A Clinical Study to Compare the Performance of AQUACEL® Ag+ Extra™ and Cutimed® Sorbact® Dressing in the Management of Patients With Venous Leg Ulcers Over a 12-week Period
Phase: NA
Conditions: Venous Leg Ulcer, Diabetic Foot
Sponsor: ConvaTec Inc.

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A clinical study To Compare The Performance Of AQUACEL® Ag+ Extra™ And  Cutimed® Sorbact® 
Dressing In The Management Of Patients With Venous Leg Ulcers Over A 12-Week Period. 
 
WC-22-435 
 
 
 
 
This document is a confidential communication of Convatec Ltd. Acceptance of the document constitutes 
the agreement by the recipient that no unpublished information contained herein will be published or 
disclosed without Convatec's prior written approval, except this document may be disclosed to 
appropriate Institutional Review Committees so long as they are requested to keep it confidential. 
 
 
 
 
 
 
 

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Protocol Number: 
 
WC-22-435 
Protocol Date:  
 
16 June 2023 
Protocol Version: 
 
4.1 
 
Sponsor: 
 
 
Convatec Limited 
Registered Address: 
 
Floor 7, 3 Forbury Place 
 
 
 
 
Forbury Estate 
 
 
 
 
23 Forbury Road 
 
 
 
 
Reading  
 
 
 
 
Berkshire 
 
 
 
 
RG1 3JG 
 
 
 
 
United Kingdom 
 
Operating office for this study: Global Medical and Clinical Affairs Group 
 
Deeside Industrial Park 
Deeside 
Flintshire 
CH5 2NU 
United Kingdom 
 
Convatec Limited will be funding the study. The sponsor’s EU contact is: 
Unomedical A/S – A Convatec Company 
Aaholmvei 1-3 Osted 
4320 Lejre, Denmark 
 
 

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DOCUMENT HISTORY 
 
Version 
Date 
Comment 
1.0 
1st July 2022 
First Submission 
2.0 
6th October 2022 
The following changes have been implemented following feedback 
from Colombian EC: 
• 
Added a clarification regarding unscheduled visits: 
“Interim visits are at the discretion of the investigator. At 
each scheduled visit, the number of dressing changes is 
collected. Any interim visit for a product-related AE or SAE 
would be captured on an additional visit form including 
the AE form”. 
• 
Added a clarification regarding diabetic patients: “Subjects 
without diabetes do not require measurement of HbA1c if 
they have a recent glucose or HbA1c level over the past 
year”. 
• 
Removed IC-11: subjects who don’t have access to e-mail 
will be provided with an iPad to complete wound quality 
of life questionnaire during their site visits. 
• 
Added a clarification regarding secondary dressing: 
“Secondary dressing to be applied at the discretion of the 
investigator in accordance with the product’s IFU”. 
 
The following changes have been implemented in order to ensure 
that the inclusion and exclusion criteria and the schedule of events 
are in line with standard of care: 
• 
‘Chronic VLU’ changed to ‘VLU’ 
• 
‘Aquacel Extra’ changed to ‘non-antimicrobial silver-free 
standard of care as per sites’ normal practice’ 
• 
Updated EC-7 to include patients with uncontrolled 
diabetes, HbA1c ≥10 
• 
Removed EC-8 and EC-9 to include subjects who are 
breastfeeding or pregnant 
• 
Clarification added to the schedule of events: “After day 
28, the PI or delegate will continue treatment of the 
wound according to the clinical needs based on their 
evaluation of the wound. If an antimicrobial wound 
dressing is required, the dressing that was randomly 
assigned during the initial phase of the study can be 
used.” The flow chart on page 23 has been updated 
accordingly. 
 

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Due to limited availability, Professor Dissemond can no longer act 
as country coordinator and investigator. Therefore, his details 
have been removed from the study protocol. 
3.0 
26th October 2022 
Typo correction in Exclusion Criterion 7 (EC-7): Patients with 
uncontrolled diabetes with HbA1c ≥ 10 within last 3 months. 
Subjects without diabetes do not require measurement of HbA1c 
if they have a  glucose or HbA1c level measured over the past 
year. 
Updated table of contents 
4.0 
3 May 2023 
• 
Minor syntax and formatting changes throughout 
document to better reflect the intent of the protocol. 
• 
All references to version number updated to “4.0” with 
date 3 May, 2023. 
• 
Section 23, Abbreviations: The list of abbreviations 
updated for accuracy. 
• 
Synopsis: updates made to reflect the updates of the body 
of the protocol for accuracy. 
• 
Reference to CRO and Country Principal Investigator 
removed for accuracy. 
• 
Table of Contents updated for accuracy. 
• 
Inclusion criteria updated to allow inclusion of multiple 
wounds for the subject. 
• 
Secondary endpoints better defined in the protocol to 
reflect the current study design. 
• 
Exploratory endpoints defined to reflect the current study 
design. 
• 
Safety endpoints defined to reflect the current study 
design. 
• 
Completed subject definition added (Section 8.3) for 
accuracy. 
• 
Study wound identification added to reflect the current 
study design. 
• 
Study procedure diagram updated to reflect the current 
study design. 
• 
Section 9.4 “Enrolment of subjects with multiple wounds” 
added to reflect the current study design. 
• 
Schedule of Events has been updated to add End-of-Study 
Visit 
• 
Visit 2: Improved clarification of Investigator choice of 
treatment options. 
• 
Section 12 Safety and Event Report updated definitions of 
adverse events and reporting for regulatory compliance. 
• 
Section Role of Sponsor Representative removed as it is 
not applicable. 

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• 
Section Statistical Consideration has been updated to 
reflect the current study design. 
• 
Section Protocol Deviations: removed language related to 
analyses populations and subject withdrawal to avoid 
redundancy.  
• 
Section 21 (Good Clinical Practice and statements of 
Compliance to Section 27 (Public Registration and 
Publication) collapse into single section for simplicity. 
4.1 
16 June 2023 
• 
Sample size changed to 206 subjects corresponding to 
minimum of 206 wounds. 
 
 
 

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Table of Contents 
SYNOPSIS ...................................................................................................................................................... 9 
1 
BACKGROUND & JUSTIFICATION ........................................................................................................ 12 
1.1 
Identification and Description of the Study Devices ................................................................... 15 
1.2 
Study Device Details .................................................................................................................... 17 
1.3 
Device Regulatory Classification ................................................................................................. 18 
2 
Risks and Benefits of the Devices used in this Study .......................................................................... 19 
2.1 
Risks of the Devices ..................................................................................................................... 19 
2.2 
Residual Risks .............................................................................................................................. 19 
2.3 
Risk of Interactions with Concomitant Medical Treatments ...................................................... 19 
2.4 
Mitigation of Risk ........................................................................................................................ 19 
2.5 
Benefits of the Device ................................................................................................................. 19 
2.6 
Risk to Benefit Rationale ............................................................................................................. 19 
2.7 
Other Medical Devices to be Used in the Study ......................................................................... 19 
3 
DESIGN OF CLINICAL INVESTIGATION ................................................................................................. 20 
3.1 
Study Design................................................................................................................................ 20 
3.2 
Justification and Scientific Rationale for Design ......................................................................... 20 
3.3 
Minimisation of Bias ................................................................................................................... 20 
4 
OBJECTIVES OF THE CLINICAL STUDY .................................................................................................. 21 
4.1 
Primary Objective(s) .................................................................................................................... 21 
4.2 
Endpoints .................................................................................................................................... 21 
4.2.1 
Primary Endpoint ................................................................................................................ 21 
4.2.2 
Secondary Endpoints .......................................................................................................... 21 
4.2.3 
Exploratory Endpoints ......................................................................................................... 21 
4.2.4 
Safety endpoints ................................................................................................................. 22 
5 
POPULATION AND DURATION OF THE STUDY .................................................................................... 23 
6 
ENROLLMENT CRITERIA ...................................................................................................................... 24 
6.1 
Inclusion Criteria ......................................................................................................................... 24 
6.2 
Exclusion Criteria ......................................................................................................................... 24 
6.3 
Relationship of Investigation Population to the Target Population ........................................... 25 
7 
INFORMED CONSENT PROCESS .......................................................................................................... 26 
8 
POINT OF ENROLLMENT AND EXIT ..................................................................................................... 27 
8.1 
Point of Enrolment ...................................................................................................................... 27 
8.2 
Point of Exit ................................................................................................................................. 27 

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8.3 
Completed Subject ...................................................................................................................... 27 
8.4 
Subject Identification .................................................................................................................. 27 
8.5 
Wound Identification .................................................................................................................. 27 
9 
STUDY PROCEDURES ........................................................................................................................... 28 
9.1 
Procedure Diagram ..................................................................................................................... 28 
9.2 
Study Visits .................................................................................................................................. 29 
9.3 
Schedule of Events ...................................................................................................................... 29 
9.4 
Enrolment of Subject with Multiple Wounds ............................................................................. 29 
10 
Visits ................................................................................................................................................ 31 
10.1 
Visit 1: Screening and Baseline: Day 1 ........................................................................................ 31 
10.2 
Visit 2: Day 14 (+/- 2 days) .......................................................................................................... 31 
10.3 
Visit 3: Day 28 (+/- 2 days) .......................................................................................................... 32 
10.4 
Visits 4 - 7: Day 42 thru 84 (every 14 days +/- 2 days) ................................................................ 33 
10.5 
Unscheduled Visit ....................................................................................................................... 33 
10.6 
End of Study Visit (Study Exit) ..................................................................................................... 33 
11 
SAFETY AND EVENT REPORTING ..................................................................................................... 35 
11.1 
Definitions ................................................................................................................................... 35 
11.1.1 
Adverse Event (AE). ............................................................................................................. 35 
11.1.2 
Serious Adverse Event (SAE). .............................................................................................. 35 
11.1.3 
Adverse Device Effect (ADE) ................................................................................................ 35 
11.1.4 
Serious Adverse device Effect (SADE) ................................................................................. 35 
11.1.5 
Unanticipated Serious Adverse Device Effect (USADE) ...................................................... 35 
11.2 
Adverse Events Categories and Relationship Determination ..................................................... 36 
11.3 
Categories of Severity ................................................................................................................. 36 
11.4 
Relationship to Investigational Device ........................................................................................ 36 
11.5 
Procedure for Monitoring and Recording of Serious Adverse Events ........................................ 36 
11.6 
Safety Reporting Timelines ......................................................................................................... 37 
11.7 
Follow-Up Information for Serious Adverse Events .................................................................... 37 
11.8 
Device Deficiency ........................................................................................................................ 37 
12 
PROTOCOL DEVIATIONS .................................................................................................................. 39 
12.1 
Deviation Reporting Timelines .................................................................................................... 39 
13 
PREMATURE TERMINATION, SUSPENSION OR ROUTINE CLOSE-OUT OF THE STUDY .................... 40 
13.1 
Premature Termination or Suspension ....................................................................................... 40 
13.2 
Procedure for resuming the clinical investigation after temporary suspension ........................ 40 
13.3 
Routine Close-Out ....................................................................................................................... 40 

