Comparison of Two Skin Protection Regimes for the Prevention of Incontinence-associated Dermatitis in Geriatric Care: an Exploratory Trial (PID)
Phase: NA
Conditions: Incontinence-associated Dermatitis
Sponsor: Charite University, Berlin, Germany

Institut für Klinische Pflegewissenschaft 
Charitéplatz 1 | 10117 Berlin 
https://klinische-pflegewissenschaft.charite.de/
Tel. +49 30 450 529 412 
Email: klinische-pflegewissenschaft@charite.de
Charité  Campus Mitte  10098 Berlin 
INVESTIGATORS 
Prof. Dr. rer. cur. Jan Kottner  
Charité – Universitätsmedizin Berlin 
Institute for Clinical Nursing Science 
Charitéplatz 1  
10117 Berlin, Germany  
Email: jan.kottner@charite.de 
Priv.-Doz. Dr. rer. cur. Nils Lahmann 
Charité-Universitätsmedizin Berlin 
Research Group Geriatrics 
Reinickendorfer Straße 61 
13347 Berlin, Germany 
Email: nils.lahmann@charite.de 
PROTOCOL DEVELOPMENT 
SPONSOR 
Monira El Genedy-Kalyoncu 
Alexandra Fastner 
Bettina Völzer  
Kathrin Raeder 
Prof. Dr. rer. cur. Jan Kottner  
Priv.-Doz. Dr. rer. cur. Nils Lahmann 
Charité – Universitätsmedizin Berlin 
FUNDING 
Bundesministerium für Bildung und Forschung (BMBF), FKZ 01KG2020 
Study Protocol with Statistical Analysis Plan (SAP)
Comparison of two skin protection regimes for the Prevention of 
Incontinence-associated Dermatitis in geriatric care: An exploratory trial 
(PID) 
Study Code: PID 
NCT Number: NCT05403762
Study Protocol V1.1, 15 June 2022;  SAP V4, 17 April 2025

 
Study protocol 
Page 2 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
I. 
SUMMARY 
Title of the clinical study 
Comparison of two skin protection regimes for the Prevention 
of Incontinence-associated Dermatitis in geriatric care: an 
exploratory trial (PID) 
Funding 
Bundesministerium für Bildung und Forschung (BMBF), FKZ 
01KG2020 
Investigators 
Prof. Dr. rer. cur. Jan Kottner  
Priv.-Doz. Dr. rer. cur. Nils Lahmann 
Study period 
July 2022 to January 2024 
Study design 
Randomized controlled, parallel group, three-arm, assessor-
blinded exploratory trial 
Number of subjects 
 To be assessed for eligibility  
(n = 500 subjects) 
 To be allocated to trial  
(n = 210 subjects; n = 70 per study arm) 
 To be analyzed  
(n = 180 subjects; n = 60 subjects per study arm) 
Objectives 
The primary research objective is to compare the incidence of 
incontinence-associated dermatitis (IAD) in two intervention 
groups and one control group and to estimate effect sizes for a 
possible subsequent confirmatory randomized controlled trial 
(RCT). Additional objectives are to test the feasibility of 
conducting a confirmatory RCT to prevent IAD and to evaluate 
the feasibility of measuring the Core Outcome Domains for IAD 
trials. 
Outcomes  
 IAD incidence 
 Erythema 
 Erosion  
 Maceration 
 IAD-related pain 
 IAD-related itch 
 Satisfaction with treatment 
 Willingness to participate 
 Retention 
 Adherence to prescribed intervention 
 Adverse Events (AEs) and Serious Adverse Events (SAEs) 
according to the definition of the EU regulation 2017/745 
Medical Device Regulation (MDR) Article 2 (57) and (58)  
 Incidents and Serious Incidents according to the definition of 
the EU regulation 2017/745 MDR Article 2 (64) and (65) 

 
Study protocol 
Page 3 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
 
Eligibility criteria 
Institutional Level 
Inclusion criteria:  
 Nursing home, geriatric hospital or hospital with geriatric 
ward(s) in the federal state of Berlin 
 Expression of a clear commitment to apply the study related 
procedures 
 Willingness to regularly allow study related trainings (on site 
at the nursing home/ hospital, conducted by study 
personnel) and to allow and ensure the participation by a 
sufficient number of employees  
 Agreement that study-related documents, such as diaries, 
will be completed daily by involved caregivers to ensure 
compliance and that study personnel may review these 
documents on a regular interval 
 Commitment to adhere to the trial procedures  
 
Exclusion criteria:  
 Any circumstance that makes it unfeasible to conduct the 
study in the nursing home/ hospital in accordance to the 
study protocol 
 
Participant Level 
Inclusion criteria:  
 Geriatric patients or residents (≥ 65 years) staying/living in 
one of the participating institutions 
 being incontinent of urine and stool 
 Expected minimum length of stay of 14 days 
 Intact skin with no clinical signs of IAD  
OR  
intact skin with early clinical signs of IAD but without clinical 
signs of infection (GLOBIAD category 1 A)  
 Written informed consent  
 
Exclusion criteria:  
 Residents/patients at the end of life 
 Residents/Patients with skin loss due to IAD (GLOBIAD 
category 2 A) and/or signs of clinical infection in the IAD area 
(GLOBIAD category 1 B or2 B) 
 Any other skin condition or wounds (at investigational areas 
of the skin) requiring additional treatment (including but not 
limited to pressure ulcers, intertrigo, infection) 
 Known hypersensitivity or allergy to silicones and/or topical 
leave-on products 

 
Study protocol 
Page 4 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
 Topical treatments in the IAD area. 
Intervention(s) 
 Experimental intervention I: Standardized mild skin 
cleansing regimen and daily topical application of a film-
forming skin protectant at the exposed skin areas. 
 Experimental intervention II: Standardized mild skin 
cleansing regimen and daily topical application of a 
hydrophobic skin protectant at the exposed skin areas. 
 Control intervention: Standardized mild skin cleansing 
regimen without application of an additional skin 
protectant. 
Duration of treatment 
 Duration of intervention per patient: 14 days 
 Follow-up per patient: 14 days  
Statistical methods 
Efficacy: The endpoints will be compared descriptively between 
the three groups. No confirmatory statistical tests will be 
conducted. 
Description of the primary efficacy analysis and population: The 
intention-to-treat (ITT) principle will be applied, including all 
subjects that were allocated to a study group. 
Safety: AEs, SAEs, incidents and serious incidents will be listed 
per patient and for the total trial. 
 

 
Study protocol 
Page 5 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
II. 
TABLE OF CONTENTS 
I. 
Summary ....................................................................................................................................... 2 
II. 
Table of contents .......................................................................................................................... 5 
III. 
Tables and Figures ..................................................................................................................... 8 
IV. 
List of Abbreviations .................................................................................................................. 9 
V. 
Administrative Information ........................................................................................................ 10 
1. 
Introduction ................................................................................................................................ 12 
1.1 
Background and rationale ................................................................................................... 12 
1.2 
Objectives ............................................................................................................................ 13 
1.3 
Trial design ........................................................................................................................... 13 
2. 
Methods: Participants, interventions, and outcomes ................................................................ 14 
2.1 
Study setting ........................................................................................................................ 14 
2.2 
Eligibility criteria .................................................................................................................. 14 
2.2.1 
Institutional level .......................................................................................................... 14 
2.2.2 
Resident/patient level .................................................................................................. 14 
2.3 
Interventions ....................................................................................................................... 15 
2.3.1 
Qualitative interview part ............................................................................................ 18 
2.3.2 
Criteria for discontinuing ............................................................................................. 18 
2.4 
Education ............................................................................................................................. 19 
2.4.1 
Trainings ....................................................................................................................... 19 
2.4.2 
Materials....................................................................................................................... 19 
2.5 
Strategies to improve compliance and adherence to the study protocol .......................... 20 
2.6 
Concomitant care and interventions ................................................................................... 20 
2.7 
Outcomes and variables ...................................................................................................... 20 
2.7.1 
Initial skin assessment .................................................................................................. 26 
2.7.2 
Mexameter measurement ........................................................................................... 26 
2.7.3 
Resident/Patient reported outcome measures ........................................................... 26 
2.7.4 
Participants Timeline .................................................................................................... 28 
2.8 
Sample Size .......................................................................................................................... 30 
2.8.1 
Whole trial .................................................................................................................... 30 

 
Study protocol 
Page 6 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
2.8.2 
Interview Part ............................................................................................................... 30 
2.9 
Recruitment ......................................................................................................................... 30 
2.9.1 
Institutional Level ......................................................................................................... 30 
2.9.2 
Participant Level ........................................................................................................... 30 
3. 
Methods: Assignment of interventions ...................................................................................... 31 
3.1 
Sequence generation ........................................................................................................... 31 
3.2 
Allocation concealment mechanism ................................................................................... 31 
3.3 
Blinding ................................................................................................................................ 31 
4. 
Methods: Data collection, management, and analysis .............................................................. 32 
4.1 
Data collection methods ...................................................................................................... 32 
4.1.1 
Skin assessment............................................................................................................ 33 
4.1.2 
Skin measurements ...................................................................................................... 33 
4.1.3 
Other trial data ............................................................................................................. 33 
4.2 
Data management ............................................................................................................... 36 
4.3 
Statistical methods .............................................................................................................. 36 
4.4 
Analysis population ............................................................................................................. 37 
5. 
Methods: Monitoring .................................................................................................................. 38 
5.1 
Data monitoring ................................................................................................................... 38 
5.2 
Electronic data capture ....................................................................................................... 38 
5.3 
Harms ................................................................................................................................... 39 
5.3.1 
Definition of Adverse Events and Incidents ................................................................. 39 
5.3.2 
Incident Reporting ........................................................................................................ 41 
5.4 
Auditing................................................................................................................................ 41 
6. 
Ethics and Dissemination ............................................................................................................ 41 
6.1 
Research ethics approval ..................................................................................................... 41 
6.2 
Protocol amendments ......................................................................................................... 41 
6.3 
Consent or assent ................................................................................................................ 41 
6.4 
Insurance ............................................................................................................................. 42 
6.5 
Confidentiality and data protection .................................................................................... 42 
6.6 
Declaration of interests ....................................................................................................... 42 
6.7 
Access to data ...................................................................................................................... 42 

 
Study protocol 
Page 7 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
6.8 
Ancillary and post-trial care ................................................................................................. 43 
6.9 
Dissemination policy ............................................................................................................ 43 
VI. 
References ............................................................................................................................... 44 
 

 
Study protocol 
Page 8 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
III. 
TABLES AND FIGURES 
 
Table 1: Description of interventions according to the template for intervention description and 
replication (TIDieR) [17]. .................................................................................................................... 16 
Table 2: Outcomes and variables per participant .............................................................................. 21 
Table 3: Study schedule for individual participants. .......................................................................... 29 
Table 4: Other trial data ..................................................................................................................... 34 
 
Figure 1: Overview of the planned trial flow. .................................................................................... 28 
 
 

 
Study protocol 
Page 9 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
IV. 
LIST OF ABBREVIATIONS 
Abbreviation 
 
AE 
Adverse Event 
BlnDSG 
Berliner Datenschutzgesetz 
BMBF 
Bundesministerium für Bildung und Forschung  
BMI 
Body Mass Index 
CRF 
Case report form 
CTO 
Clinical Trial Office at the Charité 
DMP 
Data management plan 
DRKS 
Deutsches Register Klinischer Studien (German Clinical Trials Register) 
DSGVO 
Datenschutzgrundverordnung (General Data Protection Regulation) 
EC 
Ethics committee 
EU 
European Union 
eCRF 
Electronic case report form 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GDS 
Global Deterioration Scale 
GLOBIAD 
Ghent Global IAD Categorization tool 
IAD 
Incontinence associated dermatitis 
ICD 
International Classification of Diseases 
ICF 
Informed consent form  
ICH 
International Conference on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IPD 
Individual patient data 
ISF 
Investigator Site File 
IIT 
Investigator Initiated Trial 
ITT 
Intention-to-treat 
MDR 
Medical Device Regulation 
MPDG 
Medizinprodukterecht-Durchführungsgesetz 
NRF 
NRS 
Neues Rezeptur Formularium 
Numeric Rating Scale 
PU 
Pressure Ulcer 
QoL 
Quality of life 
RDE 
Remote Data Entry 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SAS 
Statistical analysis system 
SD 
Source documents 
SGB 
Sozialgesetzbuch (Codebook of Social Law) 
SOP 
Standard operating procedure  
SPSS 
Statistical Package for the social science 
SSL 
Secure Sockets Layer 
WHO 
World Health Organization  

 
Study protocol 
Page 10 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
V. 
ADMINISTRATIVE INFORMATION 
Title 
Comparison of two skin protection regimes for the Prevention of Incontinence-associated 
Dermatitis in geriatric care: An exploratory trial (PID) 
 
Trial registration 
This trial is registered at the German Clinical Trials Register https://www.drks.de (DRKS00028954) 
(Deutsches Register Klinischer Studien; DRKS) and at clinicaltrials.gov (NCT05403762). The local 
ethics committee of the Charité - Universitätsmedizin Berlin approved the trial on April 07, 2022 
(EA4/043/22).  
 
Protocol version 
Version 1.0, 25 May, 2022 
 
Funding 
This study is conducted by the Institute for Clinical Nursing Science, Charité – Universitätsmedizin 
Berlin and the Research Group Geriatrics, Charité – Universitätsmedizin Berlin. The trial is supported 
by the Federal Ministry of Education and Research (BMBF). 
 
Roles and responsibilities 
Investigators 
Prof. Dr. rer. cur. Jan Kottner  
Charité – Universitätsmedizin Berlin  
Institute for Clinical Nursing Science 
Charitéplatz 1  
10117 Berlin, Germany  
Email: jan.kottner@charite.de 
Priv.-Doz. Dr. rer. cur. Nils Lahmann  
Charité-Universitätsmedizin Berlin 
Research Group Geriatrics 
Reinickendorfer Straße 61 
13347 Berlin, Germany 
Email: nils.lahmann@charite.de 
PROTOCOL DEVELOPMENT 
SPONSOR 
Monira El Genedy-Kalyoncu 
Alexandra Fastner 
Bettina Völzer  
Kathrin Raeder 
Prof. Dr. rer. cur. Jan Kottner  
Priv.-Doz. Dr. rer. cur. Nils Lahmann  
 
 Charité – Universitätsmedizin Berlin 
 
TRIAL COORDINATION 
Monira El Genedy-Kalyoncu 
 
 
 

 
Study protocol 
Page 11 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
MONITORING 
Charité-BIH Clinical Study Center 
Clinical Trial Office (CTO) 
Charité - Universitätsmedizin Berlin 
Charitéplatz 1 
D-10117 Berlin 
DATA MANAGEMENT 
Charité-BIH Clinical Study Center 
Clinical Trial Office (CTO) 
Charité - Universitätsmedizin Berlin 
Charitéplatz 1 
D-10117 Berlin 
TRIAL STATISTICIAN 
Dr. Konrad Neumann 
Department of Biometry and Clinical Epidemiology  
Charité – Universitätsmedizin Berlin  
Charitéplatz 1, 10117 Berlin, Germany  
Email: konrad.neumann@charite.de 

 
Study protocol 
Page 12 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
1. INTRODUCTION 
1.1  
 BACKGROUND AND RATIONALE 
Incontinence-associated dermatitis (IAD) is an unwanted skin condition which is common in 
incontinent individuals. It is an inflammatory skin response due to repeated or prolonged contact 
with urine and/or stool [1, 2]. It can occur throughout the lifespan, thus it is present in babies and 
young children ("diaper dermatitis") as well as in the older individuals [1]. 
The prevalence of incontinence rises with increasing age [3]; therefore, IAD is more common 
in the aged population. IAD prevalence is 3% to 23% in long-term geriatric care and 15% to 40% in 
acute care settings [4]. A representative prevalence study in institutional geriatric long-term care 
facilities showed an IAD prevalence of 35.4% [5, 6]. Thus, around one in three residents was affected 
by some form of IAD.  
Clinically, IAD is manifested by skin redness, vesicles, nodular thickening and maceration of 
the tissue as well as defects of the skin up to the loss of the upper skin layers. For those affected, 
this can be a physical as well as psychological burden. In addition to pain, burning, and itching, IAD 
is associated with an increased risk of secondary infections and the development of pressure ulcers 
(PUs) [7, 8]. As a result of these changes, affected individuals may also suffer from a reduced quality 
of life, for example, through a loss of independence, reduction of social activities, or poor sleep due 
to IAD-related pain or itch [6, 9, 10]. 
With approximately 80%, the majority of residents in geriatric long-term care facilities, as 
well as a high proportion of geriatric patients in acute care settings, are affected by one form of 
incontinence and are therefore at potential risk of developing IAD [11-13]. If adequate preventive 
measures are taken at an early stage, IAD might be avoided. However, the high prevalence of IAD in 
these settings indicates that current prevention strategies are not optimal. Due to a lack of 
knowledge, the current nursing practices in the context of IAD prevention are mainly influenced by 
individual traditions and personal preferences and are not evidence-based [14]. At the same time, 
a clear need for support as well as assistance is expressed on the part of nurses and other caregivers 
in order to be able to perform an efficient and effective IAD prevention [15]. Therefore, it is an 
important aim to close existing evidence gaps in this area to support nurses and other caregivers 
with a solid scientific base for IAD prevention. The planned trial aims a direct comparison of the two 
most important skin protection product categories in the form of an explorative randomized 
controlled trial (RCT), taking core outcomes for IAD research into account. 

