Prospektiv Randomisierte Studie Zur Multimodalen Selbstbehandlung Von Frauen Mit Inkontinenzbeschwerden Mit Einer Digitalen Gesundheitsanwendung
Phase: NA
Conditions: Urinary Incontinence,Stress, Urinary Incontinence, Urge, Urinary Incontinence, Overactive Bladder Syndrome, Female Urinary Stress Incontinence
Sponsor: Kranus Health GmbH

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Study protocol
Prospective randomised study on multimodal self-treatment of 
women with incontinence complaints using a digital health 
application
DINKS (Digital Incontinence Study)
Study acronym: DINKS (Digital Incontinence Study) Protocol 
version: 2.1 final
Confidentiality note: The content of this study protocol is confidential and may not be disclosed to 
unauthorised persons either verbally or in writing.
This document is a translated version of the original German protocol. 
While every effort has been made to ensure accuracy, 
minor language discrepancies may occur.

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Table of contents
Table of contents ............................................................................................................................................2
Version history................................................................................................................................................5
1
General information ...............................................................................................................................6
1.1
Persons, institutions and bodies involved ..............................................................................................6
1.2
Signatures ..............................................................................................................................................7
1.3
Summary................................................................................................................................................8
1.4
Study synopsis ........................................................................................................................................9
1.5
Business round scheme.........................................................................................................................16
2
List of abbreviations .............................................................................................................................17
3
Test population.....................................................................................................................................19
3.1
Inclusion criteria...................................................................................................................................19
3.2
Exclusion criteria ..................................................................................................................................19
4
Question and background.....................................................................................................................21
4.1
Forms of urinary incontinence..............................................................................................................21
4.1.1
Stress incontinence......................................................................................................................21
4.1.2
Urge incontinence .......................................................................................................................21
4.1.3
Mixed incontinence.....................................................................................................................21
4.2
Distribution and frequency...................................................................................................................21
4.3
Diagnosis of urinary incontinence ........................................................................................................22
4.4
Treatment of urinary incontinence.......................................................................................................23
4.4.1
Underlying diseases and medication...........................................................................................23
4.4.2
Lifestyle changes .........................................................................................................................23
4.4.3
Physiotherapy/ pelvic floor training ............................................................................................23
4.4.4
Bladder training...........................................................................................................................24
4.4.5
Drug therapy ...............................................................................................................................24
4.4.6
Digital therapy programmes........................................................................................................24
4.5
Conclusions and rationale for the study...............................................................................................25
5
Study endpoints and supply effects ......................................................................................................27
5.1
Incontinence episodes frequency (IEF).................................................................................................27
5.2
Questionnaires .....................................................................................................................................27
5.2.1
ICIQ-SF Questionnaire .................................................................................................................27
5.2.2
I-QOL questionnaire ....................................................................................................................28
5.2.3
PAM-13 Questionnaire................................................................................................................28
5.2.4
PGI-I questionnaire......................................................................................................................28
5.2.5
S/U-IQ questionnaire...................................................................................................................28
5.2.6
Further questions about app usage ............................................................................................29
5.3
Therapy failure.....................................................................................................................................29

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6
Study design and description................................................................................................................30
6.1
Type of study, therapy allocation, scope of the study..........................................................................30
6.2
Patient recruitment ..............................................................................................................................30
6.3
Timetable.............................................................................................................................................30
6.4
Study centre .........................................................................................................................................30
6.5
Study programme.................................................................................................................................30
6.6
Patient insurance..................................................................................................................................31
6.7
Screening, information and consent ....................................................................................................31
6.8
Pre-screening, medical history, inclusion procedure ............................................................................32
6.9
Treatment phase..................................................................................................................................32
6.9.1
Micturition diary..........................................................................................................................33
6.9.2
Pelvic floor and physiotherapy exercises....................................................................................33
6.9.3
Bladder training / cognitive behavioural therapy........................................................................33
6.9.4
Mental exercises .........................................................................................................................33
6.9.5
Acute urge control.......................................................................................................................33
6.9.6
Knowledge section /Nutrition section.........................................................................................34
6.9.7
Further functions: .......................................................................................................................34
6.10
Visits and analyses...............................................................................................................................34
6.11
End of study participation ....................................................................................................................34
6.12
End of the study...................................................................................................................................34
7
Adverse events.....................................................................................................................................35
7.1
Complications and risks .......................................................................................................................35
7.2
Recording and documentation of adverse events................................................................................35
7.3
Adverse event ......................................................................................................................................35
7.4
Serious Adverse Event..........................................................................................................................35
7.5
Product defect or device-related adverse events.................................................................................35
7.6
Definition of the risk threshold.............................................................................................................36
7.6.1
Risk threshold for patients..........................................................................................................36
7.6.2
Risk threshold for the study........................................................................................................36
7.6.3
Occurrence of a pregnancy .........................................................................................................36
8
Statistics...............................................................................................................................................37
8.1
End points ............................................................................................................................................37
8.2
Primary endpoint .................................................................................................................................37
8.3
Secondary endpoints............................................................................................................................37
8.4
Planning the scope of the study (case number planning).....................................................................37
8.5
Discussion of the endpoints .................................................................................................................38
8.6
Primary endpoint .................................................................................................................................38
8.7
Secondary endpoints............................................................................................................................38
8.8
Statistical analysis................................................................................................................................39

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8.9
Presentation of the results...................................................................................................................41
8.10
Tables...................................................................................................................................................41
8.11
Listings.................................................................................................................................................41
8.12
Data collection/documentation forms..................................................................................................42
9
Data management................................................................................................................................43
9.1
Patient identification............................................................................................................................43
9.2
Data acquisition ...................................................................................................................................43
9.3
Data protection....................................................................................................................................43
9.4
Quality assurance.................................................................................................................................43
9.5
Archiving..............................................................................................................................................44
10
Ethical issues, legal and administrative regulations ..........................................................................45
10.1
Declaration of Helsinki and Good Clinical Practice ..............................................................................45
10.2
Independent ethics committees...........................................................................................................45
10.3
Legal regulations..................................................................................................................................45
10.4
Registration..........................................................................................................................................45
10.5
Financing..............................................................................................................................................45
10.6
Final report and publication.................................................................................................................45
11
Bibliography.....................................................................................................................................46
A.
Appendix..............................................................................................................................................48
A1.
Questionnaires used.............................................................................................................................48
A1.1
PGI-I: Patient Global Impressions Scale - Improvement..................................................................48
A1.2
I-QOL: Urinary Incontinence Quality of Life Scale ...........................................................................49
A1.3
ICIQ-SF: International Consultation on Incontinence Questionnaire-Urinary Incontinence Short 
Form
53
A1.4
PAM-13: Patient Activation Measure..............................................................................................54
A1.5
S/U-IQ: Stress/Urge Incontinence Questionnaire and Classification System..................................56

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Version history
Version
Section
Changes
date
1.0
-
Initial version
05.03.2024
Entire document
Editorial adjustments
1.4   Study synopsis
3.2   Exclusion criteria
Specification of the exclusion criterion
"OP small pelvis"
2.0
1.4   Study synopsis
6.3   Schedule
10.4 Final report and 
publication
Extension of the recruitment period, 
corresponding adjustment of the schedule
22.07.2024
1.4   Study synopsis
3.2   Exclusion criteria
8.3 Secondary endpoints
Two additional secondary endpoints were 
added, control group was described in more 
detail
5.3   Therapy failure
Definition of treatment failure was
specified in more detail
8.8
Statistical analysis
Subgroup analyses were carried out in more 
detail
specified
2.1
A1.2 Appendix
I-QOL: Urinary Incontinence Quality of Life
Scale has been corrected and completed
14.11.2024

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1
General information
1.1
Persons, institutions and bodies involved
Scientific management:
Statistics:
Prof Dr med Axel Haferkamp
Prof. Dr rer. nat. Walter Lehmacher
Urological University Clinic Mainz
Self-employed statistician, former director
Institute for   Med.   Statistics,   Informatics   
and
Epidemiology (IMSIE) at the University of Cologne
Robert-Koch-Str. 10 - Building 55
50937 Cologne
Dipl.-Stat. Michael Bulitta
CRM Biometrics GmbH 
Mary-Anderson-Str. 6
53332 Bornheim
Protocol Committee:
Prof Dr Axel Haferkamp Prof Dr 
Kurt Miller
Dr Laura Elisa Wiemer
Monitoring:
n. a.
CRO:
CW-Research & Management GmbH 
Konrad-Zuse-Platz 8
81829 Munich
Data management and project coordination:
Heike Kuse
Sponsor:
Kranus Health GmbH 
Westenriederstr. 10
80331 Munich
Laboratory/s:
n. a.
Reference institutes:
n. a.

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1.2
Signatures
 4
Prof. Dr Axel Haferkamp Scientific Director
29.11.2024
Prof. Dr rer. nat. Walter Lehmacher 
Statistician
29.11.2024
Dipl.-Stat. Michael Bulitta 
Statistician
28.11.2024
Dr Laura Elisa Wiemer
On behalf of the sponsor, Kranus Health GmbH

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1.3
Summary
Urinary incontinence in women is a very common clinical picture in which uncontrolled urine loss is 
the main symptom. Incontinence complaints are divided into stress incontinence, urge incontinence 
and mixed urinary incontinence. In Germany, around 15-25% of women are affected by various 
forms of urinary incontinence [1]. The frequency increases with age. A high number of unreported 
cases can be assumed [2]. Various treatment options are available for the different forms of 
incontinence, including lifestyle changes, physiotherapy and pelvic floor muscle training, micturition 
monitoring, as well as medication and finally surgical procedures.
Despite the recommendations of the guidelines [2, 3] and proven effectiveness [4] as a primary 
therapy, comprehensive, multimodal therapy and monitoring programmes (bladder diary, pelvic 
floor training, lifestyle changes, fluid management, bladder training) for female incontinence are 
rarely offered in clinical practice. The reason for this is the complexity of organisation and 
implementation in the "analogue" world. Although the attending physician has contact persons (e.g. 
physiotherapists) available for the individual modules, close and cross-module monitoring of 
patients, which is essential for the success of treatment [2, 5], cannot be realised in clinical practice. 
A digital health application (DiGA) can make it possible to implement the treatment concepts 
recommended in the guidelines and thus close a gap in care.
The positive care effect of such a DiGA is to be demonstrated in a randomised study for patients with 
stress incontinence (N39.3), urge incontinence (N39.42) and mixed forms of the two types of 
incontinence. In the intervention arm, patients receive access to a 12-week digital therapy 
programme (smartphone, tablet), which includes pelvic floor muscle training, bladder training, 
micturition diary and knowledge content for self-education. In the control arm, the previous 
treatments are continued. Patients in the control arm will then be given access to the digital therapy 
programme after the study is completed. The aim of the study is
Among other things, evidence of improvement in disease symptoms, quality of life and patient 
autonomy.

