Feasibility and Cost Description of Intensive Rehabilitation Involving New Technologies in Patients With Sub-acute Stroke:A Multicenter Single Arm Trial of the Swiss RehabTech Initiative
Phase: NA
Conditions: Stroke, Hemiplegia
Sponsor: Markus Wirz

New technologies in the rehabilitation of chronic stroke,   
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Clinical Study Protocol 
 
Feasibility and cost description  
of intensive rehabilitation involving new technologies in 
patients with sub-acute stroke:A multicenter single arm 
trial of the Swiss RehabTech Initiative 
 
Short title: New technologies in the rehabilitation of chronic stroke 
 
Study Type: 
Health-related intervention  
Study Categorization: 
Other Clinical Trial Category A 
Study Registration: 
U.S. National library of Medicine (https:// 
clinicaltrials.gov.) NCT03641651 
Study Identifier: 
2018-01214 
Sponsor-Investigator and 
Principal Investigator: 
Markus Wirz 
Zurich University of Applied Sciences (ZHAW) 
Institute of Physiotherapy 
Prof. Dr. Markus Wirz 
Technikumstr. 71 
CH 8401 Winterthur  
Phone: +41 (0)58 934 63 21 
Fax:  +41 58 935 63 21 
E-Mail: markus.wirz@zhaw.ch 
Study Intervention: 
Technology assisted intensive rehabilitation in 
subacute stroke  
Protocol Version and 
Date: 
Version 02,September the 12th 2018 
 
CONFIDENTIAL 
The information contained in this document is confidential and the property of the Swiss Rehabtech 
Initiative, represented by the Institute of Physiotherapy, Zurich University of Applied Sciences 
(ZHAW), Winterthur. The information may not - in full or in part - be transmitted, reproduced, 
published, or disclosed to others than the applicable Independent Ethics Committee(s) and 
Competent Authority(ies) without prior written authorization the Swiss Rehabtech Initiative, except 
to the extent necessary to obtain informed consent from those participants who will participate in 
the study.

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SIGNATURE PAGE(S) 
Study number 
2018-01214 
Study Title 
Feasibility and cost description of intensive rehabilitation 
involving new technologies in patients with sub-acute 
stroke: A multicenter single arm trial of the Swiss 
RehabTech Initiative 
 
Sponsor-Investigator, Principal Investigator and coordinating 
Investigator: 
 
This clinical trial protocol was subject to critical review and has been approved by the 
Sponsor-Investigator. The information herein is consistent with 
- the current risk/benefit evaluation of the intervention, 
- the moral, ethical and scientific principles governing clinical research as set out in the  
  current version of the Declaration of Helsinki, Good Clinical Practice.  
 
Prof. Dr. Markus Wirz 
Zurich University of applied sciences (ZHAW) 
Institute of Physiotherapy 
Technikumstr. 71 
CH 8401 Winterthur  
 
 
 
 
 
 
Winterthur, 03.10.2018 
 
 
 
Place/Date 
 
Signature 

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Local Principal Investigators at study sites: 
 
I have read and understood this protocol and agree to conduct the trial as set out in this 
study protocol. 
 
 
 
 
Site 
 
Rehakliniken Zihlschlacht 
Hauptstrasse 2-4 
8588 Zihlschlacht 
 
Principal investigator 
Carsten Möller 
 
 
 
 
Place/Date: Zihlschlacht, 05.10.2018 
 
 
 

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Local Principal Investigators at study sites: 
 
I have read and understood this protocol and agree to conduct the trial as set out in this 
study protocol. 
 
 
 
 
Site 
 
Reha Rheinfelden 
Salinenstrasse 98 
4310 Rheinfelden 
 
Principal investigator 
Frank Behrendt 
 
 
 
 
 
Rheinfelden, 05.10.2018  
 
 
Place/Date 
 
Signature 
 
 

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Local Principal Investigators at study sites: 
 
I have read and understood this protocol and agree to conduct the trial as set out in this 
study protocol. 
 
 
 
Site 
 
Kliniken Valens 
Rehabilitationszentrum 
7317 Valens 
 
Principal investigator 
Jan Kool 
 
 
 
 
 
 
 
 
Valens, 05.10.2018 
 
 
 
 
Place/Date 
 
Signature 
 
 

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Local Principal Investigators at study sites: 
 
I have read and understood this protocol and agree to conduct the trial as set out in this 
study protocol. 
 
