Silicone Adhesive Multilayer Foam Dressings as Adjuvant Prophylactic Therapy for Pressure Ulcer (PU) Prevention: a Multicentric Randomised Open Label Parallel Group Medical Device Trial in Hospitalised Patients at Risk of PU Development
Phase: NA
Conditions: Pressure Ulcer
Sponsor: Belgium Health Care Knowledge Centre

PROTOCOL KCE-16012 
THE USE OF A SILICONE ADHESIVE MULTILAYER FOAM 
DRESSING AS AN ADJUVANT PROPHYLACTIC THERAPY 
FOR PRESSURE ULCER PREVENTION: A MULTICENTRE 
RANDOMISED 
OPEN 
LABEL 
PARALLEL 
GROUP 
MEDICAL DEVICE TRIAL IN HOSPITALISED PATIENTS AT 
RISK OF PRESSURE ULCER DEVELOPMENT 

Clinical Investigation Plan: KCE-16012 
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Version 2.0, 11-Jan-2018 
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TABLE OF CONTENTS 
GENERAL INFORMATION .................................................................................. 4
KEY STUDY CONTACTS ..................................................................................... 7
STUDY SUMMARY .............................................................................................. 8
FUNDING ........................................................................................................... 13
ROLES AND RESPONSIBILITIES OF STUDY MANAGEMENT 
COMMITEES/GROUPS & INDIVIDUALS ........................................................... 13
LIST OF ABBREVIATIONS ................................................................................ 16
1
INTRODUCTION ................................................................................................ 18
1.1
BACKGROUND ................................................................................................................. 18
1.2
RATIONALE ....................................................................................................................... 22
1.2.1
Assessment and management of risk ................................................................. 23
2
OBJECTIVE AND PRIMARY ENDPOINT .......................................................... 24
2.1
OBJECTIVE ....................................................................................................................... 24
2.2
PRIMARY ENDPOINT ....................................................................................................... 24
3
INVESTIGATIONAL PLAN ................................................................................. 24
3.1
STUDY DESIGN ................................................................................................................ 24
3.2
INVESTIGATION POPULATION ....................................................................................... 24
3.2.1
Eligibility criteria ................................................................................................... 25
3.2.2
Prohibition and restrictions .................................................................................. 26
3.2.3
Discontinuation of study ...................................................................................... 27
3.2.4
Discontinuation of study intervention. .................................................................. 28
3.3
INVESTIGATIONAL PRODUCTS...................................................................................... 29
3.3.1
Identity of the investigational devices .................................................................. 29
3.3.2
Product insert ....................................................................................................... 30
3.3.3
Device storage and supply .................................................................................. 31
3.3.4
Contra-indications for use .................................................................................... 31
3.3.5
Concomitant medication/devices ......................................................................... 32
4
STUDY ASSESSMENTS .................................................................................... 33
4.1
FLOWCHART .................................................................................................................... 33
4.2
ASSESSMENTS ................................................................................................................ 34
4.3
RECRUITMENT ................................................................................................................. 35
4.3.1
Patient identification ............................................................................................ 35
4.3.2
Braden Scale ....................................................................................................... 36
4.4
VARIABLES TO BE COLLECTED ..................................................................................... 36
4.4.1
Pre-randomisation ............................................................................................... 36
4.4.2
Randomisation and post- randomisation ............................................................. 37
4.4.3
Daily assessments (as of the day after randomisation)....................................... 37
4.4.4
End of study evaluation: day 14 or day when a patient ends study .................... 38
4.4.5
Image acquisition ................................................................................................. 38
5
END OF STUDY ................................................................................................. 38
6
SAFETY REPORTING ........................................................................................ 39
6.1
DEFINITIONS .................................................................................................................... 39
6.2
EVENTS REPORTABLE BY THE PI ................................................................................. 40

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6.3
EVENTS REPORTABLE BY THE SPONSOR OR ITS DELEGATE ................................. 41
6.4
REPORTABLE INFORMATION BY THE PI AND THE SPONSOR .................................. 41
6.5
HOW TO REPORT ............................................................................................................ 41
6.5.1
 .................................................................................. 41
6.5.2
 ..................................................................................... 42
7
BIOSTATISTICAL ASPECTS ............................................................................. 42
7.1
TRIAL DESIGN AND HYPOTHESIS. ................................................................................ 42
7.2
SAMPLE SIZE CALCULATION ......................................................................................... 43
7.3
ANALYSIS SET.................................................................................................................. 43
7.4
METHODS OF STATISTICAL ANALYSIS. ....................................................................... 44
7.4.1
General statistical considerations ........................................................................ 44
7.4.2
Demographics and baseline characteristics. ....................................................... 44
7.4.3
Efficacy evaluation ............................................................................................... 44
7.4.4
Safety evaluation ................................................................................................. 45
7.5
RANDOMISATION ............................................................................................................. 45
7.6
INTERIM AND FINAL ANALYSIS ...................................................................................... 45
8
MATERIAL ......................................................................................................... 46
8.1
DATA COLLECTION TOOLS AND SOURCE DOCUMENT IDENTIFICATION ............... 46
8.2
TRIAL MASTER FILE ........................................................................................................ 46
9
DATA HANDLING AND RECORD KEEPING .................................................... 46
9.1
ACCESS TO DATA ............................................................................................................ 46
9.2
ARCHIVING ....................................................................................................................... 47
10
MONITORING & AUDIT ..................................................................................... 47
10.1
MONITORING ..................................................................................................... 47
10.2
AUDIT ................................................................................................................. 47
11
ETHICAL AND REGULATORY CONSIDERATIONS ......................................... 48
11.1
ETHICS COMMITTEE ........................................................................................ 48
11.2
PATIENT INFORMED CONSENT ...................................................................... 48
11.3
PUBLIC AND PATIENT INVOLVEMENT ........................................................... 48
11.4
REGULATORY COMPLIANCE .......................................................................... 48
11.5
PROTOCOL COMPLIANCE ............................................................................... 49
11.6
NOTIFICATION OF SERIOUS BREACHES TO GCP AND/OR THE PROTOCOL
............................................................................................................................ 49
11.7
DATA PROTECTION AND PATIENT CONFIDENTIALITY ................................ 49
11.8
FINANCIAL AND OTHER COMPETING INTERESTS........................................ 49
11.9
INDEMNITY ........................................................................................................ 50
11.10
POST-STUDY CARE .......................................................................................... 50
12
DISSEMINATION POLICY ................................................................................. 50
13
REFERENCES ................................................................................................... 51
APPENDIX 1: EQ-5D-5L INSTRUMENT ......................................................................... 53

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GENERAL INFORMATION 
FULL TITLE OF THE STUDY 
The use of a silicone adhesive multilayer foam dressing as an adjuvant prophylactic therapy for 
pressure ulcer prevention: a multicentre randomised open label parallel group medical device trial in 
hospitalised patients at risk of pressure ulcer development. 
SHORT STUDY TITLE  
Silicone adhesive multilayer foam dressings to prevent pressure ulcers.  
PROTOCOL VERSION NUMBER AND DATE 
Version 2.0, 11 Jan 2018 
RESEARCH REFERENCE NUMBERS 
EudraCT Number: 
Not Applicable 
KCE Number: 
KCE-16012

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SIGNATURE PAGE 
Title: The use of a silicone adhesive multilayer foam dressing as an adjuvant prophylactic therapy 
for pressure ulcer prevention: a multicentre randomised open label parallel group medical device trial 
in hospitalised patients at risk for pressure ulcer development. 
This medical device Clinical Trial Protocol has been reviewed and approved by the sponsor, the 
Chief Investigator and the Statistician. The undersigned agree to conduct the study in compliance 
with the approved protocol and will adhere to the principles outlined in the GCP guidelines, the 
Belgian law of May 7th
other regulatory requirements. 
The undersigned agree to ensure that the confidential information contained in this document will not 
be used for any other purpose other than the evaluation or conduct of the clinical investigation without 
the prior written consent of the Sponsor. 
The undersigned also confirm that the findings of the study will be made publically available through 
publication or other dissemination tools without any unnecessary delay and that an honest accurate 
and transparent account of the study will be given; and that any discrepancies from the study as 
planned in this protocol will be explained. 
FOR AND ON BEHALF OF THE STUDY SPONSOR 
Signature:  
...................................................................................................... 
Date: 
....../....../...... 
Frank Hulstaert, MD 
CHIEF INVESTIGATOR 
Signature: 
...................................................................................................... 
Date: 
....../....../...... 
Prof. Dimitri Beeckman 
STATISTICIAN 
Signature: 
...................................................................................................... 
Date: 
....../....../...... 
Mr. Filip Deforce 
 

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SIGNATURE PAGE  INVESTIGATOR 
Title: The use of a silicone adhesive multilayer foam dressing as an adjuvant prophylactic therapy 
for pressure ulcer prevention: a multicentre randomised parallel group open label medical device 
clinical trial in hospitalised patients at risk for pressure ulcer development 
I, the undersigned, confirm that the following protocol has been agreed and accepted and that the 
study will be conducted in compliance with the approved protocol and will adhere to the principles 
outlined in the GCP guidelines, the Belgian law of May 7th 2004 regarding experiments on the human 
. 
I agree to ensure that the confidential information contained in this document will not be used for any 
other purpose other than the evaluation or conduct of the clinical investigation without the prior written 
consent of the Sponsor. 
________________________________ _________________________________ ___________ 
Investigator Name  
Signature  
Date 

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KEY STUDY CONTACTS 
Chief Investigator
Prof. Dimitri Beeckman, RN, PhD 
University Centre for Nursing and Midwifery 
Department of Public Health, Ghent University 
De Pintelaan 185 
B- 9000 Ghent, Belgium 
Mail: Dimitri.Beeckman@UGent.be
Tel. +32 (0) 9 332 83 48
Sponsor
Belgian Health Care Knowledge Centre (KCE) 
Administrative Centre Botanique (Doorbuilding)  
Boulevard du Jardin Botanique 55 
B- 1000 Brussels, Belgium 
Mail: trials@kce.fgov.be
Tel. +32 (0) 2 287 33 88
Safety reporting 
Ludwig Everaert 
Archemin BVBA 
Lange Nieuwstraat 1 
B-2800 Mechelen 
Tel: +32 (0)15 28 74 11 
Mobile: +32 (0)476 41 51 35 
pharmacovigilance@archemin.eu
Study management
Data Investigation Company Europe (DICE) 
Koning Albertlaan 160 
B- 1082 Sint Agatha Berchem, Belgium  
Mail: mail@dice-cro.com
Tel +32 (0) 2 465 76 50
Key Protocol Contributors
 
Dimitri Beeckman 
 
Dorien De Meyer 
Bénédicte Manderlier
 
Karen Van den Bussche 
 
Nele Van Damme 
 
Mieke Denys 
 
Filip Deforce 
 
Ludwig Everaert 
 
Jillian Harrison 
 
Frank Hulstaert  
 
Jane Nixon 
Statistician
Data Investigation Company Europe (DICE)
Koning Albertlaan  160 
B- 1082 Sint Agatha Berchem, Belgium  
Tel +32 (0) 2 465 76 50  
Data Manager 
Data Investigation Company Europe (DICE)
Koning Albertlaan  160 
B- 1082 Sint Agatha Berchem, Belgium  
Tel +32 (0) 2 465 76 50
Monitoring 
Denys Research Consultants (DRC) BVBA 
Kantestraat 5 
B- 8700 Tielt, Belgium 
Mail: mieke.denys@drc-bvba.be
Tel: +32 (0)51 67.91.12  
Committees 
Trial Steering Committee (TSC) 
 
Dimitri Beeckman (chair) 
 
Frank Hulstaert 
 
Marianne Devis  
 
Mieke Denys  
Bénédicte Manderlier 
 
Filip Deforce  

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Version 2.0, 11-Jan-2018 
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A representative from a participating site 
 
Up to two representatives of patients or the public 
STUDY SUMMARY 
Study Title 
The use of a silicone adhesive multilayer foam dressing as an adjuvant 
prophylactic therapy for pressure ulcer prevention: a multicentre
randomised open label parallel group medical device trial in hospitalised 
patients at risk for pressure ulcer development. 
Protocol version and Date 
Version 2.0, 11 Jan 2018 
Internal ref. no. and short 
title 
KCE-16012: Silicone adhesive multilayer foam dressings to prevent 
pressure ulcers. 
Objective 
The objective of this study is to determine if silicone adhesive multilayer 
foam dressings applied to the sacrum, heels and greater trochanter in 
addition to standard prevention reduce pressure ulcer incidence category 
II, III, IV, Unstageable, and Deep Tissue Injury (DTI) compared to 
standard pressure ulcer prevention alone in at risk hospitalised patients.  
Note: Medical device related pressure ulcers are out of the scope of this 
trial. 
Primary endpoint 
The primary endpoint of this study is the incidence rate during the study 
period of the patient (during maximum 14 days) of at least one new 
pressure ulcer category II, III, IV, Unstageable, Deep Tissue Injury (DTI) 
(briefly referred to as pressure ulcers category II or worse) on sacrum, 
heels and greater trochanter as judged on site. 
Study Design 
 
Multicentre randomised controlled open label parallel group medical 
device trial in approximately 8 hospitals in Belgium.  
 