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14 
MONITORING .................................................................................................................................. 41 
15 
DEVICE ACCOUNTABILITY................................................................................................................ 42 
16 
CONFIDENTIALITY............................................................................................................................ 43 
17 
DATA HANDLING AND RECORD KEEPING ....................................................................................... 44 
17.1 
Data Collection and Management Responsibilities .................................................................... 44 
17.2 
Study Records Retention............................................................................................................. 44 
17.3 
Sponsor Oversight ....................................................................................................................... 44 
18 
STATISTICAL CONSIDERATIONS ....................................................................................................... 45 
18.1 
Alpha Value ................................................................................................................................. 45 
18.2 
Statistical Approach for the Primary Endpoint ........................................................................... 45 
18.3 
Statistical Approach to Secondary and Exploratory Endpoints .................................................. 45 
18.4 
Sample Size Determination ......................................................................................................... 45 
18.5 
Multiplicity .................................................................................................................................. 45 
18.6 
Randomisation ............................................................................................................................ 46 
18.7 
Statistical Populations ................................................................................................................. 46 
19 
CONFLICT OF INTEREST ................................................................................................................... 47 
20 
GOOD CLINICAL PRACTICE AND STATEMENTS OF COMPLIANCE ................................................... 48 
20.1 
Ethical Approval .......................................................................................................................... 48 
20.2 
Protocol Modifications ................................................................................................................ 48 
20.3 
Periodic Reviews ......................................................................................................................... 48 
20.4 
Insurance ..................................................................................................................................... 48 
20.5 
Patients’ Compensation .............................................................................................................. 48 
20.6 
Principal Investigator, Coordinating Investigator(S), Investigational Sites and External 
Organisations .......................................................................................................................................... 48 
20.7 
Public Registration and Publication ............................................................................................ 49 
21 
LITERATURE .................................................................................................................................... 50 
22 
GLOSSARY, ABBREVIATIONS & ACRONYMS .................................................................................. 53 
 
 
 

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SYNOPSIS 
Study Title 
A clinical study to compare the performance of AQUACEL® Ag+ Extra™ and 
Cutimed® Sorbact® dressing in the management of patients with Venous Leg Ulcers 
over a 12-week period 
Study Type 
Post-market  
Principal 
Investigator (PI) 
Catarina Saavedra, M.D. 
Device(s) Under 
Investigation 
AQUACEL® Ag+ Extra™ (Experimental Arm) and Cutimed® Sorbact® (Control Arm) 
 
Sponsor 
Convatec Limited, GDC, First Avenue, Deeside Industrial Park, Deeside, Flintshire, 
CH5 2NU, United Kingdom 
 
Purpose 
The primary purpose of this study is to evaluate performance of AQUACEL® Ag+ 
Extra™ in comparison to Cutimed® Sorbact® in the progression of wounds towards 
healing.  
Design 
Randomised, active-controlled, open label, multi-centre, global study  
Selection of 
Subjects 
Inclusion Criteria  
Subjects must meet the following criteria:  
IC-1  
Venous insufficiency as defined by CEAP Classification of C6. 
IC-2  
At least one chronic venous ulcer (wound) amendable to treatment with 
AQUACEL® Ag+ Extra™ and Cutimed® Sorbact®. 
IC-3  
Wound(s) that have been present for at least 60 days (2 months) and ≤18 
months  
IC-4  
Reliable and available for follow-up, in the opinion of the investigator 
IC-5  
18 years or older at the time of consent  
IC-6  
Able and willing to provide informed consent  
IC-7  
Able to tolerate compression therapy for VLU (40 mmHg)  
IC-8  
Wound must be ≥1 cm2 and ≤100 cm2  
IC-9  
Must be able to be compliant with compression therapy  
IC-10  ABPI should be in the range between 0.8 and 1.3 
Exclusion Criteria  
Subjects must be excluded from participating in this study if they meet any of the 
following criteria:  
EC-1  
Known sensitivities or allergies to components of the AQUACEL® Ag+ 
Extra™ or Cutimed® Sorbact®  
EC-2  
Continued use of petroleum gel/ creams/ oil-based products on the target 
wound  

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EC-3  
Active treatment for cancer or completed within the last 3 months  
EC-4  
Documented severe malnutrition at any time  
EC-5  
Malignant wounds  
EC-6  
Systemic infection actively treated with antibiotics  
EC-7  
Patients with uncontrolled diabetes with HbA1c ≥ 10 within last 3 months. 
Subjects without diabetes do not require measurement of HbA1c if they 
have a glucose or HbA1c level measured over the past year.  
EC-8  
Chronic conditions such as autoimmune disorders in an acute flare phase, 
which in the opinion of the investigator, would directly impact wound 
healing. Use of immunosuppressant medications are allowed, as long as 
they have been on a stable dose and regimen over the past 3 months  
MDR Device 
Regulatory 
Classification 
AQUACEL® Ag+ Extra™  is a Class III device  
Cutimed® Sorbact® is a Class IIb device 
Primary 
Objective(s) 
The primary objective of the study is to compare the effectiveness of AQUACEL® 
Ag+ Extra™ to Cutimed® Sorbact® on wound management when used in 
accordance with the instructions for use.  
Endpoint(s) 
The primary end point is complete wound closure as defined by 100% 
epithelialisation of the wound surface. 
 Secondary endpoints are percent change in target wound area at 4 weeks (primary 
treatment period); Satisfactory clinical progress defined as 40% reduction in study 
wound area at 4 weeks (primary treatment period) and percent change in target 
wound area at 12 weeks. 
Exploratory endpoints are time to complete wound closure, wound clinical 
characteristics (e.g. wound healing status, condition of surrounding skin and signs 
of infection), Wound Quality of Life (Wound-QoL) 14, pain, wound management 
after the study mandated treatment. 
Safety will be characterized by a summary of the incidence of adverse events (AEs), 
device-related AEs, and serious device-related AEs. 
Randomisation 
Subjects will be randomised on a 1:1 basis to either the AQAUCEL® Ag+ Extra™ or 
Cutimed® Sorbact® dressing. Subjects will be randomised to product at Visit 1 once 
it has been determined the subject is suitable to participate in the study. 
Study Duration 
The subject participation is up to 12 weeks. It is anticipated enrolment will take 12 
months and the overall study duration is anticipated to be approximately 18 
months. 
Sponsor Study 
Contact 
Kristina Aare 
Clinical Project Manager  
Convatec Limited  
Medical Affairs and Clinical Affairs  
GDC (Global Development Centre)  
 First Avenue  

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Deeside Industrial Park  
Deeside  
Flintshire  
CH5 2NU  
United Kingdom  
Kristina.aare@convatec.com  
+44 (0) 7423635549 
 
Medical Monitor 
Contact 
Kerem Ozer, MD 
Director, Global Medical Affairs and Clinical Development  
20 Maguire Rd #201  
Lexington, MA 02421  
Kerem.Ozer@convatec.com  
+1 (617) 2187138  
 
 
 
 
 

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1  BACKGROUND & JUSTIFICATION  
The burden of chronic wounds 
Caring for patients with acute and chronic wounds represent a significant challenge on healthcare 
systems and societies around the world. Real-world data from the UK (2017/2018) has shown that the 
total costs to the UK health system of caring for patients with wounds was around GBP£8.3BN per year.1 
This is equivalent to the UK spend on systemic diseases such as osteoarthritis and rheumatoid arthritis 
which was GBP£10.2 billion in 2017/2018. Whilst 89% of acute wounds heal within a year, just 49% of 
chronic wounds close within the same period. Whilst the understanding of how to treat chronic wounds 
has improved over time, the increased age of the population and their attendant co-morbidities means 
that healing rates don’t appear to have improved.1,2 
The significance of venous leg ulcers 
One of the most prevalent chronic wounds are venous leg ulcers (VLU). In Germany, about 0.6–1% of the 
population are diagnosed with a VLU, with the prevalence in people above the age of 60 being much 
higher (3.9%). VLU are wounds on the lower extremity resulting from venous hypertension and 
hypervolemia. The pooling of venous blood gives rise to oedema which leads to poor perfusion and 
tissue breakdown. The mainstay of conservative treatment is compression therapy to counteract the 
oedema and assist venous return. Many VLU are in fact mixed ulcers as patients often have a degree of 
arterial disease.3 Only about half of VLUs heal within 4 months, leaving a significant proportion of non-
healing ulcers to place a burden on heath resources and patient quality of life. Improvements in healing 
of VLU would have a significant impact. 
The importance of bacteria and infection in chronic wounds 
Much of the present day understanding of the clinical interventions required to improve healing in 
chronic wounds is enshrined in the widely used concept of Wound Bed Preparation (WBP). 5-8 Several 
derivations and additions to the TIME principles have since been developed.9 The key concept at the 
heart of the WBP scheme is to break the clinical problem down into a series of interconnected barriers 
to intrinsic healing. The barriers are grouped into 4 areas:  Tissue; Infection/Inflammation; 
Moisture/Exudate; Edge/Epithelialisation: the so called “TIME” paradigm.  
Real world data show that chronic wounds which have required antimicrobial treatments for infection, 
have worse healing rates that wounds that have not become infected.1 The importance of infection on 
chronic wounds has been a central tenet of healing since the studies of Robson showed that tissues that 
contained more than 105 colony forming units per gram of tissue were unlikely to heal without 
antimicrobial intervention.10 It is now understood that an excessive inflammatory environment is 
counterproductive for healing as proteolytic activity from the inflammatory cell infiltrate secrete high 
levels of the matrix metalloproteases (MMP2 and MMP9) impedes the ability of cells to lay down extra 
cellular matrix that is critical for angiogenesis and epithelial migration. 5 
The Infection continuum 
It is widely agreed that indiscriminate use of antibiotics in medicine and agriculture since their 
emergence in the middle of the previous century, has driven the selection and spread of antibiotic 
resistance. Research has established that it is unnecessary to set a target of zero bacteria in a healing 
wound, but rather that a balance between bacteria and host is a more desirable goal.11 Evidence shows 
that systemic antibiotics do not lead to rapid improvement in chronic wound healing and long-term use 
of antibiotics would not be desirable because of concerns of selecting resistance. A useful way to 