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1.4
Study synopsis
Title of the study:
Prospective randomised study on multimodal self-treatment of 
women with incontinence complaints using a digital health 
application
Abbreviation of the study 
(acronym):
DINKS (Digital Incontinence Study)
Number of study centres:
1
EudraCT number:
2024-512094-27-00
EUDAMED-No. UDI-DI:
PP11745MICTERA96
Planned
number
of 
study participants:
198
Scientific management:
Professor Dr Axel Haferkamp
Clinic and Polyclinic for Urology and Paediatric Urology University 
Medicine
Johannes Gutenberg University Mainz Langenbeckstraße 
1
55131 Mainz
Diagnoses:
assigned to the female sex at birth ≥
18
years
with
incontinence
of different
(stress 
incontinence, urge incontinence, mixed incontinence)
ICD-10 codes:
- N39.3 Stress incontinence [stress incontinence]
- N39.42 Urge incontinence
Study design/methodology:
Randomised, controlled, 2-arm study, single-blind, monocentric.
Arm A: Intervention through digital therapy in addition to real-life 
care
(Intervention group;
multimodal 
self-treatment of incontinence)
Arm B: No access to digital therapy, access is granted after the end 
of the study, patient continues to have access to normal care reality 
(control group; waiting group design)
Duration of the intervention: 12 weeks

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Goals
of the
clinical 
trial/objectives:
This superiority study is intended to demonstrate the following 
objectives:
Primary objective:
●
Reduction in the frequency of incontinence episodes
(IEF) Secondary objectives:
●
Improvement of disease symptoms in the ICIQ-SF
●
Improving the quality of life in the I-QOL
●
Improvement in the PAM-13 questionnaire (patient
activation)
●
Superiority in the PGI-I questionnaire (overall improvement
after treatment)
●
Increase in the proportion of patients without incontinence
(cured patients)
●
Reduction in micturition frequency during the day and at
night
●
Reduction of template consumption (pad use)
●
Reduction of the imperative urge to urinate
●
Improvement of functional bladder capacity
●
Reduction in body weight
●
Reduction
of the share
of
patients
with treatment failure
●
Increase in the proportion of patients with a reduction in
IEF from baseline to week 12 by at least 50%
●
Reduction
of the
frequency
of 
stress incontinence episodes in the S/U-IQ
●
Reduction in the frequency of urge incontinence episodes in
the S/U-IQ

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Target 
values/criteria/endpoints:
Primary endpoint:
(1) Relative change (rel-CfB-IEF) in IEF from baseline to week 12 
relative to baseline; desired reduction in mean relative IEF 
by 50% [6] [7]; IEF per 24 hours - averaged over 72 hours
Secondary targets / secondary target criteria:
(2) Change (CfB) in the ICIQ-SF from baseline to week 12; 
expected mean difference between the groups of> 2.9 
points [8, 9]
(3) Change in I-QOL from baseline to week 12; expected mean 
difference between the groups of
> 6.3 points [9]
(4) Change in the PAM-13 questionnaire from baseline to week 
12
(5) PGI-I questionnaire (overall improvement after treatment) 
at week 12
(6) Share
of thepatients
without
incontinence
(cured patients) at the end of 
the study
(7) Change in micturition frequency per day from baseline to 
week 12
(8) Change in micturition frequency at night from baseline to 
week 12
(9) Change in pad consumption from baseline to week 12
(10)Change in imperative urge to urinate from baseline to week 
12
(11)Change in functional bladder capacity from baseline to 
week 12
(12) Change in body weight from baseline to week 12
(13)Proportion of patients with treatment failure within the 
study period
(14)Proportion of patients with at least 50% reduction in IEF 
from baseline to week 12
(15) Change in stress incontinence episodes of the S/U-
IQ from baseline to week 12
(16) Change in urge incontinence episodes of the S/U-IQ from
Baseline at week 12

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number of patients:
Randomised: Arm A to Arm B in a 1:1 ratio 
Planning of study size (case number planning)
1.
Relative reduction in incontinence episodes (rel-CfB-IEF),
desired improvement of 50%, Minimum Important
Difference (MID) approx. 45% from Yalcin 2010; significance
level α= 5% 2-sided and Power 1 - β= 90%: N= 2 x 44= 88;+
30% due to drop outs and their conservative imputation as
well as subgroup analyses:
N=  120
2.
ICIQ-SF: d= 2.9 MID from Nyström et al., 2015 and Asklund
et al., 2017
Significance level α = 5% 2-sided and power 1 - β = 90%: N =
2 x 44= 88;+ 20% due to drop outs and their conservative
imputation: N = 110
3.
I-QOL: d= 6.3 (MID) from Yalcin et al., 2006
Significance level α = 5% 2-sided and power 80%: due to
drop outs and their conservative imputation:
N = 158 + 40=  198
4.
PAM-13: CfB with desired improvement by 6 points vs.
control (MCID = 6, i.e. approx. 15% of the PAM rank from 13
- 52 and from John, 2020) by d/s = 6/12 = 0.5 (with α = 5%
2-sided and power = 80%: N = 2 x 64.
Based on these calculations, a case number of 198 is planned.
Inclusion criteria:
●
ICD-10 codes:
N39.3 Stress incontinence N39.42 Urge
incontinence
Mixed incontinence
●
Persons assigned to the female sex at birth with urge
incontinence, stress incontinence, mixed incontinence (IE ≥
1 per day)
●
Age≥ 18 years
●
Mastery of the German language
●
Internet access
●
Tablet or smartphone access (Android not older than
version 7 and iPhone not older than iPhone 9)
●
Informed
Consent:
Written
consent
of 
the participating patients

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Exclusion criteria:
1. Absolute exclusion criteria that can be coded according to ICD-10
(incl. ICD-10 codes):
●
None
2. Absolute exclusion criteria that cannot be coded according to
ICD-10:
●
None
3. Relative exclusion criteria that can be coded according to ICD-10
(incl. ICD-10 codes):
●
Acute cystitis N30.0
●
Urinary bladder calculi N21.0
●
Conservative
not
controllable,
recurrent 
macrohaematuria R31
●
Newly diagnosed bladder carcinoma< 3 months C67
4. Relative exclusion criteria that cannot be coded according to ICD-
10:
●
Inability
physically
participate in the
to 
participate in the therapy programme
●
Active pregnancy
●
Botulinum toxin treatment of the urinary bladder in the
last 6 months
5. Study-specific methodological exclusion criteria:
●
Generally patients who are unable to understand and
sign the consent form independently
●
Newly initiated drug or physical therapy for micturition
symptoms (anticholinergics, beta
3 
receptor 
agonists, 
phytopharmaceuticals,
biofeedback, EMS) in the last 4 weeks
●
Severe psychiatric disorders that make it impossible to
use the app
●
Neurological diseases that affect the urinary tract
●
Tumour and incontinence operations in the small pelvis
●
Obesity per magna (BMI >35)
●
Recurrent urinary tract infections N39.0
(at least 2 within 6 months or 3 infections within one
year)
●
Participation of the patient in another clinical trial
within the last 4 weeks prior to the
Inclusion

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●
addiction or other illnesses that do not allow the person 
concerned to assess the nature, scope and possible 
consequences of the clinical trial
Treatments/procedures 
Treatment plan
(incl. 
aftercare):
The digital therapy to be tested via app contains the following 
components:
●
Micturition diary
●
Pelvic floor training and physiotherapy exercises
●
Bladder training / cognitive behavioural therapy
●
Mental exercises
o
Mindfulness
o
Progressive muscle relaxation (PMR)
o
Stimulus control methods
●
Acute urge control
●
Knowledge section / Nutrition section
●
Progress tracking and motivation
The   therapy instructions   are available at   via   a 
smartphone.
/tablet-based app in the form of audio, video and text. The medical 
benefit is assessed via self-reported data points and validated 
questionnaires from the baseline survey compared to the end of the 
survey after 12 weeks.
Timetable (duration of 
study):
Patient-centred:
Duration of study-related measures: 12 weeks 
follow-up period:
12 months 
Study-related:
Recruitment phase: 01.04.2024 to 31.10.2024
Start date:
01.04.2024
Treatment duration: 12 weeks
End of study:
15.02.2025
Final report:
15.04.2025
Test centres:
Clinic and Polyclinic for Urology and Paediatric Urology University 
Medicine
Johannes Gutenberg University Mainz Langenbeckstraße 
1
55131 Mainz

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Statistical methods:
The primary endpoint (1) relative change rel-CfB-IEF week 12 
regarding baseline of incontinence episodes is analysed using an 
analysis of covariance with the baseline value of the IEF as covariate 
and the factor treatment; the significance level is 5% 2-sided. 
Endpoint (2) change in the ICIQ-SF questionnaire, endpoint (3) 
change in quality of life in the I-QOL questionnaire and endpoint (4), 
change in PAM-13, are tested analogously with an ANCOVA at the 
5% 2-sided level; to control for multiplicity, the analyses of 
endpoints (1) - (4) are tested sequentially using the method of a 
priori ordered hypotheses.
The other endpoints are analysed descriptively with p-values and 
95% CIs.
Financing/Sponsor:
Kranus Health GmbH

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Study implementation / treatment phase
Follow Up
1.5
Business 
round scheme
Table 1: Visit scheme for the 
DINKS study
Before 
enrolment/ 
pre-
screening
Inclu
sion
Baseline/tele
phone 
V1 
week 1*
Onboarding IG/ 
after study 
inclusion
Technical 
support call 
week 2
V2 Week 6*
End of study 
Telephone V3 
week 12*
Onboarding 
KG/IG
Follow-up 
questionnaire 
week 24* (IG, KG)
Follow-up 
questionnaire 
week 36* (IG, KG)
Follow-up 
questionnaire 
week 48* (IG, KG)
Medical history/basic data 
collection
X
X
Stress-Urge-Incontinence-
questionnaire (S/U-IQ)
X
X
X
X
X
Verification of input and 
output
Exclusion criteria
X
X
Clarification,
Declaration of consent
X
Randomisation
X
Questionnaires (I-QOL and ICIQ-
UI-
SF)
X
X
X
X
X
PGI-I
X
X
X
X
Technical support
X (IG)
X (IG)
X
Micturition diary
X (ongoing
documentation 
possible)
X
X
X
X
X
X
Incontinence documentation
over 72h
X
X
X
X
X
Acquisition (new)
Concomitant 
medication/therapies
X
X
X
X
X
X
X
X
Recording of adverse 
events**
X
X
X
X
Additional 
telephone 
enquiry
X
X
X
X
X
*Week +/-7 d
**IA/SAE/Incidentes via SZ, by telephone (Tel: +49 89 380 38658) or by e-mailstudy-safety@kranus.de IG: 
Intervention group
KG: Control group