 
Study protocol 
Page 13 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
1.2  OBJECTIVES 
The primary research objective is to compare the incidence of IAD in the intervention and control 
groups to estimate effect sizes for a possible subsequent confirmatory RCT. Another objective is to 
evaluate the feasibility of the planned interventional skin care regimen in geriatric populations. This 
will be the first time, the recently developed set of IAD-specific outcomes (CONSIDER) [16] will be 
used and evaluated in the context of a clinical trial. This Core Outcome Set (COS) is intended to 
improve the comparability and pooling of future data from different studies in the field of IAD 
research to provide a basis for evidence-based health care. 
 
The trial will answer the following research questions: 
 What are the effect sizes of the outcomes? 
 Is the implementation of a standardized skin protection regime for the prevention of IAD 
feasible in geriatric hospital wards and nursing homes?  
 Does the implementation of a standardized skin protection regime for the prevention of IAD 
reduce itch and IAD-related pain? 
 Is the measurement of Core Outcome Domains for IAD trials feasible? 
1.3  TRIAL DESIGN 
Randomized controlled, parallel group, three-arm, assessor-blinded exploratory trial 

 
 
2. METHODS: PARTICIPANTS, INTERVENTIONS, AND OUTCOMES 
2.1  STUDY SETTING 
The study will be conducted in geriatric hospitals/geriatric wards of participating hospitals and in 
institutional long-term care facilities of the federal state of Berlin, Germany. 
2.2  ELIGIBILITY CRITERIA  
2.2.1 INSTITUTIONAL LEVEL 
Inclusion criteria:  
(1) Nursing home, geriatric hospital or hospital with geriatric ward(s) in the federal state of Berlin 
(2) Expression of a clear commitment to apply the study related procedures 
(3) Willingness to regularly allow study related trainings (on site at the nursing home/ hospital, 
conducted by study personnel) and to allow and ensure the participation by a sufficient number 
of employees  
(4) Agreement that study-related documents, such as diaries, will be completed daily by involved 
caregivers to ensure compliance and that study personnel may review these documents on a 
regular interval 
(5) Commitment to adhere to the trial procedures  
 
Exclusion criteria: 
(1) Any circumstance that makes it unfeasible to conduct the study in the nursing home/ hospital 
in accordance to the study protocol 
2.2.2 RESIDENT/PATIENT LEVEL 
Inclusion criteria:  
Geriatric patients (≥ 65 years) admitted to geriatric wards of participating hospitals or residents of 
participating nursing homes can be included if the following criteria are met:  
(1) Being incontinent of urine and stool 
(2) Expected minimum length of stay of 14 days 
(3) Intact skin with no clinical signs of IAD  
OR  
Intact skin with early clinical signs of IAD (erythema) but without clinical signs of infection (GLOBIAD 
category 1 A)  
(4) Written informed consent (by legal representative, if required) 
 

 
Study protocol 
Page 15 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
Exclusion criteria:  
(1) Residents/patients at the end of life 
(2) Residents/Patients with skin loss due to IAD (GLOBIAD category 2 A)and/or signs of clinical 
infection in the IAD area (GLOBIAD category 1 B, category 2 B) 
(3) Any other skin condition or wounds (at investigational areas of the skin) requiring additional 
treatment  (including but not limited to pressure ulcers, intertrigo, infection) 
(4) Known hypersensitivity or allergy to silicones and/or topical leave-on products 
(5) Topical treatments in the IAD area. 
2.3  INTERVENTIONS 
Included participants of all three groups receive a standardized skin cleansing regime consisting of 
cleansing of the skin with water and the addition of a mild cleansing product. Cleansing is done using 
disposable washing mitts. To remove possible residual stool from the skin, an additional skin oil can 
be used. After subsequent gentle drying of the skin, elastic disposable breathable incontinence 
pants are put on. This is considered as 'standard incontinence care'. In order to ensure the greatest 
possible standardization and uniformity, the same predefined products and procedures are used for 
all participants. The required products for the participants will be provided by the investigators and 
are listed in Table 1.  
After baseline visits, included residents/patients will be randomly assigned on Day 0 to one of the 
following three study arms: 
 Study arm 1 (Experimental intervention I): Standard incontinence care with additional daily 
topical application of a film-forming leave-on skin protectant (ESENTA™ Hautschutz Spray) 
that builds a protective layer on the surface of the skin 
 Study arm 2 (Experimental intervention II): Standard incontinence care with additional daily 
topical application of a lipophilic leave-on skin protectant (Hydrophobes Basisgel DAC) that 
forms a hydrophobic physical barrier on the skin 
 Study arm 3 (Control group): Standard incontinence care alone, no additional intervention 
in the control group 
The interventions are described in detail according to the template for intervention description and 
replication (TIDieR) checklist [17] in Table 1. The items 10 and 12 do not apply for study protocols 
and are therefore not listed in the table [17]. 
 

 
Study protocol 
Page 16 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
Table 1: Description of interventions according to the template for intervention description and replication (TIDieR) [17]. 
Item 
Experimental intervention I 
Experimental intervention II 
Control group 
1. Brief name  
Film-forming 
leave-on 
skin 
protectant for IAD prevention  
Hydrophobic 
leave-on 
skin 
protectant for IAD prevention  
No skin protectant  
2. Rationale  
Film-forming 
topical 
leave-on 
products are widely used to 
protect the skin from irritants 
including urine and/or stool in 
incontinent patients [18, 19]. 
Whether film-forming products 
are better than hydrophobic 
ointments/emulsions or no skin 
protectants is unclear.  
Monophasic 
or 
biphasic 
hydrophobic (emulsions) topical 
leave-on products are widely used 
to protect the skin from irritants 
including urine and/or stool in 
incontinent 
patients 
[18]. 
Whether hydrophobic leave-on 
products are better than film-
forming products or no products 
is unclear.  
Most incontinent patients do not 
receive any topical skin protectant 
when the skin is intact. The 
relative and absolute benefit of 
applying any skin protectant to 
intact skin of incontinent geriatric 
patients in unclear.  
3. Materials  
- Skin will be cleansed with water 
and the addition of a mild 
cleanser (preferably non-alkaline 
skin cleansers with a pH range 
similar 
to 
normal 
skin 
and 
non-ionic 
surfactants, 
e.g. 
Bübchen Creme Pflegebad, Nestlé 
Nutrition GmbH, Germany) using 
disposable 
wash 
mitts/cloths 
(e.g. 
Waschhandschuh 
PLUS, 
Desomed AG, Germany)  
 
- A skin oil (perfume-free, dye-
free, e.g. Baby Öl, Nestlé Nutrition 
GmbH, Germany) may be used in 
addition to remove stool.  
 
- ESENTA™ Skin Barrier (ConvaTec 
Inc., UK) will be applied on clean 
and dry skin exposed to urine and 
stool. 
After 
application, 
the 
solvent evaporates leaving a 
silicone film on the skin surface.  
 
- Elastic disposable breathable 
incontinence pants are put on 
(e.g. Seni active classic, TZMO 
Deutschland GmbH, Germany).  
- Skin will be cleansed with water 
and the addition of a mild 
cleanser (preferably non-alkaline 
skin cleansers with a pH range 
similar 
to 
normal 
skin 
and 
non-ionic 
surfactants, 
e.g. 
Bübchen Creme Pflegebad, Nestlé 
Nutrition GmbH, Germany) using 
disposable 
wash 
mitts/cloths 
(e.g. 
Waschhandschuh 
PLUS, 
Desomed AG, Germany)  
 
- A skin oil (perfume-free, dye-
free, e.g. Baby Öl, Nestlé Nutrition 
GmbH, Germany) may be used in 
addition to remove stool.  
 
- Hydrophobes Basisgel DAC will 
be applied on clean and dry skin. 
It contains 95% paraffin oil and 
creates a hydrophobic layer on 
the skin surface [20].  
 
 
- Elastic disposable breathable 
incontinence pants are put on 
(e.g. Seni active classic, TZMO 
Deutschland GmbH, Germany).  
- Skin will be cleansed with water 
and the addition of a mild 
cleanser (preferably non-alkaline 
skin cleansers with a pH range 
similar 
to 
normal 
skin 
and 
non-ionic 
surfactants, 
e.g. 
Bübchen Creme Pflegebad, Nestlé 
Nutrition GmbH, Germany) using 
disposable 
wash 
mitts/cloths 
(e.g. 
Waschhandschuh 
PLUS, 
Desomed AG, Germany)  
  
- A skin oil (perfume-free, dye-
free, e.g. Baby Öl, Nestlé Nutrition 
GmbH, Germany) may be used in 
addition to remove stool.  
 
 
 
 
 
 
 
 
- Elastic disposable breathable 
incontinence pants are put on 
(e.g. Seni active classic, TZMO 
Deutschland GmbH, Germany).  
4. Procedures  
After regular skin cleansing in the 
morning, the skin protectant is 
applied to dry skin.  
After regular skin cleansing in the 
morning and evening, the skin 
protectant is applied to dry skin. 
In 
addition, 
the 
product 
is 
reapplied 
following 
the 
skin 
cleansing 
after 
a 
stool 
incontinence episode. 
After regular skin cleansing, no 
additional 
skin 
protectant 
is 
applied.  
Prior to the beginning of the study, ward nurses are educated in interactive face-to-face meetings. Handouts 
will be provided and posters summarizing the study procedures are placed on the wards. Regular refresher 
meetings are held every three months under the supervision of the investigators.  

 
Study protocol 
Page 17 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
5. Who 
provides? 
Ward nurses who participated in an educational session about this study and the procedures and thus have 
study-relevant knowledge.  
6. How  
 
- 
After 
removal 
of 
the 
incontinence briefs, the skin is 
cleansed and dried.  
 
- An oil may be used to remove 
stool and/or residual products.  
 
- The skin protectant is applied to 
dry 
skin. 
According 
to 
manufacturer instructions, the 
spray must be hold approximately 
10 cm away from the skin surface. 
A uniform layer of the product is 
applied using a sweeping motion 
over the area to be protected. The 
film must be completely dry 
before the person is turned onto 
their back, new incontinence 
materials are placed or clothing is 
put on.  
 
- New incontinence pants are put 
on (if needed from the view of the 
nurses).  
- 
After 
removal 
of 
the 
incontinence briefs, the skin is 
cleansed and dried.  
 
- An oil may be used to remove 
stool and/or residual products. 
 
- The skin protectant is applied to 
dry skin.  
 
 
 
 
 
 
 
 
 
 
 
 
- New incontinence pants are put 
on (if needed from the view of the 
nurses).  
- 
After 
removal 
of 
the 
incontinence briefs, the skin is 
cleansed and dried.  
 
- An oil may be used to remove 
stool and/or residual products. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
- New incontinence pants are put 
on (if needed from the view of the 
nurses). 
7. Where  
In the patient rooms, in or outside of the bed.  
8. When and 
how much  
It 
is 
widely 
assumed 
that 
polymeric films protect the skin 
up to 72 hours [21]. According to 
manufactures 
instruction, 
reapplication of ESENTA™ Skin 
Barrier (ConvaTec Inc., UK) is 
recommended every 12 to 72 
hours. To ensure sufficient skin 
protection and to standardize 
application within this trial, the 
product will be applied once daily 
in the morning as a uniform film to 
cover the exposed skin area.  
Because 
traditional 
lipophilic 
leave-on products do not adhere 
to the skin surface that strongly, it 
may be removed more easily. To 
ensure sufficient protection the 
Hydrophobes Basisgel DAC will be 
applied 
twice 
daily 
(in 
the 
morning and evening) as a thin 
layer on the skin exposed to urine 
and stool.  
Not applicable  
9. Tailoring* 
The frequency and intensity of skin cleansing and the application of new incontinence material will be based 
on the number and intensity of incontinence episodes.  
Not applicable 
The skin protectant will be reap-
plied in addition after every stool 
removal from the skin. 
Not applicable 
11. How well* 
Ward nurses are initially trained and retrained after 3 months, after 6 month, and as needed at individual 
additional meetings. During the study, the nurses continuously document the study related procedures 
performed (cleansing, use of leave-on products, used materials) in a resident/patient-specific diary. The 
study personnel check these diaries daily for completeness and consistency to ensure and improve 
compliance and adherence to the protocol.  
*Item 10 and 12 do not apply for study protocols and are therefore not listed in the table 

 
Study protocol 
Page 18 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
2.3.1 QUALITATIVE INTERVIEW PART 
In total, n = 12 qualitative interviews will be conducted with four patients per study group to explore 
the patient perspectives and preferences regarding IAD prevention. This number is based on the 
recommendations for doing qualitative research in feasibility studies for RCTs [22]. To consider 
possible sex related differences, two male and two female participants will be included per group. 
To be eligible, patients need to have a MMSE score of 24 or higher. A separate consent is required 
for participation in the interview. Interviews will be transcribed verbatim and qualitative content 
analyzes conducted.  
2.3.2 CRITERIA FOR DISCONTINUING  
Nursing home/hospital level:  
(1) If the institution no longer wants to participate, 
(2) Any circumstance that makes it impossible or irresponsible to continue study at the respective 
institution 
 
Resident/patient level: 
(1) If a participant or its legal representative withdraws its consent,  
(2) Adverse events (AEs) that, in the judgment of study personnel, interfere with further 
participation in the trial, 
(3) Serious adverse events (SEAs),  
(4) Incidents that, in the judgment of study personnel, interfere with further trial participation, 
(5)  Serious incidents,  
(6) The occurrence of a medical condition which is incompatible with continued trial participation.  
These include, for example: 
a. Mycotic or bacterial inflammation, or other skin conditions in the study area that require 
topical (drug) treatment of the skin area with other products, 
b. The development of a category II,  III, IV pressure ulcer, or an unstageable pressure ulcer, 
or a suspected deep tissue injury (DTI) 
(7) If participants are permanently transferred outside the study site 
(8) In the intervention groups: missing application of study products for more than 72 hours 
(9) More than three missing study visits  

 
Study protocol 
Page 19 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
An "adverse event" or "serious adverse event" is in accordance with the definitions of Regulation 
(EU) 2017/745 (MDR) as defined in Article 2(57) and (58). An "incident" or "serious incident" is in 
accordance with the definitions of Regulation (EU) 2017/745 (MDR) as defined in Article 2(64) and 
(65). 
For the whole trial:  
(1) If the ethics committee withdraws the ethics approval 
(2) If after 8 months of recruitment less than n = 60 participants have been included 
(3) The CTAB unanimously decides after 8 months that study continuation is not suitable to answer 
the research questions. 
2.4  EDUCATION  
2.4.1 TRAININGS 
Training courses of 60 minutes will be conducted by the research team to educate the nurses and 
involved care givers in study-relevant procedures. This includes the demonstration of the study 
related procedures by the research team as well as an exercise for the caregivers on the correct use 
of the products. The trainings will be conducted before the study starts in the participating 
institutions. The number of trainings held initially is based on the number of staff to be trained, to 
ensure that a sufficient number of the involved caregivers have received the training. At regular 
intervals of about three months, follow-up training sessions are conducted by the study staff in the 
institutions to check and refresh knowledge about the study and its procedures and to involve new 
caregivers. 
2.4.2 MATERIALS 
In addition to the trainings, written/illustrated instructions, explaining the correct use of materials 
and describing the protocol-compliant conduct of study related procedures, will be provided to give 
nurses the possibility to review and refresh relevant information at any time. It is planned that these 
materials will be made available in print as well as digital form. For this purpose, booklets and 
presentations will be prepared. Furthermore, DIN-A1 posters will be placed in the participating 
wards to increase the awareness of the study and to provide a quick overview of the related 
procedures at any time. 
In addition, color-coded laminated cards will be placed in the participants' rooms, preferably 
close to their incontinence materials. The color of the card reflects the assignment to the study 

 
Study protocol 
Page 20 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
group and contains a minimum of information about the correct conduct of procedures in the 
respective study group. These cards will serve as a reminder for caregivers and help to avoid 
confusion regarding group assignment. Measures to prevent accidental unblinding of the outcome 
assessor are taken (see section 3.3 , page 31). 
2.5  STRATEGIES TO IMPROVE COMPLIANCE AND ADHERENCE TO THE STUDY PROTOCOL 
Prior to inclusion of an institution, interested institutions are visited by the study coordinators. 
During this visit, the background and procedures of the study are explained and the importance of 
adhering to the study protocol and the provision of sufficient nurses and other caregivers is 
emphasized. If the study coordinators are confident that the institution meets the requirements, 
has the impression that the study-related procedures can be performed correctly and the institution 
demonstrates willingness to participate, the institution is eligible for inclusion in the study. Prior to 
participation, institutions sign a written informed consent form. After inclusion, ongoing 
communication with nursing homes and hospitals will be maintained throughout the study to 
prevent premature loss of participating institutions. 
During the study visits in the participating institutions, the study personnel will review diaries 
completed by the caregivers at least every second day. The high frequency of visits will increase the 
caregivers' attention of the study and provide the opportunity for regular communication between 
the caregivers and the study staff. The study staff can immediately identify missing data and 
inconsistencies in the diaries and discuss and resolve them directly with the caregivers. This timely 
and prompt approach will significantly contribute to data quality and completeness. Likewise, the 
caregiver has the opportunity to clarify open questions with the study staff promptly at any time. 
2.6  CONCOMITANT CARE AND INTERVENTIONS 
According to the pragmatic nature of this study there are no restrictions regarding concomitant care 
or treatments as long as they do not interfere with the conduct of the study.  
2.7  
 OUTCOMES AND VARIABLES 
Because of the exploratory nature of the trial and according to methodological guidance for 
exploratory trials, a distinction between primary and secondary endpoints is not made [23]. Because 
the main aim is to prevent IAD, IAD incidence is likely to be considered as a primary outcome in a 
possible subsequent confirmatory trial. 
 