 
Site 
 
Klinik Lengg AG 
Bleulerstrasse 60 
CH-8008 Zürich 
 
Principal investigator 
Christian Sturzenegger 
 
 
 
 
Zürich, 06.10. 2018  
Place/ Date  
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
STUDY SYNOPSIS ................................................................................................................ 10 
LIST OF ABBREVIATIONS .................................................................................................... 14 
1 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ............................. 15 
1.1 
Sponsor, Sponsor-Investigator (Principal Investigator) ....................................... 15 
1.2 
Coordinating Investigator ..................................................................................... 15 
1.3 
Principal Investigator(s) ....................................................................................... 15 
1.4 
Statistician (Biometrician) .................................................................................... 16 
1.5 
Monitoring Institution ............................................................................................ 16 
2 
ETHICAL AND REGULATOR ASPECTS ..................................................................... 17 
2.1 
Study Registration ............................................................................................... 17 
2.2 
Categorization of the Study ................................................................................. 17 
2.3 
Competent Ethics Committee (CEC) ................................................................... 17 
2.4 
Ethical Conduct of the Study ............................................................................... 17 
2.5 
Declaration of Interest .......................................................................................... 17 
2.6 
Participant Information and Informed Consent .................................................... 18 
2.7 
Participant Privacy and Confidentiality ................................................................ 18 
2.8 
Early Termination of the Study ............................................................................ 18 
2.9 
Protocol Amendments ......................................................................................... 19 
3 
INTRODUCTION........................................................................................................... 20 
3.1 
Background and Rationale .................................................................................. 20 
3.2 
Study Intervention and Indication ........................................................................ 21 
3.3 
Clinical Evidence to Date ..................................................................................... 21 
3.4 
Justification of Study Intervention ........................................................................ 21 
3.5 
Explanation for Choice of Comparator Intervention ............................................. 22 
3.6 
Risk / Benefits ...................................................................................................... 22 
3.7 
Study Population .................................................................................................. 22 
4 
STUDY OBJECTIVES................................................................................................... 23 
4.1 
Overall Objective ................................................................................................. 23 
4.2 
Primary Objective ................................................................................................ 23 
4.3 
Secondary Objectives .......................................................................................... 23 
4.4 
Safety Objectives ................................................................................................. 23 
4.5 
Primary Outcome ................................................................................................. 23 
4.6 
Secondary Outcomes .......................................................................................... 24 
4.7 
Safety Outcomes ................................................................................................. 24 
5 
STUDY DESIGN AND COURSE OF STUDY ............................................................... 25 
5.1 
General Study Design and Justification of the Design ......................................... 25 
5.2 
Study Duration and Study Schedule .................................................................... 25 
5.3 
Methods of Minimizing Bias ................................................................................. 25 
6 
STUDY POPULATION .................................................................................................. 26 