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2
List of abbreviations
AE
Adverse event
Fig.
Illustration
AK
Exclusion criteria
AWMF
Working Group of the Scientific Medical Societies
BfArM
Federal Institute for Drugs and Medical Devices
BMI
Body mass index
CCS
Complete cases
CfB
Change from baseline
d
Day - Day(s)
DiGA
Digital health application
DINKS
Digital incontinence study (study acronym)
eCRF
electronic Case Report Form
ePRO
electronic Patient-Reported-Outcomes
EK
Inclusion criteria
EMS
Electrical muscle stimulation
FAS
Full Analysis Set
FPI
First Patient In
FPO
First Patient Out
GCP
Good Clinical Practice
ICD
International Classification of Diseases
ICH-E3
Structure and Content of Clinical Study Reports E3
ICH-GCP
International Conference on Harmonisation - Good Clinical Practice Guidelines
ICIQ-SF
Incontinence Questionnaire-Urinary Incontinence Short Form
I-QOL
Incontinence quality of life questionnaire
IEF
Incontinence episode frequency

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ISO
International Organization for Standardisation
JtR
Jump-To-Reference
AI
Confidence interval
LOCF
Last Observation Carried Forward
LPI
Last Patient In
LPO
Last Patient Out
n. a.
Not applicable
NN
Nomen nominandum
NtF
Note to File
MDR
Medical Device Regulation
MID
Minimum Important Difference
OAB
Overactive Bladder
PAM-13
Patient Activation Measure 13
PGI-I
Patient Global Impression of Improvement -Incontinence
PMR
Progressive muscle relaxation
PPS
Per protocol set
Rel-CfB
Relative Change from Baseline (CfB/Baseline)
PROM
Patient reported outcome measures
QOL
Quality of Life
SAE
Serious Adverse Event
SAP
Statistical analysis plan
SAF
Safety Set
SF
Short Form
S/U-IQ
Stress/Urge Incontinence Questionnaire
V
Visit
vs.
Versus
WoC
Withdrawal of Consent

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3
Test population
3.1
Inclusion criteria
●
ICD-10 codes:
N39.3 Stress incontinence N39.42 Urge incontinence
Mixed incontinence
•
Persons with urge incontinence who were assigned to the female sex at birth,
Stress incontinence, mixed incontinence (IE≥ 1 per day)
●
Age≥ 18 years
●
Mastery of the German language
●
Internet access
●
Tablet or smartphone access (Android not older than version 7 and iPhone not older than 
iPhone 9)
●
Informed consent: written consent of the participating patients
3.2
Exclusion criteria
Absolute exclusion criteria that can be coded according to ICD-10 (incl. ICD-10 codes):
●
None
Absolute exclusion criteria that cannot be coded according to ICD-10:
●
None
Relative exclusion criteria that can be coded according to ICD-10 (incl. ICD-10 codes):
●
Acute cystitis N30.0
●
Urinary bladder calculi N21.0
●
Recurrent macrohaematuria that cannot be controlled conservatively R31
●
Newly diagnosed bladder carcinoma< 3 months C67
Relative exclusion criteria that cannot be coded according to ICD-10:
●
Inability to physically participate in the therapy programme
●
Active pregnancy
●
Botulinum toxin treatment of the urinary bladder in the last 6 months
Study-specific methodological exclusion criteria:
●
Generally patients who are unable to understand and sign the consent form independently

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●
Newly started drug or physical therapy for micturition symptoms (anticholinergics, beta-3 
receptor agonists, phytopharmaceuticals, biofeedback, EMS) in the last 4 weeks
●
Severe psychiatric disorders that make it impossible to use the app
●
Neurological diseases that affect the urinary tract
●
Tumour and incontinence operations in the small pelvis
●
Obesity per magna (BMI >35)
●
Recurrent urinary tract infections N39.0 (at least 2 within 6 months or 3 infections within 
one year)
●
Participation of the patient in another clinical trial within the last 4 weeks prior to inclusion
●
addiction or other illnesses that do not allow the person concerned to assess the nature, 
scope and possible consequences of the clinical trial
Both groups, intervention and control group, have access to the treatment options of the regular 
care reality during the study period. In order to be able to evaluate the effect of the intervention in a 
differentiated manner, ongoing incontinence treatment (e.g. medication, interventional or surgical 
measures) should have been started at least four weeks before the start of the study. New therapies 
before the start of the study are considered an exclusion criterion.
During the study period, all newly initiated therapies for incontinence treatment (e.g. medication, 
interventional or surgical measures) are recorded and categorised as treatment failure. Treatment 
failure is also deemed to have occurred if the patient reports a deterioration in the PGI-I 
questionnaire at the end of the study.
The number of treatment failures is calculated and documented separately for the intervention and 
control groups.
Patients in the control group are not given access to the app-based intervention during the twelve-
week study period. After completion of the survey at the end of the study (week 12, see 1.5. Visit 
schedule), they are free to use the app-based therapy.

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4
Question and background
Urinary incontinence in women is a very common, often under-diagnosed and taboo condition, the 
main symptom of which is uncontrolled urine loss. This is accompanied by a significant reduction in 
quality of life and considerable suffering. Incontinence complaints are divided into stress 
incontinence, urge incontinence and mixed urinary incontinence.
4.1
Forms of urinary incontinence
4.1.1
Stress incontinence
Stress with an increase in intra-abdominal pressure (lifting, coughing, sneezing, laughing, jumping, 
etc.) leads to involuntary loss of urine, which is known as stress incontinence. One of the causes is a 
decrease in tone or pre-damaged pelvic floor muscles, for example after pregnancy and childbirth or 
in old age as a result of sarcopenia and decreasing muscle strength.
The severity of stress incontinence is determined by the intensity of the stress:
Grade 1: Leakage of urine when coughing, sneezing, pressing, lifting, carrying heavy objects. 
Grade 2: Urine leakage when walking or standing up.
Grade 3: Urine leakage even when lying down.
4.1.2
Urge incontinence
Urge incontinence is when there is an involuntary loss of urine combined with a sudden urge to 
urinate (imperative urge to urinate). This is caused by involuntary spontaneous contractions of the 
detrusor of the bladder (detrusor hyperactivity, OAB overactive bladder).
4.1.3
Mixed incontinence
Mixed incontinence is when there  involuntary loss of urine during physical exertion on the one hand 
and an imperative urge to urinate in the sense of urge incontinence on the other. In most cases, one 
of the components predominates.
4.2
Distribution and frequency
According to clinical studies, the distribution is as follows: Stress incontinence (50%), urge 
incontinence (14%), mixed form (32%) [10].
In Germany, around 15-25% of women are affected by various forms of urinary incontinence [1]. The 
frequency increases age. A high number of unreported cases can be assumed [2].

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4.3
Diagnosis of urinary incontinence
The diagnostic recommendations for urinary incontinence in the German S2 guidelines are based on 
expert opinion and clinical studies [2]. The diagnostic steps are outlined below:
A detailed medical history enables incontinence to be categorised in the majority of cases [11]. In 
addition to the obstetric and gynaecological history, concomitant illnesses and medication are also 
relevant. The patient's individual impairment and level of suffering should also be enquired about.
The general clinical examination serves to rule out high residual urine volumes, resistance or masses 
in the pelvis. The gynaecological examination can be used to assess possible diseases of the external 
genitalia and a prolapse of the internal genitalia (descensus, prolapse). Palpation of the pelvic floor 
muscles enables an assessment of their contractility.
The use of validated questionnaires is recommended in guidelines. The severity of the disease, type 
of incontinence and disease-related quality of life can be recorded.
The micturition diary is used to quantify symptoms and record the frequency of incontinence 
episodes. It also enables the measurement of micturition volumes and the determination of the 24-
hour total urine volume or the nocturnal urine volume. The use of the micturition diary is strongly 
recommended in the guidelines for all forms of incontinence [2]. To increase the accuracy of the 
results, the use of a three-day micturition diary is used to determine a 24-hour average [12].
The pad test quantifies urine loss by wearing pads during documented physical activity and weighing 
them after a set period of time. Both the 1-hour pad test and the 24-hour pad test exist. Although 
the 24-hour test is more precisely reproducible, the standardisation of physical activities is more 
complex [13].
It is important to know if there is residual urine before initiating treatment for incontinence, as drug 
therapy options such as anticholinergics can impair bladder emptying. The amount of residual urine 
is determined by ultrasound examination. However, studies on the determination of residual urine in 
women are rare and there is no standard definition for a pathological amount of residual urine. In 
women with stress incontinence, only 16% had residual urine > 100 ml [14].
Urodynamics with bladder manometry, uroflowmetry and urethral pressure profile are used to 
assess the bladder during the filling and emptying phase. Routine use of this examination prior to 
conservative treatment of uncomplicated stress incontinence and untreated overactive bladder is 
not recommended in the guidelines [2].
Of the imaging procedures, sonography plays an important role in determining residual urine (see 
above). Transcavitary functional sonographic procedures are only relevant in the context of surgical 
treatment of incontinence.
To summarise, it can be stated that, of the diagnostic procedures described, only questionnaires and 
pad tests for the quantitative assessment of the

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incontinence and to test the effectiveness of therapy. However, the use of the various validated 
questionnaires is heterogeneous [4].
4.4
Treatment of urinary incontinence
In the clinical practice of incontinence treatment, conservative therapies (less invasive, reversibility) 
are generally used before surgical therapies. For all types of incontinence, pelvic floor muscle 
training, cognitive behavioural therapy, lifestyle changes and self-management therapies are 
successful and represent an alternative to drug therapies [15]. For this reason, both the German 
AWMF guidelines [2] and the European guidelines for urology (EAU guidelines) recommend these 
measures with strong scientific evidence [3].
4.4.1
Underlying diseases and medication
Existing underlying diseases (e.g. diabetes, heart failure, obesity, neurological disorders, etc.) can 
have an impact on incontinence and should be treated appropriately. The influence of obesity as a 
risk factor for urinary incontinence has been demonstrated [16]. Studies on the therapeutic effect of 
weight reduction show contradictory results [2].
The influence of medication for comorbidities on urinary incontinence is difficult to assess and the 
benefit of adapting drug therapies to improve incontinence has not been proven [2].
4.4.2
Lifestyle changes
Lifestyle factors that can be associated with incontinence include obesity, smoking, lack of physical 
activity, drinking habits and diet. Adjusting these factors can improve urinary incontinence [2].
4.4.3
Physiotherapy/ pelvic floor training
Pelvic floor exercises are used to improve the function of the pelvic floor and urethral stability.
Meta-analyses have shown that pelvic floor muscle training is effective in terms of curing and 
relieving urinary incontinence and improving the quality of life of those affected [4] [15] [17] [18]. 
These effects apply to women with stress incontinence, urge incontinence and mixed urinary 
incontinence [19].
Improved pelvic floor function can inhibit non-physiological bladder contractions in patients with an 
overactive bladder, leading to an improvement in symptoms [20]. Pelvic floor training also increases 
the likelihood of continence 12 months after birth in cases of urinary incontinence caused by 
pregnancy and childbirth [21]. In addition, older women with stress incontinence benefit from pelvic 
floor muscle training just as much as younger women [22] [23].
Accordingly, the guidelines recommend carrying out pelvic floor muscle training for both urge and 
stress incontinence for a period of at least three months [2].