Patients will be randomly allocated to three study arms based on a 
1:1:1 allocation:  
- Study arm 1:
 Patients at risk for pressure ulcer category II, III, IV, Unstageable, 
and Deep Tissue Injury (DTI) development will receive standard 
pressure ulcer prevention strategies (as described in the hospital 
protocol) which include ongoing risk assessment, regular 
repositioning and skin care. 
 Skin sites (restricted to sacrum, heel right/left and greater 
trochanter right/left) will be treated with silicone adhesive 
multilayer foam dressings by Smith & Nephew (Allevyn® brand). 
- Study arm 2:
 Patients at risk for pressure ulcer category II, III, IV, Unstageable, 
and Deep Tissue Injury (DTI) development will receive standard 
pressure ulcer prevention strategies (as described in the hospital 
protocol) which include ongoing risk assessment, regular 
repositioning and skin care. 
 Skin sites (restricted to sacrum, heel right/left and greater 
trochanter right/left) will be treated with silicone adhesive 
multilayer foam dressings by Mölnlycke Health care (Mepilex®
brand). 
- Study arm 3:
 Patients at risk for pressure ulcer category II, III, IV, Unstageable, 
and Deep Tissue Injury (DTI) development will receive standard 
pressure ulcer prevention strategies (as described in the hospital 
protocol) which include ongoing risk assessment, regular 
repositioning and skin care. 

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 No silicone adhesive multilayer foam dressings will be applied
on the skin sites of interest for this trial (sacrum, heel right/left, 
greater trochanter right/left). 
 
Skin sites (restricted to sacrum, heel right/left, greater trochanter
right/left) of patients at risk for pressure ulcer category II, III, IV, 
Unstageable, and Deep Tissue Injury (DTI) development will be 
assessed daily for a maximum period of 14 days. 
Statistical analyses  
Primary analysis:  
- Patients in study arms 1 and 2 will be pooled as the treatment group 
and the incidence rate of pressure ulcers category II or worse as 
judged on site will be compared between the treatment group and 
the usual care group as per randomisation scheme.  
- The primary evaluation will be performed on the basis of the
Intention to Treat (ITT) set consisting of all patients randomised. A 
sensitivity analysis will be performed on the Per Protocol (PP) set. 
Exploratory analyses: 
- Comparison (both on the ITT and PP sets) of incidence rates 
(primary endpoint) between the experimental investigational 
devices (arms 1 and 2). 
- Analysis (both on the ITT and PP sets) of the primary endpoint 
based on the central reading of the images. 
- Sensitivity analysis of the primary endpoint (both on the ITT and PP 
sets) using time to event approach (cox proportional hazard) and 
logistic mixed models. 
Hospital eligibility 
In most hospitals in Belgium no dressings are currently used in the 
prevention of pressure ulcers. Those hospitals where dressings are 
currently used in the prevention of pressure ulcer in smaller or larger at risk 
groups as part of the standard of care cannot participate to this trial and 
need to discontinue their participation to the trial if the hospital introduces 
such practice. The use of dressings for routine care prevention of pressure 
ulcers in participating hospitals will therefore remain limited to exceptional 
cases. and, if known in advance, such patients will not be eligible for trial 
participation.
Inclusion and exclusion 
criteria  
Inclusion criteria: 
1. At risk for pressure ulcer development based on Braden risk 
assessment (Braden score 17). 
2. Admitted to hospital within the previous 48 hours. 
Note: Not more than 25% of patients per site should be recruited at 
ICU wards.
3. Skin at sacrum is assessable and there is no clinically relevant 
incontinence- associated dermatitis (IAD*) or another skin condition 
that would be a contra-indication for the application of the devices 
under study, and there is no pressure ulcer category II or worse 
present. 
*clinically relevant IAD is defined as any of the 4 categories described 
in the publication http://users.ugent.be/~dibeeckm/globiadnl/nlv1.0.pdf
4. For at least 3 of the following 4 skin sites (heel left, heel right, greater 
trochanter left, greater trochanter right) one of the following two 
conditions should apply: 
 
A study dressing can be applied as prevention of a pressure 
ulcer category II or worse at that skin site (there is no contra-
indication) 
OR

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There is already a pressure ulcer category II or worse at that skin 
site. 
5. Written informed consent by the patient or his/her legal 
representative. 
Exclusion criteria:  
1. Aged < 18 years.  
2. The length of stay counting from first day of admission in one or (if the 
patient is transferred to another ward) more participating wards is < 7 
days. 
3. Both heels amputated 
4. Previously known/documented allergy for substances used in the 
devices under study. 
5. A clinical condition not allowing participation in a clinical study. 
6. Participation in another interventional clinical trial. 
7. Patients who exceptionally receive or are planned to receive a 
dressing for the prevention of pressure ulcers at sacrum, heels and 
trochanters based on best medical judgment and outside of the 
surgery setting.
Sample Size 
The following assumptions were applied to calculate the sample size: 
 
The incidence rate of pressure ulcers category II, III, IV, Unstageable 
and DTI at sacrum, heels and greater trochanter is 6% in the control
group (Schoonhoven, Bousema & Buskens, 2007). 
 
The treatment groups will have a 50% reduction in pressure ulcer
incidence category II, III, IV, Unstageable and DTI incidence on 
sacrum, heels and greater trochanter (Demarré, Beeckman, 
Vanderwee, Defloor & Grypdonck, 2012; Nixon, Cranny, Iglesias, 
Nelson, Hawkins et al., 2006). 
 
In order to have 80% power to show superiority, data should be 
available for 1578 patients in total of which 526 are allocated to the 
control group and 1052 are allocated to the treatment group. 
 
Considering approximately 5% dropout, a total of 1662 patients are to 
be randomised to ensure that sufficient patients complete the study 
without compromising the study power. 
Treatment  
Experimental arms: 
 
Patients in an experimental arm will: 
- 
be cared for on the available support surfaces of the hospital 
(mattresses, cushions) for the duration of their hospital admission.
- 
receive standard pressure ulcer prevention strategies (as 
described in the hospital protocol) which include ongoing risk 
assessment, regular repositioning and skin care. 
 
Silicone adhesive multilayer foam dressings will be applied on to dry 
intact skin on sacrum, heel right/left, greater trochanter right/left, in 
addition to standard pressure ulcer prevention. 
 
Dressings will not be applied in skin areas affected by clinically relevant
incontinence- associated dermatitis (IAD) or other skin conditions that 
are a contra-indication for the application of the dressing. 
 
Emollients or other skin barrier products will not be applied to prevent 
adhesion issues of the dressing to the skin site. 
 
The procedure for dressing application and frequency of re- application 
be followed is as described by the manufacturer. Dressings will be 
maintained on the treatable skin sites throughout the conduct of the 
trial and changed if they become soiled or dislodged. 
 
The skin beneath the dressing will be inspected daily. 

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The maximum treatment duration is 14 days. 
Control arm: 
 
Patients in the control arm will: 
- 
be cared for on the available support surfaces of the hospital 
(mattresses, cushions) for the duration of their hospital 
admission.  
- 
receive standard pressure ulcer prevention strategies (as 
described in the hospital protocol) which include ongoing risk 
assessment, regular repositioning and skin care.  
No silicone adhesive multilayer foam dressings will be applied on any 
skin sites to prevent pressure ulcer development.  
The skin on sacrum, heel right/left, trochanter right/left will be inspected 
daily. 
The maximum observation period under study is 14 days. 
Planned Study Period 
Accrual: estimated at 9 months, starting Q1 2018, data cleaning: 3 months, 
analysis and reporting: 6 months  
Investigational Devices 
 
Silicone adhesive multilayer foam dressings by Smith & Nephew 
(Allevyn® brand, type: Allevyn® Life, Allevyn® Life Sacrum and 
Allevyn® Life Heel) 
 
Silicone adhesive multilayer foam dressings by Mölnlycke Health care 
(Mepilex® brand, type: Mepilex® Border, Mepilex® Border Sacrum, 
Mepilex® Border Heel) 
Note: C
same range of indications) and marketing driven relabelling of the current 
investigational devices may occur and will be discussed by the trial steering 
committee (TSC). After approval by the TSC, these dressings will be 
allowed in the trial. An ad hoc TSC meeting may be needed in order not to 
put the study on hold at any time for this reason. 

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Application of the 
Investigational Devices 
The investigational dressings will be applied on the sacrum (upper, back 
part of the pelvic cavity, between the two wings of the pelvis), the heels 
(large bony prominence connecting with the talus and cuboid bones), and 
the greater trochanter of the femur (large, irregular, quadrilateral bony 
prominence) 
The investigational dressings will only be applied on dry intact skin sites  

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FUNDING  
FUNDER 
FINANCIAL AND NON-FINANCIAL 
SUPPORT GIVEN
BELGIAN HEALTH CARE KNOWLEDGE 
CENTRE, Administrative Centre Botanique 
(Doorbuilding) 
Boulevard du Jardin Botanique 55 
1000 Brussels, Belgium
ROLES AND RESPONSIBILITIES OF STUDY 
MANAGEMENT COMMITEES/GROUPS & 
INDIVIDUALS 
Trial Management and Oversight Committees 
Following trial management and oversight committees will be involved in the set-up, management 
and monitoring of the clinical study:  
Project Team (PT) 
The Project Team (PT) is responsible for the day-to-day management of the study. It is 
composed of the Chief Investigator (CI) team and project management team from 
DICE/DRC. 
Trial Steering Committee (TSC) 
The Trial Steering Committee (TSC) shall oversee the performance of the study and discuss 
important topics in relation thereto. The TSC shall meet every 4 months as required and 
send reports to the study funder. It is composed of the following members:  
Dimitri Beeckman (chair) 
Frank Hulstaert 
Marianne Devis  
Mieke Denys  
Bénédicte Manderlier 
Filip Deforce  
A representative from a participating site 
Up to two representatives of patients or the public 

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Protocol contributors 
Name 
Prof. Dimitri Beeckman (Chief investigator) 
Department of Public Health, 
University Centre for Nursing and 
Midwifery, Ghent University 
De Pintelaan 185 
B-9000 Ghent 
Mail: Dimitri.Beeckman@UGent.be 
Tel. +32 (0) 9 332 83 48
Dorien De Meyer 
Department of Public Health, 
University Centre for Nursing and 
Midwifery, Ghent University 
De Pintelaan 185 
B-9000 Ghent 
Dorien.DeMeyer@UGent.be
Bénédicte Manderlier
Department of Public Health, 
University Centre for Nursing and 
Midwifery, Ghent University 
De Pintelaan 185 
B-9000 Ghent 
Bénédicte.Manderlier@UGent.be
Karen Van den Bussche 
Department of Public Health, 
University Centre for Nursing and 
Midwifery, Ghent University 
De Pintelaan 185, 
B-9000 Ghent 
Karen.VandenBussche@UGent.be
Nele Van Damme 
Department of Public Health, 
University Centre for Nursing and 
Midwifery, Ghent University 
De Pintelaan 185 
B-9000 Ghent 
Nele.VanDamme@UGent.be
Mieke Denys 
Denys Research Consultants BVBA 
Kantestraat 5 
B-8700 Kanegem, Belgium 
Mail: mieke.denys@drc-bvba.be  
Tel +32 (0) 51 67 91 12
Filip Deforce 
DICE NV/SA 
Koning Albertlaan 160  
B-1082 Brussels, Belgium 
Mail: filip.deforce@dice-cro.com 
Tel:+32 (0) 2 465 76 50
Ludwig Everaert 
Archemin BVBA 
Lange Nieuwstraat 1 
B-2800 Mechelen 
Tel: +32 (0)15 28 74 11 

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Prof. Jane Nixon 
Institute of Clinical Trials Research 
Clinical Trials Research Unit
University of Leeds 
Leeds, LS2 9JT, UK 
Mail: j.e.nixon@leeds.ac.uk
Tel: +44 (0) 113 343 1477
Dr. Jillian Harrison  
Belgian Health Care Knowledge Centre (KCE) 
Administrative Centre Botanique (Doorbuilding)  
Boulevard du Jardin Botanique 55 
B-1000 Brussels, Belgium 
Mail: trials@kce.fgov.be  
Tel. +32 (0) 2 287 33 88
Dr. Frank Hulstaert  
Belgian Health Care Knowledge Centre (KCE) 
Administrative Centre Botanique (Doorbuilding)  
Boulevard du Jardin Botanique 55 
B-1000 Brussels, Belgium 
Mail: trials@kce.fgov.be
Tel. +32 (0) 2 287 33 88
KEY WORDS:
Pressure ulcer, prevention, multilayer foam dressings, 
multicentre randomised controlled parallel group medical 
device trial. 