 
Study protocol 
Page 21 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
Table 2: Outcomes and variables per participant 
 
Outcome 
Name 
Device/Measurement 
instrument/Scale and metric 
Time points 
Response 
Options/Categories/ Range 
IAD 
incidence 
 
IAD Classification according to 
GLOBIAD 
[24] 
and 
distinction 
between intact and eroded skin 
according to Proceedings of the 
Global IAD Expert Panel [10] 
 
Cumulative incidence 
 
IAD Localization according to the 
following definition: 
o Back: Sacral region going 
down to the upper thighs, 
bordered 
approximately 
5 cm below the gluteal fold 
o Front: Navel to upper thigh 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
Presence of IAD: 
(1) None;  
(2) Category 1 A;  
(3) Category 1 B;  
(4) Category 2 A; 
(5) Category 2 B 
 
 
Localization of IAD: 
(1) Back 
(2) Front 
 
Erythema 
 
Rating according to the item 
'Redness' of the incontinence-
associated 
dermatitis 
and 
its 
severity (IADS) instrument [25] 
 
 
3-Item-Scale (ordinal) 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
Redness: 
(1) None; 
(2) Pink;  
(3) Red/Bright red 

 
Study protocol 
Page 22 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
Outcome 
Name 
Device/Measurement 
instrument/Scale and metric 
Time points 
Response 
Options/Categories/ Range 
 
Mexameter MX18 with MDD 4 
(Courage + Khazaka Electronic 
GmbH) [26]  
(measurements according to SOP 
„Mexameter® MX 18” Version 1.0, 
18.05.2022) 
(see 
Fehler! 
Verweisquelle 
konnte 
nicht 
gefunden werden.) 
 
Arbitrary units (AU) from 0 (= no 
erythema) to 999 (= extreme 
erythema) 
 
Means of duplicate measurements 
at the cranial end of the gluteal cleft 
 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
Erythema level: 
0 - 999 [numeric; AU] 
Erosion 
 
Definition of erosion according to 
the latest International League of 
Dermatological Societies glossary 
of 
cutaneous 
lesions 
[27]:  
“Loss of either a portion of or the 
entire epidermis” 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
Presence of Erosion: 
(1) No; 
(2) Yes 
Maceration 
 
Definition of maceration according 
to 
review 
article 
[28]: 
“(…) maceration (…) is the result of 
prolonged exposure (of the skin) to 
moisture and causes the skin to 
soften and breakdown so that the 
connective fibres can be teased 
apart and the skin often exhibits a 
white appearance.” 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
Presence of Maceration: 
(0) No; 
(1) Yes 

 
Study protocol 
Page 23 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
Outcome 
Name 
Device/Measurement 
instrument/Scale and metric 
Time points 
Response 
Options/Categories/ Range 
IAD related 
pain 
 
Numeric rating scale (NRS) from 0 
(= no pain) to 10 (= worst possible 
pain) (see Fehler! Verweisquelle 
konnte nicht gefunden werden.) 
for 
patients/residents 
without 
cognitive impairment (according to 
Mini-Mental-State-Examination 
(MMSE) [29] with scores of 24 or 
higher) 
 
Means  
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
IAD related pain: 
0 - 10 [numeric] 
 
Pain Assessment in Advanced 
Dementia (PAINAD-G) scale [30, 31] 
(see Fehler! Verweisquelle konnte 
nicht gefunden werden.) will be 
used for patients/residents with 
dementia (according to MMSE [29] 
scores 
of < 24; 
see 
Fehler! 
Verweisquelle 
konnte 
nicht 
gefunden werden.) 
 
Means 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
IAD related pain: 
0 - 10 [numeric] 
Patient 
satisfaction 
 
Definition according to [32]. NRS 
from 0 (= dissatisfied) to 10 (= very 
satisfied) 
(see 
Fehler! 
Verweisquelle 
konnte 
nicht 
gefunden 
werden.) 
for 
patients/residents with MMSE [29] 
scores of 24 or higher 
 
Means 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
Patient satisfaction: 
0 - 10 [numeric] 
IAD related 
Itch 
 
Patient reported IAD related itch 
 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
 
Presence of IAD related 
itch 
(0) No 
(1) Yes  

 
Study protocol 
Page 24 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
Outcome 
Name 
Device/Measurement 
instrument/Scale and metric 
Time points 
Response 
Options/Categories/ Range 
Safety 
 
Local intolerances according to [34] 
 
5-Item-Scale (ordinal) 
Days 0, 2, 4, 6, 
8, 10, 12, 14 
 
 
Presence of Local 
intolerances: 
(0) None; 
(1) homogeneous redness 
with scattered 
papules; 
(2) homogeneous redness 
and homogeneous 
infiltration 
(3) homogeneous redness 
and infiltration with 
vesicles 
(4) homogeneous redness 
and infiltration with 
coalescing vesicles 
 
Adverse Events (AEs):  
According to the definition of the 
EU regulation 2017/745 Medical 
Device Regulation (MDR) Article 2 
(57) 
 
Serious Adverse Events (SAEs): 
According to the definition of the 
EU 
regulation 
2017/745 
MDR 
Article 2 (58)  
 
Incidents: 
According to the definition of the 
EU 
regulation 
2017/745 
MDR 
Article 2 (64) 
 
Serious incidents:  
According to the definition of the 
EU 
regulation 
2017/745 
MDR 
Article 2 (65) 
Day 0, Day 2, 
Day 4, Day 6, 
Day 8, Day 10, 
Day 12, Day 14 
 
 
SAEs according to the 
definition 
of 
the 
EU 
regulation 2017/745 MDR 
Article 2 (58) will be 
documented on separate 
reporting 
forms 
(see 
Fehler! 
Verweisquelle 
konnte nicht gefunden 
werden.) 
 
 
Incidents 
and 
Serious 
Incidents according to the 
definition 
of 
the 
EU 
regulation 2017/745 MDR 
Article 2 (64) and (65) will 
be 
documented 
and 
reported 
to 
the 
Bundesinstitut 
für 
Arzneimittel 
und 
Medizinprodukte (BfArM) 

 
Study protocol 
Page 25 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
Outcome 
Name 
Device/Measurement 
instrument/Scale and metric 
Time points 
Response 
Options/Categories/ Range 
Feasibility 
 
Willingness 
to 
participate 
(proportion of participants from all 
eligible patients, reasons for non-
participation) 
 
 
 
Percentage of persons 
from the eligible 
population who are 
willing to participate: 
xx [%] 
 
Reasons for declining 
participation: 
(1) Feel too old or too ill 
to participate 
(2) Perceive study 
participation as a 
burden  
(3) Do not want 
additional/ other 
treatment 
(4) Do not see benefits in 
participating  
(5) Not interested in 
research 
(6) Do not want to be 
randomly assigned to 
a treatment 
(7) Not interested (reason 
not specified) 
(8) Other [free-text] 
 
Adherence/ 
compliance 
to 
prescribed 
intervention 
 
Number of applied skin care 
procedures per day according to 
diary 
 
 
Percentage of completely/ 
correctly documented 
days: 
xx [%] 
 
 
Number of used products 
xx [quantity] 
 
 

 
Study protocol 
Page 26 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
2.7.1 INITIAL SKIN ASSESSMENT 
At the baseline visit on day 0, a skin assessment is performed to check and document the initial 
condition of the skin in the study area. It will be documented whether an IAD (classified according 
to GLOBIAD [25]) is already present and if the skin is intact or eroded (according to Proceedings of 
the Global IAD Expert Panel [35]). Other dermatological conditions in the study area will also be 
documented.  
Study participation with pre-existing IAD is only possible if it is a mild form with early signs of 
IAD and intact skin (GLOBIAD category 1 A). If the initial skin assessment reveals a moderate or 
severe form (including skin loss or clinical sign of infection) of IAD (GLOBIAD category 1 B; 2 A or 
2 B), the participant will be excluded. Other dermatological conditions or skin affections (at 
investigational areas of the skin) requiring dermatological treatment or interfering with the conduct 
of the study also lead to exclusion. 
2.7.2 MEXAMETER MEASUREMENT 
The erythema level will be measured with a modular system consisting of the Mexameter® MX 18 
probe, connected to the basic device Multi Display Device (MDD) 4 (Courage + Khazaka, Cologne, 
Germany). The probe measures the haemoglobin (erythema) components of the skin, which are 
mainly responsible for its color. The measuring principle is based on absorption and reflection. For 
the measurement, the probe emits light with three specific wavelengths and a receiver unit 
measures the reflected light from the skin. As the quantity of emitted light is standardized, it is 
possible to calculate the quantity of light absorbed, by measuring the light reflected by the skin. 
Values are displayed in device-specific arbitrary units (AU) and range from 0 AU to 999 AU, whereby 
higher readings indicate more extreme erythema.  
2.7.3 RESIDENT/PATIENT REPORTED OUTCOME MEASURES 
Participants are asked if IAD related itch is present or not. IAD related pain will be assessed with a 
numeric rating scale (NRS) from 0 (= no pain) to 10 (= worst possible pain) (Fehler! Verweisquelle 
konnte nicht gefunden werden.) for patients/residents without cognitive impairment (according to 
Mini-Mental-State-Examination (MMSE) [29] (Fehler! Verweisquelle konnte nicht gefunden 
werden.) with scores of 24 or higher). For patients/residents with dementia (according to MMSE 
[29] scores of < 24) the Pain Assessment in Advanced Dementia (PAINAD-G) [30, 31] scale will be 
used (Fehler! Verweisquelle konnte nicht gefunden werden.). Patient satisfaction is assessed by 

 
Study protocol 
Page 27 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
NRS from 0 (= dissatisfied) to 10 (= very satisfied) (Fehler! Verweisquelle konnte nicht gefunden w
erden.) for patients/residents with MMSE [29] scores of 24 or higher. Definition according to [32].  

 
Study protocol 
Page 28 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
2.7.4 PARTICIPANTS TIMELINE 
In total, eight study visits are planned. After inclusion, residents will be followed-up for 14 days. 
Written informed consent will be obtained prior study participation by the residents/patients 
themselves or their legal representatives, if applicable. Demographic information (e. g. age, sex, 
care level), incontinence type according to medical records, medical information (e. g. relevant main 
medical diagnoses and relevant regular medication) and further care specific data is collected for all 
participants. A detailed list of variables and how they will be collected (e. g. device/instrument/scale 
and metric as well as measurement time points) is shown in Table 4. The planned trial flow is shown 
in Figure 1 and a schematic overview of the detailed study schedule for the individual participants 
is shown in Table 3. 
 
 
Figure 1: Overview of the planned trial flow.  

 
Study protocol 
Page 29 of 45 
 
 
Study Code: PID 
Version 1.1, 15 June 2022 
 
 
 
Table 3: Study schedule for 
individual participants. 
 
 
Days 
 
Enrollment Allocation 
Post-allocation 
Close-
out 
Timepoint 
-5 to 0 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 13 
14 
Formal requirements and allocation 
Eligibility screening  
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent  
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization and allocation  
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant characteristics 
Demographic variables  
(e.g. age, sex, care level)  
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical diseases  
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medications  
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical function  
(Barthel-Index) 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cognitive status (MMSE) 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Incontinence characteristics  
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical skin assessment 
Gent Global IAD categorization 
(GLOBIAD)  
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
Erythema (visual inspection) 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
Erythema (instrumental 
measurement)  
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
Erosion  
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
Maceration 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
IAD-related 
pain 
(NRS 
or 
PAINAD-G)  
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
IAD-related itch  
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
Patient satisfaction (NRS) 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
(Serious) Adverse Events or 
Incidents 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
Interventions and study-related procedures 
Study arm 1: Conduction of the 
standardized skin cleansing 
regime and application of the 
film-forming skin protectant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study arm 2: Conduction of the 
standardized skin cleansing 
regime and application of the  
hydrophobic skin protectant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study arm 3: Conduction of the 
standardized skin cleansing 
regime, no additional skin 
protectant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
Skin care diary completed by 
nurses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study protocol 
Page 30 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
2.8  SAMPLE SIZE 
2.8.1 WHOLE TRIAL 
Due to the exploratory nature of the trial, a formal sample size calculation is not applicable [23]. The 
trial has two strata (I) sex (male/female); (II) condition of the skin (no IAD vs. IAD Category I) and 
three study arms. Based on these conditions and following the recommendations for exploratory 
trials [36], a sample size of n = 60 participants per group is considered feasible and sufficient to 
describe group differences. In order to compensate a possible loss-to-follow-up, n = 70 patients per 
group will be included.  
2.8.2 INTERVIEW PART 
From the patients included in the trial, n = 12 participants (four participants per study arm) will be 
invited to participate in a qualitative interview. This number is based on the recommendations for 
doing qualitative research in feasibility studies for RCTs [22]. To identify possible sex-specific 
differences, two male and two female participants will be interviewed per study arm. 
2.9  RECRUITMENT 
2.9.1 INSTITUTIONAL LEVEL 
Potentially eligible local nursing homes and geriatric hospitals or hospitals with geriatric wards will 
be contacted and invited to participate by letter, Email or phone. If the institution is interested in 
the project, an initial in-person meeting is arranged at the facility. Nursing homes and geriatric 
hospital wards are informed about the aims and scope of the project. 
The following advantages or rewards will be offered to the nursing homes in case of participation: 
(1) Certificate of participation if desired (e.g. for marketing purposes of the institution) 
(2) Free in-house education (certificates of attendance for the employees if desired) 
(3)  Free educational materials (printed materials including booklets, handouts, posters) 
(4) Free provision of skin cleansing and protection products as well as incontinence materials 
(including disposable wash mitts, incontinence pants) for participating residents/patients. 
2.9.2 PARTICIPANT LEVEL 
The recruitment of participants in the geriatric hospitals/wards and the nursing homes will be 
realized in close cooperation with the local responsible contact person on-site. The responsible 
contact person can either be the nursing home manager itself or a qualified person, delegated by 
the management, such as the nursing care manager. The responsible person in the institution will 
inform possible eligible residents/patients and hand out a first study information leaflet. Interested 
residents or their legal representatives will then be contacted by the study team in person and will 
be informed about the conduct of the study. 