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6.1 
Eligibility Criteria .................................................................................................. 26 
6.1.1 Inclusion Criteria ...................................................................................... 26 
6.1.2 Exclusion Criteria ..................................................................................... 26 
6.2 
Recruitment and Screening ................................................................................. 28 
6.3 
Assignment to Study Groups ............................................................................... 28 
6.4 
Criteria for Withdrawal/ Discontinuation of Participants ....................................... 28 
7 
STUDY INTERVENTION .............................................................................................. 29 
7.1 
General Information ............................................................................................. 29 
7.1.1 Study Intervention .................................................................................... 29 
7.2 
Administration of Study Intervention .................................................................... 29 
7.2.1 Study Intervention .................................................................................... 29 
7.2.2 Control Intervention .................................................................................. 29 
7.3 
Compliance with Intervention ............................................................................... 29 
7.4 
Data Collection and Follow-up for Withdrawn Participants .................................. 29 
7.5 
Concomitant Intervention(s) ................................................................................. 29 
8 
STUDY PROCEDURES................................................................................................ 30 
8.1 
Study Flow Diagram ............................................................................................ 30 
8.2 
Assessments of Outcomes .................................................................................. 31 
8.2.1 Assessment of Primary Outcome (daily) .................................................. 31 
8.2.2 Assessment of Secondary Outcomes (Baseline and end of study) ......... 31 
8.2.3 Assessment of Safety Outcomes ............................................................. 32 
8.2.4 Assessments in Participants who Prematurely Stop the Study ................ 32 
8.3 
Procedures at each training day .......................................................................... 32 
8.3.1 Screening Visit ......................................................................................... 32 
8.3.2 Baseline Visit ............................................................................................ 32 
8.3.3 Start of training ......................................................................................... 33 
8.3.4 End of study ............................................................................................. 33 
9 
SAFETY ........................................................................................................................ 34 
9.1 
Definitions ............................................................................................................ 34 
9.2 
Recording and Assessment of Serious Adverse Events ..................................... 34 
9.3 
Reporting of Serious Adverse Events .................................................................. 35 
9.4 
Follow up of (Serious) Adverse Events ................................................................ 35 
10 
STATISTICAL METHODS ............................................................................................ 36 
10.1 Hypothesis ........................................................................................................... 36 
10.2 Determination of Sample Size ............................................................................. 36 
10.3 Planned Analyses ................................................................................................ 36 
10.3.1 Primary Analysis ...................................................................................... 36 
10.3.2 Secondary Analyses ................................................................................ 36 
10.3.3 Interim Analyses ....................................................................................... 36 
10.3.4 Safety Analysis ......................................................................................... 36 
10.3.5 Deviation(s) from the Original Statistical Plan .......................................... 36 
10.4 Handling of Missing Data and Drop-Outs ............................................................ 36 
11 
ELIGIBILITY OF THE PROJECT SITE(S) .................................................................... 38 
12 
DATA QUALITY ASSURANCE AND CONTROL .......................................................... 39 

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12.1 DATA HANDLING AND RECORD KEEPING ..................................................... 39 
12.1.1 Case Report Forms .................................................................................. 39 
12.1.2 Specification of Source Documents ......................................................... 39 
12.1.3 Record Keeping / Archiving ...................................................................... 40 
12.2 Data Management ............................................................................................... 40 
12.3 Routine Monitoring ............................................................................................... 40 
12.4 Audits and Inspections ......................................................................................... 41 
12.5 Confidentiality, Data Protection ........................................................................... 41 
13 
PUBLICATION AND DISSEMINATION POLICY .......................................................... 42 
14 
FUNDING AND SUPPORT ........................................................................................... 43 
14.1 Funding ................................................................................................................ 43 
14.2 Other Support ...................................................................................................... 43 
15 
INSURANCE ................................................................................................................. 44 
16 
REFERENCES ............................................................................................................. 45 
 
 

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STUDY SYNOPSIS 
Sponsor / Sponsor-
Investigator 
Markus Wirz 
Study Title 
Feasibility and cost description of intensive 
rehabilitation involving new technologies in patients 
with sub-acute stroke: A multicenter single arm trial of 
the Swiss RehabTech Initiative 
Short Title / Study ID 
New technologies in the rehabilitation of chronic stroke 
2018-01214 
Protocol Version and Date 
Version 02, September the 12th 2018 
Trial registration 
clinicalTrials.gov: NCT03641651 
Study category and 
Rationale 
Other clinical study Category A 
The phase of development covered by this study 
pertains to the efficient application of a combination of 
commercially available rehabilitation technology, 
corresponding to phase III. 
Background and Rationale 
Limitations in the performance of activities are a 
frequent consequence of a cerebro-vascular stroke. 
Partial paresis, abnormal muscle tone and 
deteriorated coordination are among others reasons 
for these deficits. From rehabilitation and motor (re-) 
learning studies it is known that skilled movements 
can be trained. The success of such training depends 
on the context of training, the motivation of the 
patients and the training intensity. These factors can 
be tailored and controlled with the use of rehabilitation 
technologies such as robotics or audio-visual 
feedback devices. However, up to now only sparse 
evidence and experience is available on the efficient 
application of such devices. 
Objective(s) 
The objective of the current study is to develop and 
investigate training concepts involving rehabilitation 
technology, which aim at exploiting the potential for 
regaining the ability to perform skilled movements by 
maximizing training intensity while keeping the 
motivation of patients high. The evaluation focuses on 
feasibility and cost-benefit analyses. 