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4.4.4
Bladder training
Through bladder training, the patient learns to better assess the filling status of the bladder and not to
"preventive" emptying of the bladder. Gradually adapted voiding intervals are built up. The specific 
aims are to correct incorrect habitual patterns, gain control over urge incontinence and ultimately 
extend the voiding intervals by increasing functional bladder capacity. Incontinence episodes can 
thus be reduced and patients' self-confidence in their ability to control their bladder function 
independently is strengthened [2].
4.4.5
Drug therapy
Antimuscarinic drugs are a relevant option in the secondary (after failed non-medication therapy) 
treatment of overactive bladder and urge incontinence. Although the available drugs differ in their 
pharmacological profiles, what they all have in common is their inhibitory effect on the muscarinic 
receptors of the detrusor cells. This leads to a reduction in spontaneous, uncoordinated detrusor 
contractions [2]. The efficacy of antimuscarinic drugs has been proven in numerous studies 
(overview e.g. in [24]).
Side effects include dry mouth, constipation, accommodation disorders of the eyes, cognitive 
impairment, tachycardia and fatigue. There is a relatively high discontinuation rate with the main 
causes being ineffectiveness, side effects and the ability to manage symptoms without medication 
[2].
The ß3-adrenoreceptor agonist mirabegron has also shown efficacy in clinical trials [25]. The side 
effect profile differs from that of antimuscarinics, whereby the risk of arterial hypertension in 
particular should be taken into account. However, mirabegron does not lead to any impairment of 
bladder contractility [2].
Duloxetine prevents the presynaptic reuptake of the neurotransmitters serotonin and 
noradrenaline. This results in increased stimulation of the 5-hydroxytryptamine and noradrenaline 
receptors on motor pudendal nerves. This leads to increased resting tone and increased contraction 
force at the striated urethral sphincter [2]. The results from clinical studies are heterogeneous. The 
German S2 guidelines recommend that women with moderate urinary incontinence and above 
should be informed about duloxetine as a treatment option [2].
4.4.6
Digital therapy programmes
There are currently no digital health applications for the treatment of female incontinence listed on 
the BfArM website in Germany (https://diga.bfarm.de/de/verzeichnis). However, self-management 
programmes using smartphones or tablets are listed in the literature. For example, a randomised 
controlled trial on the effectiveness of an app-based intervention for female urinary incontinence 
through pelvic floor muscle training, bladder training and knowledge transfer showed after four 
months that the app therapy was as effective as guideline-based care by general practitioners in the 
Netherlands [26]. Both treatments led to a relevant reduction in urinary incontinence symptoms, 
improvement in quality of life and fewer daily incontinence episodes. The authors conclude that app-
based therapy is a comparably effective but more accessible alternative to conventional care [26].

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A systematic review that investigated the intervention of pelvic floor training using an app in women 
with stress incontinence or stress-related mixed incontinence using six randomised intervention 
studies found that app-based pelvic floor training significantly reduced the severity of symptoms of 
stress incontinence in the ICIQ-SF questionnaire and improved the quality of life of the women 
affected [27]. This demonstrates the effectiveness of app-based pelvic floor exercises for the 
treatment of stress urinary incontinence and for improving the quality of life of affected women. The 
results of the Patient Global Impression of Improvement (PGI-I) at follow-up of the studies analysed 
indicate that participants in the app group experienced a significant improvement [27]. This 
systematic review focuses on apps that only offer pelvic floor muscle training as an intervention for 
stress urinary incontinence. A digital health application (DiGA) that integrates other elements of 
urinary incontinence therapy in addition to pelvic floor muscle training, such as lifestyle changes, 
fluid management and bladder training - in line with German and European guidelines - could 
potentially increase effectiveness. A multimodal therapy approach could therefore increase the 
likelihood of sustainable therapeutic success.
4.5
Conclusions and rationale for the study
Urinary incontinence in women is a very common condition that can be categorised as stress, urge or 
mixed urinary incontinence. There are various treatment options for different forms of incontinence, 
including lifestyle changes, physiotherapy/pelvic floor exercises, micturition monitoring and also 
medication and surgical procedures.
Despite the recommendation in the guidelines [2, 3] and proven effectiveness [4] as a primary 
therapy, comprehensive, multimodal therapy and monitoring programmes (bladder diary, pelvic 
floor training, lifestyle changes, fluid management, bladder training, etc.) for female incontinence 
are rarely offered in clinical practice. The reason for this is the complexity of organisation and 
implementation in the "analogue" world. Although the treating physician has contact persons (e.g. 
physiotherapists) available for the individual modules, close and cross-module monitoring of 
patients, which is essential for the success of treatment [2, 19], cannot be realised in clinical 
practice. A DiGA can help to close a gap in care by monitoring, treating and alleviating urinary 
incontinence in line with the areas of application defined in the Digital Healthcare Act.
The positive care effect of such a DiGA is to be demonstrated in a randomised study for patients with 
stress incontinence (N39.3) and urge incontinence (N39.42) as well as mixed forms. In the 
intervention arm, patients will have access to a 12-week digital therapy programme based on 
evidence-based approaches and including measures recommended by German and European 
guidelines for the treatment of incontinence (see 4.4 Treatment of urinary incontinence). This 
therapy programme specifically includes pelvic floor training, bladder training, keeping a micturition 
diary and informative sections on knowledge transfer and education. Previous treatments can be 
continued in the control arm, i.e. control group patients continue to have access to the reality of 
care. During the study period, all newly initiated incontinence treatment therapies (e.g. medication, 
interventional or

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surgical measures) and categorised as treatment failure. The aim of the study is, among other things, 
to prove the improvement of disease symptoms, quality of life and patient autonomy.

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5
Study endpoints and supply effects
The aim of this study is to test a multimodal digital therapy via app for women with stress 
incontinence, urge incontinence and mixed urinary incontinence. The assessment of the positive 
effects of the treatment is based self-reported documentation by the study patients and validated 
questionnaires (see appendix).
5.1
Incontinence episodes frequency (IEF)
To increase the accuracy of the results, the incontinence episodes are recorded over a period of 72 
hours and an average is calculated over 24 hours [12]. This average value per 24 hours is used as the 
IEF for the assessment of the primary endpoint. The aim is a relative reduction in incontinence 
episodes (rel-CfB-IEF) of 50% in the app group compared to the control group.
5.2
Questionnaires
The standardised assessment of urinary incontinence is carried out using questionnaires validated 
German (see
Table 2). All of the incontinence-specific questionnaires listed below that were selected to record 
the secondary endpoints of this study are considered Category A questionnaires according to the 
guidelines and therefore fulfil the criteria for validity, reliability and the recording of changes [2] .
Table 2: Questionnaires
Questionnaire
Purpose
ICIQ-SF
Incontinence symptoms
I-QOL
Quality of life
PAM-13
Self-management skills
PGI-I
Overall improvement
S/U-IQ
Distinction
between
stress
and
Urge incontinence
5.2.1
ICIQ-SF questionnaire
The International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) is a 
standardised questionnaire  to assess urinary incontinence in urology. It was developed to assess the 
frequency and severity of urinary incontinence and its impact on the quality of life of those affected. 
The ICIQ-SF comprises four questions, three of which are used to calculate a score with a maximum 
score of 21 points. The fourth question is asked to determine the urinary leakage situation. Clinically 
relevant urinary incontinence is defined as four points or more. The German S2 guidelines for urinary 
incontinence recommend the use of the ICIQ-SF questionnaire to assess the severity of urinary 
incontinence and to measure changes during the course of interventions. In the study described 
here, this questionnaire is at the beginning (baseline) and after 12 weeks. This endpoint is

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is achieved if the change in the ICIQ-SF from baseline to week 12 is > 2.9 points [8, 9].
5.2.2
I-QOL questionnaire
The Incontinence Quality-of-Life (I-QOL) is a validated questionnaire recommended by the German 
guidelines for urinary incontinence, which has been validated for both stress and urge incontinence 
and assesses the impact of urinary incontinence on quality of life. This questionnaire specialises in 
assessing the quality of life associated with incontinence problems. The I-QOL questionnaire takes 
into account emotional, social and physical aspects. Higher scores on the I-QOL indicate a better 
quality of life, while lower scores indicate greater impairment due to urinary incontinence. There are 
often specific sub-areas that represent individual aspects of quality of life and scoring can also be 
done separately for these areas. To assess the change in quality of life, this questionnaire is 
completed at baseline and after 12 weeks. The endpoint is reached when the change in I-QOL from 
baseline to week 12 is > 6.3 points [9].
5.2.3
PAM-13 Questionnaire
The Patient Activation Measure-13 (PAM-13) is a validated questionnaire designed to measure 
patients' level of activation in relation to their healthcare. The PAM-13 was developed to assess 
patients' self-competence and knowledge about their own healthcare. The questionnaire consists of 
13 questions that relate to different aspects of patient activation. The questions can cover topics 
such as understanding of health information, ability to self-organise and willingness to actively 
participate in their own healthcare. The questionnaire uses a Likert scale anchored between 1 and 4 
(1=disagree, 2=somewhat disagree, 3=somewhat agree, 4=strongly agree); the range is from 13 - 52 
score points; it is transformed to a scale of 0-100, with higher scores  a higher level of activation. 
Four activation levels are distinguished, reflecting low, basic, moderate and high activation. The 
PAM-13 enables the assessment of empowerment and the self-management skills of patients. This is 
completed at the beginning and after 12 weeks.
5.2.4
PGI-I questionnaire
The PGI-I questionnaire stands for "Patient Global Impression of Improvement". It is used to record 
patients' subjective assessment of the improvement in their state of health or symptoms. The 
questionnaire consists of a single question that asks patients to give their own assessment of the 
improvement in their state of health. Using the PGI-I questionnaire, patients can rate their health 
status from "much better" to "much worse". In research and clinical practice, the PGI-I questionnaire 
is used to take the patient perspective into account when evaluating the effectiveness of 
interventions. In the study described here, this questionnaire is completed at the end of the study 
[28].

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5.2.5
S/U-IQ questionnaire
The stress/urge incontinence questionnaire is a validated questionnaire that consists of two 
questions and makes it possible to differentiate between stress and urge incontinence. In the case of 
mixed incontinence, this questionnaire helps to determine the dominant incontinence component 
[29]. It is completed at the beginning and after 12 weeks.
5.2.6
Further questions about app use
In week 12, the intervention group receives the following additional questions, which the patient can 
answer voluntarily:
•
Please select the number that best describes the condition of your incontinence now 
compared to before the therapy: A scale of 1-7 (1 much better - 7 much worse) is provided 
here.
•
How often have you accessed Mictera? (Several times a week, weekly, with longer breaks 
than 1 week, with longer breaks of between 2-6 weeks, with longer breaks of over 6 weeks, I 
have not used Mictera)
•
If you took longer breaks or did not train with Mictera, what was the reason for this? (free 
text)
•
How  are you to recommend Kranus Mictera to others? Answer on a scale of 1-10 (1 Not at 
all - 10 Very much)
•
How satisfied are you with the app? Answer on a scale of 1-10 (1 Not at all - 10 Very much)
•
Do you have any comments or suggestions for us? The answer is given here in free text.
The control group is only asked one further question in week 12:
•
Do you have any comments for us? This question can be answered in a free text field.
Both groups are asked questions in week 1:
•
Please  your year of birth.
•
Please enter your current weight. (in kg)
•
How tall are you? (in cm)
5.3
Therapy failure
Treatment failure is defined as any reported worsening in the PGI-I questionnaire at the end of the 
study or the start of any interventions against the incontinence symptoms (conservative and invasive 
methods).