 
Study protocol 
Page 31 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
3. METHODS: ASSIGNMENT OF INTERVENTIONS 
3.1  SEQUENCE GENERATION 
A computer-generated, block-randomization with 1:1:1 allocation ratio per trial arm will be used. In 
order to detect any possible sex-related differences or interactions [37] the randomization will be 
stratified according to males and females. Two independent randomization lists are generated 
according to the same principle, one for participants in the geriatric hospitals/wards and one for the 
participants of the nursing homes. This is done to ensure that there is an equal distribution of 
allocation in both settings. Computerized random numbers will be generated by the statistician not 
involved in study planning or any further study-related procedures or the associated data analysis. 
The random number list is kept with the statistician until the end of the study. 
3.2  ALLOCATION CONCEALMENT MECHANISM  
The allocation will be conducted by the investigator using numbered opaque envelopes (GH-001 to 
GH-200 for participants in geriatric hospitals/wards; NH-001 to NH-200 for participants in the 
nursing homes) containing the computer-generated random numbers. The used envelopes are 
prepared by an employee who is not involved in the planning of the study, the associated data 
analysis, or any further study-related procedures.  
3.3  BLINDING 
Due to the nature of the intervention, involved caregivers and participants will not be blinded. In 
addition, the person of the study team who reviews the diaries and verifies the correct performance 
of study-related procedures by nurses is also not blinded. Because the diaries provide information 
about assignment to the study arm, blinding of the reviewer is not possible due to the given 
circumstances. In order to enhance the internal validity, every visit will be performed by two 
members of the study team.  
Member 1 of the study team performs the following tasks:  
(I) 
Conduct of the study visit and its related tasks as listed in Table 3 under the section 
"Clinical skin assessment" (including assessment of IAD-related pain, itch, patient 
satisfaction as well as the instrumental measurement of the erythema). Member 1 does 
not conduct any part of the assessment regarding the condition of the skin, which 
includes GLOBIAD IAD categorization as well as the visual inspection of erythema, 
erosion and maceration.  
(II) 
Conduct of monitoring activities as described in Table 1 under the section "11. How well".  

 
Study protocol 
Page 32 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
Member 2 ("outcome assessor") of the study team is blinded and does the skin condition-related 
assessments only (including GLOBIAD IAD categorization as well as the visual inspection of 
erythema, erosion and maceration). The blinded person documents the results of the skin 
assessment on a separate "Skin Assessment Data Collection Form" (see Fehler! Verweisquelle 
konnte nicht gefunden werden.), independently from the main CRF (see Fehler! Verweisquelle 
konnte nicht gefunden werden.). This procedure is necessary to prevent accidental unblinding of 
the outcome assessor by trial group-specific information collected in the main CRF. The Skin 
Assessment Forms will be reintegrated into the main CRF after the respective participant has 
completed the study or ended its participation. 
The data manager will be blinded throughout the period of data entry and verification until data 
base closure. The trial statistician will be blinded during statistical analysis.  
4. METHODS: DATA COLLECTION, MANAGEMENT, AND ANALYSIS 
4.1  DATA COLLECTION METHODS 
All data collectors will be trained in obtaining accurately the variables of interest (see 2.7 and 4.1.3). 
Paper source data (SD) and paper case report forms (CRFs) will be used to document all study 
variables of interest. SDs will include originals/copies/transcripts of resident-/patient-related 
records, physicians’, nurses’ and research assistans’ notes, visit schedules, diaries, dispensing LOGS, 
signed ICFs other relevant reports. 
All examinations, assessments, and measurements will be performed onsite in the 
participating geriatric hospitals/wards and nursing homes in the patients'/residents' room. 
Demographic characteristics and basic medical information such as main medical diagnoses and 
regular medication will be extracted from the master data records of the respective institutions. The 
skin assessments will be performed by an experienced and qualified member of the study team 
who, as a blinded outcome assessor, will be constantly vigilant to avoid accidental unblinding. Other 
assessments and the skin measurements will be conducted by trained members of the study team, 
which are not involved in the skin condition assessments (including GLOBIAD IAD categorization and 
visual inspection of erythema, erosion and maceration).  
All study data has to be continuously documented in the CRFs and associated forms by the 
investigator or his authorized staff. Data entries have to be made by using a non-erasable blue or 
black ballpoint pen. Data corrections must be made in a way which does not obscure the original 
entry. The corrected data must be dated and initialed by the corrector. Predefined variables will be 

 
Study protocol 
Page 33 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
entered into an eCRF provided by the CTO of the Charité meeting GCP standards (including 
personalized login and track change). 
4.1.1 SKIN ASSESSMENT 
The skin assessments visits will be performed at Days 0, 2, 4, 6, 8, 10, 12 and 14. This will be 
performed by GCP-trained members of the study team. Nursing home residents/patients in geriatric 
hospitals/wards will be assisted to undress at the area of interest. In close cooperation with the 
caregivers, this will be ideally combined with the scheduled regular general basic care procedures, 
clothing changes or medical procedures. 
The variables regarding IAD categorization, erythema, erosion and maceration will be 
documented by the blinded assessor. In case that a dermatological/medical condition is detected 
which is, in the opinion of the assessor, incompatible with further study conduct, participation for 
this subject will be terminated with specification of the underlying reason  
4.1.2 SKIN MEASUREMENTS 
Erythema level measurements will be conducted at Days 0, 2, 4, 6, 8, 10, 12 and 14 in duplicates at 
the cranial end of the gluteal cleft. Study team members will conduct the measurements according 
manufacturer’s instruction manual (Fehler! Verweisquelle konnte nicht gefunden werden.; Fehler! 
Verweisquelle konnte nicht gefunden werden.) and the respective SOP (see Fehler! Verweisquelle 
konnte nicht gefunden werden.). All study team members who perform the measurements will 
have a documented training prior to the study and undergo a brief examination to ensure similar 
measurement performance. Used measurement devices will be calibrated and serviced periodically 
according to the manufacturer instructions.  
4.1.3 OTHER TRIAL DATA 
Other collected trial data are shown in Table 4. 
 

 
Study protocol 
Page 34 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
Table 4: Other trial data 
Variable 
Name 
Device/Measurement 
instrument/Scale and metric 
Time 
points 
Response Options/Categories/Range 
Demographics 
Age 
 
Age in years  
Day 0 
XXX [years; numeric] 
 
Sex 
 
Obtained from medical 
record 
Day 0 
(1) Male 
(2) Female 
 
 
 
Care level 
 
Obtained from medical 
record in nursing homes 
 
According to Volume XII 
of the  German Social 
Security Code (SGB XII), 
defined by § 61b SGB XII  
Day 0 
(1) none; 
(2) Grade 1 
(3) Grade 2 
(4) Grade 3 
(5) Grade 4 
(6) Grade 5 
Smoking status 
 
Smoking status 
according to 
participant’s statement  
Day 0 
 
Smoking status:  
(1) Smoker 
(2) Non-smoker 
Body height  
 
Obtained from medical 
record 
 
Height in cm 
Day 0 
XXX [numeric] 
 
Body weight 
 
Obtained from medical 
record 
 
Weight in kg 
Day 0 
XXX [numeric] 
 
BMI 
 
Calculated from body 
weight and body height 
 
BMI = kg/m2 
 
 
XX [numeric] 
 
Skin phototype 
 
According to Fitzpatrick 
classification  
Day 0 
(1) Skin Type I;  
(2) Skin Type II; 
(3) Skin Type III; 
(4) Skin Type IV; 
(5) Skin Type V;  
(6) Skin Type VI 
Medical History/ Functional Assessments 
Main 
medical 
diagnoses 
 
Relevant main diagnoses 
obtained from medical 
records 
 
Day 0 
 
Main medical diagnosis  
1. Hypertension 
2. Dementia 
3. Renal failure 
4. Diabetes mellitus 
5. Heart arrhythmia 

 
Study protocol 
Page 35 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
Medications 
 
Relevant 
medications 
obtained from medical 
records 
 
Day 0 
 
Category of medication  
 
(1) Antithrombotic medication 
(2) Beta-adrenoreceptor antagonists 
(3) Diuretics 
(4) Medication 
influencing 
the 
renin-angiotensin 
(5) Psychoanaleptics 
(6) Antibiotics 
Cognitive Ability 
 
Assessed with the MMSE 
 
Score range: 0 to 30  
Day 0 
(1) ≥ 24  
(Normal cognition; no dementia) 
(2) 19 to 23 
(Mild dementia) 
 
(3) 10 to 18 
 
(Moderate dementia) 
(4) 9 and lower 
 
(Severe dementia) 
Physical function  
Barthel – Index 
 
Score range: 0 to 100 
 
Means 
Day 0 
 
Item 1: Feeding  
(0; 5 or 10 points) 
 
Item 2: Bathing  
(0 or 5 points) 
 
Item 3: Personal toilet  
(0 or 5 points) 
 
Item 4: Dressing and undressing  
(0; 5 or 10 points) 
 
Item 5: Controlling bowels  
(0; 5 or 10 points) 
 
Item 6: Controlling bladder  
(0; 5 or 10 points) 
 
Item 7: Toilet use  
(0; 5 or 10 points) 
 
Item 8: Transfer (bed to chair and 
back)  
(0; 5; 10 or 15 points) 
 
Item 9: Standing up and Mobility  
(0; 5; 10 or 15 points) 
 
Item 10: Ascend and descend stairs  
(0; 5 or 10 points) 
Diarrhoea 
 
Interview 
by 
study 
assistant 
or 
obtained 
from medical records 
Day 0 
 
Diarrhoea  
(0) No 
(1) Yes 
Urinary 
tract 
infection 
 
Interview 
by 
study 
assistant 
or 
obtained 
from medical records 
 
Day 0 
 
Urinary tract infection 
(0) No 
(1) Yes 
 
 

 
Study protocol 
Page 36 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
Demographic variables (age, sex, care level,), main medical diseases, medications and, if possible, 
Barthel-Index scores will be obtained from medical records by trained study assistants. Data 
regarding incontinence will be obtained from the medical records or if possible via interview of the 
participants or the responsible caregiver. 
A possible cognitive impairment will be rated using the MMSE [29]. Only residents with a 
score of 24 or higher will receive the questionnaires regarding itch, pain and patient satisfaction. A 
functional assessment using the Barthel-Index will be conducted by study assistants, if this has not 
already been done by the nursing home. The Barthel-Index measures physical function related to 
the daily activities using ten items (e.g. washing and toilet use, eating and mobility or incontinence). 
Scores ranges from 0 (= very dependent) to 100 (= not dependent) [38]. 
4.2  DATA MANAGEMENT 
A paper SD file will be created for the study. Data (informed consent process and consent retrieval, 
demographics, medical history, skin assessments, skin measurements, clinical scores, rating scales) 
will be collected during the study visits in written form. An eCRF will be developed by the CTO. Data 
from the SD will be extracted and entered into an eCRF. The investigator agrees to maintain accurate 
CRF and source documentation as part of the research under this protocol. Data management and 
handling of data will be conducted according to the trial specific Data Management Plan (DMP) of 
the CTO in accordance with ICH guidelines. 
Data entry will be performed by the trial site personnel. Validation and data queries will be 
handled by the data management team of the study. According to a pre-defined query process 
changes to data entries in the eCRF (if any) will be made at the site by the qualified trial site 
personnel. The eCRF will have an audit trail with appropriate functionality for data capture, tracking 
and documentation of any queries or changes. Electronic signatures will be used to verify the data 
and identify the person entering or changing the data (SecuTrial). 
After all data management activities (query and cleaning process) are completed, the 
database will be locked and exported as SPSS datasets. Any deviations, i.e. discrepancies and 
additions from the process defined in the DMP, will be described in a trial specific data management 
report. 
4.3  STATISTICAL METHODS 
All statistical evaluations will be conducted using the statistical programming language R and IBM 
SPSS statistics.  

 
Study protocol 
Page 37 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
Variables will be described for each setting (geriatric hospitals/hospital wards and nursing homes) 
and individual level on an intention-to-treat (ITT) basis. Outcomes will be described using means, 
medians, proportions (including the cumulative incidence) and corresponding spread estimates per 
group. Mean differences between groups and time points will be calculated. In addition, we will 
provide Kaplan-Meier curves for the time from inclusion in the study to the onset of IAD in the three 
study groups. The observations are censored if patients withdraw from the study before the onset 
of an IAD or if the study is terminated before the onset of an IAD. Because this is an exploratory trial 
no group comparisons using formal statistical tests will be performed. However, we will calculate 
two-sided 95% confidence intervals for all means and proportions and for the differences in means 
and proportions between the three study groups. All statistical analyses will be performed for the 
whole sample and for both sex strata separately. 
The interviews and free text responses will be analyzed using qualitative methods including 
labelling, coding, and inductive outcome extraction. 
4.4  ANALYSIS POPULATION 
The statistical analysis will be based on the ITT principle, this includes the whole study population 
and is considered as the 'full analysis set'. The IIT analysis bases on the initial treatment intent. The 
analysis contains all participants that met the inclusion criteria and were randomized, irrespective 
of possible protocol deviations, discontinuation of the study treatment or withdrawal from the 
study by the subject. Participants that die, discontinue participation or leave the institution during 
the study period will be analyzed until that time point (early termination). As only exception, the 
following reasons cause an exclusion of participants from the full analysis set: (I) No treatment was 
applied at all or (II) there are no data available after the subject's randomization. Subjects excluded 
from the full analysis set will be mentioned in the study report and reasons for exclusion will be 
documented per group. In case of consent withdrawal, all subject's data collected until this time 
point will remain part of the study database and may not be removed. This will be clearly stated in 
the ICF.  
 
An additional per protocol (PP) analysis will be performed. The parameters for inclusion in 
the PP analysis set are defined as follows: (I) Participants that completed the study without major 
protocol deviations or violations (i. e. wrong product/incorrect application, missing application for 
more than 72 h, more than three missing study visits, inclusion/exclusion criteria not met) and 
(II) terminated the study regularly (study participation of at least 7 consecutive days). For all subjects 
included in the full analysis set but not in the PP set, the reason for exclusion will be stated in the 

 
Study protocol 
Page 38 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
study report per group. As the ITT analysis is intended to preserve the original randomization and 
to avoid potential bias due to exclusion, the PP analysis aims to analyze the possible effects of the 
intervention administered under optimal conditions. Therefore, both analyzes are a necessary 
component to determine the feasibility of the applied procedures as well as possible effects of the 
intervention. Especially with regard to planning of a subsequent confirmatory trial. 
5. METHODS: MONITORING 
5.1  DATA MONITORING 
A clinical trial advisory board (CTAB) will be implemented. It consists of national and international 
experts in the field of dermatology, geriatrics and nursing science. Further, representatives of the 
German Incontinence Support Group (Deutsche Inkontinenz Selbsthilfe e.V.) will be part of the 
CTAB, representing the interests of the nursing home residents and patients. The support group will 
invite incontinent patients to be part of the study committee. A meeting will be held in which the 
background and aims of the study were presented and the general aspects of the planning, 
implementation and analysis of the study were explained. The CTAB will then actively participate in 
full clinical trial protocol development, review and supervision of the study progress. 
Monitoring of the study is the responsibility of the Investigator and is delegated to CTO. The 
monitor is responsible for reviewing the progress of the study, verifies the adherence to the protocol 
as well as compliance to ICH-GCP. The monitor works according to the SOPs of the CTO. The monitor 
will visit the center before, during, and after completion of the study to ensure that the study is 
conducted, recorded, and reported according to the protocol. During the on-site visits, parts of the 
eCRF will be reviewed for completeness with corresponding SDs. As part of the data audit, SDs will 
be made available for review by the study monitor. The study monitor may periodically request 
review of the ISF to ensure completeness of documentation in all respects of study conduct. The 
monitor may verify the participation of an institution via phone call with the responsible contact 
person of the nursing home/ hospital/ hospital ward.  
5.2  ELECTRONIC DATA CAPTURE 
Data entry 
The CTO uses secuTrial® - a Remote Data Entry (RDE) software solution of interActive Systems (iAS) 
- to capture trial data and transfer them to a central database. SecuTrial® is in compliance with the 
regulatory standards (FDA CRF 21 Part 11 and GCP) and contains the required features like audit 
trail, assigned roles and rights of study employees, management concept and electronic signatures. 