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summarise the need for the deployment of antimicrobials in wound healing is the model known as the 
Infection Continuum.12,13  
 
The Infection continuum characterises wounds into 5 categories according to increasing levels of bacteria: 
1. 
Contamination 
2. 
Colonisation 
3. 
Local infection (has in the past been called Critical Colonisation) 
4. 
Spreading infection 
5. 
Systemic infection 
 
 
As shown in the Figure reading left to right, Categories 1 and 2 represent wounds containing bacteria, 
but not at levels where antimicrobial intervention is recommended for prevention of infection or 
accelerating healing. Category 3 is a wound with clinical signs indicating local infection like pain, 
exudate, and erythema but not one where antibiotics show good efficacy. It is now widely recognised 
that systemic antibiotics have a poor efficacy on chronic, delayed healing wounds, because of their 
intrinsic poor perfusion and peri wound oedema. The evidence-based medicine Cochrane collaboration 
regularly reviews the use of antibiotics and topical antiseptics for the prevention or treatment of 
infection, or the acceleration of healing in VLU. There were no positive effects of antibiotics, systemic or 
topical, demonstrated versus standard care amongst 45 RCTs reporting 53 comparisons and recruiting a 
total of 4486 participants and only limited evidence for topical cadexomer iodine, a slow-release 
formulation eluting molecular iodine (I2) and very limited evidence for widely used silver-based 
antimicrobials.14,15 Others have disputed the view that there is no platform of evidence for the use of 
antimicrobial dressings containing silver ions.16 Infection continuum wound categories 4 and 5 indicate 
infection spreading into adjacent tissue (4) or systemic infection (5) (bacteraemia) and here evidence 
supports the use systemic antibiotics simultaneously with the use of topical antimicrobials and 
antiseptics to improve the wound.12-14    
In routine clinical practice, the identification of the different categories of bacterial presence are based 
on the observation of clinical signs such as pain, erythema, exudate, oedema, rather than any attempt at 

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quantitative microbiology. Recently a panel of experts revisited the use of clinical signs of infection in 
order to identify wounds that should receive topical antimicrobials.17 The Therapeutic Index for Local 
Infections (TILI score) has subsequently been validated as an easy to operate assessment tool for 
identification of locally infected wounds (category 3). In a study of a total of 307 patients with leg ulcers 
recruited from 5 European countries, 22% of proved to have a local infection.18  
The importance of biofilms 
It has been known for many years that bacteria can switch between two phenotypes: free-living single-
cell planktonic forms and sessile forms growing as multicellular biofilms encased in extracellular 
polymeric substance (EPS).19 However, evidence that a large fraction, and probably all non-healing 
wounds contain biofilms, was only published as recently as 2008.20 Since that time, the science of 
biofilms and wound healing has developed quickly.19 Evidence is also now accumulating that surgical 
wounds may also become colonised with multispecies biofilms, and these may play a role in the 
development of surgical site infections.21 Wound dressings whose function is to sequester exudate and 
reduce the risk of a direct fluid path into the wound, may represent good conditions for the 
establishment of biofilms from which it is possible to repeatedly re-seed the healing wound below.21 
When present in a biofilm, the carbohydrate-based extracellular polymeric substance (EPS) ensures 
bacteria are many times more resistant to the presence of antibiotics than free-living bacteria and 
equally important, inflammatory cells are less able to attack and engulf bacterial cells living in a 
biofilm.22 Investigations reveal that, biofilms are frequently composed of multiple species, and contrary 
to popular belief, biofilms are typically present as microcolonies embedded in granulation tissue, rather 
than a thin film on the surface of the wound. Anaerobic and aerobic species frequently co-exist, with 
certain sectors of the biofilm becoming significantly anoxic.23  
For several years it was unclear whether biofilms were simply benign occupants of non-healing tissues, 
or whether biofilms themselves were implicated in the failure of the wound to heal. Evidence for a 
causal relationship between delayed wound healing and the presence of biofilm has been obtained with 
experiments in pigs. Researchers began by isolating a Methicillin-resistant Staphylococcus aureus 
(MRSA) strain from a contaminated pig wound, which when inoculated again into full thickness porcine 
wounds, gave a more extreme biofilm phenotype: it was more multicellular with more EPS than the 
parental strain. Moreover, it was observed that the new strain delayed healing to a greater extent than 
the parental strain.24 Thus the link was made between the biofilm phenotype and the degree of 
inhibition of the normal healing trajectory.  
Anti-biofilm strategies 
The realisation that non-healing wounds are colonised by bacterial biofilms which have reduced 
sensitivity to topical and systemic antimicrobial therapies and cause inhibition of wound healing, has 
made clinicians think more carefully how they deliver antimicrobial therapy to chronic wounds. Seen in 
the context of the scheme of wound bed preparation, “biofilm-based wound care” builds on the concept 
that debridement is an excellent means of removing biofilm colonised tissue, but that at this point there 
is a window of opportunity to apply appropriate topical antimicrobials which will have increased efficacy 
on any planktonic bacteria liberated from the bulk biofilm population as the result of the 
debridement.25,26 Application of the antimicrobial after debridement, rather than before, reduces the 
opportunity for biofilms to grow back. A cycle of debridement, followed by antimicrobial, followed by 
debridement, is now regarded as the most efficacious strategy.27   
AQUACEL® Ag + Extra™ 
The understanding that biofilms are pivotal to the imposition of delayed healing on chronic wounds, has 
driven innovation in the antimicrobial sector. In one approach, the commercially successful silver gelling-

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hydrofibre dressing Aquacel Ag™ (Convatec Inc) was modified, following a systematic search for 
synergistic activities, by the addition of the metal ion chelator EDTA and the surfactant antimicrobial 
benzethonium chloride. Branded Aquacel Ag+ (Convatec Inc) with the aim of allowing deeper 
penetration of silver ions into biofilms through destabilisation of the EPS.28 Aquacel gelling fibre has 
subsequently been modified to have improved handling strength (Aquacel® Extra) and the Aquacel Ag+ 
dressing with Ag, EDTA and benzethonium is now available in the improved strength format: Aquacel 
Ag+ Extra. In vitro, in vivo, and clinical studies of AQUACEL® Ag+ Extra™ have been summarised.29,30  
Cutimed® Sorbact® 
A completely different approach to reducing the levels of bioburden in wounds is the development of 
hydrophobic dialkylcarbamoyl chloride (DACC) coated dressings. Hydrophobic bacteria become 
irreversibly bound to the DACC coated surfaces. Branded Cutimed® Sorbact® (BSN Medical GmbH), the 
bound bacteria can be removed at dressing changes, but DACC-bound bacteria don’t proliferate and 
aren’t lysed with subsequent release of potentially inflammatory substances. In vitro, in vivo, and clinical 
studies of Cutimed® Sorbact® dressings have recently been summarised.31-33 
In an analysis of use in clinical practice in Germany, both AQUACEL® Ag+ Extra™ and Cutimed® Sorbact® 
are utilised significantly.4 There have been no published reports of substantive randomized comparative 
trials with either dressing technology versus controls, and no direct head-to-head comparative studies of 
the two approaches to address the effects of microbial bioburden on the healing of VLU wounds. It is 
not clear how the DACC coated dressings might counter embedded biofilms. One recently published 
protocol describes a randomised comparison of Cutimed® Sorbact® DACC dressings versus AQUACEL® 
Ag+ Extra™  (the version without EDTA and benzethonium): NCT03667937 www.clinicaltrials.gov.34 The 
study will look for effects on levels of bioburden in VLUs assessed with a primary endpoint of rDNA qRT-
PCR determined levels of culturable and non-culturable bacteria. The wounds will be assessed following 
treatment with the two kinds of dressings at weeks 4, 8 and 12. It is not known how advanced this study 
is in recruitment.  
Purpose of the present study 
The purpose of the present protocol is to compare effectiveness of two antimicrobial dressing 
technologies in patients with VLU. The study is justified as both dressings are in widespread clinical use, 
each has significant pre-clinical and clinical data that demonstrates safety, but no comparative trials 
including either product have previously been undertaken.  
1.1 
Identification and Description of the Study Devices 
Table 1.1.1 provides an identification and description of the study devices.  
 
 
 
 

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TABLE: 1.1.1: Identification and Description of Study Devices 
Study 
Device  
Legal 
Manufacturer 
Description 
Identification 
AQUACEL® 
Ag+ Extra™  
 
Convatec 
Limited 
Deeside 
Industrial Park 
Deeside 
Flintshire 
CH5 2NU 
 
 
Convatec’s 
Limited EU 
Representative 
is 
Unomedical A/S  
Aahomvej 1-3 
Osted 
4320 Lejre, 
Denmark 
 
AQUACEL® Ag+ Extra™ 
dressings (Figure 1) 
comprise a needle-bonded 
nonwoven fabric layered 
and stitch-bonded to 
provide a dressing 
approximately 2-3 mm 
thick, and which is then cut 
to the dimensions specified 
on the packaging. They are 
constructed of two layers of 
optimally textiled 70 gsm 
Hydrofiber™ (sodium 
carboxymethylcellulose) 
into which ionic silver 
(antimicrobial agent) and 
the excipients 
ethylenediaminetetra-
acetic acid di-sodium salt 
(EDTA) (a chelating agent) 
and benzethonium chloride 
(a surface-active agent) 
have been added to disrupt 
biofilm and expose 
microorganisms to the 
antimicrobial effects of 
ionic silver. The dressings 
are stitch-bonded together 
using Lyocell (Tencel™ 
regenerated cellulose) 
yarns. 
 
 

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Study 
Device  
Legal 
Manufacturer 
Description 
Identification 
Cutimed® 
Sorbact® 
BSN medical 
GmbH, 
Quickbornstraße 
24, 20253 
Hamburg, 
Germany 
Cutimed® Sorbact® dressing 
is approved as a bacterial 
and fungi binding wound 
dressing. It consists of a 
green Sorbact® wound 
contact layer combined 
with an absorbent core and 
a white backing. Sorbact® 
dressing absorbs and 
retains exudate, thereby 
reducing the risk of 
maceration and enabling a 
moist wound environment. 
The dressing can be used in 
combination with 
compression therapy. 
 
 
 
 
 
 
 
1.2 
Study Device Details 
The table below demonstrates many aspects of the devices under study. 
 
 
AQUACEL® Ag+ Extra™ 
Cutimed® Sorbact® 
Mode of Action 
The mode of action of these wound 
dressings is by absorption and fluid 
retention. When in contact with wound 
exudate, the dressing forms a cohesive 
gel; this gelled material enables intimate 
contact of the dressing with the wound 
bed.   
 