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LIST OF ABBREVIATIONS 
ABBREVIATION 
DEFINITION 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
APR 
Annual Progress Report 
AR 
Adverse Reaction 
ASADE 
Anticipated Serious Adverse Device Effect 
CA 
Competent Authority 
CE 
Conformité Européenne
CI 
Chief Investigator 
CMH 
Cochran-Mantel-Haenszel 
COS 
Core Outcome Set 
CRF 
Case Report Form 
CRO 
Contract Research Organisation 
DSUR 
Development Safety Update Report 
DTI 
Deep Tissue Injury 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
EU 
European Union 
GCP 
Good Clinical Practice 
IAD 
Incontinence-associated dermatitis  
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation of technical 
requirements for registration of pharmaceuticals for human use. 
ICU 
Intensive Care Unit 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committee 
ISF 
Investigator Site File 
ITT 
Intent to treat 
KCE 
Belgian Healthcare Knowledge Centre 
MDI 
Medical Device Incident 
MRI 
Magnetic Resonance Imaging 
MS 
Member State 
NIMP 
Non-Investigational Medicinal Product 
PI 
Principal Investigator 
PIS 
Patient Information Sheet 
PP 
Per Protocol 

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PU 
Pressure Ulcer 
QA 
Quality Assurance 
QC 
Quality Control 
QP 
Qualified Person  
RCT 
Randomised Controlled Trial 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SDV 
Source Data Verification 
SOP 
Standard Operating Procedure  
SmPC 
Summary of Product Characteristics  
SSI 
Site Specific Information 
USADE 
Unanticipated Serious Adverse Device Effect 
TSC 
Trial Steering Committee 
TMF 
Trial Master File 

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1 
INTRODUCTION 
1.1 
BACKGROUND 
A pressure ulcer is defined as a localized injury to the skin and/or underlying tissue 
usually over a bony prominence, as a result of pressure, or pressure in combination with 
shear (National Pressure Ulcer Advisory Panel, 2014). The NPUAP/EPUAP classification 
system distinguishes four categories of pressure ulcers: non-blanchable erythema of the 
intact skin (category I), partial thickness loss of dermis (category II), full thickness tissue 
loss (category III) and full thickness tissue loss with exposed bone, tendon or muscle
(category IV).  Also unstageable pressure ulcers and deep tissue injuries can be recognised 
(National Pressure Ulcer Advisory Panel, 2014). Pressure ulcers are associated with 
prolonged exposure to an applied external mechanical load. This load comprises all 
skin and underlying tissue due to contact 
with support surfaces. The extent of skin and/or tissue damage depends on the duration 
and magnitude of the applied load (pressure and shear).  
Medical device related pressure ulcers are out of the scope of the current trial. These 
pressure ulcers result from the use of devices designed and applied for diagnostic or 
therapeutic purposes. The resultant pressure ulcer generally conforms to the pattern or 
shape of the device.  

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Pressure ulcers may occur on all body locations covering a bony prominence. However, 
two large scale studies, one in Belgium (Vanderwee, Defloor, Beeckman, Demarré, 
Verhaeghe et al., 2011) (n= 19968), and one in the Netherlands (Schoonhoven et al., 2007) 
(n=1229), reported that prevalence of pressure ulcers varies according to body location. 
Both studies determined that most of the category II-IV pressure ulcers occur in the 
sacral/ischial tuberosity/coccyx area (45.0% - 51.7%), and the heels (26.7% - 40.7%), 
followed by the greater trochanter (1.8% - 2.6%).  
Table 1: Prevalence of pressure ulcer category II-IV  
Location 
PU prevalence (Cat. II-IV) 
Vanderwee et al. (2011)  
n = 1676*
Schoonhoven et al. 
(2007) n = 172*
Sacral/ischial tuberosity/coccyx area 
754 (45.0%) 
89 (51.7%) 
Heel area
682 (40.7%) 
46 (26.7%) 
Greater trochanter
44 (2.6%) 
3 (1.8%) 
Other (elbows, spine, ankle)
196 (11.7%) 
34 (19.8%) 
* Total number of observed pressure ulcers (Cat. II  IV) in the study 
Figure 1: Pressure ulcer categories National Pressure Ulcer Advisory Panel (2014) 

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To prevent the development of pressure ulcers, the KCE clinical practice guideline 
recommends to reduce both the amount and the duration of pressure and shear 
(Beeckman, Matheï, Van Lancker, Van Houdt, Vanwalleghem et al., 2013). This includes 
the application of appropriate support surfaces (such as mattresses or cushions), 
combined with correct patient repositioning on a continuous basis. Heels should be free 
of all pressure permanently. A general comment of the authors was the limited available 
RCT evidence concerning preventive measurements or evidence based on studies with 
methodological weaknesses (Beeckman et al., 2013). Alternative approaches to achieving 
modification of applied mechanical loads (such as the use of multilayer foam dressings) 
were not considered in these practice guidelines. 
Currently, interest is growing in the application of multilayer foam dressings (initially 
being used for wound treatment) as an adjuvant prophylactic therapy for pressure ulcer 
prevention. A multilayer foam dressing aims to act as an absorbent cushion on the skin. 
The foam dressing aims to promote the redistribution of pressure and shearing forces 
over a larger area and reduce the amount of pressure over the bony prominence (e.g. 
sacrum). In addition, it is suggested that the presence of multiple layers reduces shearing 
forces. Furthermore, the foam structure of the dressing aims to promote the moisture 
absorbing capacity of the dressing, which is assumed to be beneficial for the moisture 
balance on the skin (microclimate) (Clark, Black, Alves, Brindle, Call et al., 2014; Davies, 
2016; Santamaria et al., 2015). Referring to the KCE clinical practice guideline described 
above, multilayer foam dressings focus on the reduction of the amount of pressure and 
shear (not on the duration of the applied load on the tissue). 
The biomechanical efficacy of dressings in preventing heel ulcers has been recently 
studied by the research group of Amit Gefen (Levy, Frank, & Gefen, 2015; Levy & Gefen, 
2016). For this purpose, a 3D computational model was derived from medical imaging 
compression, tension and shear without any dressing, with a single layer dressing and a 
multilayer dressing. The use of the multilayer dressing consistently and considerably 
reduced soft tissue exposures to strains due to compression or combined compression and 
shear on various support surfaces (Levy et al., 2015). Furthermore, the exposure to 
elevated strains was also reduced in diabetic tissue conditions (Levy & Gefen, 2016). 
According to the authors, these results suggest that a multilayer foam dressing provides a 
cushioning effect to the soft tissues of the heel, and tempers tissue deformation and 
the consequent risk for pressure ulcer development (Levy & Gefen, 2016). Randomised
controlled clinical trials were recommended to examine the clinical effectiveness of 
dressings for the prevention of heel pressure ulcers (Levy et al., 2015).  
The clinical effectiveness of a multilayer foam dressing as a preventative intervention for 
pressure ulcers has been summarized in three systematic reviews (Clark et al., 2014; 
Davies, 2016; Moore & Webster, 2013). In addition, a consensus panel formulated 
recommendations based on a literature search (Black, Clark, Dealey, Brindle, Alves et al., 
2015).  
A first (Cochrane) systematic review, including four randomised controlled trials and 561 
participants, concluded that the use of dressings (foam dressings or a hydrocolloid 
dressing) was associated with a significant decrease in pressure ulcer incidence (Moore & 
Webster, 2013) (relative risk 0.21, 95% confidence interval 0.09-0.51). Foam dressings 
 (Jing, Guizhi, Aimin 
et al., 2011), ICU patients (Kalowes, Carlson, Carr, Llantero, Lukaszka et al., 2013), and  
neurosurgical patients (Qiuli, 2010). For two trials, little information was found on the 
methods used (Jing, 2011; Kalowes et al., 2013). The authors reported unclear or high
risk of bias for all included studies (e.g. small sample sizes, short follow-up periods) and 
recommended further well-designed trials addressing important clinical, and economic 
outcomes based on the incidence of the problem and the high costs associated with PU 
management. 

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A second systematic review
suggested that the introduction of a dressing as part of pressure ulcer prevention may help 
reduce pressure ulcer incidence, especially in immobile intensive care patients (Clark et 
al., 2014). The authors found no evidence that one dressing type was more effective 
than another. 
high. Only one RCT (Santamaria, Gerdtz et al., 2015) compared foam dressings with the 
use of no dressings. This RCT determined a significant reduction in pressure ulcer 
studies concerned lack of randomisation, small sample size, blinding of treatment allocation 
and outcome assessment, and insufficient reporting of statistical data. The authors 
recommended large scale studies, similar to the RCT from Santamaria, Gerdtz 
(Santamaria, Gerdtz et al., 2015), to ascertain the most appropriate patient populations, 
and anatomical locations for the use of multilayer foam dressings as a preventative 
intervention  for pressure ulcers. 
A third systematic review was restricted to studies examining the benefits of multilayer 
foam dressings with Safetec® technology: 3 RCTs, 6 non-randomised trials with concurrent 
controls, 17 non-randomised trials with historical controls, 4 case series without controls, 
and 10 reviews. The reviewers concluded that the use of a multi-layer foam dressing 
can reduce the occurrence of PUs on anatomical locations such as the sacrum and 
the heel, and underneath medical devices
(Black et al., 2015; Levy 
& Gefen, 2016; Moore & Webster, 2013) were similar to those included in the reviews 
above. It is important to address that no quality assessments of the included studies
were reported. 
A 2016 best practice document recommends the use of multilayer foam dressings 
combined with standard preventive interventions  for pressure ulcer prevention in 
emergency care, intensive care 
and during surgery (WUWHS, 2016). The 
recommendations were based on one RCT (Santamaria, Gerdtz et al., 2015) and three 
cohort studies (Brindle & Wegelin, 2012; Chaiken, 2012; Walsh, Blanck, Smith, Cross, 
Andersson et al., 2012). The development of the document was funded by Mölnlycke 
Healthcare and was not based on a systematic review of original studies. None of the 
primary studies was subjected to a quality assessment of the research methods. The 
experts expressed the need for comparative studies in other patient groups. 
One single centre non- blinded RCT on the effectiveness of foam dressings was found 
which was adequately powered (Santamaria, Gerdtz et al., 2015). This study was 
performed in a specific population of 440 trauma patients and critically ill patients. A 
five-layer silicone foam dressing was applied to the sacrum and a three-layer foam dressing 
was applied to heels. Significantly less patients from the intervention group developed 
pressure ulcers at the sacrum (2/219 vs. 8/221, p = 0.001) and at the heels (5/219 vs. 
19/221, p = 0.002). A reduction in pressure ulcer incidence of 10.0% (3.1% versus 13.1%) 
was determined. Data about pressure ulcer severity/grading were not reported. The 
authors recommended future multicentre studies, not restricted to critically ill patients to 
confirm their results and to enhance generalizability. Mölnlycke Healthcare provided a 
research grant and the dressings for this trial.  
The RCT mentioned in above paragraph was the only study which also examined the cost 
effectiveness of multi-layered foam dressings to prevent sacral and heel pressure ulcers 
(Santamaria, Liu et al., 2015). The stu
perspective in one Australian hospital. The costs were derived from dressing material costs 
and labour costs. The authors concluded that the costs of the dressings and the time 
for dressing application were largely exceeded by the costs associated with 
pressure ulcer treatment in critically ill patients. Costs associated with a prolonged 
length of hospital stay were not taken into account because in these particular patient 
group, pressure ulcers were not assumed to prolong the hospital stay. Follow-up of patients 
undergoing pressure ulcer treatment, after transferring from intensive care to at least other 
hospital wards, has been recommended for a more accurate calculation of treatment costs 
(Santamaria, Liu et al., 2015). 