 
Study protocol 
Page 39 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
The system provides the eCRF which allows the documentation of trial data online at any time by 
using a standard internet browser (e.g. Chrome, Firefox, Opera, etc.). Furthermore the eCRF 
contains functions to perform plausibility, consistency and range checks of the entered data to get 
a high level of data quality. Access to the eCRF is person-specific and password protected. All access 
rights (read or enter data) will be defined depending on their function in the trial (principle or clinical 
investigator, study assistant etc.). 
The communication between the client-PC and the trial database on the server is based on 
the secure data-transfer-protocol (SSL - Secure Sockets Layer). This will prevent any illegal access to 
the trial data by unauthorized parties. 
Query Management 
There is a Query management tool as an integrated part of the RDE system. This tool allows the 
communication between the CTO and the clinical investigator at the site. In case of uncertainties, 
errors or improper data, the CTO or the monitor can set queries to clarify the affected question. 
5.3  HARMS 
One investigational product for skin protection is ' ESENTA™ Hautschutz Spray' (PZN: 16866747). It 
is CE certified in accordance with Article 20 (1) of Regulation (EU) 2017/745. The investigational 
product is used and evaluated within its defined intended purpose in the context of the planned 
clinical trial. Therefore, its use is considered safe and the use of the investigational product does not 
impose any additional burden on the participants. The other product used for skin protection is 
'Hydrophobes Basisgel DAC'. It may be regarded as a cosmetic product according to the EU 
Regulation No 1223/2009 on cosmetic products.  
5.3.1 DEFINITION OF ADVERSE EVENTS AND INCIDENTS 
Long-term care residents and patients in acute care are affected by a variety of diseases and medical 
problems. Therefore, the Adverse Events (AEs) and Serious Adverse Events (SAEs) terminology 
(according to EU regulation 2017/745 MDR Article 2 (57) and (58)) will be adopted for this trial.  
Adverse Event 
An AE is any untoward medical occurrence, unintended disease or injury or any untoward clinical 
signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context 
of the clinical investigation, and is related to the investigational device. 
The observation period for AEs begins at the time the resident/patient gives informed 
consent and continues until the study is completed. All residents experiencing AEs will be monitored 

 
Study protocol 
Page 40 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
until symptoms subside, or until there is a satisfactory explanation for the changes observed. If the 
interval between two episodes of an AE is less than seven days, these episodes will be counted as 
one AE. 
The investigator will be responsible for the necessary acute medical treatment of any 
adverse event that occurs during the trial and that is related to the investigational product. The 
investigator ensures that appropriate medical care is also provided thereafter, if necessary. 
Serious Adverse Event 
Serious Adverse Event (SAE) means any AE that led to any of the following: 
(a) 
death, 
(b) 
serious deterioration in the health of the subject, that resulted in any of the following: 
(i) life-threatening illness or injury, 
(ii) permanent impairment of a body structure or a body function, 
(iii) hospitalization or prolongation of patient hospitalization, 
(iv) medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, 
(v) chronic disease 
Hospitalization solely for the purpose of diagnostic tests, even if related to an AE, elective 
hospitalization for an intervention which was already planned before the inclusion of the resident 
in the clinical study, and admission to a day-care facility may not themselves constitute sufficient 
reasons to be considered as a SAE. 
 
Incident 
“An 'incident' means any malfunction or deterioration in the characteristics or performance of a 
device made available on the market, including use-error due to ergonomic features, as well as any 
inadequacy in the information supplied by the manufacturer and any undesirable side-effect” (EU 
regulation 2017/745 MDR Article 2 (64)) 
 
Serious Incident 
"A ‘serious incident’ means any incident that directly or indirectly led, might have led or might lead 
to any of the following: 
(a) 
The death of a patient, user or other person, 
(b) 
The temporary or permanent serious deterioration of a patient’s, user’s or other person’s 
state of health, 
(c) 
A serious public health threat" 
(EU regulation 2017/745 MDR Article 2 (65)) 
 

 
Study protocol 
Page 41 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
5.3.2 INCIDENT REPORTING 
(Serious) incidents must be documented in an incident report form (available online from BfArM) 
and reported via online platform to the BfArM.  
5.4  AUDITING 
The BMBF or its representatives may perform audits or inspections. 
6. ETHICS AND DISSEMINATION 
6.1  RESEARCH ETHICS APPROVAL 
The study was developed and will be conducted in accordance with the principles stated in the 
Declaration of Helsinki and subsequent amendments and in accordance with the Guidelines for 
Good Clinical Practice (ICH Topic E 6 (R1)). 
An ethical approval application together with the ICF, study information and any other requested 
documentation has been submitted to the responsible EC of the Charité - Universitätsmedizin 
Berlin. The study received EC approval on 07.04.2022 (EA4/043/22). 
6.2  PROTOCOL AMENDMENTS 
Substantial amendments to the protocol will be submitted to the EC. The investigator is responsible 
for informing the EC of all problems involving risks to residents. If changes in the ICF become 
necessary, these documents must be submitted to the EC as well. Changes will be filed in the ISF. 
6.3  CONSENT OR ASSENT 
The investigator is obliged to give full written and verbal information to the residents/patients and 
if applicable their legal representatives about the nature of the study, its purpose, the procedures 
involved, the expected duration, potential risks and discomforts as well as about the right to 
discontinue participation in the study without affecting their further relationship with the 
investigator or their future care. 
Prior to inclusion into the study, the consent for each participating subject must be obtained on 
a written statement (ICF) which is approved by the EC. The ICF has to be written in national language 
and an easily understanding target group adapted wording has to be used. Two original ICFs must 
be personally dated and signed by the residents/patients or if applicable by their legal 
representatives. In all cases, the Investigator must also personally date and sign the original ICFs 
and confirm by this way that he/she has provided all information regarding this study. One original 
is intended for the resident/patient and the other one for the ISF. 

 
Study protocol 
Page 42 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
The signed ICF must be obtained before engaging any study-related procedure with the 
resident/patient or data collection. The information and consent procedure is the responsibility of 
the investigator. The investigator can delegate qualified study team members to obtain the 
informed consent.  
6.4  INSURANCE 
All subjects enrolled in this study are covered against negligent conduct of the Investigator or study 
assistants by the liability insurance of the Charité - Universitätsmedizin Berlin. 
6.5  CONFIDENTIALITY AND DATA PROTECTION 
All personal information about potential and enrolled participants is confidential. This ensures the 
strictly split between the personal data and participant-related dataset (trial data). 
A pseudonym is generated for every new participant. The pseudonym will be a combination 
of two characters (GH for participants in geriatric hospitals/wards; NH for participants in the nursing 
homes) and three numbers with ascending sequence (001 to 250). All trial data of the resident will 
be linked with this pseudonym. Personal data of the resident will not be saved in the trial database 
at any time. 
The investigator affirms and upholds the principle of the participant's right to protection against 
invasion of privacy. Throughout this study all data recorded or passed on for further evaluation will 
be coded by the randomization number. Identification is restricted to authorized persons. 
Participant's data may be stored and electronically processed by the investigator for a scientific 
purpose. This study will comply with the requirements of the Berliner Datenschutzgesetz (BlnDSG), 
the General Data Protection Regulation (GDPR; EU 2016/679) and the Kirchengesetz über den 
Datenschutz der Evangelischen Kirche in Deutschland (EKD). 
6.6  DECLARATION OF INTERESTS 
The principal investigator declares, that he has no financial or competing interests for the overall 
trial.  
6.7  ACCESS TO DATA 
All study-related information will be stored securely at the Institute for Clinical Nursing Science. All 
information regarding the participants will be stored in locked file cabinets in areas with limited 
access. Electronically data (e.g. photographs) are stored on a secured digital server of the Institute 
for Clinical Nursing Science.  

 
Study protocol 
Page 43 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
The investigator: 
1. Ensures that the study is conducted in accordance with the protocol and the applicable 
ethical and regulatory requirements and that all data generated during the study are 
accurate, relevant and valid and are entered into the SD; 
2. Keeps an ISF in order to ensure filing and subsequent archiving of all relevant study 
documents during and after the study (original protocol, ethics committee approval and 
administrative documents, etc.); 
3. Retains a subject identification list containing the participants names, addresses and 
randomization numbers to allow checking of data reported on CRFs with those from SD; 
4. Enables direct access to SDs for monitoring, audits and inspections, thus ensuring accuracy 
of the data (if applicable). All representatives that have been granted access to the data 
documentation to perform quality monitoring/audit keep professional confidentiality with 
regards to the participant's data. 
The Investigator is responsible for ensuring that all study records, including SD, ISF, signed ICFs, and 
the subject identification list are archived for the period of time required by law.  
6.8  ANCILLARY AND POST-TRIAL CARE 
Ancillary and post-trial care will not be provided. 
6.9  DISSEMINATION POLICY 
Results dissemination will start with registration at Clinicaltrials.gov and at the DRKS before 
enrollment of the first participant. In addition, the trial protocol will be published in the journal 
'Trials' or any other comparable open access journal. After study completion, results will be 
uploaded at clinicaltrials.gov and published in international journals and at least in one German 
journal (e.g. 'Pflege'). All articles will be published open access. Results will be further presented at 
national and international conferences. To support dissemination of the trial results for subsequent 
research purposes (e.g. individual-patient data (IPD) meta-analyses or secondary analyses), we will 
provide access to anonymized IPD from this trial according to the recommendations of the 
International Committee of Medical Journal Editors (ICMJE) [39]. It is planned to share the data at 
zenodo.org supported by the European Commission.

 
Study protocol 
Page 44 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
VI. 
REFERENCES 
[1] Gray M, Bliss DZ, Doughty DB, Ermer-Seltun J, Kennedy-Evans KL, Palmer MH. Incontinence-associated dermatitis: a 
consensus. J Wound Ostomy Continence Nurs. 2007;34:45-54; quiz 5-6.10.1097/00152192-200701000-00008. 
[2] Gray M, Beeckman D, Bliss DZ, Fader M, Logan S, Junkin J, et al. Incontinence-associated dermatitis: a comprehensive 
review and update. J Wound Ostomy Continence Nurs. 2012;39:61-74.10.1097/WON.0b013e31823fe246. 
[3] Van Damme N, Van den Bussche K, De Meyer D, Van Hecke A, Verhaeghe S, Beeckman D. Independent risk factors for 
the development of skin erosion due to incontinence (incontinence-associated dermatitis category 2) in nursing 
home residents: results from a multivariate binary regression analysis. Int Wound J. 2017;14:801-
10.10.1111/iwj.12699. 
[4] Kottner J, Blume-Peytavi U. Incontinence-associated dermatitis (IAD): aetiology, pathogenesis, risk and 
epidemiology. Wund Management. 2016;10:248-51. 
[5] Hahnel E, Blume-Peytavi U, Trojahn C, Dobos G, Jahnke I, Kanti V, et al. Prevalence and associated factors of skin diseases 
in aged nursing home residents: a multicentre prevalence study. BMJ Open. 2017;7:e018283.10.1136/bmjopen-
2017-018283. 
[6] Kottner J, Beeckman D. Incontinence-associated dermatitis and pressure ulcers in geriatric patients. G Ital Dermatol 
Venereol. 2015;150:717-29. 
[7] Gray M, Giuliano KK. Incontinence-Associated Dermatitis, Characteristics and Relationship to Pressure Injury: A Multisite 
Epidemiologic Analysis. J Wound Ostomy Continence Nurs. 2018;45:63-7.10.1097/WON.0000000000000390. 
[8] Van Damme N  , Vanryckeghem E  , Verhaeghe S  , D B. Incontinence-associated dermatitis in elderly: a qualitative 
phenomenological study on patient experiences. Annual Conference of the European Pressure Ulcer Advisory Panel 
;   Gent, Belgium. 2015. 
[9] Beele H, Smet S, Van Damme N, Beeckman D. Incontinence-Associated Dermatitis: Pathogenesis, Contributing Factors, 
Prevention and Management Options. Drugs Aging. 2018;35:1-10.10.1007/s40266-017-0507-1. 
[10] Beeckman D. Proceedings of the Global IAD Expert Panel. Incontinene-associated Dermatitis: moving prevention 
forward. London: Wounds International; 2015. 
[11] Bliss DZ, Savik K, Harms S, Fan Q, Wyman JF. Prevalence and correlates of perineal dermatitis in nursing home residents. 
Nurs Res. 2006;55:243-51.10.1097/00006199-200607000-00004. 
[12] Saxer S, Halfens RJ, de Bie RA, Dassen T. Prevalence and incidence of urinary incontinence of Swiss nursing home 
residents at admission and after six, 12 and 24 months. J Clin Nurs. 2008;17:2490-6.10.1111/j.1365-
2702.2007.02055.x. 
[13] Zurcher S, Saxer S, Schwendimann R. Urinary incontinence in hospitalised elderly patients: do nurses recognise and 
manage the problem? Nurs Res Pract. 2011;2011:671302.10.1155/2011/671302. 
[14] Kottner J, Rahn Y, Blume-Peytavi U, Lahmann N. Skin care practice in German nursing homes: a German-wide cross-
sectional study. J Dtsch Dermatol Ges. 2013;11:329-36.10.1111/ddg.12008. 
[15] Lichterfeld A, Peters T, Hauss A, Surber C, Kottner J, Blume-Peytavi U. Hautpflege im Krankenhaus: eine deskriptive 
Studie. Pflegezeitschrift. 2016;69:349a-f. 
[16] Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: version 1.0. 
Trials. 2017;18:280.10.1186/s13063-017-1978-4. 
[17] Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, et al. Better reporting of interventions: template for 
intervention description and replication (TIDieR) checklist and guide. BMJ (Clinical research ed). 
2014;348:g1687.10.1136/bmj.g1687. 
[18] Beeckman D, Van Damme N, Schoonhoven L, Van Lancker A, Kottner J, Beele H, et al. Interventions for preventing and 
treating 
incontinence-associated 
dermatitis 
in 
adults. 
Cochrane 
Database 
Syst 
Rev. 
2016;11:CD011627.10.1002/14651858.CD011627.pub2. 
[19] Woo K, Hill R, LeBlanc K, Schultz G, Swanson T, Weir D, et al. Technological features of advanced skin protectants and 
an examination of the evidence base. J Wound Care. 2019;28:110-25.10.12968/jowc.2019.28.2.110. 
[20] Garbe C, Reimann H. Dermatologische Rezepturen. 3rd ed. Stuttgart: Thieme; 2017. 
[21] Comparative Study to Assess an Advanced Skin Protectant in the Management of Incontinence-associated Dermatitis. 
United States National Library of Medicine. 2019. 
[22] O'Cathain A, Hoddinott P, Lewin S, Thomas KJ, Young B, Adamson J, et al. Maximising the impact of qualitative research 
in feasibility studies for randomised controlled trials: guidance for researchers. Pilot Feasibility Stud. 
2015;1:32.10.1186/s40814-015-0026-y. 

 
Study protocol 
Page 45 of 45 
 
Study code PID 
Version 1.1, 15 June 2022 
 
[23] Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to 
randomised pilot and feasibility trials. Pilot Feasibility Stud. 2016;2:64.10.1186/s40814-016-0105-8. 
[24] Beeckman D, Van den Bussche K, Alves P, Arnold Long MC, Beele H, Ciprandi G, et al. Towards an international language 
for incontinence-associated dermatitis (IAD): design and evaluation of psychometric properties of the Ghent 
Global IAD Categorization Tool (GLOBIAD) in 30 countries. Br J Dermatol. 2018;178:1331-40.10.1111/bjd.16327. 
[25] Borchert K, Bliss DZ, Savik K, Radosevich DM. The incontinence-associated dermatitis and its severity instrument: 
development 
and 
validation. 
J 
Wound 
Ostomy 
Continence 
Nurs. 
2010;37:527-
35.10.1097/WON.0b013e3181edac3e. 
[26] Courage and Khazaka electronic GmbH. Mexameter® MX 18, https://www.courage-khazaka.de/de/16-
wissenschaftliche-produkte/alle-produkte/92-mexameter-d; 2021 [accessed 17 December 2021]. 
[27] Nast A, Griffiths CE, Hay R, Sterry W, Bolognia JL. The 2016 International League of Dermatological Societies' revised 
glossary for the description of cutaneous lesions. Br J Dermatol. 2016;174:1351-8.10.1111/bjd.14419. 
[28] Whitehead F, Giampieri S, Graham T, Grocott P. Identifying, managing and preventing skin maceration: a rapid review 
of the clinical evidence. J Wound Care. 2017;26:159-65.10.12968/jowc.2017.26.4.159. 
[29] Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients 
for the clinician. J Psychiatr Res. 1975;12:189-98.10.1016/0022-3956(75)90026-6. 
[30] Basler HD, Hüger D, Kunz R, Luckmann J, Lukas A, Nikolaus T, et al. [Assessment of pain in advanced dementia. Construct 
validity of the German PAINAD]. Schmerz. 2006;20:519-26.10.1007/s00482-006-0490-7. 
[31] Lukas A, Hagg-Grün U, Mayer B, Fischer T, Schuler M. Pain assessment in advanced dementia. Validity of the German 
PAINAD-a 
prospective 
double-blind 
randomised 
placebo-controlled 
trial. 
Pain. 
2019;160:742-
53.10.1097/j.pain.0000000000001430. 
[32] Van den Bussche K, Kottner J, Beele H, De Meyer D, Dunk AM, Ersser S, et al. Core outcome domains in incontinence-
associated dermatitis research. Journal of advanced nursing. 2018;74:1605-17.10.1111/jan.13562. 
[33] Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. The British journal of dermatology. 
2010;162:587-93.10.1111/j.1365-2133.2009.09586.x. 
[34] Menne T, White I. Standardization in Contact Dermatitis. Contact Dermatitis. 2008;58:321.10.1111/j.1600-
0536.2008.01385.x. 
[35] Beeckman D. Proceedings of the Global IAD Expert Panel. Incontinence-associated dermatitis: moving prevention 
forward. .  Wounds International 20152015. 
[36] Teare MD, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters SJ. Sample size requirements to estimate key 
design 
parameters 
from 
external 
pilot 
randomised 
controlled 
trials: 
a 
simulation 
study. 
Trials. 
2014;15:264.10.1186/1745-6215-15-264. 
[37] Sechzer JA, Rabinowitz VC, Denmark FL, McGinn MF, Weeks BM, Wilkens CL. Sex and gender bias in animal research 
and in clinical studies of cancer, cardiovascular disease, and depression. Ann N Y Acad Sci. 1994;736:21-
48.10.1111/j.1749-6632.1994.tb12816.x. 
[38] Mahoney FI, Barthel DW. FUNCTIONAL EVALUATION: THE BARTHEL INDEX. Maryland state medical journal. 1965;14:61-
5. 
[39] Taichman DB, Backus J, Baethge C, Bauchner H, de Leeuw PW, Drazen JM, et al. Sharing clinical trial data: a proposal 
from the International Committee of Medical Journal Editors. Lancet (London, England). 2016;387:e9-
e11.10.1016/s0140-6736(15)01279-9. 
 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in 
geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 1 of 24 
 
Comparison of two skin protection regimes for the Prevention of 
Incontinence-associated Dermatitis in geriatric care:  
An exploratory trial 
Acronym: PID 
DRKS00028954 
Statistical Analysis Plan 
Version 04, 04/17/2025 
 
 
 
Intervention therapy: 
Intervention arm I: Standardized mild skin cleansing 
regimen and daily topical application of a film-forming 
skin protectant at the exposed skin areas.  
Intervention arm II: Standardized mild skin cleansing 
regimen and daily topical application of a hydrophobic 
skin protectant at the exposed skin areas. 
 