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6
Study design and description
6.1
Type of study, therapy allocation, scope of the study
This is a single-blind, two-arm, randomised study with an intervention and a control group. The study 
is being conducted at Mainz University Hospital and recruitment is taking place throughout 
Germany. A total of 198 patients will be included, 99 in the intervention group and 99 in the control 
group.
6.2
Patient recruitment
The study centre is a urological university clinic. Patients  recruited via the study centre as well as via 
urological, general practitioner or gynaecological outpatient clinics and practices throughout 
Germany and via direct contact with affected patients.
6.3
Timetable
Recruitment phase: 01.04.2024 to 31.10.2024 Study start: 
with positive ethics vote (FPI) Treatment duration: 12 weeks.
End of studies: 15 February 2025 (LPO)
Final report: by 15 April 2025
6.4
Study centre
The responsible study centre is the Urological University Clinic Mainz. The centre receives training on 
the study and the corresponding information and training documents. The training is documented in 
writing. The centre receives the complete study documents.
6.5
Study programme
The study will be recruited via the Kranus Health GmbH network of gynaecologists, general 
practitioners and urologists, by directly approaching patients, a study landing page and, if necessary, 
online advertising. Figure 1 outlines the study process.

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Figure 1: Study flow chart
The end of the programme is planned for 12 weeks after LPI.
6.6
Patient insurance
During the study, all study participants are insured in accordance with the applicable law. According 
to the General Terms and Conditions of Insurance, the insurance cover extends to all damage to 
health that occurs as a result of the study during and after participation. Only financial disadvantage 
is covered; no compensation for pain and suffering is paid.
6.7
Screening, information and consent
The initial screening of patients takes place via the study portal and urological, gynaecological and 
general medical practices. If patients are interested in participating in the study, they register in the 
study tool (Dacima from Evident IQ, information on data security and compliance of the server 
structure is provided in accordance with ISO27001 and specified in the other documents attached to 
the submission) and are assigned a patient ID. The study centre in Mainz will check the inclusion and 
exclusion criteria and, if necessary, subsequently inform the patients. The study participant will be 
informed about the nature, significance, objectives, possible risks, expected benefits, scope and 
other aspects of the study.
After the information session, each patient is given sufficient time and opportunity to clarify any 
unanswered questions and decide whether to participate.
Each eligible patient signs and dates her consent to participate in the study, voluntarily, in person on 
the consent form online or by hand. The patient's consent also expressly refers to the collection and 
processing of personal data.

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data. Patients are therefore explicitly informed about the purpose and scope of the collection and 
use of this data, in particular health data.
One copy of the signed consent form (copy or 2nd original) remains with the patient or is sent by 
email, the other in electronic form on the study server, to which only the study centre has access.
The patient can withdraw consent at any time and without giving reasons and discontinue treatment 
or end the study. In such cases, the patient is asked to state the reason for withdrawal (for 
treatment or participation), but is advised that she does not have to do so. The time of withdrawal of 
the declaration of consent for the study must be documented.
The patient information and consent form is a separate document to this study protocol.
Patients for whom it becomes apparent during the informed consent discussion with the study 
centre that they do not meet an inclusion criterion, meet an exclusion criterion or for whom it 
becomes apparent after signing the informed consent form that they do not meet the eligibility 
criteria for participation in the study are assessed and documented as screening failures.
6.8
Pre-screening, medical history, inclusion procedure
In the first step, the prospective patient registers via the study portal and fills out a few questions to 
initially check potential eligibility based on the inclusion and exclusion criteria. If the result of the 
check is positive, the patient registers in Evident IQ's Dacima study tool, receives a patient ID, fills 
out a medical history form and provides proof of diagnosis. If the criteria are met, an appointment is 
made with the study centre, which checks the inclusion and exclusion criteria again. The patient is 
then informed about the study and can ask questions about the study and its procedure. Once the 
consent form has  signed voluntarily and independently, the patient is included in the study.
Essential basic information (study centre, date of consent, year of birth, age, gender, 
inclusion/exclusion criteria, etc.) is stored in the eCRF. All patients record their incontinence 
episodes over a period of three days (3 x 24 h). The baseline data collection then takes place in the 
study tool, followed by randomisation to the respective study arm in the study tool. For 
documentation purposes, a form on the randomisation result (block randomisation 1:1) is generated 
via the study tool. Furthermore, the intervention patients fill out a micturition diary in the app to 
record micturition frequency, drinking volume and other symptoms.
6.9
Treatment phase
During the treatment phase, the patient is required to log into the Mictera app regularly and carry 
out the activities described for the day in question. Compliance with the set therapy goals is 
monitored via the Mictera app in pseudonymised form and reminders are communicated to the 
patient if necessary. The activity of app use is automatically documented.
The therapy is based on the principle of digital content, which includes personalised multimodal 
therapy with a focus on        pelvic floor training,    physiotherapy,    mental    training 
and

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behavioural therapy with methods of urinary urgency control and relaxation techniques. Another key 
component is the micturition diary, which patients can use to document their micturition behaviour. 
The approach includes several therapy programme elements whose effectiveness in the treatment 
of incontinence has been proven in the literature.
6.9.1
Micturition diary
Patients can document the amount they drink, meals, amount and frequency of micturition and 
symptoms. An algorithm helps with patient-individualised information. The visually simplified 
presentation helps patients to recognise correlations and motivate them.
6.9.2
Pelvic floor and physiotherapy exercises
The daily training consists of exercises focussing on the ability to repeatedly contract the pelvic floor 
muscles relevant for the function of the sphincter and the bladder reflex. The exercises are taught 
with the help of text, video instructions and interactive software elements. Special physiotherapy 
exercises for training the pelvic floor are suggested once a week. They are aimed at improving and 
supporting the pelvic floor. Here too, the exercises are taught with the help of text and detailed 
video instructions.
6.9.3
Bladder training / cognitive behavioural therapy
Behavioural therapy exercises are used to increase functional bladder capacity, reduce micturition 
frequency and urge problems. The patient therefore receives new content and goals in the app every 
week.
6.9.4
Mental exercises
•
Mindfulness: Every week, patients receive new content on mindfulness-based approaches 
based on cognitive behavioural therapy strategies.
•
Progressive muscle relaxation (PMR): The deliberate and conscious tensing and relaxing of 
certain muscle groups leads patients into a state of deep relaxation.
•
Stimulus control methods: Unwanted thoughts such as the acute urge to urinate are acutely 
suppressed.
•
All methods help patients to manage their symptoms and break through urge or urge 
conditioning. The content is provided in the form of audio sequences.
6.9.5
Acute urge control
In the event of a strong urge to urinate, the patient is given access to short versions of the structured 
exercises for mindfulness, PMR and thought control. They can also access a short pelvic floor training 
exercise or select a game to provide a situational distraction from the issue and gain control over the 
micturition reflex.

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6.9.6
Knowledge section /Nutrition section
Users receive daily educational content on the causes and underlying principles of incontinence. 
Another focus is on nutrition-specific correlations. General therapeutic measures are explained as 
well as psychological, habitual and organic correlations.
6.9.7
Further functions:
Participants have the opportunity to monitor the course of their symptoms and the progress of their 
therapy and are motivated by receiving progress awards.
6.10 Visits and analyses
During the 12-week treatment phase, no routine visits to the study centre are planned. However, if 
necessary, the patient can contact her gynaecologist, urologist, etc., the study centre or the study 
hotline at any time.
The study-specific surveys are listed in the ward round schedule (see Table 1: ward round schedule 
for the DINKS study).
6.11 End of study participation
The regular end of study participation for each study participant is after 12 weeks and completion of 
the questionnaire in week 12. Participation in the study is voluntary. Each participant has the right to 
withdraw from the study at any time at her own request, prematurely and without giving reasons 
(consent can also be withdrawn in this case) or to decide to discontinue treatment (no further 
treatment) without any disadvantages for her further (medical) treatment. In a follow-up period of 
12 months after the primary survey period, the patient has the opportunity to take part in further 
surveys. Patients in both groups (arm A and B) are given the opportunity to continue using the app. 
During this time, the patient can contact her study centre, her treating gynaecologist, urologist or 
the study hotline at any time.
If a patient withdraws her consent and leaves the study, this constitutes a withdrawal from 
participation (WoC). If it is possible and the patient is willing to provide information, the study centre 
will attempt to  out the reason for the premature termination of the study. The participant is asked 
to state the reason for discontinuation, but is advised that she does not have to do so. It will be 
documented when and, if applicable, why she withdrew her consent.
6.12 End of the study
The planned end of the study is immediately after LPO.

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7
Adverse events
7.1
Complications and risks
Muscle and joint complaints due to the physical strain are possible side effects of the therapy 
programme. Serious injuries should not occur due to the exclusion criteria.
7.2
Recording and documentation of adverse events
7.3
Adverse event
An "adverse event", hereinafter referred to as "AE", is an adverse medical event, inappropriate 
patient management decision, illness or injury, or adverse clinical symptoms, including abnormal 
laboratory findings, in study participants in the clinical trial, even if not related to the product tested 
in the clinical trial.
7.4
Serious Adverse Event
The SAE according to ICH-GCP (serious adverse event) or "serious adverse event" refers to 
an adverse event that had one of the following consequences:
1.
a patient management decision that has resulted in death or an immediate life-
threatening situation for the subject or the death of the subject's offspring;
2.
Death;
3.
serious deterioration in the subject's state of health, which in turn had one of the
following consequences:
a.
life-threatening illness or injury;
b.
Permanent physical injury or permanent impairment of a bodily function;
c.
inpatient treatment or extension of the 's inpatient treatment;
d.
Medical or surgical intervention to prevent a life-threatening illness or injury or
permanent physical damage or permanent impairment of a bodily function;
e.
chronic disease;
f.
foetal endangerment, death of the foetus or congenital physical or mental
impairment or birth defects.
7.5
Product defect or device-related adverse events
The "product defect" means an inadequacy in the identification, quality, durability, reliability, safety 
or performance of the product, including malfunctions, application errors or inadequacy of 
information provided by the manufacturer and will also be reported, documented and evaluated to 
the sponsor.
Adverse events are documented in the eCRF by the study centre after consultation with the patient. 
In addition, patients are contacted by telephone once after six weeks to ask about potential SAEs 
and AEs.