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Currently, two single centre studies on the use of foam dressings are in progress. 
One study examines the effectiveness of two silicone dressings for sacral and heel 
pressure ulcer prevention in critically ill patients (ClinicalTrial.gov: NCT02295735). Data 
are collected between June 2015 and December 2017 in one teaching hospital in Germany. 
The other study examines the effectiveness of a polyurethane foam for sacral pressure 
ulcer prevention in elderly people with hip fractures (ClinicalTrial.gov: NCT02692482). Data 
are collected between March and August 2016 in an Italian hospital. The results of this trial 
are not yet published.  
By conducting this randomised controlled trial, we aim to gain insight into the effectiveness 
of silicone adhesive multilayer foam dressings, as an adjuvant prophylactic therapy for 
pressure ulcer prevention. The study will be performed on a large scale, including 1662 
hospitalised patients at risk of pressure ulcer development. The study will be executed in 
different wards in both teaching hospitals and general hospitals in Belgium to increase the 
likelihood of an appropriate case mix and thus generalizability of the conclusions. 
The following silicone adhesive multilayer foam dressings will be included in this study: 
 
Silicone adhesive multilayer foam dressings by Smith & Nephew (Allevyn® brand, 
type: Allevyn® Life, Allevyn® Life Sacrum and Allevyn® Life Heel) 
Silicone adhesive multilayer foam dressings by Mölnlycke Health care (Mepilex®
brand, type: Mepilex® Border, Mepilex® Border Sacrum, Mepilex® Border Heel) 
Note: 
range 
of indications) and marketing driven relabeling of the current investigational devices may 
occur and will be discussed by the trial steering committee (TSC). After approval by the 
TSC, these dressings will be allowed in the trial. An ad hoc TSC meeting may be needed 
in order not to put the study on hold at any time for this reason. 
1.2 
RATIONALE  
In 2012 and 2013, the Belgian Healthcare Knowledge Centre (KCE) and the CI of the 
current application published two practice guidelines for the prevention and treatment of 
pressure ulcers (Beeckman et al., 2013; Beeckman et al., 2013). Pressure ulcers are (and 
remain) a common problem for healthcare. A large scale Belgian prevalence study in 2008 
(n = 19968) reported a pressure ulcer prevalence of 12.1% in hospitals (Vanderwee et al., 
2011). Since 2008, many international studies have been published about pressure ulcer 
epidemiology and all of them showed similar results in both primary and secondary 
healthcare (Gorecki, Brown, Nelson, Briggs, Schoonhoven et al., 2009). The 
consequences of pressure ulcers for patients include pain, discomfort, a decrease in quality 
of life and an increase in morbidity and mortality (Gorecki et al., 2009; Hopkins, Dealey, 
Bale, Defloor, & Worboys, 2006). Besides, treatment of pressure ulcers is associated with 
an increase in health care expenditures, as a consequence of supplementary work load, 
wound care products, hospitalisation or prolonged hospitalisation (Demarré, Verhaeghe, 
Annemans, Van Hecke, Grypdonck et al., 2015; Schuurman, Schoonhoven, Defloor, van 
Engelshoven, van Ramshorst et al., 2009; Severens, Habraken, Duivenvoorden & 
Frederiks, 2002). According to Demarré et al. (2015), the mean costs for pressure ulcer 
treatment in Belgian hospitals varies between 2.34 EURO and 77.36 EURO per patient per 
day. Internationally, the cost of pressure ulcer prevention per patient per day varied 
between 2.65 EURO to 87.57 EURO across all settings. The cost of pressure ulcer 
treatment per patient per day ranged from 1.71 EURO to 470.49 EURO across different 
settings. The methodological heterogeneity among studies was considerable, and 
encompassed differences regarding type of health economic design, perspective, cost 
components, and health outcomes (Demarré et al., 2015). 
Based on the literature review, we can conclude that there is limited and not 
generalizable evidence on prophylactic dressings for preventing pressure ulcers. 
The current evidence on effectiveness and cost effectiveness of prophylactic dressings is 

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limited to individuals requiring critical care/intensive care, with dressings generally applied 
on first contact with health professionals (e.g. in the emergency department). The 
evidence mainly focuses on one specific dressing (Mepilex®, Mölnlycke Health 
Care). This dressing  comprises five layers: a backing film which faces the support surface, 
an airlaid layer, a nonwoven layer, a polyurethane foam layer and a Safetec® layer that 
adheres to the skin and minimises trauma on dressing removal (Levy & Gefen, 2016). In 
clinical practice, a broad range of foam dressings are currently being applied, varying 
in composition, size, adhesion to the skin, and whether or not designed to fit specific 
anatomical locations (e.g. sacrum, heels). The available dressings are mainly applied for 
the treatment of pressure ulcers (or other skin lesions) rather than for the prevention of 
pressure ulcers.  
Since the prevalence of pressure ulcers remains high (Vanderwee et al., 2011) and the 
treatment of pressure ulcers is associated with considerable costs (Demarré et al., 2015), 
high quality research on additional interventions for the prevention of pressure ulcers is 
urgently needed. (Multilayer) foam dressings seem to be promising as an additional 
prophylactic intervention. However, evidence demonstrating that the clinical and cost 
effectiveness of foam dressing for pressure ulcer prevention in a heterogeneous patient 
population is lacking. 
The control intervention is defined as pressure ulcer prevention according to the current 
national prevention guidelines. Current practice in hospitals in Belgium reflect the KCE 
guidelines for prevention and treatment of pressure ulcers (Beeckman et al., 2013; 
Beeckman et al., 2013) and the 2014 international guidelines (National Pressure Ulcer 
Advisory Panel, 2014). In summary, current practice includes: 
 
The application of a structured approach for risk assessment at the first contact 
with the patient. Reassessment is performed at regular time intervals and if there is 
 
The conduct of a comprehensive head-to-toe skin assessment with special 
attention to vulnerable areas. 
 
The introduction and documentation of a tailored repositioning plan (including 
specifications about posture and frequency) for each patient at risk for pressure ulcer 
development. 
 
The use of appropriate pressure redistributing devices (low-tech constant low 
pressure surfaces or high-tech support surfaces) for individuals at risk of pressure 
ulcers development. Decisions about which pressure redistributing device to use are 
based on an overall assessment of the individual including level of risk, comfort and 
general health state. 
 
The use of devices to ensure that heels are free of the support surface
 
Monitoring of the nutritional status of individuals as part of a general assessment 
procedure 
Pressure ulcers may occur on all bony prominences and prevalence figures vary depending 
on body location. In addition, silicone adhesive multilayer foam dressings are expensive. 
In this randomised controlled clinical trial, silicone adhesive multilayer foam dressings will 
be used on sacrum, heels, and greater trochanter. The specific skin sites cover the vast 
majority of all body locations at risk for pressure ulcer development (Vanderwee et al., 
2011; Schoonhoven et al., 2007).  
1.2.1 
Assessment and management of risk 
This study is considered a low risk clinical study. The silicone adhesive multilayer foam 
dressings are CE-marked and available on the Belgian market. They will be used in 
accordance with the product insert. Furthermore, all investigator teams will be trained by 
the dressing suppliers in the application and use of their respective dressings. The study 
will be conducted and monitored according to GCP guidelines. 

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2 
OBJECTIVE AND PRIMARY ENDPOINT 
2.1 
Objective 
The objective of this study is to determine if silicone adhesive multilayer foam dressings 
applied to the sacrum, heels and greater trochanter in addition to standard prevention 
reduce pressure ulcer incidence category II, III, IV, Unstageable and Deep Tissue Injury 
(DTI) compared to standard pressure ulcer prevention alone, in at risk hospitalised patients. 
In particular, this trial extends previous trial results obtained in ICU setting. Therefore, only 
a maximum of 25% of patients will be recruited from ICU settings.  
The hypothesis
silicone adhesive multilayer foam dressings as adjuvant 
prophylactic therapy for pressure ulcer prevention is more effective in reducing pressure 
ulcer category II, III, IV, Unstageable, and Deep Tissue Injury (DTI) incidence rate on 
sacrum, heels and greater trochanter, compared to standard pressure ulcer prevention 
alone
The null hypothesis
silicone adhesive multilayer foam dressings as 
adjuvant prophylactic therapy for pressure ulcer prevention is not more effective in reducing 
pressure ulcer category II, III, IV, Unstageable, and Deep Tissue Injury (DTI) incidence rate 
on sacrum, heels and greater trochanter, compared to standard pressure ulcer prevention 
alone
2.2 
Primary Endpoint 
The primary endpoint of this study is the incidence rate during the study period of the patient 
(during maximum 14 days) of at least one new pressure ulcer category II, III, IV, 
Unstageable, Deep Tissue Injury (DTI) (briefly referred to as pressure ulcers category II or 
worse) on sacrum, heels and greater trochanter as judged on site. 
3 
INVESTIGATIONAL PLAN 
3.1 
Study Design 
Multicentre, randomised, open label, parallel group medical device trial in approximately 8 
hospitals in Belgium. 
3.2 
Investigation Population 
The investigational population includes hospitalised patients at risk for pressure ulcer 
development in teaching and general hospitals.  

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Note that most (about 70%) patients admitted to the participating wards are not at risk for 
pressure ulcer development according to Braden score cut-off used in this study (<= 17). 
In addition, about 15% of patients at risk will likely not meet all eligibility criteria. 
3.2.1 
Hospital eligibility. 
In most hospitals in Belgium no dressings are currently used in the prevention of pressure 
ulcers. Those hospitals where dressings are currently used in the prevention of pressure 
ulcer in smaller or larger at risk groups as part of the standard of care cannot participate to 
this trial and need to discontinue their participation to the trial if the hospital introduces such 
practice. The use of dressings for routine care prevention of pressure ulcers in participating 
hospitals will therefore remain limited to exceptional cases. and, if known in advance, such 
patients will not be eligible for trial participation. 
3.2.2 
Patient Eligibility criteria 
3.2.2.1 Inclusion criteria 
Following inclusion criteria will be applied:  
1. At risk for pressure ulcer development based on Braden risk assessment (Braden 
2. Admitted to hospital within the previous 48 hours.  
Note: Not more than 25% of patients per site should be recruited at ICU wards.

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3. Skin at sacrum is assessable and there is no clinically relevant incontinence- 
associated dermatitis (IAD) or another skin condition that would be a contra-
indication for the application of the devices under study, and there is no pressure 
ulcer category II or worse present. 
*clinically relevant IAD is defined as any of the 4 categories described in the 
publication http://users.ugent.be/~dibeeckm/globiadnl/nlv1.0.pdf
4. for at least 3 of the following 4 skin sites (heel left, heel right, greater trochanter 
left, greater trochanter right) one of the following two conditions should apply: 
 
A study dressing can be applied as prevention of a pressure ulcer category 
II or worse at that skin site (there is no contra-indication) 
OR 
 
There is already a pressure ulcer category II or worse at that skin site. 
5. Written informed consent by the patient or his/her legal representative. 
3.2.2.2 Exclusion criteria 
Following exclusion criteria will be applied:  
1. Aged < 18 years.  
2. The length of stay counting from first day of admission in one or (if the patient is 
transferred to another ward) more participating wards is < 7 days. 
3. Both heels amputated 
4. Previously known/documented allergy for substances used in the devices under 
study. 
5. A clinical condition not allowing participation in a clinical study. 
6. Participation in another interventional clinical trial. 
7. Patients who exceptionally receive or are planned to receive a dressing for the 
prevention of pressure ulcers at sacrum, heels and trochanters based on best 
medical judgment and outside of the surgery setting.
3.2.3 
Prohibition and restrictions 
Following instructions will be followed regarding the admission of patients within the Clinical 
Investigation. 
Study arm 1: 
 
Patients will be cared for on the available support surfaces of the hospital (mattresses, 
cushions) for the duration of their hospital admission.  
 
Patients will receive standard pressure ulcer prevention strategies (as described in the 
hospital protocol) which include ongoing risk assessment, regular repositioning and 
skin care.  
 
Silicone adhesive multilayer foam dressings by Smith & Nephew (Allevyn® brand, 
type: Allevyn® Life, Allevyn® Life Sacrum and Allevyn® Life Heel) will be applied on 
to dry intact skin on sacrum, heel right/left, greater trochanter right/left, in addition to 
standard pressure ulcer prevention. 
 
