also be performed. 
The monitor or other Mölnlycke Health Care  personnel will be available between visits if the 
investigator or other staff at the site needs information and/or advice. 
Authorized representatives of Mölnlycke Health Care 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. 
 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
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© Mölnlycke Health Care 2018 November 
 
 
 
 
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: 
• Compilation of an eCRF  
• Randomization 
• Set-up of eCRF and database 
• Specification of on-line checks 
• Data entry / Data editing 
• Export of data from Viedoc to SAS 
• Creation of post-entry checks and listings 
• Reconciliation of (SAE), (SADE), (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 Mölnlycke Health Care can immediately 
view the data, send queries if necessary and lock eCRF pages when they have been validated.  
Photos will be uploaded in Viedoc and are marked with the subject code. Uploaded photos shall 
not contain any information that can reveal the identity of the subject. All uploaded photos will 
be reviewed by personnel at Mölnlycke Health Care 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 Mölnlycke Health Care 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. 

 
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                                                                          Central Amendment 2 Approval date 
 
 
 
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© Mölnlycke Health Care 2018 November 
 
 
 
 
A clean-file meeting will be held prior to database lock. All decisions on the evaluability of the 
data from each individual subject for the statistical analysis must be made and documented 
before locking the database.] 
 
4.8 Statistical Methods and Determination of Sample Size 
4.8.1 Statistical Evaluation 
Two cross-over studies AB/BA will be performed. In the first one Mepilex® Border Flex will be 
compared with Optifoam and in the second one Mepilex® Border Flex will be compared with 
Allevyn Life. Exactly the same statistical methods will be used in both these cross-over studies. 
In this statistical section Optifoam and Allevyn Life will be substituted with active control. 
 
Primary efficacy variable, days to strikethrough, and probably all of the other efficacy variables 
are 
non-normal 
distributed. 
Therefore, 
non-parametric 
tests 
are 
used. 
 
it is likely the status of the wounds will be better in the second period of the cross-over. This 
implies that the statistical analysis must adjust for period effect in the AB/BA crossover study. 
For primary efficacy variable days to strikethrough, all other continuous outcome variables, all 
ordered categorical variables and all dichotomous variables the adjustment for period effect will 
be performed in the following way: 
For all subjects the difference in the efficacy variable between Period 2 and Period 1 in the 
cross-over will be calculated.  
These differences will then be compared between subjects started with Mepilex® Border Flex in 
Period 1 and subjects started with active control in Period 1 with an optimal two-sided two-
sample test. For continuous variables the differences will be analyzed with Fisher’s non-
parametric permutation tests between the two groups and for ordered categorical variables and 
dichotomous variables the differences, number and percentages improved, not changed and 
worsened, will be analyzed with Mantel-Haenszel Exact Chi-square test.  
The main statistical analysis will be performed on the full analysis set (ITT). Complementary 
statistical analysis will be performed on the Per Protocol (PP) set. 
The Full Analysis Set will include all subjects with at least one measurement of follow up. The 
Per Protocol population will include all subjects that fulfil all inclusion/exclusion criteria and that 
are not described as protocol violators. They should have been followed for the 2x2 weeks 
treatment period. Subjects identified as protocol violators will be documented and agreed 
between Mölnlycke Health Care and the Principal Investigator before declaration of clean-file, 
please see Section 4.7. 
The Safety population include all subjects that have at least one application of the Mepilex® 
Border dressing or at least one of the other study dressings. 

 
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© Mölnlycke Health Care 2018 November 
 
 
 
 
The distribution of continuous variables and change in continuous variables will be given as 
mean, standard deviation, median, minimum and maximum and the distribution of categorical 
and dichotomous variables will be given as numbers and percentages. 
All statistical tests will be two-sided and conducted at the 5% significance level. 
A baseline table will be given for all included subjects with the distribution of demographics and 
baseline variables. 
 
4.8.2 Primary Efficacy Analysis 
Primary efficacy analysis comparison of days to strikethrough between Mepilex® Border Flex 
and active control will be performed on the full analysis set (FAS) in the following way. 
 
For subjects randomized to Mepilex® Border Flex in the first period the difference in days to 
strikethrough between period 2 (active control) and period 1 (Mepilex® Border Flex) will be 
compared to subjects randomized to active control in the first period regarding the differences in 
days to strikethrough between period 2 (Mepilex® Border Flex) and period 1 (active control) 
with two-sided Fisher’s non-parametric permutation tests at significance level 0.05. Period 
adjusted mean differences in days to strikethrough between Mepilex® Border Flex and active 
control will be given with 95% confidence interval based on Fisher’s non-parametric permutation 
tests. 
 