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All AEs and SAEs are documented in the eCRF in accordance with ISO14155. SAEs must be 
documented and transmitted to the sponsor within 24 hours of becoming known via the eCRF 
system (via eCRF and automatic e-mail from the eCRF to study-safety@kranus.de). The sponsor is 
then obliged to assess and report the SAE in accordance with its reporting obligations.
When using the Mictera therapy programme, the risk of undesirable side effects is generally very 
low. A comprehensive literature search was carried out for the authorisation as a medical device and 
for the study protocol. No relevant risks were described when carrying out the corresponding 
exercises.
7.6
Definition of the risk threshold
7.6.1
Risk threshold for patients
Patients should not have SAEs due to the use of Kranus Mictera or need to see a doctor due to this 
digital therapy.
For the study, a contact is made after 6 weeks within the 12-week therapy with Kranus Mictera as 
part of the monitoring of SAEs of study participants. If the patient reports an SAE during the course 
of the study, or if the patient has to see a doctor as a consequence of using Kranus Mictera, this is 
documented in the eCRF (including an automatic e-mail to study-safety@kranus.de) and the sponsor 
assesses whether there is a connection with the use of Kranus Mictera. If there is a connection with 
the digital therapy,  will be evaluated whether further participation in the study is justifiable for the 
patient.
7.6.2
Risk threshold for the study
The study should not cause more than five identical or similar SAEs due to the use of Kranus Mictera.
The sponsor is informed of (S)AEs via eCRF andstudy-safety@kranus.de and monitors and assesses 
the SAEs that occur. If more than five SAEs occur, which firstly are directly related to the product and 
secondly have the same or a similar cause after assessment, it is assumed that the risk threshold for 
the study  exceeded and the study is discontinued.
If necessary, the product "Kranus Mictera" can be withdrawn from the market immediately. In the 
event of serious risks, the sponsor shall also immediately inform the competent authorities and, 
where appropriate, the notified body that issued the certificate of conformity, providing in particular 
details of the non-conformity and of any corrective action already taken.
7.6.3
Onset of pregnancy
The occurrence of pregnancy is considered an adverse event (AE) in this clinical trial for safety 
reasons. If a pregnancy is reported, the patient will be excluded from the study as soon as it 
becomes known and access to the Kranus Mictera app will be withdrawn.

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8
Statistics
8.1
Endpoints
The time point of interest for the target evaluation is after 12 weeks, i.e. the end of  study for 
intervention arm A and the delayed start of the intervention in control arm B.
8.2
Primary endpoint
1)
Relative change (rel-CfB-IEF) of the IEF from baseline to week 12 in relation to baseline
8.3
Secondary endpoints
2)
Change in ICIQ-SF from baseline to week 12
3)
Change in I-QOL from baseline to week 12
4)
Change in the PAM-13 questionnaire from baseline to week 12
5)
PGI-I questionnaire (overall improvement after treatment) at the end of the study
6)
Proportion of patients without incontinence (cured patients) at the end of the study
7)
Reduction in micturition frequency during the day
8)
Reduction in micturition frequency at night
9)
Reduction in pad consumption
10) Reduction of the imperative urge to urinate
11) Change in functional bladder capacity
12) Reduction in body weight
13) Reduction in the proportion of patients with treatment failure within the study period
14) Proportion of patients with at least 50% reduction in IEF from baseline to week 12
15) Reduction in the frequency of stress incontinence episodes in the S/U-IQ
16) Reduction in the frequency of urge incontinence episodes in the S/U-IQ
8.4
Planning the scope of the study (case number planning)
Randomised: Arm A to Arm B in a 1:1 ratio
Planning the scope of the study for comparisons between the groups:
•
IEF: Relative reduction in incontinence episodes (rel-CfB-IEF) with desired improvement
of 50%, Minimum Important Difference (MID) approx. 50% from Yalcin 2010; at d/s = 0.7
with significance level α = 5% 2-sided and power 1 - β = 90%: N = 2 x 44 = 88, + 20% due
to drop outs and their conservative imputation as well as subgroup analyses: N = 120.
•
ICIQ-SF: CfB with desired improvement by d = 2.9 vs. control (MID = 2.5 from Nyström
2014 and Asklund 2017) by d/s = 2.9/3.2 = 0.9 with α = 5% 2-sided and power 1
- β= 90%: N= 2 x 28.
•
I-QOL: CfB with desired improvement by 6.3 vs. control (MID= 6.3 from Yalcin 2006) by
d/s = 6.3/ 14 = 0.45 (with α = 5% 2-sided and power = 80%: N = 2 x 90.

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•
PAM-13: CfB with desired improvement by 6 points vs. control (MCID= 6, i.e. approx.
15% of the PAM rank from 13 - 52 and from John, 2020) by d/s = 6/12 = 0.5 (with α = 5%
2-sided and power = 80%: N = 2 x 64.
Due to drop-outs and their conservative imputation, the total number of cases is set at 2 x 99 study 
participants for the evaluation of the primary endpoints.
8.5
Discussion of the end points
Primary and secondary endpoints for urinary incontinence are not uniformly defined in the literature 
and are used heterogeneously in the various studies [30, 4, 31].
In principle, a distinction can be made between so-called subjective (based on questionnaires) and 
objective (number of incontinence episodes, pad tests) [32].
Both types of endpoints are used in studies as the primary "outcome variable" and
accepted.
8.6
Primary endpoint
There is no standardised method for measuring incontinence episodes. In a study very similar to ours 
(app-based pelvic floor muscle training for stress incontinence), the incontinence episodes were 
measured in the micturition diary on 2 days and then multiplied by 3.5 to obtain a weekly average 
[8]. In a similar, internet-based pelvic floor training study, Sjöström et al. used an analogue 
measurement system [33]. In a study with different conservative measures (including pelvic floor 
muscle training), Bo et al.  the incontinence episodes over 3 days [34]. Castro et al [35] measured 
incontinence episodes over 7 days in a similar study.
In the present study, incontinence episodes were measured over 3 days (baseline and end-of-study), 
the mean value per day was calculated and this was used as the primary endpoint.
There is a lack of data in the literature on the minimum clinically relevant difference (MID) in 
connection with specific measures such as medication or pelvic floor muscle training. In general, a 
reduction of 50% is described as clinically relevant for conservative measures for incontinence [6, 
31]. Based on the literature, we define a reduction in incontinence episodes as the quantitative 
primary endpoint.
Statistically analysed is primarily the relative change (rel-CfB-IEF= CfB/B) of the IEF from baseline to 
week 12 in relation to baseline; desired reduction of the mean relative IEF by 50% versus control; IEF 
frequency= mean value of IEs over 24 hours calculated from IEs over 72 hours.
8.7
Secondary endpoints
The ICIQ-SF is used as a validated questionnaire [36] to assess the severity and impact of 
incontinence by the patient in several studies [30] [37].
An improvement of 2.5 score points is specified as the MID in Nystrom et al [38]. In the study by 
Sjöström [33] an improvement of 20% is aimed for, in the study by Asklund [8] an improvement of 
2.9 points (based on the results of the Sjöström study) is described as the target (3.2 points were 
achieved in the study). Based on the various data in the

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literature, we are aiming for an improvement of 2.9 points in the ICIQ-SF in this study (see Table 3:
ICIQ-SF).
Table 3: ICIQ-SF
Tool/ 
Parameter
Questionnai
re
Possible answers
Result range
Targeted 
improvement
ICIQ-SF
3
1. Question: 0-5
2. Question: 0,2,4,6
3. Question: 0-10
0-21
> 2.9 points
As further secondary endpoints, the disease-related quality of life is measured using the validated I-
QOL and the patients' level of activation in relation to their healthcare using the PAM-13 
questionnaire, which has also been validated. The change in specific incontinence episodes, 
measured using the S/U-IQ questionnaire, is also recorded. Other endpoints include changes in 
micturition frequency during the day and night, reduction in pad use, decrease in imperative urge to 
urinate and an increase in functional bladder capacity as well as surveys on body weight changes, 
treatment failure and overall improvement (PGI questionnaire) and app use in the intervention 
group.
8.8
Statistical analysis
In general, continuous data is summarised using descriptive statistics, i.e. with the number of 
observations, mean, standard deviation, minimum, median and maximum. For some variables such 
as the primary endpoints, the change from baseline to the end of the study (change from baseline, 
CfB) is also output and summarised as "post-baseline". Where appropriate, 95% confidence intervals 
are also calculated and reported.
Categorical data is summarised using absolute and relative frequency.
The hypotheses for analysing the mean group differences in the primary endpoint are:
H0: rel-CfB arm A = rel-CfB arm B 
versus
H1: rel-CfB Arm A≠ rel-CfB Arm B
This is analysed using an analysis of covariance with the factor treatment group and the covariate 
baseline. As a sensitivity analysis, the relevant changes are analysed using 2-sample Wilcoxon tests.
The continuous target variables are analysed analogously with the CfBs. The results of these analyses 
are presented graphically using progression curves (mean values and LS mean changes) of the 
original mean values and the CfBs. Ordinal endpoints (e.g. PGI) are compared between the groups 
using 2-sample Wilcoxon tests.
Binary endpoints (rates) are compared using Fisher tests; in addition, 95% CIs are provided for 
comparison between groups.

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Multiplicity: The primary endpoint (1) and the first 3 secondary endpoints (2) - (4) are tested 
sequentially according to the method of a priori ordered hypotheses: The primary endpoint (1) 
relative change rel-CfB-IEF week 12 with respect to baseline of incontinence episodes is analysed 
using an analysis of covariance with the factor treatment group and the baseline value of the IEF as 
covariate; the significance level is 5% 2-sided. If significance is reached for endpoint (1), endpoint 2 
(change in the ICIQ-SF questionnaire) is tested analogue to the 5% 2-sided level. If significance is 
reached for endpoint (2), endpoint (3) (change in quality of life in the I-QOL questionnaire) is tested 
2-sided analogue to the 5% level. If significance is reached for endpoint 3, endpoint 4 (PAM-13) is 
tested 2-sided analogue to the 5% level. The other endpoints are analysed descriptively with p-
values and 95% CIs. The FAS (ITT) is the primary evaluation collective for efficacy; missing values for 
the main outcome variables (1) - (4) are imputed using the JtR method.
Subgroup analyses:
Descriptive subgroup analyses are performed for the primary and secondary efficacy variables using 
the ICD code:
•
N39.3 Stress incontinence [stress incontinence]
•
N39.42 Urge incontinence
•
Mixed incontinence - both codes
and using the S/U-IQ (Stress/Urge Incontinence Questionnaire and Classification System) for the 
indications:
•
pure stress urinary incontinence (SUI≥ 4, UUI=0),
•
Mixed urinary incontinence, predominantly stress component (SUI >0, SUI > UUI; UUI>  0),
•
balanced mixed urinary incontinence (SUI> 0, SUI=UUI),
•
Mixed urinary incontinence, predominantly urge component (SUI> 0, UUI> 0, UUI> SUI)
•
Pure urge incontinence (UUI≥ 4, SUI =0)
carried out.
Further subgroup analyses are carried out:
•
Medication for the treatment of incontinence (yes/no),
•
Premenopausal/menopausal/postmenopausal status,
•
Age categories< 45, 45-60,> 60 years,
•
BMI,
•
Country of birth,
•
Level of education,
•
Secondary diseases,
•
Smoking behaviour,
•
Alcohol consumption,
•
Number of births,