Cutimed® Sorbact® binds microorganisms, 
such as Staphylococcus aureus (including 
MRSA), Streptococcus species, Escherichia 
coli, Pseudomonas aeruginosa and 
Candida albicans, as shown in-vitro. These 
microorganisms are removed from the 
wound each time the dressing is changed. 
 

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AQUACEL® Ag+ Extra™ 
Cutimed® Sorbact® 
The dressings demonstrate antimicrobial 
activity through the presence of silver, an 
antimicrobial agent. 
 
The addition of EDTA and benzethonium 
chloride enables the dressing to disrupt 
wound biofilm and sessile attached 
bacteria in contact with the dressing 
Duration of Use 
AQUACEL® Ag+ Extra™ can be worn for up 
to 7 days, dressings should be changed 
earlier if clinically indicated. On partial 
thickness (second degree) burns, 
dressings may remain in place for up to 14 
days. The need for AQUACEL® Ag+ Extra™ 
should be re-assessed after 14 days and 
alternative wound management 
considered where appropriate 
Cutimed® Sorbact® can be left in place for 
up to 7 days, should the clinical condition 
allow 
Intended Use 
AQUACEL® Ag+ Extra™ Dressings have 
been designed to be used as a primary 
dressing. They are intended to be used 
under the direction of a healthcare 
professional for wounds, which are at risk 
of infection or show signs infection, or 
where biofilm is suspected to be present, 
and in accordance with the indications for 
use. 
Cutimed® Sorbact® is indicated for use in 
management of clean, contaminated, 
colonised, or infected wounds with 
moderate to high levels of exudate, such 
as surgical wounds, traumatic wounds, 
pressure ulcers, diabetic ulcers, and leg 
ulcers. 
Storage 
Conditions 
According to manufacturer’s packaging 
According to manufacturer’s packaging 
 
1.3 
 Device Regulatory Classification 
The study devices used in this study are approved in Europe and are classified according to MDR in the 
table below. 
 
AQUACEL® Ag+ Extra™ 
Cutimed® Sorbact® 
MDR Classification 
Class III 
Class IIb 
 

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2  Risks and Benefits of the Devices used in this Study 
The section below details the risks and benefits of the devices used in this study.  
2.1 
Risks of the Devices 
The risks associated with using the study device(s) in the study are no different than in standard of care, 
as they will be used according to their intended use statements. Please refer to IFU Sections 
PRECAUTIONS and OBSERVATIONS for any information regarding adverse events and any steps that 
should be taken to avoid them, as well as information about other warnings and precautions in relation 
to the device. 
Anticipated Adverse Device Effects 
The anticipated adverse device effects are known reactions to the study devices. The list of known 
anticipated adverse device effects include, but are not limited to: allergic reaction, bleeding, 
pain/discomfort in area of wound, skin irritation around wound, and infection.  
2.2 
Residual Risks  
The study devices used on this study are applied according to indications for use. By participating in this 
study, it is anticipated that the residual risks are the same as not participating in the study. The device 
manufacturers have performed qualification testing on the device and device components and 
appropriate quality control measures have been implemented into production. 
2.3 
Risk of Interactions with Concomitant Medical Treatments 
No interactions with concomitant medications are noted in the IFU for either study device. 
2.4 
Mitigation of Risk 
Additional action to mitigate risks are not anticipated, as the devices are used in a way that is standard 
of care.  
2.5 
Benefits of the Device 
There are no additional benefits of using this device in the study than in standard of care.  
2.6 
Risk to Benefit Rationale 
Considering the information listed in this section, it can be concluded that there are no additional risks 
to individuals exposed to devices in the study compared to in standard of care. There are no risks of 
physical harm associated with participation in this study, as this is a study evaluating a commercially 
approved wound dressing when used as intended, with follow up procedures performed per standard of 
care. No treatment is added or removed due to a patient’s participation in the study. The device IFUs 
contain additional information related to the anticipated risks associated with the use of the dressings 
and wound care.  
2.7 
Other Medical Devices to be Used in the Study 
Any additional dressings or complimentary therapies such as compression, off-loading devices, and 
similar used in this study will be applied as in intended use and availability in the market while following 
their respective IFUs.  

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3  DESIGN OF CLINICAL INVESTIGATION 
3.1 
Study Design 
The study is a post market, multi-centre, randomised, open label, global prospective study to compare 
the performance of AQUACEL® Ag+ Extra™ and Cutimed® Sorbact® dressing in the management of 
patients with venous leg ulcers (VLUs).  
The VLUs will be treated with AQUACEL® Ag+ Extra™ (Experimental Arm) or Cutimed® Sorbact® (Control 
Arm) for up to 4 weeks. The WLUs will then be managed the with Standard of Care for up to 10 weeks, 
or until the wound has healed or the dressing is no longer clinically indicated. Crossover of dressings is 
not permitted. 
3.2 
Justification and Scientific Rationale for Design 
This study compares the performance of AQAUCEL® Ag+ Extra™ verses Cutimed® Sorbact® in patients 
with VLUs. Literature supports the use of silver dressings in these types of wounds, as this may promote 
healing. This study is designed to collect this type of data on Convatec’s AQUACEL® Ag+ Extra™.  
3.3 
Minimisation of Bias 
Bias in studies can impact results in any study. To minimise bias, the following steps, which include, but 
are not limited to, have been taken:  
• 
Multiple sites and geographies have been selected, which reduces the instrumentation and 
performance biases.  
• 
Randomization minimizes confounding bias. 
 

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4  OBJECTIVES OF THE CLINICAL STUDY 
4.1 
Primary Objective(s) 
The primary objective of the study is to compare the effectiveness of AQUACEL® Ag+ Extra™ verses 
Cutimed® Sorbact® in the management of patients with venous leg ulcers (VLUs).  
4.2 
Endpoints 
4.2.1 
Primary Endpoint 
• 
Complete wound closure as defined by 100% epithelialisation of the wound surface (Gould 
2019). 
4.2.2 
Secondary Endpoints 
• 
Percent change in study wound area at 4 weeks (primary treatment period).  
• 
Satisfactory clinical progress defined as 40% reduction in study wound area at 4 weeks (primary 
treatment period) 
• 
Percent change in target wound area at 12 weeks. 
4.2.3 
Exploratory Endpoints 
• 
Time to complete wound closure. 
• 
Wound characteristics: 
o  Eschar tissue presence and percentage 
o  Slogh/Fibring tissue presence and percentage 
o  Healthy granulation tissue presence and percentage 
o  Unhealthy granulation tissue presence and percentage 
o  Epithelial tissue presence and percentage 
o  Exudate volume category (low, medium, high) 
o  Exudate type 
o  Odour 
o  Condition of the wound edge 
o  Condition of the peri-wound skin 
o  Presence of erythema 
o  Signs of infection 
• 
Wound-QOL-14. 
• 
Pain on a Numeric Rating Scale from 0 to 10 where 0 is no pain at all and 10 is the worst 
imaginable pain. 
• 
Wound treatment type after the study mandated treatment. 

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4.2.4 
Safety endpoints 
Safety will be characterized by a summary of the incidence of adverse events (AEs), device-related AEs, 
and serious device-related AEs. 
 

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5  POPULATION AND DURATION OF THE STUDY 
It is proposed that the study is conducted in Poland, Germany, and Colombia. Additional sites in 
additional countries may be recruited. The study sample will be recruited from the Investigators 
available clinical population.  
Individual subject duration of participation in the study is up to 12 weeks. It is anticipated enrolment will 
take 12 months and the overall study duration is anticipated to be approximately 18 months. 

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6  ENROLLMENT CRITERIA 
6.1 
Inclusion Criteria 
Subjects must meet the following criteria: 
TABLE: 6.1-1: Inclusion Criteria 
Number 
Inclusion Criteria 
IC-1 
Venous insufficiency as defined by CEAP Classification of C6  
IC-2 
At least one chronic venous ulcer (wound) amendable to treatment with AQUACEL® 
Ag+ Extra™ and Cutimed® Sorbact® 
IC-3 
Wound(s) that have been present for at least 60 days (2 months) and less than ≤18 
months 
IC-4 
Reliable and available for follow-up, in the opinion of the investigator 
IC-5 
18 years or older at the time of consent 
IC-6 
Able and willing to provide informed consent 
IC-7 
Able to tolerate compression therapy for VLU (40 mmHg) 
IC-8 
Wound must be ≥1 cm2 and ≤100 cm2 
IC-9 
Must be able to be compliant with compression therapy 
IC-10 
ABPI should be in the range between 0.8 and 1.3   
 
6.2 
Exclusion Criteria 
Subjects must be excluded from participating in this study if they meet any of the following criteria: 
TABLE: 6.2-1: Exclusion Criteria 
Number 
Exclusion Criteria 
EC-1 
Known sensitivities or allergies to components of the AQUACEL® Ag+ Extra™ or 
Cutimed® Sorbact® 
EC-2 
Continued use of petroleum gel/ creams/ oil-based products on the target wound 
EC-3 
Active treatment for cancer or completed within the last 3 months 
EC-4 
Documented severe malnutrition at any time 
EC-5 
Malignant wounds or other than VLU wounds 
EC-6 
Systemic infection actively treated with antibiotics 
EC-7 
Patients with uncontrolled diabetes within last 3 months with HbA1c ≥ 10. Subjects 
without diabetes do not require measurement of HbA1c if they have a  glucose or 
HbA1c level measured over the past year.   

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Number 
Exclusion Criteria 
EC-8 
Chronic conditions such as autoimmune disorders in an acute flare phase, which in the 
opinion of the investigator would directly impact wound healing. Use of 
immunosuppressant medications are allowed as long as they have been on a stable 
dose and regimen over the past three months 
 
6.3 
Relationship of Investigation Population to the Target Population 
Silver and non-silver wound dressings are used to assist in the management of chronic wounds. The 
inclusion and exclusion criteria are representative of the population with chronic wounds who would be 
prescribed AQUACEL® Ag+ Extra™ and Cutimed® Sorbact® dressing. 

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7  INFORMED CONSENT PROCESS 
Informed Consent must be obtained for all subjects prior to any study activities being performed or data 
collected. The Investigator or designee will review all relevant aspects of the study with the potential 
study subject that are relevant to the subject’s decision to participate throughout the study. The 
investigator or designee will provide ample time for the subject to read and understand the IRB/EC 
approved Informed Consent Form and to consider participation in the study.  
Informed consent will not be collected until all the patient questions have been answered to their 
satisfaction. If agreeable, the subject (or legally authorised representative) must sign and date the 
Informed Consent Form, along with the Investigator or designee. As required by country-specific 
regulatory agencies, a witness will sign the Informed Consent Form. The Subject must receive a copy of 
the signed Informed Consent, with the original remaining with the Investigator. 