In both cross-over studies, Mepilex® Border Flex compared to Optifoam study and Mepilex® 
Border Flex compared to Allevyn Life, the same above analysis will be the primary analyses. 
Since there are two separated studies no multiplicity adjustment will be performed. 
4.8.3 Determination of Sample Size 
The expected mean differences in days to strikethrough between the differences Period 1-
Period 2 between the two groups Mepilex® Border Flex and active control will be two times the 
difference in the effect Mepilex® Border Flex minus active control. 
We estimate (assume) the SD for the difference in time to strikethrough between Period 2 and 
Period 1 to be 0.65 days both in the group started with Mepilex® Border Flex and in the group 
started with active control.  
In order to find a difference in one half day between days to strikethrough between Mepilex® 
Border Flex and active control with a power of 80% a total of 16 evaluable subjects is needed. 
This implies that in the first cross-over study 16 subjects will be randomized to the sequence 
Mepilex® Border Flex in the first period and Optifoam in the second period and to the sequence 
Optifoam in the first period and Mepilex® Border Flex in the second period in proportions 1:1. 
 
In the second cross-over study 16 subjects will be randomized to the sequence Mepilex® 
Border Flex in the first period and Allevyn Life in the second period and to the sequence Allevyn 
Life in the first period and Mepilex® Border Flex in the second period in proportions 1:1. Both 

 
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© Mölnlycke Health Care 2018 November 
 
 
 
 
the randomizations above will be stratified by diagnosis Venous Leg Ulcer / Diabetic Foot Ulcer. 
 
A total of 32 subjects will be included in the two cross-over studies. 
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 Mölnlycke Health Care. 
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. 
Mölnlycke Health Care  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. 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 is responsible for 
informing the EC/IRB of any amendment to the Clinical Investigation Plan as per local 
requirements. 
 
5.1.2 Ethical Conduct of the Investigation 
The clinical 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 

 
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© Mölnlycke Health Care 2018 November 
 
 
 
 
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 D). If 
modifications are made according to local requirements, the new version must be approved by 
Mölnlycke Health Care. 
 
5.2 Regulatory and standards 
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 clinical investigation. Mölnlycke Health Care is 
responsible for informing the CA of any amendment to the Clinical 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. 21 CFR 50 
Protection of Human Subjects, 21 CFR 56 Institutional Review Boards and 21 CFR 54 Financial 
Disclosure. The abbreviated requirements as described in 21 CFR 812.2(b).  
 
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 authorized 
representatives of Mölnlycke Health Care 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 Mölnlycke Health Care 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. 
 

 
Clinical Investigation Plan 
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Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
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© Mölnlycke Health Care 2018 November 
 
 
 
 
5.3.2 Insurance 
Mölnlycke Health Care AB has product liability insurance, which also covers test products. 
  
6. INVESTIGATION TIMETABLE AND TERMINATION 
 
Investigation start: November 2018 
Inclusion completed: May 2019 
Last subject out: June 2019 
 
The investigation could be prematurely discontinued if the dropout rate is higher than 15% 
and/or the investigation site is unable to fulfill the inclusion period according to the Clinical Trial 
Agreement. 
  
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. 
Gould L, Abadir P, Brem H, Carter M, Conner-Kerr T, Davidson J, et al. Chronic wound 
repair and healing in older adults: Current status and future research. Wound Repair and 
Regeneration. 2015;23(1):1-13. 
2. 
Young T, Clark M, Augustin M, Carville K, Curran J, Flour M, et al. International 
consensus. Optimising wellbeing in people living with a wound. An expert working group 
review. Wounds International. 2012. 
3. 
Tickle J. Wound exudate: a survey of current understanding and clinical competency. 
British Journal of Nursing. 2016;25(2):102-9. 
4. 
Rippon M, Davies P, White R. Taking the trauma out of wound care: the importance of 
undisturbed healing. Journal of Wound Care. 2012;21(8):359-68. 
5. 
Davies P, Rippon M. Evidence review: the clinical and economic benefits of Safetac 
technology in wound care Medical Communications UK. 2011. 
6. 
Van De Looverbosch D, Andersson A, Husmark A, Körner V. An open randomized 
explorative study comparing Mepilex® Border with Tielle in patients with pressure ulcers 
according to stage ll, EPUAP guidelines. Clinical Investigation Report (MPXB201), 
Mölnlycke Health Care. 2001. 
7. 
White R. A multinational survey of the assessment of pain when removing dressings. 
Wounds UK. 2008;4:14-22. 