Dressings will not be applied to skin areas affected by clinically relevant incontinence- 
associated dermatitis (IAD) or other skin conditions that are a contra-indication for the 
application of the dressing and there is no pressure ulcer category II or worse present  
 
Emollients or other skin barrier products will not be applied to prevent adhesion issues 
of the dressing to the skin site. 

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The procedure for dressing application and frequency of re- application will be followed 
as described by the manufacturer.  
 
Dressings will be maintained on the treatable skin sites and changed if they become 
soiled or dislodged. 
 
The skin beneath the dressing will be inspected on a daily basis.   
Study arm 2: 
 
Patients will be cared for on the available support surfaces of the hospital (mattresses, 
cushions) for the duration of their hospital admission.  
 
Patients will receive standard pressure ulcer prevention strategies (as described in the 
hospital protocol) which include ongoing risk assessment, regular repositioning and 
skin care.  
 
Silicone adhesive multilayer foam dressings by Mölnlycke Health care (Mepilex® 
brand, type: Mepilex® Border) will be applied on to dry intact skin on sacrum, heel 
right/left, greater trochanter right/left, in addition to standard pressure ulcer prevention. 
 
Dressings will not be applied in skin areas affected by clinically relevant incontinence- 
associated dermatitis (IAD) or other skin conditions that are a contra-indication for the 
application of the dressing and there is no pressure ulcer category II or worse present. 
 
Emollients or other skin barrier products will not be applied to prevent adhesion issues 
of the dressing to the skin site. 
 
The procedure for dressing application and frequency of re- application will be followed 
as described by the manufacturer. 
 
Dressings will be maintained on the treatable skin sites and changed if they become 
soiled or dislodged. 
 
The skin beneath the dressing will be inspected on a daily basis.  
Study arm 3: 
 
Patients will be cared for on the available support surfaces of the hospital (mattresses, 
cushions) for the duration of their hospital admission. 
 
Patients will receive standard pressure ulcer prevention strategies (as described in the 
hospital protocol) which include ongoing risk assessment, regular repositioning and 
skin care. 
No silicone adhesive multilayer foam dressings will be applied on any skin sites to 
prevent pressure ulcer development. 
 
The skin on sacrum, heel right/left, trochanter right/left will be inspected on a daily 
basis. 
3.2.4 
Discontinuation of study 
Patients will be informed prior to study entry that they are free to withdraw from the study at 
any time and for any reason, without jeopardizing their clinical care. Patients withdrawing 
from the study before Day 14 will be encouraged (if possible) to complete the assessments 
as listed for Day 14 (see section 4.4.4). 
The study for the patient will be discontinued for any of the following reasons: 
The patient is no longer at risk of pressure ulcer development according to the 
Braden scale (Braden score >17).  
The sponsor closes the study 
The patient wishes to withdraw from the study* 
Discharged from the hospital 
Moved to a non-participating ward 
Death 

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*In case the patient or their legal representative withdraws consent, it should be documented 
whether the data collected from that patient can still be kept in the study and used for the 
analysis which will be the default assumption.  
3.2.5 
Discontinuation of study intervention. 
The investigator may discontinue the study intervention for any of the following reasons: 
  Non-compliance with study procedures 
Life-threatening AE or serious adverse event (SAE) that places the patient at 
immediate risk if the study intervention would be continued 
  The patient shows a worsening of his/her medical condition, which in the 
However, the investigator should continue the collection of patient data and study 
endpoints as long as possible up to study day 14 (see section 4.4.4) if the patient is still 
on a participating ward and still at risk for pressure ulcer development (Braden score 
<=17).
The intent to treat principle 
Despite the fact that at one or more body location dressings are not or no longer applied 
because of incontinence- associated dermatitis or for whatever reason, the daily 
assessments of the body locations under study and recording of any new pressure ulcers 
category II or worse should continue as long as the patient is considered at risk for the 
development of pressure ulcers or until the patient is discharged from the participating 
wards or until study day 14, whatever comes first. Any such new pressure ulcers of 
category II or worse will be included in the ITT analysis, but may be excluded from the PP 
analysis if a major protocol violation was detected. 
In case the patient or their legal representative withdraws consent, it should be documented 
whether the data collected from that patient can still be kept in the study and used for the 
analysis which will be the default assumption. 

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3.3 
Investigational products 
3.3.1 
Identity of the investigational devices 
Two silicone adhesive multilayer foam dressings will be tested in this study: (1) Allevyn® 
Life (Smith & Nephew) and (2) Mepilex® Border (Mölnlycke Health care). Both are available 
on the Belgian market. The different shapes and sizes of the dressings are shown below. 
3.3.1.1 Allevyn® Life  Smith & Nephew 
Smith & Nephew developed the Allevyn® range of absorbent foam dressings for the 
treatment and prevention of wounds. The Allevyn® range is divided into the Allevyn® Classic 
products, such as Allevyn® (non-)Adhesive and Allevyn® Gentle (Border), and the Allevyn®
Life, an advanced layered dressing used for treatment and prevention of pressure ulcers. 
An overview of the different sizes and shapes are presented in the table below. The 
procedure for dressing application and frequency of re- application should be followed as 
described by the manufacturer.  
Allevyn® Life 
12.9 X 12.9  
Allevyn® Life Sacrum 
21.6 x 23 
Allevyn® Life Heel 
25 x 25.2 

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3.3.1.2 Mepilex® Border 
Mölnlycke Health care
Mölnlycke Health care developed foam dressings for the treatment and prevention of 
wounds under the brand name Mepilex®. Different foam dressings are available on the 
Belgian market e.g. adhesive and non-adhesive. The prevention of pressure ulcers has 
been studied using the Mepilex® Border. An overview of the different sizes and shapes are 
presented in the table below. The procedure for dressing application and frequency of re- 
application should be followed as described by the manufacturer.  
Mepiplex®  Border 
15x15 
Mepilex® Border Sacrum  
22 X 25 
Mepilex® Border Heel  
22 X 23 
3.3.2 
Product insert 
The study devices will be used in accordance with their insert in this study. All devices used 
in this study are CE-marked. The CE certificate numbers are CE 01965 (Mepilex® foam 
dressings), and CE 00356 (Allevyn® foam dressings). Both the Allevyn® and Mepilex®
Border are silicone adhesive multilayer foam dressings. The two technologies are 
described below. 

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3.3.2.1 Allevyn® (Smith & Nephew) 
The Allevyn® Life dressings consist of 5 layers: (1) the top layer consists of a breathable 
film of polyurethane film with an acrylic adhesive (Opsite®), (2) a protective layer consisting 
of polyester, (3) a hyperabsorbent padding layer consisting of cellulose and polyacrylate, 
(4) an absorbent hydrocellular polyurethane foam and (5) the layer in contact with the skin 
consisting of a polyurethane film coated with a silicone gel adhesive. The Allevyn® Life 
products do not contain latex, colophony and PVC.   
Figure 2: Allevyn® Life technology 
3.3.2.2 Mepilex® (Mölnlycke Healthcare) 
The Mepilex® dressings consists of a 5-layer absorbent foam structure including the 
Safetac® technology (see figure below). Safetac® is the adhesive layer of the dressing, 
which gently adheres to the skin, minimizing damage and trauma to the skin. 
Figure 3: Mepilex® Safetac® technology 
3.3.3 
Device storage and supply  
The silicone adhesive multilayer foam dressings need to be stored in a dry location at room 
temperature, and away from sunlight. The devices will be delivered to the hospital 
pharmacy.  
3.3.4 
Contra-indications for use 
3.3.4.1 Allevyn® (Smith & Nephew) 
According to the product label, do not use ALLEVYN® Life dressing with oxidising agents 
such as hypochlorite solutions (e.g. EUSOL) or hydrogen peroxide, as these can break 
down the absorbent polyurethane component of the dressing 
Do not use on infected wounds. 
In addition, as per inclusion criterium 3, do not use on skin site with clinically relevant IAD. 

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3.3.4.2 Mepilex® (Mölnlycke Healthcare)
According to the product label, do not use in conjunction with oxidizing agents such as 
hypochlorite solutions or hydrogen peroxide. 
Do not use on infected wounds  
In addition, as per inclusion criterium 3, do not use on skin site with clinically relevant IAD. 
3.3.5 
Concomitant medication/devices 
During the study period, all other care provided is at the discretion of the attending clinical 
team.   

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4 
STUDY ASSESSMENTS 
4.1 
Flowchart 
Assessments (Day) 
Procedure 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14* 
Pre-
randomisation 
baseline data 
Randomisation 
and after 
randomisation 
Informed consent 
X 
Demographics (date of 
birth, gender, weight, 
length, BMI, diabetes, 
X 
Applied PU prevention 
(support 
surface, 
repositioning, 
heel 
elevation) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Braden Risk 
assessment (including 
sub-scores) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pre-existing pressure 
ulcer category I 
X 
Visual inspection of 
the skin sites   
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Check 
in- 
and 
exclusion criteria 
X 
Ward type 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Skin moisture 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Quality of life (EQ5D) 
X 
X 
 
(x*) 
Randomisation 
X 
Dressings application 
X 
(x)
(x)
(x) 
(x)
(x)
(x)
(x)
(x)
(x)
(x) 
(x)
(x)
(x) 
Number of dressing 
changes between 
assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pressure ulcer Cat. II, 
III, IV, Unstageable, 
Deep Tissue Injury 
(DTI) 
(x)
(x)
(x) 
(x)
(x)
(x)
(x)
(x)
(x)
(x) 
(x)
(x)
(x) 
Photograph of new 
pressure ulcer Cat II 
and above 
(x)
(x)
(x) 
(x)
(x)
(x)
(x)
(x)
(x)
(x) 
(x)
(x)
(x) 
Photograph on last 
day in trial 
 
(x)* 
Safety evaluation 
(x) 
(x)
(x)
(x) 
(x)
(x)
(x)
(x)
(x)
(x)
(x) 
(x)
(x)
(x) 
Early discontinuation 
of intervention 
(including reason) 
(x)
(x)
(x) 
(x)
(x)
(x)
(x)
(x)
(x)
(x) 
(x)
(x)
(x) 
X = obligatory, (x) = if appropriate, * If the study duration of the patient is shorter than 14 days, these 
assessments will be done on the last day of the study participation of the patient.  

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4.2 
Assessments 
Pre-randomisation  
 
Possible eligible patients will be identified at ward level based on an initial 
assessment of pressure ulcer risk and estimated length of stay in the hospital 
(taking into account possible transfer to non- participating wards during hospital 
admission). 
 
The initial risk assessment will be performed using the risk assessment procedure 
of the hospital.  
 
The trial nurse will evaluate how many new patients that can be enrolled in the 
trial (based on workload) and will select those patients from the list with the highest
pressure ulcer risk profile (evaluation based on hospital procedures) for further 
screening.  
 
The trial nurse will visit possible eligible patients and will check all criteria for 
participation (including risk assessment according to Braden). If a patient is 
deemed eligible for inclusion, information about the trial procedures will be 
provided and the patient or the legal representative will be invited to sign the 
informed consent documents. 
 
The trial nurse will collect all pre- randomisation data (see section 4.4.1) and 
performs all data input using eCRF.  
 
The skin sites of interest (sacrum, heels right/left and greater trochanter right/left) 
will be assessed by the trial nurse.  
 
Skin sites being affected at baseline by a pressure ulcer category II, III, IV, 
Unstageable, DTI will be treated according to hospital standard care and followed-
up by the local wound care team and ward nurses according to hospital 
procedures. These particular skin sites will not be treated nor be followed- up for 
the purpose of this trial.  
Randomisation and post- randomisation  
 
After informed consent has been obtained, the patient will randomly be assigned 
(based on eCRF allocation information) to one of the study arms.  
 
For patients in the experimental group (study arms 1 and 2), the investigational 
dressings will be applied on the sacrum (upper, back part of the pelvic cavity, 
between the two wings of the pelvis), the heels (large bony prominence 
connecting with the talus and cuboid bones), and the greater trochanter of the 
femur (large, irregular quadrilateral bony prominence).  
 
The dressings will only be applied on dry intact skin sites. The procedure for 
dressing application be followed is as described by the manufacturer. 
 
The trial nurse will collect post- randomisation data (see section 4.4.2) and 
performs all data input using eCRF. 
Daily assessments (Day 2  14 or end of study)* 
 
The trial nurse will collect follow- up data (see section 4.4.3) and performs all data 
input in the eCRF.  
 