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Outcome(s) 
• Variables from the devices such as 
o number of trainings 
o training duration, number of repetitions 
o support 
o success rate (for game-like tasks) 
• Patient related outcomes 
o Lower extremities  
o Upper extremities  
o Functional independence Measurement 
(FIM) 
o Questionnaire for the patients covering: 
▪ motivation 
▪ adherence 
▪ perceived support (Fühlen sie sich 
gut betreut) 
▪ desire to continue such a training 
▪ subjective rating of the training 
modalities (which was the best, which 
was the most interesting) 
• Adverse events  
o Medical complications  
o organizational challenges 
• Economic variables 
o Descriptives (quantities, prices, operational 
procedures in the use of the technology) 
o Efficiency analysis 
o Reimbursement 
Study design 
Multicenter-single arm feasibility study 
Inclusion / Exclusion criteria Inclusion: 
• Patients with residual hemiparesis after 
cerebrovascular accident 
• Up to 12 months after the event 
• Primary rehabilitation terminated 
• Able to cognitively comprehend the aim of the 
project 
• General health condition allows for intensive 
rehabilitative training with limited supervision i.e. 
clearance of responsible physician 
• Understand written and spoken German language 
Exclusion: 
• 
Presents with contraindication for the training with 
the respective devices 

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Study Intervention 
• Series of tailored rehabilitative trainings with the 
use of new technology which provide feedback and 
allow for a targeted, intensive and dense training. 
• With limited supervision based on patients 
preconditions and therapy device (e.g. patient/ 
therapist ratio= 3/1). 
• A training series lasts four weeks and comprises 3-
5 training-days per week. Maximum training break 
of 7 days. A minimum of five blocks of training with 
duration of 45 min per training day each are 
foreseen.  
 
The training can take place in an in- or outpatient 
setting 
Reference Intervention 
Not applicable  
Number of Participants with 
Rationale 
As this study is a feasibility study: N= 20 (five subjects 
for every clinical site). 
Study Duration 
Thirty months (30m) in total. 
Study Schedule 
11/2018 First-Participant-In (planned) 
05/2020 of Last-Participant-Out (planned) 
Investigator(s) 
Carsten Möller 
Rehakliniken Zihlschlacht  
Hauptstrasse 2-4 
8588 Zihlschlacht 
Phone 071 424 33 33 
c.moeller@rehaklinik-zihlschlacht.ch  
 
Frank Behrendt 
Reha Rheinfelden 
Salinenstrasse 98 
4310 Rheinfelden 
Phone 061 / 836 5385 
F.Behrendt@reha-rhf.ch 
 
Jan Kool  
Kliniken Valens 
Rehabilitationszentrum 
7317 Valens 
Phone 081 303 11 11 
jan.kool@kliniken-valens.ch   
 
Christian Sturzenegger 
Klinik Lengg AG 
Bleulerstrasse 60 
CH-8008 Zürich 
Phone 044 387 6901 
christian.sturzenegger@kliniklengg.ch 
Study Centre(s) 
see above 

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Statistical Considerations 
Descriptive analysis 
Pre-post comparisons of patient–related outcomes 
GCP Statement 
This study will be conducted in compliance with the 
protocol, the current version of the Declaration of 
Helsinki, the ICH-GCP as well as all national legal and 
regulatory requirements.  

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LIST OF ABBREVIATIONS 
AE 
Adverse Event  
ClinO 
Clinical Trial Ordinance (KlinV) 
CRF 
Case Report Form  
eCRF 
Electronic Case Report Form  
GCP 
Good Clinical Practice  
ICH 
International Council on Harmonization 
ISF 
Investigator Site File  
PI 
Principal Investigator  
SAE 
Serious Adverse Event  
SDV 
Source Data Verification  
SNCTP 
Swiss National Clinical Trial Portal 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File  

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1 INVESTIGATORS AND STUDY ADMINISTRATIVE 
STRUCTURE  
1.1 Sponsor, Sponsor-Investigator (Principal Investigator) 
Markus Wirz PT, PhD 
Zurich University of Applied Sciences (ZHAW)  
Institute of Physiotherapy 
Technikumstrasse 71 
8401 Winterthur  
markus.wirz@zhaw.ch.  
1.2 Coordinating Investigator 
See Sponsor 
1.3 Principal Investigator(s) 
Carsten Möller 
Rehakliniken Zihlschlacht  
Hauptstrasse 2-4 
8588 Zihlschlacht 
Phone 071 424 33 33 
c.moeller@rehaklinik-zihlschlacht.ch 
 