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8  POINT OF ENROLLMENT AND EXIT 
The study will be conducted in accordance with ISO 14155:2020 and in compliance with national and 
local laws in the geographies the study will be conducted. 
8.1 
Point of Enrolment 
Subjects are considered enrolled in this study at the time the Informed Consent process has been 
completed. In the event of subject withdrawal or discontinuation prior to study completion, study 
subjects will not be replaced. 
8.2 
Point of Exit 
Study subjects may exit the study for a variety of reasons. The Investigator shall record the reason for 
study exit in the applicable Study Completion CRF. These reasons include, but are not limited to: 
• 
Study completion. 
• 
Withdrawal by the Subject. 
• 
Withdrawal by the Investigator. 
• 
Lost to follow-up. 
• 
Death. 
• 
Study Termination. 
Data collected until the last known contact of study subject may be used in the analysis of study data. 
For study subjects lost to follow-up, the Investigator shall make three (3) documented attempts before 
confirming the subject is lost to follow-up. If the study subject withdraws from the study for any reason 
and there is an ongoing safety event, additional safety event information may need to be collected by 
the Investigator and shared with the Sponsor. 
8.3 
Completed Subject 
Subject has completed the study if the subject has completed the final study visit (84 days follow-up 
visit) or earlier if all study wounds have healed prior to 84-day follow-up visit. If subject has multiple 
wounds, the subject exits the study when the last study wound heals or when subject attends the final 
study visit, whichever occurs first. Study completion can occur between the scheduled study visits.  
8.4 
Subject Identification 
Subjects will be allocated a unique study identifier on all study documentation. The only documents 
which will contain any personal details is the consent form and the Subject Identification Log, which are 
maintained by the Investigator or designated study staff. Their identification is a number attributed 
regarding the country, number of the site and number dedicated to inclusion. For example: 57-0001-
0005: country number 57, centre number 1, inclusion number 5. 
8.5 
Wound Identification 
Each study wound will be allocated a sequential number within the subject starting with number 1. For 
example, subject 57-0001-0005, Wound 01, Wound 02; subject 57-0001-0006, Wound 01, Wound 02.  

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9  STUDY PROCEDURES 
The following section describes the study procedures and data which will be collected at each procedure 
for the duration of the study.  
9.1 
Procedure Diagram  
 

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9.2 
Study Visits 
After Informed Consent has been obtained, the following study procedures will be performed. All data is 
to be entered into the applicable Case Report Form (CRF). 
9.3 
Schedule of Events 
A schedule of events is in the table below. 
9.4 
Enrolment of Subject with Multiple Wounds 
Subjects with multiple wounds are allowed into study. Each wound that meets all wound-specific 
inclusion and none of the wound-specific exclusion criteria should be enrolled into study. The 
randomization occurs at the subject level. All study wounds for a specific subject will be treated with the 
same study device (e.g., all study wounds in a subject randomized to AQUACEL® Ag+ Extra™ will be 
treated with AQUACEL® Ag+ Extra™. No wound-level cross-over is allowed. 
 

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TABLE 9.3-1: Schedule of Events 
 
Visit 1 
Day 1 
 
Visit 2 
Day 14 
(+/- 2 days) 
Visit 3 
Day 28 
(+/- 2 days) 
Visit 4 
Day 42 
(+/- 2 days) 
Visit 5 
Day 56 
(+/- 2 days) 
Visit 6 
Day 70 
(+/- 2 days) 
Visit 7 
Day 84 
(+/- 2 days) 
Additional Visit 
End of Study 
Visit^ 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
Inclusion / 
Exclusion 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Concomitant 
Medication 
X 
X 
X 
X 
X 
X 
X 
 
X 
Wound History 
X 
 
 
 
 
 
 
 
 
Wound-QoL-14 
X 
X* 
X* 
 
 
 
X 
 
X@ 
Wound 
debridement per 
usual practice 
X 
X 
X 
X 
X 
X 
 
 
 
Wound 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomisation 
X 
 
 
 
 
 
 
 
 
Decision to 
continue with 
randomised 
dressing or 
Standard of Care 
 
X 
 
 
 
 
 
 
 
Randomised 
Dressing 
Application 
X 
X 
X$ 
X& 
X& 
X& 
 
 
 
Secondary 
Dressing 
Application# 
X 
X 
X 
X 
X 
X 
 
 
 
Apply 
compression 
therapy 
X 
X 
X 
X 
X 
X 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device 
Deficiency% 
X 
X 
X 
X 
X 
X 
X 
X 
X 
* Wound-QOL-14 will be completed following the completion of treatment with randomized dressing on Day 14 (+/- 2 days) or on Day 28 (+/- 2 days) if additional 14 days of 
treatment with the randomised dressing occurred.  
@ Collect QOL-14 if the Additional Visit is Study Completion visit. 
$ Application of the randomised dressing after Visit 2 (14-day visit) at the discretion of the investigator. 
& After day 28, the PI or delegate will continue treatment of the wound according to the clinical needs based on their evaluation of the wound. If an antimicrobial wound 
dressing is required, the dressing that was randomly assigned during the initial phase of the study can continue to be used 
# Secondary dressing to be applied at the discretion of the investigator. 
% If applicable 
^ If end of study visit is not Visit 7 

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10 Visits 
After Informed Consent has been obtained, the following study procedures will be performed.  
10.1  Visit 1: Screening and Baseline: Day 1 
The following procedures and data are collected at Visit 1. All information on this visit is required. 
Missing data and assessments will be considered a protocol deviation.  
• 
Obtain Informed Consent 
• 
Inclusion and Exclusion Criteria Review and Documentation  
• 
Demographics (Sex, Age, Height, Weight, BMI calculation, Ethnicity) 
• 
Medical History (Cardiovascular, Respiratory, Gastro-Intestinal, Endocrine, 
Haematological, Musculo-skeletal, Neoplasia, Neurological, Immunological, 
Dermatological, Allergies, Psychological, and Other) 
• 
Obtain Concomitant Medications (Medication Used, Route, Dose, Unit, Frequency, 
Indication, Start Date, Stop Date or Ongoing) 
• 
Study Wound(s) Assessment  
o  Duration of wound 
o  Location of the wound (I.e., left/right leg, posterior/ anterior, medial/ lateral, 
etc.) 
o  Wound size (measured in cm at the longest point and across the widest point) 
o  Wound bed appearance 
o  Exudate level, colour, and consistency 
o  Condition of peri-wound skin 
o  Maximum pain level on a scale of 0 to 10 within the last 24 hours 
o  Level of odour on a scale of 0 to 10 for the study participants and 
mild/medium/strong for the clinician. 
o  Therapeutic Index for Local Infections (TILI) score 
• 
Wound-QoL-14 
• 
Randomisation to either AQUACEL® Ag+ Extra™ or Cutimed® Sorbact®  
• 
Randomised dressing application (Size and Lot Number)  
• 
Apply compression per standard of care (documentation of type used)  
• 
Documentation of the use of secondary dressings, if applicable 
Each study wound in subject with multiple study wounds is assessed independently.  
10.2  Visit 2: Day 14 (+/- 2 days) 
The following procedures and data are collected at this visit. All information on this visit is required. 
Crossover to the non-randomized study dressing is not permitted. 
• 
Review of concomitant medications, documenting any changes (medication used, route, 
dose, unit, frequency, indication, start date, stop date or ongoing) 
• 
Wound assessment  
o  Wound size (measured in cm at the longest point and across the widest point, as 
well as depth) 
o  Wound bed appearance 
o  Exudate level, colour and consistency 
o  Condition of peri-wound skin 
o  Maximum pain level on a scale of 0 to 10 within the last 24 hours 

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o  Level of odour on a scale of 0 to 10 for the study participants and 
mild/medium/strong for the clinician. 
o  Therapeutic Index for Local Infections (TILI) score 
• 
Number of days, since last visit, where compression was not applied (including 
documentation of reason for no compression) 
A clinician decision is required at this visit regarding continuation of the randomised dressing 
(AQUACEL® AG+ Extra™ or Cutimed® Sorbact®) or transition to long-term management per standard of 
care. In subject with multiple study wounds the decision is made for each study wound separately. For 
example, one wound can be selected for Option 1 and another wound for option 3. 
Option 1: An additional 14 days of treatment with randomised dressing (AQUACEL™ Ag+ Extra™ or 
Cutimed® Sorbact®) is required.  
Option 2: Further treatment with randomised dressing is not indicated. The wound should be further 
managed per standard of care.  
Option 3: Clinician determines that a non-standard of care treatment is needed. Treatment with the 
randomised dressing is discontinued. 
Regardless of the option chosen, the subject remains in the study and is followed-up until the study exit 
(see section 8.2)  
Once the decision has been made on the treatment option, the following information will be collected. 
• 
Dressing application according to clinician decision (randomised dressing or other dressing) 
(name, size and lot number is recorded)  
• 
Documentation of any additional products used 
• 
Document any additional therapies  
• 
Document and address any Adverse Events 
• 
Document and address any Serious Adverse Events 
• 
Number of intermediate visits where dressings were changed between scheduled visits (this is 
the number of times a subject received a new dressing since the last visit) 
• 
Wound-QOL-14 (only if Option 2 or 3 has been selected).  
10.3  Visit 3: Day 28 (+/- 2 days) 
The following procedures and data are collected at this visit. All information on this visit is required. 
Following this visit, if the wound has not healed, the type of the further treatment is per investigator 
discretion and it can include continuous application of randomised dressing (if per standard of care) and 
other standard of care and non-standard of care options. Regardless of the type of the treatment 
continuation chosen, the subject remains in the study and is followed-up until the study exit (see section 
8.2)  
• 
Review of concomitant medications, documenting any changes (medication used, route, dose, 
unit, frequency, indication, start date, stop date or ongoing) 
• 
Wound assessment  
o  Wound size (measured in cm at the longest point and across the widest point, as well as 
depth) 
o  Wound bed appearance 
o  Exudate level, colour and consistency 
o  Condition of peri-wound skin 
o  Maximum pain level on a scale of 0 to 10 within the last 24 hours 

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o  Level of odour on a scale of 0 to 10 for the study participants and mild/medium/strong 
for the clinician. 
o  Therapeutic Index for Local Infections (TILI) score 
• 
Number of days, since last visit, where compression was not applied (including documentation 
of reason for no compression) 
• 
Dressing application according to clinician decision (randomised dressing or Standard of Care) 
(name, size and lot number is recorded)  
• 
Documentation of any additional products used 
• 
Document any additional therapies  
• 
Document and address Adverse Device Events 
• 
Document and address Serious Adverse Events 
• 
Number of intermediate visits where dressings were changed between scheduled visits (this is 
the number of times a subject received a new dressing since the last visit) 
• 
Wound-QOL-14 (only if not collected at Visit 2).  
 