Quality of life data will be collected on day 3 and day 14 (or when the patient has 
a last daily assessment before day 14, at this time). * 
 
The skin sites of interest (sacrum, heels right/left and greater trochanter right/left) 
will be assessed by the trial nurse. In the experimental arms, the dressing will be 
lifted and re-applied to allow daily skin assessment.  
 
The occurrence of a new pressure ulcer category II, III, IV, Unstageable, DTI will 
be recorded. Photographs will be taken whenever a new category II, III, IV, 
Unstageable, DTI is observed. All photographs will be transferred to the CI for 
blinded central endpoint review. Guidelines on the taking and transfer of 
photographs can be found in the trial guidelines. 

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Any newly occurred pressure ulcer will be treated according to hospital standard 
care and followed- up according to hospital procedures by the local wound team 
and ward nurses.  
 
Particular skin sites affected by a pressure ulcer category II or worse will no longer
be treated within the trial. A high quality photograph will be taken of each pressure 
ulcer that occurred during the trial period at end of treatment of the location. All 
photographs will be transferred to the CI for blinded central review. * 
 
Other skin sites (not affected with a pressure ulcer category II or higher or clinically 
relevant IAD) will still be treated with trial intervention and followed- up for the 
purpose of the trial. 
 
For patients in the experimental group (study arm 1 and study arm 2), the 
procedure for dressing application and frequency of re- application be followed is 
as described by the manufacturer. 
 
Dressings will be changed if exudate is visible at the edge of the dressing 
(saturated dressing), when the dressing is no longer able to adhere fully, 
dislodged, rolled at the edges, wrinkled, creased or damaged, soiled or 
compromised in some other way. Each dressing change will be documented 
(including a justification). Each dressing change between two follow-up visits will 
be documented by the trial nurse in the eCRF.  
* If patient prematurely discontinues trial intervention then these assessments should be performed 
on the last day of trial participation 
End of study evaluation   
 
The trial nurse will collect end of study evaluation data (see section 4.4.4) and 
performs all data input using eCRF. 
4.3 
Recruitment 
4.3.1 
Patient identification 
Eligible patients will be identified on participating wards, based on the inclusion and 
exclusion criteria. If a risk assessment tool other than the Braden scale is used on 
admission (e.g. Norton scale), this tool will be maintained to identify patients. Each day, the 
trial nurse will evaluate how many new patients that can be enrolled in the trial (based on 
workload) and will select those patients from the list with the highest pressure ulcer risk 
profile (evaluation based on hospital procedures) for further screening. 
Eligible patients will be provided information concerning informed consent (see section 
11.2).  
After a patient is considered eligible according to the pressure ulcer risk assessment using 
the Braden score (Braden score < 17), informed consent will be obtained for each patient. 
In addition, sacrum, heels, and greater trochanter will be assessed for the presence of 
pressure ulcers category II, III, IV, Unstageable, DTI and clinically relevant IAD or other 
skin conditions that are a contra-indication for the application of the study dressings.  

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4.3.2 
Braden Scale 
Figure 4: The Braden Scale for Predicting Pressure Sore Risk (Bergstrom, Braden, Laguzza & Holman, 1987). 
Copyright. Barbara Braden and Nancy Bergstrom, 1988. Reprinted with permission. All Rights Reserved. 
4.4 
Variables to be collected 
4.4.1 
Pre-randomisation   
 Did the patient sign informed consent? 
 What is the Braden score (including sub-scores)? 
 How many skin sites at risk for pressure ulcer development are dry and intact (free of 
skin damage, including incontinence- associated dermatitis), treatable and assessable? 
 Is there a pre-existing pressure ulcer category I (non-blanchable erythema) present on 
the sacrum, heels right/left, greater trochanter right/left?  
 Skin assessment of all 5 sites (pre-existing pressure ulcer, skin condition such that a 
dressing could potentially be applied, the skin condition is such that no dressing should 
be applied, skin site missing/not assessable, presence of another dermatological 
condition, presence of a pre-existing category I pressure ulcer  can answer more than 
1 answer) 
 Are there any known allergies to substances used in the investigational devices?  
 What was the date of admission to hospital? 
 What was the date of elective surgery (if any)? 
 What is the expected length of stay on the participating wards?  

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 Is the skin at sacrum assessable and likely to remain assessable during the follow- up 
period? 
 On which ward is the patient at the time of assessment? 
 What is the date of birth of the patient? 
 What is the gender of the patient? 
 Quality of life: EQ-5D-5L subscales (mobility, self-care, daily activities, pain and 
discomfort, anxiety and depression, self-reported general health) completed by the 
patient or if the patient is not able completed by a proxy. In case the patient is 
unconscious a standard value will be used. 
 If a skin site comes in contact with moisture: what is the type of moisture (sweat, urine, 
diarrhoea)? 
 What is the patient s weight? 
 What is the patient s length/height?  
 What is the patient s Body Mass Index (calculated automatically)? 
 Does the patient have diabetes? 
 What type of support surface is used? 
 Are the heels elevated from the bed? 
 What is the frequency of repositioning (every 2 hours or more often, every 3-4 hours, 
every 5-6 hours or every 6 hours or longer)? 
4.4.2 
Randomisation and post- randomisation  
 If randomised to an experimental group (study arms 1 and 2):  
- 
What is the type, shape and size of dressings used on the sacrum, heels right/left, 
greater trochanter right/left?
4.4.3 
Daily assessments (as of the day after randomisation)  
 On which ward is the patient at the time of assessment? 
 What is the Braden score (including sub-scores)? 
 If a skin site comes in contact with moisture: what is the type of moisture (sweat, urine, 
diarrhoea)? 
 What was the number of re- applications of investigational devices since the last patient 
visit (and reason for change, type and shape)? 
 Is there a pressure ulcer category II, III, IV, Unstageable, DTI present on the sacrum, 
heels right/left, greater trochanter right/left since the last patient visit?    
 Has a photograph being taken if a pressure ulcer category II, III, IV, Unstageable, DTI 
present on the sacrum, heels right/left, greater trochanter right/left developed since the 
last patient visit?   
 Did any Adverse Device Effect occur or was any Device Deficiency observed since the 
last patient visit?   
 What type of support surface is used? 
 Are the heels elevated from the bed? 
 What is the frequency of repositioning (every 2 hours or more often, every 3-4 hours, 
every 5-6 hours or every 6 hours or longer)? 
 If the patient completes/stops the study before Day 14: what was the reason for stopping 
prematurely (reasons have to be specified)?  
 Only on Day 3: Quality of life: Consciousness status of the patient and EQ-5D-5L 
subscales (mobility, self-care, daily activities, pain and discomfort, anxiety and 
depression, self-reported general health) completed by the patient or if the patient is not 
able completed by a proxy. In case the patient is unconscious a standard value will be 
considered for the analysis.

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4.4.4 
End of study evaluation: day 14 or day when a patient ends study 
 On which ward is the patient at the time of assessment? 
 What is the Braden score (including sub-scores)? 
 If a skin site comes in contact with moisture: what is the type of moisture (sweat, urine, 
diarrhoea)? 
 What was the number of re- applications of investigational devices since the last patient 
visit (and reason for change)? 
 Is there a pressure ulcer category II, III, IV, Unstageable, DTI present on the sacrum, 
heels right/left, greater trochanter right/left since the last patient visit?    
 Is a photograph being taken if a pressure ulcer category II, III, IV, Unstageable, DTI 
present on the sacrum, greater trochanter right/left, heels right/left developed since the 
last patient visit?   
 Is a photograph being taken of all pressure ulcer category II, III, IV, Unstageable, DTI 
on the sacrum, heels right/left, greater trochanter right/left developed during the study 
period?   
 What type of support surface is used? 
 Are the heels elevated from the bed? 
 What is the frequency of repositioning (every 2 hours or more often, every 3-4 hours, 
every 5-6 hours or every 6 hours or longer)? 
 Did any Adverse Device Effect occur or was any Device Deficiency observed since the 
last patient visit?   
 If the patient completes/stops the study before Day 14: what was the reason for stopping 
prematurely (reasons have to be specified)?  
 Quality of life: Consciousness status of the patient and EQ-5D-5L subscales (mobility, 
self-care, daily activities, pain and discomfort, anxiety and depression, self-reported 
general health) completed by the patient or if the patient is not able completed by a 
proxy. In case the patient is unconscious a standard value will be considered for the 
analysis.
4.4.5 
Image acquisition 
Trials nurses will be trained to take photographs of pressure ulcers. This will be described 
in the trial guidelines.  
5 
END OF STUDY 
The end of Clinical Investigation is 30 days after last patient last visit. The sponsor will 
notify the central EC of the end of the study within 90 days of database lock for the primary 
endpoint. 

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6 
SAFETY REPORTING 
This section is structured in the following way. First of all definitions are given of the different 
events that might occur during a study. These definitions are structured along two axis: 
seriousness of the event and if the event is related to the device or not. Secondly it described 
what information is collected during this study. Only events related to the medical device 
will be collected. Thirdly it is explained what must be reported, who needs to report and 
how this reporting needs to be done.  
6.1 
Definitions 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury or any untoward clinical 
signs (including an abnormal laboratory finding) in patients, users or other persons whether 
or not related to the investigational medical device.  
NOTE 1: This definition includes events related to the investigational device.  
NOTE 2: This definition includes events related to the procedures involved.  
NOTE 3: For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
Serious Adverse Event (SAE) 
Adverse event that: 
a) Led to a death, injury or permanent impairment to a body structure or a body function 
b) Led to a serious deterioration in health of the patient, that either resulted in: 
 
as life-threatening illness or injury, or 
 
a permanent impairment of a body structure or a body function, or 
 
requires in-patient hospitalisation or prolongation of existing hospitalisation, or 
 
in medical or surgical intervention to prevent life threatening illness 
c) Led to foetal distress, foetal death or a congenital abnormality or birth defect. 
NOTE 1: Planned hospitalisation for a pre-existing condition, or a procedure required by 
the Clinical Investigation Plan, without a serious deterioration in health, is not considered a 
serious adverse event. 
Adverse Device Effect (ADE)  
Adverse event related to the use of an investigational medical device.  
NOTE 1- This includes any adverse event resulting from insufficiencies or inadequacies in 
the instructions for use, the deployment, the implantation, the installation, the operation, or 
any malfunction of the investigational medical device.  
NOTE 2- This includes any event that is a result of a use error or intentional abnormal use 
of the investigational medical device.  
Serious Adverse Device Effect (SADE)  
Adverse device effect that has resulted in any of the consequences characteristic of a 
serious adverse event. 
Unanticipated Serious Adverse Device Effect (USADE)  
A Serious Adverse Device Effect of which the nature or severity is not consistent with the 
applicable product information (e.g. Instructions for Use as compiled by the manufacturer). 
Reports which add significant information on the specificity, increase of occurrence, or 
severity of a known, already documented serious adverse reaction constitute unexpected 
MDIs.  

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NOTE: Anticipated SADE (ASADE): an effect which by its nature, incidence, severity or 
outcome has been previously identified in the risk analysis report. 
Device deficiency 
Inadequacy of an investigational medical device related to its identity, quality, durability, 
reliability, safety or performance. This may include malfunctions, use error, or inadequacy 
in the information supplied by the manufacturer. 
Medical Device Incident (MDI)
Any malfunction or deterioration in the characteristics and/or performance of a device (i.e. 
any device deficiency), as well as any inadequacy in the labelling or the instructions for use 
which, directly or indirectly, might lead to or might have led to the death of a patient, or user 
or of other persons or to a serious deterioration in their state of health. 
6.2 
Events Reportable by the PI 
For this study only ADEs, SADEs (i.e. AE/SAEs considered related to the study intervention 
being the study dressings and their application) and device deficiencies will be recorded in 
the eCRF. 
They will be recorded between the first usage of the study dressings and the last study 
related intervention for that patient for ADEs and till 30 days after last study related 
intervention for SADEs/MDIs. 
ADEs, i.e. AEs considered related to the trial intervention, will be  
recorded in the eCRF by the PI, which in practice means: 
- the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
- the event has a temporal relationship with device use/application or procedures; 
- the event involves a body-site or organ that  
the device or procedures are applied to  
the device or procedures have an effect on 
- the event follows a known response pattern to the medical device (if the response 
pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of activation/ 
exposure) and reintroduction of its use (or increase of the level of activation/exposure), 
impact on the event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and 
an effect of another device, drug or treatment) have been adequately ruled out; 
- harm to the patient is due to error in use; 
Ultimately i
to determine whether an 
adverse event is related or not. 
Device deficiencies. 
Any device deficiencies have to be recorded in the eCRF by the PI. 