Control therapy: 
Standardized mild skin cleansing regimen without 
application of an additional skin protectant 
 
Study population: 
Incontinent geriatric patients 
 
Sponsor: 
Charité - Universitätsmedizin Berlin,  
Charitéplatz 1, 10117 Berlin, Germany 
 
Financial support: 
Federal 
Ministry 
of 
Education 
and 
Research 
(Bundesministerium für Bildung und Forschung (BMBF)) 
by grant number 01KG2020. 
 
Protocol registry identification: 
DRKS00028954 
 
Clinical phase: 
Randomized controlled, parallel group, three-arm, 
assessor-blinded exploratory trial 
 
 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in 
geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 2 of 24 
 
Approved by 
Prof. Dr. rer. cur. Jan Kottner 
Name, Principal Investigator  
 
_____________________________________ 
 
 
 
 
 
 
Place, Date, Signature 
Dipl.-Math. Maximilian Mönch 
Name, Statistician 
 
 
 
_____________________________________  
 
 
 
 
 
 
Place, Date, Signature 
PD Dr. phil. Ulrike Grittner 
Name, Statistician 
 
 
 
_____________________________________            
 
 
 
 
 
 
Place, Date, Signature 
Dr. rer. medic. Monira El Genedy-Kalyoncu 
Name, Trial Coordinator 
 
 
_____________________________________ 
 
 
 
 
 
 
Place, Date, Signature 
File history 
Version 
Date 
Major changes 
Comment 
01 
01/14/2025 
 
Initial SAP 
02 
03/20/2025 
• 
Erythema level 1 and 2 reporting 
 
The mean of Erythema levels 1 and 2 will be 
aggregated and analyzed as endpoint 
 
 
• 
Exclusion of feasibility assessment 
 
The percentage of eligible individuals who 
were willing to participate could not be 
assessed. 
 
 
• 
Analysis of erosion: no adjustment 
for baseline 
Erosion at baseline was exclusion criterion 
 
 
 
• 
Correction of cognitive condition 
for patient satisfaction 
assessment 
If IAD present and MMSE ≥ 24 
 
 
 
• 
Specification of timepoints for 
secondary outcome assessments 
If IAD present 
 
 
 
• 
Addition of location (front/back) 
for subgroup analyses 
For Erosion 
 
Remark: 
additional 
minor 
changes 
(formatting, spelling and grammar) 
03 
04/15/2025 
• 
Flow chart adjustment 
The flow chart was modified and now 
includes updated information on participant 
flow, and exclusions; starting from the set of 
included subjects.  
 
 
• 
Enumeration of participating 
wards 
The number of nursing homes and the 
respective participant counts have been 
added 
 
 
• 
Clarification on patient 
satisfaction measurement 
Patient satisfaction was measured at each 
visit day if MMSE ≥24, regardless of IAD 
presence 
 
 
 
Remark: additional minor changes 
(formatting, clarifications) 
04 
04/16/2025 
• 
Adding the secondary analysis for 
patients with no initial IAD 
Additional subgroup analysis 
 
 
Remark: additional formatting 
SIGN
SIGN
SIGN
SIGN

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in 
geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 3 of 24 
 
Abbreviations 
 
AE  
Adverse Event  
BlnDSG  
Berliner Datenschutzgesetz  
BMBF  
Bundesministerium für Bildung und Forschung  
BMI  
Body Mass Index  
CRF  
Case report form  
CTO  
Clinical Trial Office at the Charité  
DMP  
Data management plan  
DRKS  
Deutsches Register Klinischer Studien (German Clinical Trials 
Register)  
DSGVO  
Datenschutzgrundverordnung (General Data Protection 
Regulation)  
EC  
Ethics committee  
EU  
European Union  
eCRF  
Electronic case report form  
GCP  
Good Clinical Practice  
GDPR  
General Data Protection Regulation  
GDS  
Global Deterioration Scale  
GLOBIAD  Ghent Global IAD Categorization tool  
IAD  
Incontinence associated dermatitis  
ICD  
International Classification of Diseases  
ICF  
Informed consent form  
ICH  
International Conference on Harmonization  
ICMJE  
International Committee of Medical Journal Editors  
IPD  
Individual patient data  
ISF  
Investigator Site File  
IIT  
Investigator Initiated Trial  
ITT  
Intention-to-treat  
MDR  
Medical Device Regulation  
MPDG  
Medizinprodukterecht-Durchführungsgesetz  
NRS 
Numeric Rating Scale 
PU  
Pressure Ulcer  
QoL  
Quality of life  

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in 
geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 4 of 24 
 
RDE  
Remote Data Entry  
SAE  
Serious Adverse Event  
SAP  
Statistical analysis plan  
SAS  
Statistical analysis system  
SD  
Source documents  
SGB  
Sozialgesetzbuch (Codebook of Social Law)  
SOP  
Standard operating procedure  
SPSS  
Statistical Package for the social science  
SSL  
Secure Sockets Layer  
WHO  
World Health Organization  
 
 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in 
geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 5 of 24 
 
1 Background 
Incontinence-associated dermatitis (IAD) is an unwanted skin condition which is common in 
incontinent individuals. It is an inflammatory skin response due to repeated or prolonged contact with 
urine and/or stool [1, 2]. It can occur throughout the lifespan; thus, it is present in babies and young 
children ("diaper dermatitis") as well as in the older individuals [1]. 
The prevalence of incontinence rises with increasing age [3]; therefore, IAD is more common in aged 
populations. IAD prevalence is 3% to 23% in long-term geriatric care and 15% to 40% in acute care 
settings [4]. A representative prevalence study in institutional geriatric long-term care facilities showed 
an IAD prevalence of 35.4% [5, 6]. Thus, around one in three residents was affected by some form of 
IAD. 
Clinically, IAD is manifested by skin redness, vesicles, nodular thickening and maceration of the tissue 
as well as defects of the skin up to the loss of the upper skin layers. For those affected, this can be a 
physical as well as psychological burden. In addition to pain, burning, and itching, IAD is associated 
with an increased risk of secondary infections and the development of pressure ulcers (PUs) [7, 8]. As 
a result of these changes, affected individuals may also suffer from a reduced quality of life, for 
example, through a loss of independence, reduction of social activities, or poor sleep due to IAD-
related pain or itch [6, 9, 10]. 
With approximately 80%, the majority of residents in geriatric long-term care facilities, as well as a 
high proportion of geriatric patients in acute care settings, are affected by one form of incontinence 
and are therefore at potential risk of developing IAD [11-13]. If adequate preventive measures are 
taken at an early stage, IAD might be avoided. However, the high prevalence of IAD in these settings 
indicates that current prevention strategies are not optimal. Due to a lack of knowledge, the current 
nursing practices in the context of IAD prevention are mainly influenced by individual traditions and 
personal preferences and are not evidence-based [14]. At the same time, a clear need for support as 
well as assistance is expressed on the part of nurses and other caregivers in order to be able to perform 
an efficient and effective IAD prevention [15]. Therefore, it is an important aim to close existing 
evidence gaps in this area to support nurses and other caregivers with a solid scientific base for IAD 
prevention. The planned trial aims a direct comparison of the two most important skin protection 
product categories in the form of an explorative randomized controlled trial (RCT), taking core 
outcomes for IAD research into account. 
1.1 
Trial objectives 
1.1.1 Primary objective 
The primary research objective is to compare the incidence of IAD in two intervention groups and one 
control group and to estimate effect sizes for a possible subsequent confirmatory RCT. 
1.1.2 Secondary objectives 
Additional objectives are to test the feasibility of conducting a confirmatory RCT to prevent IAD and to 
evaluate the feasibility of measuring the Core Outcome Domains for IAD trials. 
The trial will answer the following research questions:  
• 
What are the effect sizes of the outcomes when comparing the intervention groups and the control 
group?  
• 
Is the implementation of a standardized skin protection regime for the prevention of IAD feasible 
in geriatric hospital wards and nursing homes?  
• 
Does the implementation of a standardized skin protection regime for the prevention of IAD 
reduce IAD-related itch and IAD-related pain?  
• 
Is the measurement of Core Outcome Domains for IAD trials feasible? 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in 
geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 6 of 24 
 
1.2 
Trial design 
The trial is designed as a randomized controlled (ratio 1:1:1), parallel group, three-arm, assessor-
blinded exploratory trial. Patients are randomized stratified by sex (male/female) into the treatment 
arms.The study was conducted in geriatric hospitals/geriatric wards of participating hospitals and in 
institutional long-term care facilities of the federal state of Berlin, Germany. 
2 Analysis sets 
2.1 
Definitions 
Intention-to-treat/Full analysis population 
The full analysis set (FAS) contains all participants that met the inclusion criteria and were randomized, 
irrespective of possible protocol deviations, discontinuation of the study treatment or withdrawal from 
the study by the subject. Study participants will be categorized according to the intended treatment. 
As only exception, the following reasons cause an exclusion of participants from the full analysis set: 
(I) No treatment was applied at all or (II) there are no data available after the subject's randomization. 
Subjects excluded from the full analysis set will be mentioned in the study report and reasons for 
exclusion will be documented per group. In case of consent withdrawal, all subject's data collected 
until this time point will remain part of the study database and may not be removed.  
Per protocol population 
The per protocol (PP) set is defined as follows: (I) Participants that completed the study without major 
protocol deviations or violations (i. e. wrong product/incorrect application, missing application for 
more than 72 h, more than three missing study visits, inclusion/exclusion criteria not met) and (II) 
terminated the study regularly (study participation of at least 7 consecutive days).  
For all subjects included in the full analysis set but not in the PP set, the reason for exclusion will be 
stated in the study report per group. 
Safety analysis set  
The safety population comprises all patients. Due to blinding, it doesn’t matter whether they received 
one dose of the product or not. 
Nr. 
Inclusion criteria 
Variable name 
Comment 
1 
Geriatric patients or residents (≥ 65 years) staying/living in 
one of the participating institutions 
sc_0080, 
sc_0091 
sc_0091 
for 
age; 
see 
sc_0020 
at 
mnppid_visit 
for detailed info 
2 
Being incontinent of urine and stool 
sc_0100 
 
3 
Expected minimum length of stay of 14 days 
sc_0110 
 
4 
Intact skin with no clinical signs of IAD 
or 
intact skin with early clinical signs of IAD but without clinical 
signs of infection (GLOBIAD category 1 A 
sc_0121 
Check sc_0122 for IAD 
category 
5 
Written informed consent 
sc_0130 
 
Nr. 
Exclusion criteria 
Variable name 
Comment/Analysis 
1 
Residents/patients at the end of life 
sc_0140 
 
2 
Residents/Patients with skin loss due to IAD (GLOBIAD 
category 2 A) and/or signs of clinical infection in the IAD area 
(GLOBIAD category 1 B or2 B) 
sc_0150 
 
3 
Any other skin condition or wounds (at investigational areas 
of the skin) requiring additional treatment (including but not 
limited to pressure ulcers, intertrigo, infection) 
sc_0160 
 
4 
Known hypersensitivity or allergy to silicones and/or topical 
leave-on products 
sc_0170 
 
5 
Topical treatments in the IAD area. 
sc_0180 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in 
geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 7 of 24 
 
2.2 
Application 
The primary efficacy analysis will be done using the FAS including estimated values from multiple 
imputations for missing values (ITT framework). Participants that die, discontinue participation or 
leave the institution during the study period will be analyzed until that time point (early termination). 
An additional analysis of the primary efficacy variable in the PP analysis set will be used as sensitivity 
analysis. The safety analysis includes calculation of frequencies and rates of adverse and serious 
adverse events in the safety analysis set. 
As the ITT analysis is intended to preserve the original randomization and to avoid potential bias due 
to exclusion, the PP analysis aims to analyze the possible effects of the intervention administered 
under optimal conditions. Therefore, both analyzes are a necessary component to determine the 
feasibility of the applied procedures as well as possible effects of the intervention. Especially with 
regard to planning of a subsequent confirmatory trial 
 
3 Trial centres 
The study was conducted in geriatric hospitals/geriatric wards (acute care setting) of participating 
hospitals and in institutional long-term care facilities (nursing home setting) of the federal state of 
Berlin, Germany with a recruitment of n = 220 patients. Of these, 25 subjects were enrolled from acute 
care settings (14 EGZB; 11 Charité-ITS) and 195 subjects were recruited across 18 different nursing 
homes.  
 
Nr 
Participating ward 
Number of patients (n) 
Geriatric hospitals 
1 
EGZB 
14 
2 
Charité intern ITS 
11 
Nursing homes  
1 
NH-01 
11 
2 
NH-02 
19 
3 
NH-03 
5 
4 
NH-04 
19 
5 
NH-05 
17 
6 
NH-06 
10 
7 
NH-07 
6 
8 
NH-08 
9 
9 
NH-09 
7 
10 
NH-10 
19 
11 
NH-11 
4 
12 
NH-12 
25 
13 
NH-13 
8 
14 
NH-14 
7 
15 
NH-15 
3 
16 
NH-16 
3 
17 
NH-17 
13 
18 
NH-18 
10 
 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 8 of 24 
 
3.1 
Recruitment 
All study procedures will be performed at the Charité.  
 
 
 
 
 
 
 
 
 
 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 9 of 24 
 
4 Analysis variables 
According to study protocol version 1.1, 15th June 2022, the following table presents the collected 
variables (first column). In total, eight study visits are planned. After inclusion, residents will be followed-
up for 14 days. 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 10 of 24 
 
4.1 
Demography and baseline characteristics 
Demographic information (e. g. age, sex, care level), incontinence type according to medical records, 
medical information (e. g. relevant main medical diagnoses and relevant regular medication) and further 
care specific data is collected for all participants. 
Characteristic 
eCRF table 
Variable name 
Type 
Scale 
Comment/Analysis 
Patient-ID 
 
mnpaid 
 
 
 
Visit Number 
 
mnpvisno 
 
 
 
 
mnppid_rand
om 
 
 
 
Randomization information 
(strata) 
arm 
 
rd_0050 
cat 
1-A 
2-B 
3-C 
Blinded 
(label permutated) 
 
mnppid_visit 
 
 
 
Visit information 
Visit 
performed? 
 
visit_0011 
Cat. 
 
 
Date of visit 
 
visit_0012 
Date 
 
 
Reason for no 
visit 
 
visit_0013 
Char. 
 