 
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2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
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© Mölnlycke Health Care 2018 November 
 
 
 
 
8. 
Woo K, Bergström C. An Open Randomised Cross-over Investigation Assessing 
Perceived Pain at Dressing Change Comparing A Soft Silicone Dressing, Mepilex® 
Border, with a Adhesive hydrocellular polyurethane dressing, Allevyn® Adhesive in 
Patients with chronic ulcer. Clinical Investigation Report (MXB408, Part A, Mölnlycke 
Health Care). 2007. 
9. 
Rippon M, Waring M, Bielfeldt S. An evaluation of properties related to wear time of four 
dressings during a five-day period. Wounds UK. 2015;11(1):45-54. 
10. 
Benbow M. The expense of exudate management. British Journal of Nursing. 
2015;24(15):S8. 
11. 
Faucher N, Safar H, Baret M, Philippe A, Farid R. Superabsorbent dressings for 
copiously exuding wounds. British Journal of Nursing. 2012;21((12 SUPPL.)):S22-S8. 
12. 
Moore Z, Strapp H. Managing the problem of excess exudate. British Journal of Nursing. 
2015;24(15 (Tissue Viability Supplement)). 
13. 
Rafter L, Anthony D, Collier M, Rafter M. Stopping the strikethrough: An audit of patient 
outcomes on four superabsorbent dressings. Wounds UK. 2015;11(4):60-7. 
14. 
Chadwick P, McCardle J. Exudate management using a gelling fibre dressing. The 
Diabetic Foot Journal. 2015;18(1):43-8. 
15. 
González de la Torre H, Quintana-Lorenzo M, Perdomo-Pérez E, Verdú J. Correlation 
between health-related quality of life and venous leg ulcer's severity and characteristics: 
a cross-sectional study. International Wound Journal. 2016. 
16. 
Jones J, Robinson J, Barr W, Carlisle C. Impact of exudate and odour from chronic 
venous leg ulceration. Nursing Standard. 2008;22(45):53-61. 
17. 
Pukki T, Tikkanen M, Halonen S. Assessing Mepilex® (registered trademark) border in 
post-operative wound care. Wounds UK. 2010;6:30-40. 
18. 
Woo K, Thorell J. An open, randomised, cross-over investigation assessing perceived 
pain at dressing change comparing a soft silicone dressing, Mepilex® Border, with an 
adhesive hydrocellular polyurethane dressing, Allevyn, in patients with chronic ulcers 
Clinical Investigation Report (MXB408, Part B), Mölnlycke Health Care. 2008. 
19. 
Registry study Bordered foam products (including Mepilex® Border). PowerPoint 
presentation GVW [unpublished data]. 2016. 
 
 

 
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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 SADE 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 AEs 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: 

 
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a) 
led to death, 
b) 
led to a serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) inpatient 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 fetal distress, fetal 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 SAE. 
 
Serious Adverse Device Effect (SADE) 
ADE that has resulted in any of the consequences characteristic of a SAE.   
 
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 , within 1 calendar day of awareness of the 
event. When a SAE/SADE has been entered into the eCRF by the investigator /authorized 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 or the comparator. 
 

 
Clinical Investigation Plan 
Document ID:  PD-545909 Rev: 01 
 
 
Title: CIP_MxBFlex_02 with Integrated Central Amendment 1 and 2 
Page 42(42) 
Investigation Code MxBFlex_02 
Final Version 
Approval date 
2018-06-19 
                                                                         Central Amendment 1  Approval date 
2018-11-08 
                                                                          Central Amendment 2 Approval date 
 
 
 
Clinical Investigation Plan 
MxBFlex02 
© Mölnlycke Health Care 2018 November 
 
 
 
 
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. 
 
PROCEDURES FOR DD REPORTING  
All DD shall be reported to Mölnlycke Health Care 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 /authorized site staff, the eCRF system will automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com  
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  
 
Procedures for ADE reporting 
All ADE shall be reported by the investigator to Mölnlycke Health Care as soon as possible 
without unjustified delay. When a ADE has been entered into the eCRF by the investigator 
/authorized site staff, the eCRF system will automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com 
This includes also ADEs occurring in the comparator arm. 
 
Causality Assessment 
The relationship between the use of the investigational device or comparator and the 
occurrence of each AE/SAE shall be assessed by the investigator and the sponsor and 
classified as device related or not related to the device.