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6.3 
Events Reportable by the Sponsor or its delegate 
Any SADE is considered as an INCIDENT and must be reported by the Sponsor to the 
Competent Authorities.  Such events meet all three-basic reporting criteria A-C listed below 
A. An event has occurred 
B. The Device is suspected to be a contributory cause of the event 
C. The event led, or might have led, to one of the following outcomes: 
- 
Death of a patient, user or other person 
- 
Serious deterioration in state of health of a patient, user or other person. 
Serious deterioration can include (non-exhaustive list): 
a) Life threatening illness 
b) Permanent impairment of body function or permanent damage 
c) Condition necessitating medical or surgical intervention to prevent a) or b) 
d) Foetal distress, foetal death or any congenital abnormality or birth defect 
Conditions where reporting under the medical device vigilance system is not usually 
required are: 
- 
Deficiency of a device found by user prior to its use 
- 
Event caused by patient conditions 
- 
Service life or shelf-life of the device exceeded 
- 
Protection against fault functioned correctly 
- 
Expected and foreseeable side effects 
- 
Negligible likelihood of occurrence of death or serious deterioration in state of health 
Medical Device Incidents 
Any medical device incidents and have to be reported by the Sponsor or its delegate. 
6.4 
Reportable Information by the PI and the Sponsor 
For each ADEs the following information will be collected: 
- 
description of the event 
- 
severity (mild, moderate, severe) 
- 
event duration (start and end dates, if applicable) 
- 
action taken 
- 
outcome 
- 
seriousness criteria 
- 
whether the event would be considered expected or unexpected. 
For each Device deficiency, the following information will be collected: 
- 
details in medical terms  
- 
start and end dates, if applicable 
- 
Relationship to any ADE/SADE (i.e. whether the event is an MDI). 
6.5 
How to report 
6.5.1 
Checking for ADEs and device deficiencies during follow-up. 
- 
Uses medical judgement in assigning seriousness, causality and expectedness  
- 
Ensuring that all SADEs and device deficiencies are recorded and reported to the 
Pharmacovigilance department (pharmacovigilance@archemin.eu) as quickly as 
possible using the quickest means possible after becoming aware of the event and 
provide further follow-up information as soon as available.  

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Each ADE and device deficiency should be recorded in the eCRF.  For SADEs and medical 
device incidents a report with the above mentioned information (section 6.4) on the event 
will be sent by mail to pharmacovigilance@archemin.eu.  
Ludwig Everaert, Archemin BVBA, Lange Nieuwstraat 1, B-2800 Mechelen 
Tel: +32 (0)15 28 74 11; Mobile: +32 (0)476 41 51 35 
6.5.2 
 or its delegate 
The sponsor will transmit to the Federal Agency for Medicines and Health Products 
the following incidents: 
- 
Any dysfunction or any change of the characteristics and/or performance of a device, 
and any inadequacy in the labelling or instructions, which might lead to or have led to 
death or serious relapse in the state of health of a patient, a user or a third party. 
- 
Any technical or medical reason related to the characteristics or performance of a 
device for reasons shown in the previous paragraph and having led to the systematic 
withdrawal from the market by a manufacturer of devices of the same type.  
The sponsor will transmit to Federal Agency for Medicines and Health Products and 
the Ethics Committee the following incidences: 
- 
An unexpected SADEs or incident which indicates an imminent risk of death, serious 
injury, or serious illness and that requires prompt remedial action for other patients, 
users or other persons or new finding to it: immediately, but not later than 2 calendar 
days after awareness by sponsor 
- 
Any other reportable events (USADEs and medical device incidents) as described in 
section 6.3 or a new finding/update to it: immediately, but not later than 7 calendar 
days following the date of awareness by the sponsor. 
The sponsor informs the sites, appropriate manufacturers if applicable. 
7 
BIOSTATISTICAL ASPECTS  
7.1 
Trial design and hypothesis. 
This is a randomised, open label, parallel group, superiority, multicentre post-marketing 
release study.  
Patients will be randomised in a 1:1:1 ratio to the Allevyn®, Mepilex® and control group and 
stratified by  
 
Hospital  
 
ICU vs non- ICU ward  
For all analyses, both treatment groups will be pooled into one group unless specified 
otherwise. The sample size calculation is based on this assumption. 
The primary objective is to compare the incidence rate of occurrence of at least one new 
pressure ulcer category II, III, IV, Unstageable, and DTI pressure ulcer at sacrum, heels 
and greater trochanter in both treatment arms versus the control arm.  
The primary hypothesis is that the incidence rate of new pressure ulcer category II, III, IV, 
Unstageable, and DTI at sacrum, heels and greater trochanter will be lower in the treatment 
groups compared to the standard of care group. Superiority will be concluded if the primary 
variable is significantly different in the treatment groups compared to the standard of care 
group, based on a two sided test at 5% level of significance.  

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Exploratory efficacy analysis will compare the effectiveness of the two treatments: Allevyn®
and Mepilex®. The null hypothesis is that there is no difference between Allevyn® and 
Mepilex®. The alternative hypothesis is that there is a difference between the treatment 
groups. The difference will be tested two- sided at 5 % level of significance.  
7.2 
Sample size calculation  
The sample size calculation is based on the results of a number of randomised trials with 
data about pressure ulcer category II, III, IV, Unstageable, and DTI incidence.  
 
The pressure ulcer category II, III, IV, Unstageable, and DTI incidence rate on 
sacrum, greater trochanter and heels is 6% in the standard of care group 
(Schoonhoven et al., 2007) 
 
The treatment groups will have a 50% reduction in pressure ulcer incidence category 
II, III, IV, Unstageable, and DTI incidence on sacrum, greater trochanter and heels. 
(Demarré et al., 2012; Nixon et al., 2006) 
In order to have 80% power to show superiority, data should be available for 1578 patients 
in total of which 526 are allocated to the control group and 1052 are allocated to the 
treatment group. Considering approximately 5% drop a total of 1662 patients are to be 
randomised to ensure that sufficient patients complete the study without compromising the 
power of the study.  
7.3 
Analysis set  
The following analysis sets will be considered: 
Total Set: 
All patients who consented to participate in the study. 
Intent-to-treat (ITT) Population: All patients of the Total set who were randomised and who 
did not explicitly ask to have their data excluded from the 
analysis. 
Per Protocol (PP) Population: 
All patients of the ITT Population who received the study 
treatment according to the protocol, without any major 
protocol 
deviation 
impacting 
the 
primary 
efficacy 
assessment. 
Safety Population: 
All patients of the ITT population who entered into the 
observation period. and, for the patients in study arms 1 
and 2, who were applied at least once study treatment. 
For the ITT Population patients will be considered in the treatment group as randomised 
(as foreseen by the attributed randomisation number). For the other analysis sets patients 
will be considered in the treatment group as treated. 
The exclusion of patients from the analysis sets will be discussed during a data review 
meeting that will be held before database lock. 
The efficacy analyses will primarily be performed for the ITT Population and supportively 
for the PP Population.  

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7.4 
Methods of statistical analysis.  
The statistical methods outlined in the protocol will be detailed in the statistical analysis 
plan which will be created and finalised before database lock. 
7.4.1 
General statistical considerations 
The statistical analysis will be performed using the SAS statistical package, version 9.2 or 
later. Unless otherwise stated, summary statistics for quantitative variables will include the 
mean, standard deviation, 95% confidence interval on the mean, minimum, 1st quartile, 
median, 3rd quartile, maximum, number of observations, and number of missing values. 
For categorical variables absolute counts (n) and percentages (%) of patients with data will 
be presented. For key categorical variables exact 95% confidence intervals will be 
presented for each treatment group and for the difference or ratio between the groups. The 
inferential statistical analysis will consist of: 
For the primary efficacy variable: 
 
Comparison of the treatment group (Allevyn®  & Mepilex®  pooled) versus the control 
group (incidence rate is frequency at which patients develop one or more such new 
pressure ulcers over the study period as judged on site) by means of the CMH test 
controlled for type of ward (ICU/Non-ICU). 
For the explorative analysis, the same analysis techniques will be used as for the primary 
efficacy analysis. Superiority tests will be performed two-tailed, at the 5% level of 
significance. 
7.4.2 
Demographics and baseline characteristics. 
A description will be given of key patient characteristics recorded at the baseline visits, for 
all patients and broken down by treatment group. 
7.4.3 
Efficacy evaluation 
7.4.3.1 Primary efficacy variable 
Primary analysis: 
Patients in study arms 1 and 2 will be pooled as the treatment group and the incidence rate 
of pressure ulcers category II or worse as judged on site will be compared between the 
treatment group and the usual care group as per randomisation scheme, by means of the 
CMH test controlled for type of ward (ICU/Non-ICU). An intention to treat (ITT) analysis 
including all patients randomised as well as a per protocol (PP) analysis will be performed. 
Exploratory analyses.
 
Comparison (ITT and PP) of incidence rates (primary endpoint) between the 
experimental investigational devices (arms 1 and 2).
 
Analysis (ITT and PP) of the primary endpoint based on the central reading of the 
images 
Sensitivity analysis of the primary endpoint using time to event approach (cox proportional 
hazard) and logistic mixed models. 
The primary endpoint of this study is the incidence rate during the study period of the patient 
(during maximum 14 days) of at least one new pressure ulcer category II, III, IV, 
Unstageable, Deep Tissue Injury (DTI) (briefly referred to as pressure ulcers category II or 
worse) on sacrum, heels and greater trochanter as judged on site. The primary analysis of 
the primary efficacy variable is a superiority analysis that compares the incidence rate in 
the pooled treatment groups versus the control group, on the ITT population by means of 
the CMH test controlled for type of ward (ICU/Non-ICU). Superiority will be concluded if the 

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estimated impact of the treatment (Allevyn®  and Mepilex® versus standard of care) is 
significant based on a 2 sided test at 5% significance level. A sensitivity analysis will be 
done using logistic regression and Cox proportional hazard models.  A sensitivity analysis 
will be conducted in the ITT and PP populations based on the reviewed photographs of the 
PU, based on the review by the CI team. This variable will be included in the database 
before database lock.  
7.4.3.2 Exploratory efficacy variables 
A comparison between the efficacy of the two treatments will be made by defining a 
contrast in the logistic mixed model. A difference between the two treatments will be 
concluded if there is a significant difference between the two treatments based on 2 sided 
testing at the 5% significance level.  
7.4.3.3 Further exploratory analyses 
Any further exploratory analyses will be detailed in a statistical analysis plan. 
7.4.4 
Safety evaluation 
Safety analyses will be performed on the basis of the Safety Set and will be descriptive. 
Statistical comparisons will be for exploratory purposes only.  
7.5 
Randomisation  
Patients eligible to participate in the study will be randomly assigned to one of the following 
arms: 
 
Experimental study arm 1 
 
Experimental study arm 2 
 
Control study arm 3 
Description of the different arms to be based on the description in section 4. 
The randomisation plan is based on allocation of ratio 1:1:1. Randomisation will be stratified 
by: 
 
Hospital  
 
ICU vs. non- ICU 
The randomisation will be based on a permuted-block randomisation with varying block 
sizes used to reduce the probability to predict the next treatment assignment. 
For each ward (ICU versus non-ICU), the randomisation schedule will ensure balance of 
the three intervention arms at the intended number of randomised patients. The permuted-
block randomisation will also allow balance at the end of each block 
7.6 
Interim and final analysis 
The analyses will be done after database lock. There are no interim analyses planned. 

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8 
MATERIAL 
8.1 
Data collection tools and source document identification 
 
Following source data will be used:  
 
Data collection forms, to be used during observations 
 
Secondly, data will be entered in an electronic data capture (EDC) system  
8.2 
Trial Master File 
The sponsor representative will set up a Trial Master File (TMF) at the beginning of the 
study and will manage the collection/storage of essential trial documents during the course 
and at the end of the study. The list of essential documents (the Master TMF List) will be 
in accordance with the GCP-guidelines and will specify which essential study documents 
are created and which are kept electronically and/or in paper. Additionally, the Master TMF 
List will identify where all the potential documentation, part of the Master TMF, is located 
as the Master TMF will include documents across different parties/departments other than 
clinical 
operations, 
such 
as 
Data 
Management, 
Statistics, 
Medical 
Writing, 
Pharmacovigilance, device supplies, Pharmacy, Legal, Regulatory Affairs. Provisions will 
be made to identify these documents and retain them as part of the TMF for the required 
retention period, even if stored separately from the main TMF itself.  
Any documentation which has been created during the study and that helps reconstruct 
and evaluate the study conduct must be filed in the TMF. 
The TMF is composed of:  
 
an investigator TMF held by the investigator(s). The investigator TMF is referred to as 
the Investigator Site File (ISF). 
The TMF held by sponsor representative will be established following a hybrid model, i.e. 
will contain both paper and electronic records:  
 
The eTMF is a cloud-based document management system (VEEVA vault). 
 