10.4  Visits 4 - 7: Day 42 thru 84 (every 14 days +/- 2 days) 
The following procedures are performed and data collected at the intermediate visits (every 14 days +/- 
2 days until day 84). All information is required. 
• 
Review of concomitant medications, documenting any changes (medication used, route, dose, 
unit, frequency, indication, start date, stop date or ongoing) 
• 
Wound Assessment  
o  Wound size (measured in cm at the longest point and across the widest point, as well as 
depth) 
o  Wound bed appearance 
o  Exudate level, colour and consistency 
o  Condition of peri-wound skin 
o  Maximum pain level on a scale of 0 to 10 within the last 24 hours 
o  Level of odour on a scale of 0 to 10 for the study participants and mild/medium/strong 
for the clinician. 
o  Therapeutic Index for Local Infections (TILI) score 
• 
Dressing application Care (required), documentation of any additional products used 
• 
Document any additional therapies  
• 
Document and address Adverse Events 
• 
Document and address Serious Adverse Events 
• 
Number of intermediate visits where dressings were changed between scheduled visits (this is 
the number of times a subject received a new dressing since the last visit) 
• 
Wound-QOL-14 at the study exit or last visit (Visit 7).  
10.5  Unscheduled Visit 
Unscheduled visit is any visit that is not a scheduled study visit and is not a pre-planned standard of care 
clinical visit.  
10.6  End of Study Visit (Study Exit) 
The study exit visit will occur when: 
• 
the subject exits the study for any reason, including that all study wounds have healed; or 
• 
The subject attends Visit 7.  

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Completion of end of study or appropriate forms is required. 

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11 SAFETY AND EVENT REPORTING 
The Medical and Clinical Affairs group at Convatec Ltd will be responsible for the safety of the study. The 
Medical and Clinical Affairs group are located at Convatec, Global Development Centre Deeside, First 
Avenue Deeside Industrial Park Deeside Flintshire CH5 2NU, Telephone +44 (0) 1244 284882. 
11.1  Definitions 
11.1.1  Adverse Event (AE). 
An untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including 
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the 
investigational medical device and whether anticipated or unanticipated. 
11.1.2  Serious Adverse Event (SAE).  
An adverse event that results in one of the following outcomes:  
• 
Death 
• 
Serious deterioration in the health of the subject, users, or other persons as defined by one or 
more of the following: 
o  a life-threatening illness or injury, or 
o  a permanent impairment of a body structure or a body function including chronic 
diseases, or 
o  in-patient or prolonged hospitalization, or 
o  medical or surgical intervention to prevent life-threatening illness or injury, or 
permanent impairment to a body structure or a body function, 
• 
Fetal distress, fetal death, a congenital abnormality, or birth defect including physical or mental 
impairment. 
11.1.3  Adverse Device Effect (ADE) 
An adverse device effect (ADE) is an AE related to the use of an Investigational Product. It includes 
AEs resulting from: 
• 
Insufficient or inadequate Instructions for Use (IFU), deployment, implantation, installation, or 
operation,  
• 
Any malfunction of the investigational medical device. 
• 
Any event resulting from use error or from intentional misuse of the investigational medical 
device. 
In this study, an investigational medical device is either of the randomised study dressings (AQUACEL® 
Ag+ Extra™ or Cutimed® Sorbact®).  
11.1.4  Serious Adverse device Effect (SADE) 
A serious adverse device effect (SADE) is an ADE that has resulted in any of the consequences 
characteristic of an SAE. 
11.1.5  Unanticipated Serious Adverse Device Effect (USADE) 
Serious adverse device effect, which by its nature, incidence, severity, or outcome has not been 
identified in the current version of the risk analysis report. 

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11.2  Adverse Events Categories and Relationship Determination 
All AEs (regardless of relationship to the study procedures or severity) occurring from enrolment up to 
and including the subject’s final study visit will be recorded by the Investigator. AEs may be either 
spontaneously reported to Investigator or elicited during questioning and examination of a subject. All 
identified AEs must be recorded in the patient record and on the Adverse Event case report form. If 
known, the diagnosis of the underlying illness or disorder should be recorded, rather than its individual 
symptoms.  
11.3  Categories of Severity 
The following definitions will be used for the categories of “Severity”: 
• 
Mild: awareness of sign or symptom, but easily tolerated 
• 
Moderate: discomfort enough to cause interference with usual activity 
• 
Severe: incapacitating, with inability to work or do usual activity  
11.4  Relationship to Investigational Device 
Causality assessment is required for AEs and SAEs that occur during clinical investigations. There is 
currently no standard international nomenclature to describe the degree of causality or relatedness of 
an AE with the Investigational Product. The following terms will be used during this study: 
Related - The AE is directly and clearly related to the Investigational Product. 
Possibly Related - There is a reasonable likelihood that the AE is due to the Investigational Product, as 
evidenced by the following: 
• 
There may be temporal association with the Investigational Product (e.g., within 24 hours of 
device placement). 
• 
The AE, or level of severity of the AE, is unlikely to be explained by other etiologies (known to be 
related to the study disease, Subject’s baseline medical condition, or concomitant medication). 
Not Related - The AE is definitely not related to the Investigational Product, or the AE is unlikely to be 
related to the Investigational Product because of a lack of temporal association or is known to be related 
to one or more of the following: 
• 
Morbidity associated with underlying medical condition. 
• 
Treatment procedure. 
• 
Concomitant medication. 
• 
A relationship to the Investigational Product is not biologically plausible. 
11.5  Procedure for Monitoring and Recording of Serious Adverse Events  
All SAEs occurring after from enrolment up to and including the subject’s final study visit will be 
reported. All SAEs must be followed until the event no longer meets serious reporting criteria, resolves, 
stabilizes, or the subject is considered lost to follow-up. 
All SAEs that occur during the collection period must be reported by the Investigator and/or their 
appointed Designee within 24 hours of first becoming aware of the occurrence of the SAE. Reports 
should be submitted to the responsible monitor and Convatec Safety & Compliance on an Initial SAE 
Report (SAER) form provided by Convatec Ltd. Available supporting documentation, if applicable, (e.g., 
discharge summary, laboratory reports) should be included. Personal identifiable information will be 

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deleted, and the subject number will be written on the report. All attempts should be made by the 
Investigator to follow the progress of the SAE.  
Serious adverse events will be listed as a single diagnosis (e.g., septic shock, flu-like syndrome) or a 
single event (e.g., headache, bone pain) whenever possible. Each single event, even if concurrent, 
should be reported on separate SAE Form.  
Convatec Ltd. has the responsibility to expeditiously review and report all SAEs to comply with 
regulatory requirements. Where applicable, Convatec Ltd. must:  
• 
Report the SAE or SADE to the Lead Investigators at each site. 
• 
Report the SAE or SADE to the appropriate regulatory authorities in accordance with local 
requirements. 
• 
Ensure that Competent Authorities and all responsible IRB/Ethic Committees are notified of the 
events in the appropriate timeframe in accordance with local requirements. 
If deemed appropriate (e.g. SADE) Convatec will update the Risk Assessment accordingly. 
11.6  Safety Reporting Timelines 
Type of Event 
Report to Sponsor 
Method 
Adverse Event 
Per Protocol Visit 
Complete eCRF 
Adverse Device Effect 
Per protocol visits 
Complete eCRF 
SAE 
Within 24 hours of study staff 
becoming aware of event 
Initial: phone/email to sponsor  
Followed by: Complete CRF 
SADE 
Within 24 hours of study staff 
becoming aware of event 
Initial: phone/email to sponsor  
Followed by: Complete CRF 
USADE 
Within 24 hours of study staff 
becoming aware of event 
Initial: phone/email to sponsor  
Followed by: Complete CRF 
 
11.7  Follow-Up Information for Serious Adverse Events 
Subsequent or new information will be submitted by the site staff to the Sponsor or its designee, in the 
form of an updated Adverse Event Report Form. Personal identifiable information will be 
deleted/blacked out and the subject number will be written on the report. Every attempt should be 
made to obtain follow-up SAE information. All unresolved SAEs for subjects considered lost to follow up 
should be documented appropriately in source documentation and reported to Convatec Ltd. on a 
follow-up form. 
11.8  Device Deficiency 
A device deficiency is an inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety, or performance. This may include malfunctions, use errors, and inadequacy in the 
information supplied by the manufacturer including labelling. This definition includes device deficiencies 
related to the investigational medical devices or to a comparator, i.e., a medical device, therapy (e.g., 
active treatment, normal clinical practice), placebo or no treatment, used in the control group in a 
clinical investigation (ISO 14155:2020). Device deficiencies may occur before use, during use, or after 
use. All Investigational Product deficiencies will be collected throughout the study and captured on the 
Device Deficiency eCRF. Any treatment delay that was caused by the device deficiency will be collected 
as well if the device will be returned to the Sponsor. 

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The Investigator is responsible for assessing the reportability of each event, and submitting the Device 
Deficiency Report when the deficiency meets the following criteria: 
• 
Any device deficiency that led to an SAE (the PI must submit both an SAE Report and the associated 
Device Deficiency Report to the Sponsor/designee). 
• 
Any device deficiency that might have led to an SAE if any of the following is true. 
o  Suitable action had not been taken. 
o  Intervention had not been made. 
o  Circumstances had been less fortunate. 
The PI must submit the Device Deficiency Report to the Sponsor as soon as possible, but not later than 5 
business days, following the date of awareness of the event. The PI is responsible for reporting the 
device deficiency to the ethics committee, if required per ethics committee regulations. 
The Sponsor will promptly evaluate the report to determine further actions. When applicable, 
appropriate Corrective and Preventive Actions (CAPAs) will be taken to protect the safety of Subjects, 
users, and other persons. The Sponsor will arrange for the safe return of the Investigational Product that 
is subject to a Device Deficiency. 