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•
Type of delivery,
•
Time since last delivery
•
Duration of illness,
•
Pre-existing pelvic floor course,
•
Non-bladder-specific medication,
•
Frequency of use of the app.
The I-QOL and ICIQ are also analysed individually.
The results of the subgroup analyses are also graphically presented and summarised using forest plots.
Evaluation collectives:
•
Full Analysis Set (FAS) contains all patients who were randomised. Patients who withdrew 
their consent immediately after randomisation are not included in this data set.
•
Per-Protocol Set (PPS) contains all FAS patients from whom no significant study protocol 
violations were reported.
•
Complete cases (CCS): Patients with complete data per evaluation.
•
Safety Set (SAF) contains all patients who are included in the study (signed informed consent 
form). It is expected that SAF and FAS are identical.
Sensitivity analyses are carried out:
1.
CCS analysis
2.
FAS analysis with last-observation-carried-forward-option (LOCF).
8.9
Presentation of the results
The results are presented in close accordance with the guideline "Structure and Content of Clinical 
Study
Reports E3" (ICH-E3) are presented in tabular form (Section 8.10) and as listings (Section 8.11).
8.10 Tables
•
Demographic data and other baseline characteristics
•
Primary endpoint
•
Secondary endpoints
8.11 Listings
•
List of dropouts who have withdrawn their declaration of consent (WoC)
•
Curriculum deviations - (NtF)

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•
Patients for whom deviations from the study plan lead to exclusion from the PPS (drop-outs)
•
Demographic data (height, age, weight, etc.)
•
Other baseline characteristics
•
Individual data and results for primary and secondary endpoints
•
Adverse events (AE/SAE and events)
8.12 Data collection/documentation forms
In order to achieve the study objective, it is necessary to collect and process medical data from 
individual patients. Data is collected using electronic questionnaires, which are completed by the 
patients at the beginning (baseline) and at the end of the study (PROM).
The data to be analysed from the patients is collected in the app on the one hand and via an ePRO 
system on the other, and the latter is stored in an eCRF. The questionnaires, which are to be 
completed independently at the beginning (baseline/V1) and at the end of the study (V3), are 
collected via an ePRO system and stored in the EvidentIQ software. Further technical parameters are 
listed in the separate document "Confirmation of validation of EvidentIQ Germany's Marvin software 
and secure data hosting".
A detailed statistical analysis plan (SAP) is created before the evaluation.

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9
Data management
9.1
Patient identification
All patient-related data is collected by Kranus Health GmbH in pseudonymised form. For this 
purpose, a non-verbal pseudonym is used, from which alone the identity of the patient cannot be 
deduced. The patient identification number is assigned centrally as part of the internet-based 
registration process.
After registration of the patient and scheduling of the informed consent discussion, the trial centre 
receives an e-mail with the patient identification number and the information that a new 
registration and scheduling has been received. This e-mail, together with the information provided 
by the patient during registration, is used by the trial centre to carry out the patient information on 
behalf of the sponsor and to have the patient information provided by Kranus signed to obtain 
consent for participation in the trial. Once consent has been obtained, it will be  together with the 
patient identification list for the sponsor for 10 years in accordance with the requirements of the 
MDR.
9.2
Data acquisition
Electronic data recording is carried out via EvidentIQ's eCRF on a proprietary server. Information on 
data security and compliance of the server structure is specified in the appendix.
9.3
Data protection
As part of the study,  is necessary to collect and process personal data from the study participants 
(e.g. full name, initials of first name and surname, date of birth, address) and data on treatment and 
the course of the disease (e.g. medical findings, types of treatment, prescribed medication). This 
data is generated by the patients themselves and stored electronically on the study server in 
pseudonymised form (i.e. without direct reference to the patient's name) with the help of a patient 
identification number, transmitted to the responsible data processing body and evaluated.
The trial participants will be informed about the disclosure of their pseudonymised data to the 
recipients named therein as part of the documentation and notification obligations. Persons who do 
not consent to the disclosure will not be included in the clinical trial.
If patients withdraw their consent to the study, including further data collection, no further data will 
be collected from the time of withdrawal. The data collected to date will continue to be used and 
analysed within the study, but can be deleted at the patient's request during the study period. If a 
patient only cancels the study treatment, the data required for the study can continue to be 
collected and used as long as the patient has not withdrawn their consent.
9.4
Quality assurance
Only PROMs are collected in the study; monitoring is not planned.

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9.5
Archiving
All documentation forms, consent forms and other important trial documents are stored for at least 
10 years in accordance with Section 13 (10) GCP-V. The patient identification list is kept separately 
from the documentation records in all centres.

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10 Ethical issues, legal and administrative regulations
10.1 Declaration of Helsinki and Good Clinical Practice
The study is conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki [39]. The current version of the Declaration will be observed.
The recommendations of Good Clinical Practice [39], valid since 17 January 1997, are taken into 
account where applicable.
10.2 Independent ethics committees
The study protocol is submitted with the necessary additional documents to the responsible ethics 
committee of the scientific director with a request for evaluation. The study can only begin after the 
ethics committee has given its approval.
10.3 Legal regulations
The Kranus Mictera app is an approved Class I medical device.
10.4 Registration
The study should be entered in the following public register: German Clinical Trials Register (DKRS, 
https://www.drks.de).
10.5 Financing
The study is financed by Kranus Health GmbH.
10.6 Final report and publication
The final report will be completed by 15 April 2025. Publication will be primarily in a peer-reviewed 
journal. The order of authors will be determined by the scientific director in collaboration with the 
sponsor. The results of the study will be published regardless of the outcome.

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11 Bibliography
1.
Beutel, M.E., et al, [Prevalence of urinary incontinence in the German population]. Urologist 
A, 2005. 44(3): p. 232-8.
2.
DGGG, O., SGGG Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG 
(S2k- Level, AMWF Registry No. 015-91, December 2021. 2021.
3.
Burkhard, F.C., et al, EAU guidelines on Urinary Incontinence in Adults. 2020, EAU Guideline 
Office: Arnhem.
4.
Todhunter-Brown, A., et al, Conservative interventions for treating urinary incontinence in 
women: an Overview of Cochrane systematic reviews. Cochrane Database Syst Rev, 2022. 
9(9):
p. CD012337.
5.
Dumoulin, C., et al, Pelvic-Floor-Muscle Training Adherence: Tools, Measurements and 
Strategies-2011 ICS State-of-the-Science Seminar Research Paper II of IV. Neurourol Urodyn, 
2015. 34(7): p. 615-21.
6.
Yalcin, I., et al, Reductions in stress urinary incontinence episodes: what is clinically important 
for women? Neurourol Urodyn, 2010. 29(3): p. 344-7.
7.
Shamliyan, T., J. Wyman, and R.L. Kane, AHRQ Comparative Effectiveness Reviews, in 
Nonsurgical Treatments for Urinary Incontinence in Adult Women: Diagnosis and 
Comparative Effectiveness. 2012, Agency for Healthcare Research and Quality (US): Rockville 
(MD).
8.
Asklund, I., et al, Mobile app for treatment of stress urinary incontinence: A randomised 
controlled trial. Neurourol Urodyn, 2017. 36(5): p. 1369-1376.
9.
Yalcin, I., et al, Minimal clinically important differences in incontinence quality-of-life scores 
in stress urinary incontinence. Urology, 2006. 67(6): p. 1304-8.
10.
Minassian, V.A., H.P. Drutz, and A. Al-Badr, Urinary incontinence as a worldwide problem. Int 
J Gynaecol Obstet, 2003. 82(3): p. 327-38.
11.
Valdevenito, J.P., et al, Voiding symptoms obtained by open versus directed anamnesis as 
predictors of voiding dysfunction in women. Int Braz J Urol, 2019. 45(4): p. 798-806.
12.
Elmer, C., et al, Twenty-Four-Hour Voiding Diaries Versus 3-Day Voiding Diaries: A Clinical 
Comparison. Female Pelvic Med Reconstr Surg, 2017. 23(6): p. 429-432.
13.
Painter, V., E. Karantanis, and K.H. Moore, Does patient activity level affect 24-hr pad test 
results in stress-incontinent women? Neurourol Urodyn, 2012. 31(1): p. 143-7.
14.
Tseng, L.H., et al, Postvoid residual urine in women with stress incontinence. Neurourol 
Urodyn, 2008. 27(1): p. 48-51.
15.
Cacciari, L.P., C. Dumoulin, and E.J. Hay-Smith, Pelvic floor muscle training versus no 
treatment, or inactive control treatments, for urinary incontinence in women: a cochrane 
systematic review abridged republication. Braz J Phys Ther, 2019. 23(2): p. 93-107.
16.
Hunskaar, S., A systematic review of overweight and obesity as risk factors and targets for 
clinical intervention for urinary incontinence in women. Neurourol Urodyn, 2008. 27(8): p. 
749- 57.
17.
Radzimińska, A., et al, The impact of pelvic floor muscle training on the quality of life of 
women with urinary incontinence: a systematic literature review. Clin Interv Aging, 2018. 13: 
p. 957- 965.
18.
Paiva, L.L., et al, Pelvic floor muscle training in groups versus individual or home treatment of 
women with urinary incontinence: systematic review and meta-analysis. Int Urogynecol J, 
2017. 28(3): p. 351-359.
19.
Hay-Smith, E.J., et al, Comparisons of approaches to pelvic floor muscle training for urinary 
incontinence in women. Cochrane Database Syst Rev, 2011(12): p. Cd009508.
20.
Berghmans, B., et al, Efficacy of physical therapeutic modalities in women with proven 
bladder overactivity. Eur Urol, 2002. 41(6): p. 581-7.