 
Setting 
 
sc_0020 
Cat. 
1-Nursing 
home (NH) 
2-Geriatric 
Hospital (GH) 
Important: 
mnppid_visit; 
not mnppid_screening! 
=>rename 
setting_ sc_0020 
 
mnppid_compl
etion 
 
 
 
 
Date of study 
termination 
 
sc_0010 
Date 
 
For “time under study” 
Take 
diff(sc_0010,visit_0012==Day0) 
Did the 
subject 
complete the 
study 
regularly? 
 
sc_0021 
cat 
1-Yes, 
completion of 
end of study 
visit on Day 14 
2-Yes, but 
before end of 
study visit on 
Day 14 
0-No 
 
Reasons for 0 might be 
withdrawal before 
randomization or screening 
failure 
Reasons 
for 
early 
termination 
 
Sc_0031 to 
Sc_0038 
 
 
Consider sc_003x_txt 
Except for 0031,0032,0037 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 11 of 24 
 
Characteristic 
eCRF table 
Variable name 
Type 
Scale 
Comment/Analysis 
 
mnppid_demo 
 
 
 
Demography & Medical Data 
A Demography 
Age 
 
dm_0020 
Cont. 
years 
Mean (sd) 
Sex 
 
dm_0030 
cat 
1-male 
2-female 
n (%) 
Body height 
 
dm_0041 
Cont. 
cm 
Mean (sd) 
Body weight 
 
dm_0051 
Cont. 
kg 
Mean (sd) 
BMI 
 
dm_0060 
cont 
Score 
Mean (sd) 
Care level 
 
dm_0070 
cat 
0-none 
1-1 
2-2 
3-3 
4-4 
5-5 
-1-Unknown 
n (%) 
Smoking status 
 
dm_0080 
cat 
1-Smoker 
2-Non-
Smoker 
-1-Unknown 
n (%) 
Skin type 
 
dm_0090 
cat 
1-I 
2-II 
3-III 
4-IV 
5-V 
6-VI 
n (%) 
B Medical Data 
Relevant medical diagnoses (ICD 11) 
multi 
 
Multiple answers possible 
None 
 
dm_0101 
cat 
0-no 
1-yes 
n (%) 
Hypertension 
 
dm_0102 
cat 
0-no 
1-yes 
n (%) 
Dementia 
 
dm_0103 
cat 
0-no 
1-yes 
n (%) 
Renal failure 
 
dm_0104 
cat 
0-no 
1-yes 
n (%) 
Diabetes 
mellitus 
 
dm_0105 
cat 
0-no 
1-yes 
n (%) 
Heart 
arrhythmia 
 
dm_0106 
cat 
0-no 
1-yes 
n (%) 
Unknown 
 
dm_0107 
cat 
0-no 
1-yes 
n (%) 
Relevant medications 
multi 
 
Multiple answers possible 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 12 of 24 
 
Characteristic 
eCRF table 
Variable name 
Type 
Scale 
Comment/Analysis 
None 
 
dm_0111 
cat 
0-no 
1-yes 
n (%) 
Antithrombotics 
 
dm_0112 
cat 
0-no 
1-yes 
n (%) 
Beta-
adrenoreceptor 
antagonists 
 
dm_0113 
cat 
0-no 
1-yes 
n (%) 
Diuretics 
 
dm_0114 
cat 
0-no 
1-yes 
n (%) 
Medication 
influencing 
the 
renin 
angiotensin 
 
dm_0115 
cat 
0-no 
1-yes 
n (%) 
Psychoanaleptics 
 
dm_0116 
cat 
0-no 
1-yes 
n (%) 
Antibiotics 
 
dm_0117 
cat 
0-no 
1-yes 
n (%) 
Unknown 
 
dm_0118 
cat 
0-no 
1-yes 
n (%) 
Diarrhoea 
 
dm_0120 
cat 
1-Yes 
0-No 
-1-Unknown 
n (%) 
Urinary 
tract 
infection 
 
dm_0130 
cat 
1-Yes 
0-No 
-1-Unknown 
n (%) 
 
 
4.2 
Outcome variables 
Because of the exploratory nature of the trial and according to methodological guidance for exploratory trials, a 
distinction between primary and secondary endpoints is not made [23]. The presence of IAD is, however, 
with consideration of the study protocol considered as main outcome variable, i.e. primary outcome. 
Variables marked with (day0) will considered as baseline data. All outcome variables are measured in 
eight study visits in total (one baseline visit [Day0] and seven follow-up visits [Day2, Day4, …, Day14]).  
 
 
 
 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 13 of 24 
 
Characteristic 
eCRF table 
Variable 
name 
Type 
Scale 
Comment/Analysis 
IAD incidence 
mnppid_skin 
 
 
 
Main outcome 
Measured 
via 
occurrence of IAD 
at given visit 
(skin_0011) 
IAD present? 
 
skin_0011 
cat 
0-no 
1-yes 
n (%) 
Location front 
 
skin_0015 
cat 
0-no 
1-yes 
n (%) 
Location back 
 
skin_0016 
cat 
0-no 
1-yes 
n (%) 
GLOBIAD 
category (front) 
 
skin_0012 
cat 
1-1A 
2-1B 
3-2A 
4-2B 
n (%) 
(check skin_0015) 
GLOBIAD 
category (back) 
 
skin_0017 
cat 
1-1A 
2-1B 
3-2A 
4-2B 
n (%) 
(check skin_0016) 
Erythema 
(visual) 
 
 
 
 
Multi variable 
"Redness?" 
 
skin_0021 
 
0-None 
1-Pink 
2-Red/bright red 
main 
focus 
if 
available, else  
build variable based 
on 0026, 0027a and 
0028a; (highest  
level counts) 
n (%) 
n.a. 
 
skin_0023 
 
0-no 
1-yes 
Check if contradicts 
skin_0026, 0027a  
and 0028a 
None 
 
skin_0026 
 
0-no 
1-yes 
 
Pink 
 
skin_0027a 
 
0-no 
1-yes 
 
Front 
 
skin_0027b 
 
0-no 
1-yes 
n (%) 
Back 
 
skin_0027c 
 
0-no 
1-yes 
n (%) 
Red/bright red 
 
skin_0028a 
 
0-no 
1-yes 
 
Front 
 
skin_0028b 
 
0-no 
1-yes 
n (%) 
Back 
 
skin_0028c 
 
0-no 
1-yes 
n (%) 
Erythema level 
(1) 
 
Func_0081 
(day0) 
func_0141 
Numeric 
Arbitrary units (AU) from 
0 (= no erythema) to 999 
(= extreme erythema) 
Mean (sd) 
check 
func_0082 
func_0142, 
func_0143 
Erythema level 
(2) 
 
Func_0083 
(day0) 
func_0144 
Numeric 
Arbitrary units (AU) from 
0 (= no erythema) to 999 
(= extreme erythema) 
Mean (sd) 
check func_0084 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 14 of 24 
 
Characteristic 
eCRF table 
Variable 
name 
Type 
Scale 
Comment/Analysis 
func_0145, 
func_0146 
Erythema level 
(total) 
 
 
Numeric 
Arbitrary units (AU) from 
0 (= no erythema) to 999 
(= extreme erythema) 
Mean (sd) of 
(Erythema level 1 + 
Erythema level 2)/2 
Erosion 
 
 
 
 
 
"Erosion 
present?" 
 
skin_0041 
 
0-no 
1-yes 
n (%) 
Front 
 
skin_0044 
 
0-no 
1-yes 
n (%) 
Back 
 
skin_0045 
 
0-no 
1-yes 
n (%) 
Maceration 
 
 
 
 
 
"Maceration 
present?" 
 
skin_0051 
 
0-no 
1-yes 
n (%) 
Front 
 
skin_0054 
 
0-no 
1-yes 
n (%) 
Back 
 
skin_0055 
 
0-no 
1-yes 
n (%) 
Local 
intolerances 
 
 
 
 
 
Have any local 
intolerances 
occurred since 
the last visit? 
 
skin_0061 
 
0-no 
1-yes 
n (%) 
current 
condition 
 
skin_0062 
 
1-Homogeneous redness 
with scattered papules 
2- Homogeneous redness 
and 
homogeneous 
infiltration 
3- Homogeneous redness 
and 
infiltration 
with 
vesicles 
4- Homogeneous redness 
and 
infiltration 
with 
coalescing vesicles 
n (%) 
 
Functional assessments 
Characteristic 
eCRF table 
Variable 
name 
Type 
Scale 
Comment/Analysis 
MMSE 
mnppid_assessments 
(day0) 
mnppid_assessments1 
(else) 
 
 
 
Relevant for dementia 
and IAD related pain 
MMSE-Score 
mnppid_assessments 
 
Func_0021 
Numeric 
Score;  
Range 0-30 
Mean (sd) 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 15 of 24 
 
Functional assessments 
Characteristic 
eCRF table 
Variable 
name 
Type 
Scale 
Comment/Analysis 
MMSE 
Score 
unknown 
mnppid_assessments 
 
Func_0022 
cat 
0-no 
1-yes 
 
Has the subject 
a MMSE Score 
of 
24 
or 
higher? 
mnppid_assessments1 
Func_0090 
 
 
Check func_0021 
Cognitive 
Ability 
mnppid_assessments 
 
Func_0030 
 
1-≥ 
24 
(Normal 
cognition; 
no 
dementia) 
2-19 to 23 (Mild 
dementia) 3-10 to 18 
(Moderate 
dementia) 4-9 and 
lower 
(Severe 
dementia)  
N (%) 
Result of func_0021 
Barthel Index 
Physical 
function 
mnppid_assessments 
 
Func_0041 
Numeric 
Score;  
Range  
0-100 
Mean (sd) 
Barthel Index 
unknown 
mnppid_assessments 
(day0) 
Func_0042 
cat 
0-no 
1-yes 
 
IAD related 
pain 
 
 
 
 
Choice of Score 
depending on MMSE 
IAD present? 
mnppid_assessments 
(day0) 
func_0057 
cat 
0-no 
1-yes 
Compare with  
skin_0011 
NRS  
(numeric 
rating scale) 
mnppid_assessments 
(day0) 
mnppid_assessments1 
(else) 
Func_0052 
(day0) 
func_0101 
Numeric 0 - 10 [numeric]  
 
Mean (sd) 
if 
(MMSE Score ≥ 24) 
(check 
func_0051) 
(check func_0102 and 
0103) 
PAINAD-G  
mnppid_assessments 
(day0) 
mnppid_assessments1 
(else) 
Func_0054 
(day0) 
func_0111 
Numeric 0 - 10 [numeric]  
 
Mean (sd) 
if 
(MMSE Score < 24) 
(check 
func_0053) 
(check func_0112 and 
0113) 
No assessment 
mnppid_assessments 
(day0) 
Func_0055 
cat 
0-no 
1-yes 
 
IAD 
related 
itch 
 
 
 
 
 
IAD-related 
itch reported 
by patient? 
mnppid_assessments 
(day0) 
mnppid_assessments1 
(else) 
Func_0061 
(day0) 
func_0121 
cat 
-2-No assessment 
-1- N.A. (no IAD 
present) 
0-No 
1-Yes 
Func_0062  
and func_0122 
for missing analysis 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 16 of 24 
 
Functional assessments 
Characteristic 
eCRF table 
Variable 
name 
Type 
Scale 
Comment/Analysis 
Patient 
satisfaction 
(of 
incontinence 
treatment) 
mnppid_assessments 
(day0) 
mnppid_assessments1 
(else) 
Func_0071 
(day0) 
func_0131 
Numeric 
0 - 10 [numeric]  
Mean (sd) 
if 
(MMSE Score ≥ 24) 
(check 
func_0053) 
NRS 
from 
0 
(= 
dissatisfied) to 10 (= 
very 
satisfied) 
(check func_0072 for 
missings) 
and 
func_0132,func_0133) 
 
 
4.3 
Secondary variables 
The main clinical outcome is IAD incidence. All other outcome variables are considered secondary. 
 
4.4 
Efficacy 
The main efficacy variable is the IAD cumulative incidence measured by IAD presence on each visit day 
(Day0, Day2, …, Day14). Secondary efficacy variables are Erythema and Maceration level, IAD itch and 
pain level and patient satisfaction. 
• 
IAD-related itch and pain level (numeric rating scale) are measured at each visit day (Day0, Day2, 
…, Day14) if IAD is present and if MMSE ≥ 24.  
• 
IAD itch and pain level (PAINAD-G) are measured at each visit day (Day0, Day2, …, Day14) if IAD is 
present and if MMSE < 24. 
• 
Patient satisfaction is measured at each visit day (Day0, Day2, …, Day14) if MMSE ≥ 24 
• 
Erythema and Maceration level are measured at each visit day (Day0, Day2, …, Day14). 
4.4.1 Safety/Tolerability 
Events are defined according to the definition of the EU regulation 2017/745 Medical Device Regulation 
(MDR) Article 2 and will be checked regularly. 
Adverse events 
• 
Untoward medical occurrence, e.g. allergic reaction 
• 
Unintended disease or injury 
• 
Untoward clinical signs, e.g.: abnormal laboratory finding 
 
Incidents 
• 
any malfunction or deterioration in the characteristics or performance of the skin protectants 
 Serious adverse events / Serious incidents that (in-)directly lead to 
• 
Death 
• 
Serious deterioration in the health 
 
4.4.2 Quality of life 
There is no specific questionnaire for quality of life assessment. 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 17 of 24 
 
 
4.4.3 Feasibility and adherence 
Feasibility and adherence relevant outcomes are evaluated by analysing the available diaries for the study. 
Due to the nature of the diaries, they will be evaluated separately by an unblinded person of the study 
team to ensure the blindedness of the statistician for further analyses. 
 
Characteristic 
 
Type 
Scale 
Comment/Analysis 
Feasibility 
Diary 
 
 
 
- 
- 
- 
 
- 
Assessment not possible 
Adherence 
Diary 
 
 
 
Percentage 
of 
completely/ 
correctly 
documented days: 
 
Numeric 
 
xx [%] 
Count 
diary_00x1 per patient 
x…# of day 
(opt.: divide by days under study) 
 
Each diary day includes several variables (e.g. count of 
urinary incontinence episodes, count of stool 
incontinence episodes, change of incontinence 
material, product application, etc.). A day is defined as 
follows: 
• Correctly documented: All fields are fully completed 
(100% documented). 
• Partially correct: One or more fields are missing. 
• Not filled: Only the date is recorded and all other 
entries are missing. 
Note: A "missing" entry indicates that data was not 
provided, while a deliberate zero indicates that the 
event did not occur. 
 