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12 PROTOCOL DEVIATIONS 
Except for a change that is intended to eliminate an immediate hazard to the subjects, the approved 
protocol shall be conducted as described. Any significant protocol deviation must be documented. Every 
deviation recorded on Deviation Form will be evaluated for its impact.  
12.1  Deviation Reporting Timelines 
Type of Deviation 
Report to Sponsor 
Method 
Subject safety, rights, OR welfare; OR 
data integrity; OR compromise the 
statistical analysis of the study; OR 
Lack of Informed Consent; OR 
Inclusion/Exclusion Criteria 
Within 24 hours of study 
staff becoming aware of 
event 
Initial: phone/email to sponsor  
Followed by: Complete CRF 
All other protocol deviations 
Per protocol visits 
Complete CRF 
 

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13 PREMATURE TERMINATION, SUSPENSION OR ROUTINE CLOSE-OUT 
OF THE STUDY 
13.1  Premature Termination or Suspension 
Convatec may suspend or prematurely terminate a clinical investigation for significant and documented 
reasons or for no reasons or if requested by regulatory authorities. 
Convatec may terminate or suspend the participation of a site or investigator if the monitor and/or 
auditor identify serious or repeated deviations on the part of an investigator. If the suspension or 
premature termination occurs, Convatec shall justify its decision in writing and promptly inform the 
Investigator and IRB/Ethics Committee. 
If suspension or premature termination occurs,  
• 
Convatec will remain responsible for providing resources to fulfil the obligations of the study 
and existing agreements  
• 
The investigators or authorised designee will inform the enrolled subjects, if appropriate 
13.2  Procedure for resuming the clinical investigation after temporary suspension 
When the analysis of the reason for the suspension is complete, the corrective actions are implemented 
and the decision to lift the suspension reached, Convatec will inform the investigator and ethics 
committee of the rationale.  
13.3  Routine Close-Out 
Routine close out activities shall be conducted to ensure that the investigator records are complete, all 
documents needed for Convatec’s files are retrieved and previously identified issues have been resolved 
and all parties are notified. 
Within 90 days after the closure of the study Convatec will notify the Ethics Committee of the end of the 
study. Within 1 year after the end of the study, the final report will be submitted to the Ethics 
Committee. 

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14 MONITORING 
Study Monitoring is conducted to ensure that the rights, safety, and well-being of study participants are 
protected, that the reported study data are accurate, complete, and verifiable, and that the conduct of 
the study is in compliance with the currently approved protocol, GCP, and with applicable regulatory 
requirements. 
Convatec is responsible for ensuring the proper conduct of the clinical investigation with regard to 
protocol adherence and validity of the data recorded on the CRFs. Convatec has assigned study 
monitor(s) to this clinical investigation. The progress of the clinical investigation will be monitored by: 
• 
Periodic and/or remote review 
• 
Telephone communications 
• 
Review of CRFs and source documentation (e.g., subject records) 
 
The study monitor(s), other authorized representatives of the Sponsor, representatives of the IRB/EC, or 
regulatory authorities may inspect all documents and records required to be maintained by the 
Investigator, including, but not limited to subject records for the participants in this study. The clinical 
study site will permit access to such records. The Investigator will give Convatec study monitor(s) direct 
access to source documents that support data on the CRFs. This includes electronic records. 
Investigator non-compliance of required study responsibilities will require Sponsor sanctions to alleviate 
the non-compliance, including corrective and preventative actions up to and including disqualification of 
the Investigator/Site. 
Details of the clinical site monitoring are documented in a Monitoring Plan (MP), which will be written 
prior to the first monitoring visit. The MP describes in detail who will conduct the monitoring, at what 
frequency monitoring will be done, at what level of detail monitoring will be performed, and the 
distribution of monitoring reports. 
Independent audits may be conducted by Convatec or designee to ensure monitoring practices are 
performed consistently across all participating sites and that monitors are following the MP. 
Any Monitoring Visits will comply with the Government restrictions on travel due to the Covid-19 
pandemic, if applicable. 

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15 DEVICE ACCOUNTABILITY 
Investigative sites will use formulary/on-the shelf inventory for treatment of the subjects with 
AQUACEL® Ag+ Extra™ and Cutimed® Sorbact®. The sponsor will not provide any products. Therefore, 
device accountability is not required.  

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16 CONFIDENTIALITY 
Participant confidentiality and privacy is strictly held in trust by the participating Investigators, their 
staff, the Sponsor, and their authorised representatives. This confidentiality is extended to cover testing 
of biological samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the Clinical Investigational Plan, documentation, data, and all other information generated 
will be held in strict confidence. No information concerning the study, or data will be released to any 
unauthorized third party without prior written approval of the Sponsor. All research activities will be 
conducted in as private a setting as possible. 
Study data, which is for the purposes of statistical analysis and reporting, will be transmitted to and 
stored at Convatec or an approved supplier. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique study 
identification number. The electronic data capture system used by clinical sites and by Convatec 
research staff will be secured and password protected.  

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17 DATA HANDLING AND RECORD KEEPING 
Data collected for this study will be analysed and stored at Convatec or an approved supplier for use by 
researchers, including those outside of the study. Permission to transmit, store and use data outside of 
the study will be included in the informed consent. 
17.1  Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical study staff at the site under supervision of the site 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
All source documents should be completed in a neat, legible, permanent, and un-editable manner to 
ensure accurate interpretation of data. Data recorded in the electronic case report form derived from 
source documents must be consistent with the data recorded on the source documents. 
Data will be entered into a compliant data capture system provided by Convatec. The data system 
includes password protection and internal quality checks, such as automatic range checks, to identify 
data that appear inconsistent, incomplete, or inaccurate.  
17.2  Study Records Retention 
The study participant’s information will be securely stored at each clinical site for internal use during the 
study. At the end of the study, all study records will continue to be kept in a secure location for as long a 
period as dictated by the reviewing IRB/EC, Institutional policies, regulatory authorities, or Sponsor 
requirements. 
No records will be destroyed without the written consent of the Sponsor. It is the responsibility of the 
Sponsor to inform the Investigator when these documents no longer need to be retained. 
17.3  Sponsor Oversight 
Routine review of submitted study information by the Sponsor will be conducted to ensure Protocol 
compliance. Items reviewed include, but are not limited to: adverse events, deviations, number of 
withdrawn / terminated subjects; which all may impact completion of the study. Appropriate measures 
may be taken to ensure Investigator compliance with the Protocol. 

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18 STATISTICAL CONSIDERATIONS 
This study is a multi-center, prospective, parallel, concurrent RCT. Details of the statistical analysis will 
be described in the SAP. This section provides key elements of the statistical approach. 
18.1  Alpha Value  
Alpha value will be 0.05 for both one-way and two-way testing. 
18.2  Statistical Approach for the Primary Endpoint 
The study hypothesis is that the Experimental Treatment with AQUACEL® Ag+ Extra™ will have similar 
effectiveness to the Control Treatment with Cutimed® Sorbact® in proportion of wounds that have 
completely healed by 84 days. The statistical hypothesis is that Experimental Treatment with AQUACEL® 
Ag+ Extra™ will be non-inferior to Control Treatment with Cutimed® Sorbact® in proportion of wounds 
that have completely healed by 84 days. 
The statistical null and alternative hypotheses are as follows: 
𝐻0: 𝜋𝐸𝑥𝑝−𝜋𝐶𝑜𝑛≤𝛿 
𝐻𝐴: 𝜋𝐸𝑥𝑝−𝜋𝐶𝑜𝑛> 𝛿 
where 𝜋𝐸𝑥𝑝 and 𝜋𝑐𝑜𝑛 represent the true proportion of target wounds that have healed by 84 days in 
patients treated with AQUACEL® Ag+ Extra™ and Cutimed® Sorbact®, respectively, and  is the non-
inferiority margin. The non-inferiority margin () is set to -15%.  
The statistical definition of success is the rejection of H0. The null hypothesis (H0) will be tested by 
constructing a two-sided 90% confidence interval for the difference in the proportions of ulcers that 
have completely healed between the Experimental Arm and the Control Arm. If the lower boundary of 
the interval does not include , then the null hypothesis will be rejected. If non-inferiority of AQUACEL® 
Ag+ Extra™ to the Cutimed® Sorbact is demonstrated, its superiority will be tested. 
18.3  Statistical Approach to Secondary and Exploratory Endpoints 
A pre-planned analysis of the secondary endpoints will be performed testing the non-inferiority, 
followed by superiority, of the Experimental Arm compared to the Control Arm conditioned by success 
in testing of the primary efficacy endpoint. The multiplicity and Type 1 Error within the secondary 
endpoints’ family will be controlled using the fixed sequence approach and alpha value of 0.05. SAP 
provides details on the analysis of the secondary endpoints including non-inferiority margins, where 
applicable. 
Statistical approaches for exploratory endpoints are described in SAP. 
18.4  Sample Size Determination 
Under the assumption that the proportion of completely healed ulcers by day 84 is 0.8 (80%), the 
sample size of 206 subjects and minimum of 206 wounds randomized 1:1 to Experimental and Control 
arms will have 85% power to reject the null hypothesis.  
Sample size assumptions concerning the proportion variance and average number of wounds per 
subject will be verified during the study in a blinded fashion.  Such verification does not inflate alpha-
value. 
18.5  Multiplicity 
Testing of secondary endpoints will be performed in a gateway fashion and fixed sequence. No 
adjustment for the multiplicity is required. Details of the fixed sequence will be presented in SAP. 

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18.6  Randomisation 
Subjects will be randomised on a 1:1 basis to either the AQAUCEL® Ag+ Extra™ or Cutimed® Sorbact® 
dressing at the subject level. All wounds for the same subject will be treated using the randomised 
dressing. The randomization sequence will be stratified by study centre. Other details concerning the 
randomization are described in the Randomisation Plan.  
18.7  Statistical Populations 
All subjects that are randomized are considered participants. 
Safety Population includes all subjects that are randomized to and receive one of the study treatments. 
Full Analysis Data Set. This will be constructed following the Intent-to-Treat (ITT) principle and will 
include all subjects that are randomized, receive one of the study treatments, and have at least one 
follow-up visit after the baseline (Visit 1).  
Per Protocol Population (PP) This will all subjects that are randomized, receive one of the study 
treatments, do not discontinue the trial prior to 4-week follow-up visit except for the reason that all 
study ulcers have closed and have no major protocol deviations that would impact integrity of the 
statistical analysis of primary endpoint. 
Completed Cases (CC) Population is a subset of Full Analysis Data Set Population and includes all 
subjects who have the final study visit (Day 84) or have exited the study earlier due to all study wounds 
have healed. 