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21.
Boyle, R., et al, Pelvic floor muscle training for prevention and treatment of urinary and 
faecal incontinence in antenatal and postnatal women. Cochrane Database Syst Rev, 2012. 
10: p. CD007471.
22.
Kim, H., et al, Effectiveness of multidimensional exercises for the treatment of stress urinary 
incontinence in elderly community-dwelling Japanese women: a randomised, controlled, 
crossover trial. J Am Geriatr Soc, 2007. 55(12): p. 1932-9.
23.
McFall, S.L., A.M. Yerkes, and L.D. Cowan, Outcomes of a small group educational 
intervention for urinary incontinence: health-related quality of life. J Aging Health, 2000. 
12(3): p. 301-17.
24.
Cipullo, L.M., et al, Pharmacological approach to overactive bladder and urge urinary 
incontinence in women: an overview. Eur J Obstet Gynecol Reprod Biol, 2014. 174: p. 27-34.
25.
Chapple, C.R., et al, Mirabegron in overactive bladder: a review of efficacy, safety, and 
tolerability. Neurourol Urodyn, 2014. 33(1): p. 17-30.
26.
Loohuis, A.M.M., et al, App-Based Treatment in Primary Care for Urinary Incontinence: A 
Pragmatic, Randomised Controlled Trial. Ann Fam Med, 2021. 19(2): p. 102-109.
27.
Hou, Y., et al, Effect of pelvic floor muscle training using mobile health applications for stress 
urinary incontinence in women: a systematic review. BMC Womens Health, 2022. 22(1): p. 
400.
28.
Bjelic-Radisic, V., et al, Psychometric properties and validation of two global impression 
questionnaires (PGI-S, PGI-I) for stress incontinence in a German-speaking female population. 
Neurourol Urodyn, 2018. 37(4): p. 1365-1371.
29.
Bent, A.E., et al, Validation of a two-item quantitative questionnaire for the triage of women 
with urinary incontinence. Obstet Gynecol, 2005. 106(4): p. 767-73.
30.
Dumoulin, C., L.P. Cacciari, and E.J.C. Hay-Smith, Pelvic floor muscle training versus no 
treatment, or inactive control treatments, for urinary incontinence in women. Cochrane 
Database Syst Rev, 2018. 10(10): p. Cd005654.
31.
Shamliyan T, W.J., Kane RL, Nonsurgical Treatments for Urinary Incontinence in Adult 
Women: Diagnosis and Comparative Effectiveness [Internet]. in Comparative Effectiveness 
Reviews. 2012, Agency for Healthcare Research and Quality (US): Rockville (MD.
32.
Lim, R., et al, Which outcome measures should be used in stress urinary incontinence trials?
BJU Int, 2018. 121(5): p. 805-810.
33.
Sjöström, M., et al, Internet-based treatment of stress urinary incontinence: a randomised 
controlled study with focus on pelvic floor muscle training. BJU Int, 2013. 112(3): p. 362-72.
34.
Bø, K., T. Talseth, and I. Holme, Single blind, randomised controlled trial of pelvic floor 
exercises, electrical stimulation, vaginal cones, and no treatment in management of genuine 
stress incontinence in women. Bmj, 1999. 318(7182): p. 487-93.
35.
Castro, R.A., et al, Single-blind, randomised, controlled trial of pelvic floor muscle training, 
electrical stimulation, vaginal cones, and no active treatment in the management of stress 
urinary incontinence. Clinics (Sao Paulo), 2008. 63(4): p. 465-72.
36.
Avery, K., et al, ICIQ: a brief and robust measure for evaluating the symptoms and impact of 
urinary incontinence. Neurourol Urodyn, 2004. 23(4): p. 322-30.
37.
Nyström, E., L. Söderström, and E. Samuelsson, Self-management of incontinence using a 
free mobile app: factors associated with improvement. Int Urogynecol J, 2022. 33(4): p. 877-
885.
38.
Nystrom, E., et al, ICIQ symptom and quality of life instruments measure clinically relevant 
improvements in women with stress urinary incontinence. Neurourol Urodyn, 2015. 34(8): p. 
747-51.
39.
Association, W.M., WMA Declaration of Helsinki - Ethical Principles for Medical Research 
Involving Human Subjects. 2013, World Medical Association: Fortaleza (Brazil).

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A. Appendix
A1.
Questionnaires used
A1.1
PGI-I: Patient Global Impressions Scale - Improvement
Please select the number that best reflects the condition of your incontinence now in the
compared to before the therapy:
Much better
1
Much better
2
A little better
3
unchanged
4
A little worse
5
Much worse
6
Much worse
7

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A1.2
I-QOL: Urinary Incontinence Quality of Life Scale
Questions
Possible answers
1 I'm afraid I won't be able to reach the toilet in 
time.
1 very
2 quite
3 moderate
4 a little
5 not at all
2 I am afraid to cough or sneeze because of my 
urinary problems or incontinence.
1 very
2 quite
3 moderate
4 a little
5 not at all
3. because of my urinary problems or 
incontinence, I have to be careful when I get up 
from a sitting position.
1 very
2 quite
3 moderate
4 a little
5 not at all
4 I am worried about where toilets are in 
unknown places.
1 very
2 quite
3 moderate
4 a little
5 not at all
5 I feel depressed because of my urinary 
problems or incontinence.
1 very
2 quite
3 moderate
4 a little
5 not at all
6. because of my urinary problems or 
incontinence, I don't like to leave the house for 
long periods of time.
1 very
2 quite
3 moderate
4 a little
5 not at all
7 I feel frustrated because my urinary problems 
or incontinence prevent me from doing what I 
want.
1 very
2 quite
3 moderate
4 a little
5 not at all
8. i am afraid that others will smell urine on me.
1 very
2 quite
3 moderate
4 a little
5 not at all
9 My urinary problems or incontinence are 
constantly on my mind.
1 very
2 quite
3 moderate
4 a little
5 not at all
10. it is important for me to be able to go to the 
toilet frequently.
1 very
2 quite
3 moderate

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4 a little
5 not at all
11. because of my urinary problems or 
incontinence, it is important to plan every little 
thing in advance.
1 very
2 quite
3 moderate
4 a little
5 not at all
12 I am afraid that my urinary problems or 
incontinence could get worse as I get older.
1 very
2 quite
3 moderate
4 a little
5 not at all
13 I have problems sleeping well at night 
because 
of 
my 
urinary 
problems 
or 
incontinence.
1 very
2 quite
3 moderate
4 a little
5 not at all
14 I am afraid of being put in an embarrassing 
or humiliating position because of my urinary 
problems or incontinence.
1 very
2 quite
3 moderate
4 a little
5 not at all
15 I don't feel like a healthy person because of 
my urinary problems or incontinence.
1 very
2 quite
3 moderate
4 a little
5 not at all
16 My urinary problems or incontinence make 
me feel helpless.
1 very
2 quite
3 moderate
4 a little
5 not at all
17 I enjoy life less because of my urinary 
problems or incontinence.
1 very
2 quite
3 moderate
4 a little
5 not at all
18 I'm afraid of wetting myself.
1 very
2 quite
3 moderate
4 a little
5 not at all
19 I have the feeling that I can't control my 
bladder.
1 very
2 quite
3 moderate
4 a little
5 not at all
20. because of my urinary problems or 
incontinence, I have to be careful about what or 
how much I
drink.
1 very
2 quite
3 moderate

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4 a little
5 not at all
21 Because of my urinary problems or 
incontinence, I am restricted in my choice of 
clothing.
1 very
2 quite
3 moderate
4 a little
5 not at all
22 I am afraid to have sex because of my urinary 
problems or incontinence.
1 very
2 quite
3 moderate
4 a little
5 not at all

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I-QOL: About yourself
A-1 How long have you suffered from bladder problems or 
incontinence? (Please enter the number of years and months 
below)
A-2 How often have you seen a doctor or undergone physiotherapy for your bladder problems or 
incontinence in the last year?
(Please enter the number in the space provided)
A-3 How would you describe the severity of your bladder problems or incontinence? (Please circle 
the number before your answer)
1 MILD 2 MODERATE 3 SEVERE
A-4 Do you leak urine when you cough, sneeze, run, walk, jump or during certain other activities?
0 NO 1 YES
A-5 Do you lose control of your bladder before reach the toilet? 0 NO 1 YES
A-6 Do you leak urine without it being related to any particular activity or without feeling the urge to 
go to the toilet?
0 NO 1 YES
A-8 How often have you involuntarily lost urine, even small amounts, in the last month?
0 NOT AT ALL IN THE LAST MONTH
1 1 TO 2 TIMES IN THE LAST MONTH
2 4 TIMES (ABOUT ONCE A WEEK)
3 2 TO 3 TIMES A WEEK
4 ABOUT ONCE A DAY
5 1 OR 2 TIMES A DAY
6 3 OR 4 TIMES A DAY
7 5 TIMES A DAY OR MORE

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A1.3
ICIQ-SF: International Consultation on Incontinence Questionnaire- 
Urinary Incontinence Short Form
Question
Possible answers
1.   How often lose
you
urine?
0 never
1 about once a week or less
2 Two or three times a week
3 about once a day
4 several times a day
5 constantly
2. we would like to know how much 
urine you think you lose. How 
much urine do you usually leak? 
(regardless of whether you wear  
pads      or   not)
0 no urine loss
2 a small amount of urine
4 a medium amount of urine
6 a large amount of urine
3. how much does urine loss generally 
affect your everyday life? Please 
tick a number between 0 (not at all) 
and 10
(a serious problem)
0 (not at all) 1 2 3 4 5 6 7 8 9 10 (serious problem)
4. when   lose   you   urine? 
(Please tick all boxes that apply)
❑Never - no urine loss
❑Urine leakage before reaching the toilet
❑Leakage of urine when coughing or sneezing
❑Urine leakage during sleep
❑Urine loss during physical activity / sporting 
activity
❑Leakage of urine after urination and re-
dressing
❑Urine leakage without recognisable cause
❑Constant loss of urine
Result: Sum score of questions 1+2+3= ICIQ-SF Score

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A1.4
PAM-13: Patient Activation Measure
Questions
Possible answers
1. at the end of the day, I am the one who is 
responsible for looking after my health.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
2. the most important thing for my health is to 
take an active role in my healthcare.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
3. i am convinced that i can do something 
myself to prevent illness.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
4 I know why I am taking each of my medicines.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
5 I am confident that I know when I need to see 
a doctor and when I can treat a health problem 
myself.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
6 I am confident that I can tell my GP about my 
concerns, even if he doesn't address them 
directly.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
7 I am convinced that I can carry out the 
necessary medical treatments at home.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
8 I know the causes of my complaints.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
9 I know different treatment options for my 
illnesses.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
10. i have been able to maintain lifestyle 
changes such as healthy eating and exercise.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
11 I know how I can prevent my health from 
deteriorating.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right
12 I am convinced that I will find solutions if my 
health deteriorates.
1 Not true
2 Hardly true
3 Rather true
4 Exactly right

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13 I am convinced that I can make changes
1 Not true
my lifestyle habits - such as diet and
2 Hardly true
Physical exercise - even in stressful situations
3 Rather true
times.
4 Exactly right

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A1.5
S/U-IQ: Stress/Urge Incontinence Questionnaire and Classification 
System
Question
Number of events per week
1 (SUI): In the last seven days, how many times 
have you accidentally touched your hands 
during an activity such as coughing, sneezing, 
laughing, running, exercising or lifting?
Lost urine?
2 (UUI): In the last seven days, how often have 
you felt the urge to urinate so suddenly that 
you could not reach the toilet in time?
and have lost urine?
SUI: Stress urinary incontinence episodes per week UUI: 
Urge urinary incontinence episodes per week
CLASSIFICATION SYSTEM FOR INCONTINENCE SYMPTOMS WITH S/U-IQ:
- SUI≥ 4; UUI= 0: pure stress urinary incontinence
- SUI> 0; SUI> UUI; UUI> 0: mixed urinary incontinence, predominantly stress component
- SUI> 0; SUI= UUI: balanced mixed urinary incontinence
- SUI> 0; UUI> 0; UUI> SUI: mixed urinary incontinence, predominant urge component
- UUI≥ 4; SUI= 0: pure urge urinary incontinence