The paper-based documents will be filed in study binders in a secure but accessible 
manner for authorized people.  
9 
DATA HANDLING AND RECORD KEEPING 
Patients that are included in the study will be randomised by using the EDC. A code number 
will be randomly assigned to all patients entered in the EDC system. 
On forms, digital or other documents submitted to the coordinating centre, sponsor or CI, 
patients will only be identified by the code number.  
The correspondence between the code number and the patient identification will be 
safeguarded by the trial nurses. 
9.1 
Access to Data 
Direct access to eCRF and eTMF will be granted to authorised representatives from the 
Sponsor, host institution and the regulatory authorities to permit trial-related monitoring, 
audits and inspections. 

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9.2 
Archiving 
The sponsor and investigator will maintain adequate and accurate records to enable the 
conduct of the study to be fully documented and the study data to be verified. The relevant 
(essential) documents are those documents which individually and collectively permit to 
assess the conduct of the trial, the quality of the data produced and the compliance with 
GCP standards and applicable regulatory requirements. Archiving will be authorised by the 
Sponsor following submission of the end of study report. All essential documents will be 
archived for a minimum of 20 years after completion of trial. The destruction of essential 
documents will require authorisation from the Sponsor. 
If it becomes necessary for the sponsor or the appropriate Regulatory Authority to review 
any documentation relating to this trial, the investigator must permit access to such reports. 
The patient is granting access to his/her source data by signing the ICF. 
Any difficulty in storing original documents must be discussed with the monitor prior to the 
initiation of the trial. 
10 
MONITORING & AUDIT 
10.1 
Monitoring 
This Clinical Investigation will be monitored by sponsor representatives according to the 
current SOP for the monitoring of Clinical Investigations. 
The monitor will perform on-site monitoring visits as frequently as necessary which will be 
documented on the monitoring log. Shortly before the Clinical Investigation starts, the 
monitor will meet with the Trial Nurse to review the Clinical Investigation specific 
procedures on Clinical Investigation conduct and recording the data in the eCRF. The first 
monitoring visit will take place as soon as possible after enrolment and the Trial Nurse shall 
permit the monitor to verify the progress of the study on a continuous basis. The Trial Nurse 
shall make the source documents available, provide missing or corrected data and sign the 
eCRFs. Key data transcribed onto the eCRFs, such as the patient's gender, date of birth, 
assessment dates, etc., will be reviewed against the available source documents. Personal 
information will be treated as strictly confidential and will not be made publicly available. 
Any inconsistency between source data and data recorded in the eCRF will be corrected. 
The sponsor will ensure that appropriate QC steps are included into the different Clinical 
Investigation processes to guarantee adequate protection of the patients and to guarantee 
the quality of the data. 
The PI should ensure the accuracy, completeness, legibility, and timeliness of the data.  
During monitoring visits, the monitor will review the eCRFs and evaluate them for 
completeness and consistency. The eCRF will be compared with the source documents to 
ensure that there are no discrepancies between critical data. All entries, corrections and 
alterations are to be made by the responsible investigator or his/her designee. The monitor 
cannot enter data in the eCRFs. Once clinical data of the eCRF have been submitted to 
the central server, corrections to the data fields will be audit trailed, meaning that the reason 
for change, the name of the person who performed the change, together with time and date 
will be logged. Roles and rights of the clinical study centre staff responsible for entering the 
clinical data into the eCRF will be determined in advance. 
10.2 
Audit 
To ensure compliance with relevant regulations, an independent Quality Assurance (QA) 
representative, IECs may review this study. This implies that auditors will have the right to 
audit the site(s) at any time during and/or after completion of the study and will have access 
files. By participating in this Clinical Investigation, the PI agrees to this requirement. 

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11 
ETHICAL AND REGULATORY CONSIDERATIONS 
11.1 
Ethics Committee  
Before the start of the trial, approval will be sought from both central and local EC for the 
trial protocol, informed consent forms and other relevant documents. 
Substantial amendments that require review by EC will not be implemented until the EC 
grants a favourable opinion for the study. Substantial amendments according to the law of 
May 7th 2004 will need to be reviewed and accepted by EC before they can be 
implemented in practice at sites.  
The CI will notify the sponsor of the start of the study and the sponsor representative will 
notify the central EC of the start of the study. An annual progress report (APR) will be 
submitted to the central EC within 30 days of the anniversary date on which the favourable 
opinion was given, and annually until the trial is declared ended. It is the 
responsibility to produce the annual reports as required. If the study is ended prematurely, 
the CI will notify the central EC, including the reasons for the premature termination. Within 
one year after the end of the study, the Sponsor will submit a final report with the results, 
including any publications/abstracts, to the Sponsor, which in turn submits it to the central 
EC. The CI will notify the central EC of the end of the study. All correspondence with the 
ECs will be retained in the Trial Master File/Investigator Site File. 
11.2 
Patient Informed Consent 
The Trial Nurse must explain the Clinical Investigation to potential patients or their legally 
acceptable representatives prior to any Clinical Investigation-related activity. 
The patient must be informed that participation is voluntary, that they can refuse 
participation and withdraw consent at any time from the Clinical Investigation without giving 
reasons and without prejudicing his/her further treatment. Patients must be provided with 
contact details where he/she may obtain further information about the Clinical Investigation. 
Where a patient is required to re-consent or new information is required to be provided to 
a patient it is the responsibility of the PI at the site to ensure this is done in a timely way.  
Where the patient population is likely to include a significant proportion of patients who 
cannot read or write, require translators or have cognitive impairment, appropriate 
alternative methods for supporting the informed consent process should be employed. This 
reading or writing), designate a legal representative or providing Patient Information Sheets 
in other languages or in a format easily understood by the patient population (in the case 
of cognitive impairment) providing they are approved by the EC. The patient or legally 
acceptable representative will be given sufficient time to read the ICF and to ask additional 
questions. After this explanation and before entry to the Clinical Investigation, consent 
should be appropriately recorded by means of either the patient's or his/her legal 
representative's dated signature or the signature of an independent witness who certifies 
the patient's consent in writing. After having obtained the consent, a copy of the ICF must 
be given to the patient. 
Patients who are unable to comprehend the information provided can only be enrolled after 
consent of a legally acceptable representative. 
For all eligible patients with written informed consent, baseline data will be collected and 
checked before randomisation. 
11.3 
Public and Patient Involvement 
Two patient or public representatives will be invited via the network of the CI and asked to 
be part of the Trial Steering Committee. They will be asked to review the informed consent 
document and to help disseminate the results and outcomes of the study.  
11.4 
Regulatory Compliance  
This study will be conducted in accordance with the protocol, principles of current ICH-GCP 
guidelines and applicable law(s). 

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Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording and reporting studies that involve the participation of 
human patients. Compliance with this standard provides public assurance that the rights, 
safety and well-being of study patients are protected, consistent with the principles that 
have their origin in the Declaration of Helsinki, and that the clinical study data are credible. 
11.5 
Protocol compliance  
Prospective, planned deviations or waivers to the protocol are not allowed. Accidental 
protocol deviations can happen at any time. Major deviations must be adequately 
documented and reported to the CI and Sponsor immediately.  
Any deviation that potentially interferes with and/or affects the efficiency and/or quality 
conduct of the study, will be discussed during the study by Monitor with Trial Nurse/PI and 
will be documented on the protocol deviation log as well on the monitoring report including 
a proposed plan of action for resolution if applicable.  
Critical issues that significantly affect patient safety, data integrity and/or study conduct will 
be communicated and discussed by the sponsor with the EC. 
11.6 
Notification of Serious Breaches to GCP and/or the protocol  
: 
 
the safety or physical or mental integrity of the patients of the trial; or 
 
the scientific value of the trial 
The Sponsor should immediately inform the central EC and applicable local EC when the 
non-compliance is a serious breach of the trial protocol or ICH-GCP. Deviations from the 
protocol which are found to frequently recur are not acceptable, will require immediate 
action and could potentially be classified as a serious breach. 
11.7 
Data protection and patient confidentiality  
All investigators and study site staff will comply with the requirements of the Belgian Privacy 
Act of 8 December 1992 on the protection of privacy in relation to the processing of 
personal data and by the Law of 22 August 2002 on patient rights.  
A study number will be randomly assigned to participating patients.  
In order to permit easy identification of the individual subject during and after the trial, the 
PI is responsible for keeping an updated Patient Identification Code List. The monitor will 
review this document for completeness. However, the PI must guarantee the patient
anonymity will be maintained. Therefore, in order to ensure patient confidentiality, the 
Patient Identification Code List will remain at the clinical study centre and no copy will be 
made for filing in the eTMF. 
11.8 
Financial and other competing interests  
 
The CI has no financial or competing interests that might influence the design, conduct 
or reporting of the study. He has no ownership interest related to the device, no 
commercial ties with the companies, and no non-commercial potential conflicts to 
disclosure. The CI participated in one meeting of the scientific advisory board of 
Mölnlycke Health Care in 2014. Since the CI is active in pressure ulcer research since 
many years, Ghent University received multiple research grants to set- up investigator 
initiated studies to test the effectiveness of different interventions to prevent pressure 
ulcers. Research grants were received from following companies: Sage Products LLC 
(Carry, Illinois, US), 3M Healthcare Deutschland, Hill- Rom (Batesville, US), and 
Frontier Medical Group (UK). The research contracts were coordinated by UGent 
TechTransfer and the Legal Department and were in concordance with any ethical 
and legal requirements. No research has been performed using the device in this 
study.      
 
None of the protocol contributors has any financial or other competing interest to 
disclosure. 

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11.9 
Indemnity 
The sponsor will provide an insurance, even without fault, to cover its liability as the 
requesting party (as referred to in the Act of 7 May 2004 on clinical trials) in case of harm 
caused to the patient by participation in the study.  
The sponsor will consider all loss or damage caused by one and the same event or 
sequence of events to be a single claim event. 
The participating hospitals have a duty of care to patients treated, whether or not the patient 
is taking part in a clinical study and they remain liable for clinical negligence and other 
negligent harm to patients under this duty of care.
11.10 Post-study care 
In line with during trial care, after the study is completed or the patient has completed the 
protocol intervention, all patients will continue to receive standard care as determined by 
the attending clinical team.  
This is not part of a protocol. 
12 
DISSEMINATION POLICY 
This study will be fully reported and made publicly available both during conduct and after 
completion. The design of the study will be registered in the clinical studies register. The 
outcomes of the research will be reported in a research paper and will be submitted for 
publication in a suitable peer-reviewed open-access journal. The Consort Guidelines and 
checklist will be reviewed prior to generating any publication to ensure they meet the 
standards required for submission to a high-quality peer reviewed journal. If requested, 
anonymised participant level dataset, and statistical code for generating the results will be 
made available for the Journal. The data arising from this study are owned by the sponsor. 
Any appropriate funding or supporting body will be acknowledged within the publications. 
On completion of the study, the data will be analysed and tabulated and a final study report 
will be generated.  
The International Committee of Medical Journal Editors (ICMJE) guidelines on authorship 
will be applied to determine eligibility of authorship for both the final report and any 
publications arising from this study. The ICMJE recommends that authorship be based on 
the following 4 criteria: 
1. Substantial contributions to the conception or design of the work; or the acquisition, 
analysis, or interpretation of data for the work; AND 
2. Drafting the work or revising it critically for important intellectual content; AND 
3. Final approval of the version to be published; AND 
4. Agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved. 
This trial uses a competitive recruitment scheme. Authorship of the publication of the main 
study results will be according to the usual scientific guidelines, as detailed above. The 
order of the authors representing the sites will be determined based on the number of 
patients randomised, managed and documented in accordance with the protocol and the 
study agreement. The overall recruitment period is expected to last 9 months but this period 
can be shorter or longer. Patient recruitment will be considered complete and no additional 
patients will be randomised when overall 1662 patients are randomised in this trial in 
accordance with the study protocol. Sites will be informed twice a month by DICE about 
the recruitment status in all sites

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APPENDIX 1: EQ-5D-5L INSTRUMENT 

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