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19 CONFLICT OF INTEREST 
The independence of this study from any actual or perceived influence, such as by the medical device 
industry, is critical. Therefore, any actual conflict of interest of a person who has a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial. The Sponsor has 
established procedures for all Investigators to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 

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20 GOOD CLINICAL PRACTICE AND STATEMENTS OF COMPLIANCE 
20.1  Ethical Approval 
The protocol will be reviewed by a properly constituted ethics committee. A copy of the written ethical 
approval will be sent to the Sponsor/designee. 
Subject recruitment will not commence until appropriate ethical approvals/opinions have been 
received, and as appropriate, the applicable agreement(s) between the Sponsor and the Investigator 
have been documented. Any additional requirements imposed by the ethics committee will be 
incorporated into the protocol as required. 
20.2  Protocol Modifications 
Modifications to this protocol may be necessary. In collaboration with the Investigator(s), modification 
will be documented and submitted for ethical and regulatory approval (as required) prior to 
implementation. All changes will be evaluated for impact per Sponsor standard operating procedures 
(SOPs). Modifications will be considered implemented after all ethical and regulatory approvals (as 
required) are received and all key Sponsor and site staff have been trained.  
20.3  Periodic Reviews 
Ongoing review by IRB/EC is required for the duration of the clinical study. The Investigator will comply 
with local IRB/EC requirements for ongoing reviews.  
20.4  Insurance 
The Sponsor shall provide clinical study related insurance covering the reasonable, and necessary costs 
of diagnostic, therapeutic and medical treatment including hospitalization costs (treatment costs) for 
such participant injuries following the administration or use of the study device(s) in accordance with 
this clinical investigational plan and in accordance with the national regulations. The Sponsor may 
reimburse the institution and/or study participants for treatment costs, depending on who incurred 
such treatment costs if (i) the injury is attributable to the negligence or misconduct of any agent or 
employee of the institution or Investigator, or the failure of such persons to comply with a study 
protocol, (ii) the treatment costs are covered by the study participant’s medical or hospital insurance 
coverage, or (iii) the treatment costs arose as a result of the treatment of normal progression of the 
study participant’s disease or injuries resulting from interventions that the study participants would 
have incurred had they not participated in the study. 
20.5  Patients’ Compensation 
Subjects may be compensated for their time and inconvenience. Details of any remuneration will be 
documented in the Patient/Participant Information Sheet. 
20.6  Principal Investigator, Coordinating Investigator(S), Investigational Sites and External 
Organisations 
The Name(s) and Address(es) of the sites at which this study is to be conducted is maintained as part of 
the Sponsor’s files. The files will include the different roles, responsibilities, and qualifications of these 
investigators. 
The Name(s) and Address(es) of the external organisation(s), such as core laboratories, CRO consultants, 
etc. which may assist in this study are maintained as part of the Sponsor’s files. 

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20.7  Public Registration and Publication 
The Sponsor shall ensure that this study will comply with required national registration requirements. 
This study will be conducted in accordance with the applicable publication and data sharing policies and 
regulations. When applicable, attempts will be made to publish results. Publication rules will follow 
international recommendations. 

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21  LITERATURE 
1.  
Guest JF, Fuller GW, Vowden P. Cohort study evaluating the burden of wounds to the UK’s 
National Health Service in 2017/2018: update from 2012/2013. BMJ Open. 2020;10(12):e045253. 
doi:10.1136/bmjopen-2020-045253 
2.  
Guest JFJ, Fuller GWG, Vowden P. Venous leg ulcer management in clinical practice in the UK: 
costs and outcomes. Int Wound J. 2018;15(1):29-37. doi:10.1111/iwj.12814 
3.  
Fletcher J, Atkin L, Dowsett C, et al. Best Practice Statement:Addressing complexities in the 
management of venous leg ulcers. London: Wounds UK. Wounds UK. 2019. 
4.  
Gueltzow M, Khalilpour P, Kolbe K, Zoellner Y. Budget impact of antimicrobial wound dressings in 
the treatment of venous leg ulcers in the German outpatient care sector: a budget impact 
analysis. J Mark Access Heal Policy. 2018;6(1):1527654. doi:10.1080/20016689.2018.1527654 
5.  
Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systematic approach to 
wound management. Wound Repair Regen. 2003;11 Suppl 1(s1):S1-28. doi:10.1046/j.1524-
475X.11.s2.1.x 
6.  
Schultz GS, Barillo DJ, Mozingo DW, Chin GA, Wound Bed Advisory Board Members. Wound bed 
preparation and a brief history of TIME. Int Wound J. 2004;1(1):19-32. doi:10.1111/j.1742-
481x.2004.00008.x 
7.  
Schultz G, Mozingo D, Romanelli M, Claxton K. Wound healing and TIME; new concepts and 
scientific applications. Wound Repair Regen. 2005;13(4 Suppl):S1-11. doi:10.1111/j.1067-
1927.2005.1304S1.x 
8.  
Leaper DJ, Schultz G, Carville K, Fletcher J, Swanson T, Drake R. Extending the TIME concept: what 
have we learned in the past 10 years? Int Wound J. 2012;9 Suppl 2(SUPPL. 2):1-19. 
doi:10.1111/j.1742-481X.2012.01097.x 
9.  
Sibbald RG, Elliott JA, Persaud-Jaimangal R, et al. Wound Bed Preparation 2021. Adv Skin Wound 
Care. 2021;34(4):183-195. doi:10.1097/01.ASW.0000733724.87630.d6 
10.  
Robson MC. Wound infection. A failure of wound healing caused by an imbalance of bacteria. 
Surg Clin North Am. 1997;77(3):637-650. doi:10.1016/s0039-6109(05)70572-7 
11.  
Robson MC, Mannari RJ, Smith PD, Payne WG. Maintenance of wound bacterial balance. Am J 
Surg. 1999;178(5):399-402. doi:10.1016/s0002-9610(99)00208-1 
12.  
International Wound Infection Institute. Wound infection in clinical practice. Wounds Int. 2022. 
13.  
Fletcher J, Edwards-Jones V, Fumarola S, et al. Best Practice Statement: Antimicrobial 
Stewardship Strategies for Wound Management 2020. London; 2020. 
14.  
O’Meara S, Al-Kurdi D, Ologun Y, Ovington LG, Martyn-St James M, Richardson R. Antibiotics and 
antiseptics for venous leg ulcers. Cochrane Database Syst Rev. 2014;2014(1). 
doi:10.1002/14651858.CD003557.pub5 
15.  
Woo K, Dowsett C, Costa B, Ebohon S, Woodmansey EJ, Malone M. Efficacy of topical cadexomer 
iodine treatment in chronic wounds: Systematic review and meta-analysis of comparative clinical 
trials. Int Wound J. 2021;18(5):586-597. doi:10.1111/iwj.13560 
16.  
Dissemond J, Böttrich JG, Braunwarth H, Hilt J, Wilken P, Münter K-C. Evidence for silver in 
wound care - meta-analysis of clinical studies from 2000-2015. J Dtsch Dermatol Ges. 
2017;15(5):524-535. doi:10.1111/ddg.13233 

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17.  
Dissemond J, Gerber V, Lobmann R, et al. Therapeutic index for local infections score (TILI): a new 
diagnostic tool. J Wound Care. 2020;29(12):720-726. doi:10.12968/jowc.2020.29.12.720 
18.  
Dissemond J, Strohal R, Mastronicola D, et al. Therapeutic Index for Local Infections score 
validity: a retrospective European analysis. J Wound Care. 2020;29(12):726-734. 
doi:10.12968/jowc.2020.29.12.726 
19.  
Schultz G, Bjarnsholt T, James GA, et al. Consensus guidelines for the identification and treatment 
of biofilms in chronic nonhealing wounds. Wound Repair Regen. 2017;25(5):744-757. 
doi:10.1111/wrr.12590 
20.  
James GA, Swogger E, Wolcott R, et al. Biofilms in chronic wounds. Wound Repair Regen. 
2008;16(1):37-44. doi:10.1111/j.1524-475X.2007.00321.x 
21.  
Percival SL. Importance of biofilm formation in surgical infection. Br J Surg. 2017;104(2):e85-e94. 
doi:10.1002/bjs.10433 
22.  
Bjarnsholt T, Kirketerp-Møller K, Jensen PØ, et al. Why chronic wounds will not heal: A novel 
hypothesis. Wound Repair Regen. 2008;16(1):2-10. doi:10.1111/j.1524-475X.2007.00283.x 
23.  
Percival SL, Malone M, Mayer D, Salisbury A-M, Schultz G. Role of anaerobes in polymicrobial 
communities and biofilms complicating diabetic foot ulcers. Int Wound J. 2018;15(5):776-782. 
doi:10.1111/iwj.12926 
24.  
Roche ED, Renick PJ, Tetens SP, Ramsay SJ, Daniels EQ, Carson DL. Increasing the presence of 
biofilm and healing delay in a porcine model of MRSA-infected wounds. Wound Repair Regen. 
2012;20(4):537-543. doi:10.1111/j.1524-475X.2012.00808.x 
25.  
Wolcott RD, Kennedy JP, Dowd SE. Regular debridement is the main tool for maintaining a 
healthy wound bed in most chronic wounds. J Wound Care. 2009;18(2):54-56. 
doi:10.12968/jowc.2009.18.2.38743 
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antiseptics in the management of chronic wounds with critical colonisation and/or biofilm. Int 
Wound J. 2021:18(3): 342-358 2020. doi:10.1111/iwj.13537 
28.  
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Hydrofiber® wound dressing. Wound Med. 2016;14:6-11. doi:10.1016/j.wndm.2016.05.005 
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Walker M, Metcalf D, Parsons D, Bowler P. A real-life clinical evaluation of a next-generation 
antimicrobial dressing on acute and chronic wounds. J Wound Care. 2015;24(1):11-22. 
doi:10.12968/jowc.2015.24.1.11 
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Metcalf DG, Bowler PG. Clinical impact of an anti-biofilm Hydrofiber dressing in hard-to-heal 
wounds previously managed with traditional antimicrobial products and systemic antibiotics. 
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33.  
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Cutimed® Sorbact® Dressing IFU Artwork Number: 38822.01 Date: 2017:10 
AQAUCEL® Ag+ Extra™ IFU Ref No. 170881G6 

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22  GLOSSARY, ABBREVIATIONS & ACRONYMS  
Abbreviation Term 
AE 
Adverse Event 
BMI 
Body Mass Index 
CRF 
Case Report Form 
CRO 
Contract Research Organisation 
EC 
Ethics Committee 
EU 
European Union 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
IC 
Informed Consent 
ICH 
International Conference for Harmonisation 
IEC 
Independent Ethics Committee 
IFU  
Instructions for Use  
ITT 
Intent to Treat 
IRB 
Institutional Review Board 
MDR 
Medical Device Regulations 
PP 
Per Protocol Population 
QoL 
Quality of Life 
RCT 
Randomised Control Trial 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan  
SOP 
Standard Operating Procedure 
TILI 
Therapeutic Index for Local Infections score 
UADE 
Unanticipated Adverse Device Effect 
VLU 
Venus Leg Ulcer