Number of product 
applications 
 
Numeric 
Xx 
[quantity] 
Summarize 
diary_00x6y per patient, per day and week 
x…# of day 
y…letter of application on day x 
 
 
 
5 Handling of missing values and outliers 
5.1 
Missing values 
In all analyses, missing values on either the outcome measures or on the covariates will be handled by 
using multiple imputation by chained equation (MICE) with m = 30 imputed datasets if MAR or MCAR 
assumption holds. To evaluate whether individual missings are MAR, MCAR or MNAR we will use 
information on reasons of missings or drop out (e.g. if patients drop out due to worsening of health status 
or not). In case of death, no imputation will be implemented for the time afterwards. 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 18 of 24 
 
6 Sample size 
Due to the exploratory nature of the trial, a formal sample size calculation is not applicable [23]. The trial 
has two subgroup strata (I) sex (male/female); (II) condition of the skin (no IAD vs. IAD Category 1A) and 
three treatment arms. Based on these conditions and following the recommendations for exploratory 
trials [36], a sample size of n = 60 participants per treatment group is considered feasible and sufficient 
to describe group differences. In order to compensate a possible loss-to-follow-up, n = 70 patients per 
group will be included. 
7 Statistical analyses / methods 
For all analyses, appropriate descriptive statistics (mean, standard deviation, median, interquartile range, 
absolute and relative frequencies) depending on the scale and distribution of the outcome variable for 
each time point will be presented. For relative frequencies of outcome variables, their cumulative 
incidences will be reported as well. Sensitivity analyses include per protocol analyses and complete case 
analyses in the ITT (without imputation). 
7.1 
Demography and baseline characteristics 
Demography and baseline characteristics will be presented descriptively without any comparisons. 
Depending on the distribution either mean or median will be reported with standard deviation or 
interquartile range respectively. 
7.2 
Analyses of endpoints 
Because of the exploratory nature of the trial and according to methodological guidance for exploratory 
trials, a distinction between primary and secondary endpoints is not made [23]. Because the main aim is 
to prevent IAD, IAD incidence is likely to be considered as a primary outcome in a possible subsequent 
confirmatory trial and is therefore considered as primary efficacy variable. 
For all outcomes, total group differences are reported by the corresponding effect size based on the 
statistical models as outlines below and corresponding 95% confidence intervals. Relevant timepoints will 
be Day 6 and Day14. Day0 reports will be presented as is. 
The relevant blinded group comparisons are: A vs. B; A vs. C; B vs. C. 
For cumulative incidence rates of IAD, Kaplan-Meier Curves will be presented with time ranging from 
inclusion to IAD onset, i.e. the first occurrence of IAD 2A or 2B. Censoring occurs if patients withdraw from 
the study before the onset of an IAD or if the study is terminated before IAD onset. Mixed effects Cox 
regression model (shared frailty model) will be carried out for group comparisons of incidence rates. The 
latter includes group allocation, sex, setting (nursery home, geriatric hospital ward)  and time (continuous) 
as 
fixed 
effects 
and 
random 
intercepts 
for 
the 
ward 
and 
the 
patients. 
The resulting Hazard ratios for IAD will be presented. Potential non-linear time effects will be explored 
and modelled using fractional polynomials or splines.  
Group differences for categorical, dichotomous responses are calculated by estimating group effects from 
either generalized linear mixed-effects models (binary logistic) - including particular baseline status 
(maceration, IAD-related itch), group allocation, sex, setting and time as fixed effects and random 
intercepts per ward and patients - or nonparametric analysis of longitudinal data depending on the 
distribution of the data. For the Erosion model, no baseline adjustment is considered due to its presence 
is an exclusion criterion. 
List: 
• 
Erosion (no/ yes) 
• 
Maceration (no/ yes) 
• 
IAD related itch (no/ yes) [only measured if IAD present] 
• 
IAD-related pain (no/yes) [only measured if IAD present] 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 19 of 24 
 
 
Group differences for numerical, ordinal responses are calculated by estimating group effects from either 
cumulative link mixed-effects (ordinal) - adjusted for baseline status, group allocation, sex, setting and 
time as fixed effects and random intercept  per ward-ID and patient as random effects - or nonparametric 
analysis of longitudinal data depending on the distribution of the data. 
In case of non-occurrence of one category, the model will reduce to a generalized linear mixed-effects 
models (binary logistic) as stated above. 
List: 
• 
Erythema (none/pink/red or bright red) 
 
Group differences for numeric, interval scaled responses are calculated by estimating group effects from 
either linear mixed-effects models - adjusted for baseline status, group allocation, sex, setting and time 
as fixed effects and random intercept per ward and patient as random effects - or nonparametric analysis 
of longitudinal data depending on the distribution of the data. 
List: 
• 
Erythema (total) level (in arbitrary units (AU) from 0 to 999) 
• 
IAD related pain (numeric rating scale from 0 to 10) [for IAD present] 
• 
Patient satisfaction (numeric rating scale from 0 to 10) [both: for MMSE ≥ 24 and above] 
 
In case of nonlinear relationship, nonlinear mixed-effects models will be considered. The check will occur 
visually by scatterplots. 
The distribution of outcome variables will be checked by raincloud plots (boxplot + histogram). 
No adjustment for multiple comparisons will be made and results are bound to be seen exploratory. 
 
7.2.1 Efficacy 
The endpoints will be compared exploratory between the three groups. No confirmatory statistical tests 
will be conducted. Primary efficacy analyses will be carried out in an ITT framework using multiple imputed 
datasets in case of missing values (under the assumption of MCAR or MAR). 
 
7.2.2 Safety/Tolerability 
AEs, SAEs, incidents and serious incidents will be -if any occurred- listed per patient and for the total trial. 
The safety analysis based on the safety analysis set (according to the patients’ received treatment) 
includes calculation of frequencies and incidence rates as well as incidence rate ratios and corresponding 
95% confidence intervals of adverse and serious adverse events using poisson regression or negative 
binomial regression models depending on the distribution of the variables. 
Results of safety analysis will be interpreted and discussed thoroughly also for minor group differences, 
since statistically significance is not of importance here.  
 
7.2.3 Quality of life 
Quality of life is assumed to be linked with patient satisfaction and the interview part. There is no specific separate 
questionnaire. 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 20 of 24 
 
 
7.3 
Planned subgroup analyses 
Differential treatment effects will be analyzed by including interaction terms for subgroups by intervention 
group. Prespecified subgroups include sex (male/female) and patients with and without IAD 1A status at 
baseline. For the subgroup consisting of no initial IAD, a second time-to-event analysis will be realized, using 
the first occurrence of any IAD category as event and thus including 1A and 1B. Additionally, location 
(front/back) of IAD and Erosion will be considered for subgroup analyses as well. Parallel to interaction effects 
estimated marginal treatment effects of the subgroups and 95% CI will be reported.  
7.4 
Interim analyses 
No interim analyses are planned in this study. 
8 Software 
We will use the data management software REDCap for data handling and storage, as well as the open source 
software R for all analysis steps in version 4.2.0 or greater. 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 21 of 24 
 
9 
References 
[1] Gray M, Bliss DZ, Doughty DB, Ermer-Seltun J, Kennedy-Evans KL, Palmer MH. Incontinence-associated dermatitis: a 
consensus. J Wound Ostomy Continence Nurs. 2007;34:45-54; quiz 5-6.10.1097/00152192-200701000-00008. 
[2] Gray M, Beeckman D, Bliss DZ, Fader M, Logan S, Junkin J, et al. Incontinence-associated dermatitis: a comprehensive 
review and update. J Wound Ostomy Continence Nurs. 2012;39:61-74.10.1097/WON.0b013e31823fe246. 
[3] Van Damme N, Van den Bussche K, De Meyer D, Van Hecke A, Verhaeghe S, Beeckman D. Independent risk factors for 
the development of skin erosion due to incontinence (incontinence-associated dermatitis category 2) in nursing home 
residents: results from a multivariate binary regression analysis. Int Wound J. 2017;14:801-10.10.1111/iwj.12699. 
[4] Kottner J, Blume-Peytavi U. Incontinence-associated dermatitis (IAD): aetiology, pathogenesis, risk and epidemiology. 
Wund Management. 2016;10:248-51. 
[5] Hahnel E, Blume-Peytavi U, Trojahn C, Dobos G, Jahnke I, Kanti V, et al. Prevalence and associated factors of skin 
diseases in aged nursing home residents: a multicentre prevalence study. BMJ Open. 2017;7:e018283.10.1136/bmjopen-
2017-018283. 
[6] Kottner J, Beeckman D. Incontinence-associated dermatitis and pressure ulcers in geriatric patients. G Ital Dermatol 
Venereol. 2015;150:717-29. 
[7] Gray M, Giuliano KK. Incontinence-Associated Dermatitis, Characteristics and Relationship to Pressure Injury: A 
Multisite Epidemiologic Analysis. J Wound Ostomy Continence Nurs. 2018;45:63-7.10.1097/WON.0000000000000390. 
[8] Van Damme N , Vanryckeghem E , Verhaeghe S , D B. Incontinence-associated dermatitis in elderly: a qualitative 
phenomenological study on patient experiences. Annual Conference of the European Pressure Ulcer Advisory Panel ; Gent, 
Belgium. 2015. 
[9] Beele H, Smet S, Van Damme N, Beeckman D. Incontinence-Associated Dermatitis: Pathogenesis, Contributing Factors, 
Prevention and Management Options. Drugs Aging. 2018;35:1-10.10.1007/s40266-017-0507-1. 
[10] Beeckman D. Proceedings of the Global IAD Expert Panel. Incontinene-associated Dermatitis: moving prevention 
forward. London: Wounds International; 2015. 
[11] Bliss DZ, Savik K, Harms S, Fan Q, Wyman JF. Prevalence and correlates of perineal dermatitis in nursing home 
residents. Nurs Res. 2006;55:243-51.10.1097/00006199-200607000-00004. 
[12] Saxer S, Halfens RJ, de Bie RA, Dassen T. Prevalence and incidence of urinary incontinence of Swiss nursing home 
residents at admission and after six, 12 and 24 months. J Clin Nurs. 2008;17:2490-6.10.1111/j.1365-2702.2007.02055.x. 
[13] Zurcher S, Saxer S, Schwendimann R. Urinary incontinence in hospitalised elderly patients: do nurses recognise and 
manage the problem? Nurs Res Pract. 2011;2011:671302.10.1155/2011/671302. 
[14] Kottner J, Rahn Y, Blume-Peytavi U, Lahmann N. Skin care practice in German nursing homes: a German-wide cross-
sectional study. J Dtsch Dermatol Ges. 2013;11:329-36.10.1111/ddg.12008. 
[15] Lichterfeld A, Peters T, Hauss A, Surber C, Kottner J, Blume-Peytavi U. Hautpflege im Krankenhaus: eine deskriptive 
Studie. Pflegezeitschrift. 2016;69:349a-f. 
[16] Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: version 1.0. 
Trials. 2017;18:280.10.1186/s13063-017-1978-4. 
[17] Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, et al. Better reporting of interventions: template 
for intervention description and replication (TIDieR) checklist and guide. BMJ (Clinical research ed). 
2014;348:g1687.10.1136/bmj.g1687. 
[18] Beeckman D, Van Damme N, Schoonhoven L, Van Lancker A, Kottner J, Beele H, et al. Interventions for preventing and 
treating 
incontinence-associated 
dermatitis 
in 
adults. 
Cochrane 
Database 
Syst 
Rev. 
2016;11:CD011627.10.1002/14651858.CD011627.pub2. 
[19] Woo K, Hill R, LeBlanc K, Schultz G, Swanson T, Weir D, et al. Technological features of advanced skin protectants and 
an examination of the evidence base. J Wound Care. 2019;28:110-25.10.12968/jowc.2019.28.2.110. 
[20] Garbe C, Reimann H. Dermatologische Rezepturen. 3rd ed. Stuttgart: Thieme; 2017. 
[21] Comparative Study to Assess an Advanced Skin Protectant in the Management of Incontinence-associated Dermatitis. 
United States National Library of Medicine. 2019. 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 22 of 24 
 
[22] O'Cathain A, Hoddinott P, Lewin S, Thomas KJ, Young B, Adamson J, et al. Maximising the impact of qualitative research 
in feasibility studies for randomised controlled trials: guidance for researchers. Pilot Feasibility Stud. 
2015;1:32.10.1186/s40814-015-0026-y. 
[23] Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to 
randomised pilot and feasibility trials. Pilot Feasibility Stud. 2016;2:64.10.1186/s40814-016-0105-8. 
 [24] Beeckman D, Van den Bussche K, Alves P, Arnold Long MC, Beele H, Ciprandi G, et al. Towards an international 
language for incontinence-associated dermatitis (IAD): design and evaluation of psychometric properties of the Ghent 
Global IAD Categorization Tool (GLOBIAD) in 30 countries. Br J Dermatol. 2018;178:1331-40.10.1111/bjd.16327. 
[25] Borchert K, Bliss DZ, Savik K, Radosevich DM. The incontinence-associated dermatitis and its severity instrument: 
development and validation. J Wound Ostomy Continence Nurs. 2010;37:527-35.10.1097/WON.0b013e3181edac3e. 
[26] Courage and Khazaka electronic GmbH. Mexameter® MX 18, https://www.courage-khazaka.de/de/16-
wissenschaftliche-produkte/alle-produkte/92-mexameter-d; 2021 [accessed 17 December 2021]. 
[27] Nast A, Griffiths CE, Hay R, Sterry W, Bolognia JL. The 2016 International League of Dermatological Societies' revised 
glossary for the description of cutaneous lesions. Br J Dermatol. 2016;174:1351-8.10.1111/bjd.14419. 
[28] Whitehead F, Giampieri S, Graham T, Grocott P. Identifying, managing and preventing skin maceration: a rapid review 
of the clinical evidence. J Wound Care. 2017;26:159-65.10.12968/jowc.2017.26.4.159. 
[29] Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of 
patients for the clinician. J Psychiatr Res. 1975;12:189-98.10.1016/0022-3956(75)90026-6. 
[30] Basler HD, Hüger D, Kunz R, Luckmann J, Lukas A, Nikolaus T, et al. [Assessment of pain in advanced dementia. 
Construct validity of the German PAINAD]. Schmerz. 2006;20:519-26.10.1007/s00482-006-0490-7. 
[31] Lukas A, Hagg-Grün U, Mayer B, Fischer T, Schuler M. Pain assessment in advanced dementia. Validity of the German 
PAINAD-a 
prospective 
double-blind 
randomised 
placebo-controlled 
trial. 
Pain. 
2019;160:742-
53.10.1097/j.pain.0000000000001430. 
[32] Van den Bussche K, Kottner J, Beele H, De Meyer D, Dunk AM, Ersser S, et al. Core outcome domains in incontinence-
associated dermatitis research. Journal of advanced nursing. 2018;74:1605-17.10.1111/jan.13562. 
[33] Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. The British journal of 
dermatology. 2010;162:587-93.10.1111/j.1365-2133.2009.09586.x. 
[34] Menne T, White I. Standardization in Contact Dermatitis. Contact Dermatitis. 2008;58:321.10.1111/j.1600-
0536.2008.01385.x. 
[35] Beeckman D. Proceedings of the Global IAD Expert Panel. Incontinence-associated dermatitis: moving prevention 
forward. . Wounds International 20152015. 
[36] Teare MD, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters SJ. Sample size requirements to estimate key 
design parameters from external pilot randomised controlled trials: a simulation study. Trials. 2014;15:264.10.1186/1745-
6215-15-264. 
[37] Sechzer JA, Rabinowitz VC, Denmark FL, McGinn MF, Weeks BM, Wilkens CL. Sex and gender bias in animal research 
and in clinical studies of cancer, cardiovascular disease, and depression. Ann N Y Acad Sci. 1994;736:21-48.10.1111/j.1749-
6632.1994.tb12816.x. 
[38] Mahoney FI, Barthel DW. FUNCTIONAL EVALUATION: THE BARTHEL INDEX. Maryland state medical journal. 
1965;14:61-5. 
[39] Taichman DB, Backus J, Baethge C, Bauchner H, de Leeuw PW, Drazen JM, et al. Sharing clinical trial data: a proposal 
from the International Committee of Medical Journal Editors. Lancet (London, England). 2016;387:e9-e11.10.1016/s0140-
6736(15)01279-9. 
 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 23 of 24 
 
10 Appendix 
10.1 Program code 
The statistical code for analysis of the endpoints will be made available on drks.de 
10.2 Exemplary table layouts 
Table 1: PID - Demographics 
Characteristic 
Overall 
N =  
Group A,  
N =  
Group B,  
N =  
Group C,  
N =  
Age 
 
 
 
 
    Mean (SD) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
    Median [IQR] 
x.xx [x.xx; x.xx] x.xx [x.xx; x.xx] x.xx [x.xx; x.xx] x.xx [x.xx; x.xx] 
    (Minimum,Maximum) 
(x.xx, x.xx) 
(x.xx, x.xx) 
(x.xx, x.xx) 
(x.xx, x.xx) 
Sex, n (%) 
 
 
 
 
Female 
x (pp.p) 
x (pp.p) 
x (pp.p) 
x (pp.p) 
Ward setting, n (%) 
 
 
 
 
Geriatric hospital 
x (pp.p) 
x (pp.p) 
x (pp.p) 
x (pp.p) 
Nursing ward 
x (pp.p) 
x (pp.p) 
x (pp.p) 
x (pp.p) 
 
Table 2: PID – IAD incidence characteristics: Hazard Ratios 
Predictors Hazard 
Ratio 
95% CI  
Study arm 
 
 
    A 
- 
- 
    B 
x.xx x.xx to x.xx 
    C 
x.xx x.xx to x.xx 
Sex 
 
 
Female 
- 
- 
Male 
x.xx x.xx to x.xx 
 

Statistical Analysis Plan 
“Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric 
care: An exploratory trial” || Acronym: PID 
__________________________________________________________________________________________ 
Page 24 of 24 
 
Table 3: PID – Secondary outcome characteristics 
Outcome 
Contrast 
Estimate 
Effect size 
95% CI  
Maceration 
 
 
 
 
 
A vs. B 
x.xx 
x.xx a 
x.xx to x.xx 
 
A vs. C 
x.xx 
x.xx a 
x.xx to x.xx 
 
B vs. C 
x.xx 
x.xx a 
x.xx to x.xx 
Erythema level 
 
 
 
 
 
A vs. B 
x.xx 
x.xx b 
x.xx to x.xx 
 
A vs. C 
x.xx 
x.xx b 
x.xx to x.xx 
 
B vs. C 
x.xx 
x.xx b 
x.xx to x.xx 
a) Odds Ratio; b) Cohen’s d