Frank Behrendt 
Reha Rheinfelden 
Salinenstrasse 98 
4310 Rheinfelden 
Phone 061 836 5385 
F.Behrendt@reha-rhf.ch 
 
Jan Kool  
Kliniken Valens 
Rehabilitationszentrum 
7317 Valens 
Phone 081 303 11 11 
jan.kool@kliniken-valens.ch 
 
Christian Sturzenegger 
Klinik Lengg AG 
Bleulerstrasse 60 
CH-8008 Zürich 
Phone 044 387 6600 
christian.sturzenegger@kliniklengg.ch  

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1.4 Statistician (Biometrician) 
NA, feasibility study 
1.5 Monitoring Institution 
Prof. Martin E. Schwab 
Brain Research Institute, University of Zurich and Department of Health Science and 
Technology, Swiss Federal Institute of Technology Zurich 
Winterthurerstr.190, Room 55J46a 
CH-8057 Zurich 
Tel. direct +41 44 635 33 30 
Secretary +41 44 635 33 31 
schwab@hifo.uzh.ch  

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2 ETHICAL AND REGULATOR ASPECTS 
Before this study will be conducted, the protocol, the proposed participant information 
and consent form as well as other study-specific documents will be submitted to a 
properly constituted Competent Ethics Committee (CEC) in agreement with local legal 
requirements, for formal approval.  
The decision of the CEC concerning the conduct of the study will be made in writing to 
the Sponsor-Investigator before commencement of this study. The clinical study can 
only begin once approval from the CEC has been received. 
2.1 Study Registration 
The study will be registered in the Swiss National Clinical Trials Portal (SNCTP) and in 
the international trial registry ClinicalTrials.gov (clinicaltrials.gov). Registration number: 
NCT03641651 
2.2 Categorization of the Study 
Category A: the intervention is clinical standard.  
2.3 Competent Ethics Committee (CEC)  
The ethical committee of the Canton Zurich is regarded the lead ethical committee. Due 
to the multicenter status of this trial, the ethical committees of St. Gallen (EK 
Ostschweiz) and Nordwest-and Zentralschweiz (EKNZ) are also involved and will be 
asked for approval.  
 
The reporting duties and allowed time frame are respected. No substantial amendments 
are made to the protocol without prior CEC approval, except where necessary to 
eliminate apparent immediate hazards to study participants.Premature study end or 
interruption of the study is reported within 15 days. The regular end of the study is 
reported to the CEC within 90 days, the final study report shall be submitted within one 
year after study end. Amendments are reported according to chapter 2.9. 
2.4 Ethical Conduct of the Study 
The study will be carried out in accordance with principles enunciated in the current 
version of the Declaration of Helsinki, the guidelines of Good Clinical Practice (GCP) 
issued by ICH, and Swiss competent authority’s requirements. 
CEC will receive annual safety and interim reports and be informed about non-
substantial amendments, the course of the study, and the study stop/ end in agreement 
with local requirements. 
2.5 Declaration of Interest  
There is no conflict of interest by any person involved in conducting this clinical trial. 

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2.6 Participant Information and Informed Consent 
The investigator must explain to each participant the nature of the study, its purpose, 
the procedures involved, the expected duration, the potential risks and benefits and any 
discomfort it may entail. Each participant must be informed that the participation in the 
study is voluntary and that he/she may withdraw from the study at any time and that 
withdrawal of consent will not affect his/her subsequent medical treatment. 
The participant must be informed that his/her medical records may be examined by 
authorized individuals other than their treating physician. 
All participants for this study will be provided a participant information sheet and a 
consent form describing this study and providing sufficient information for participants to 
make an informed decision about their participation in this study. 
The participant information sheet and the consent form will be submitted with the 
protocol for review and approval for the study by the CEC. The formal consent of a 
participant, using the approved consent form, must be obtained before that participant is 
submitted to any study procedure. 
The participant should read and consider the statement before signing and dating the 
informed consent form, and should be given a copy of the signed document. The 
consent form must also be signed and dated by the investigator (or his designee) and it 
will be retained as part of the study records. 
2.7 Participant Privacy and Confidentiality 
The investigators are liable to treat the entire information related to the study and the 
compiled data strictly confidentially. Any passing-on of information to persons that are 
not directly involved in the study must be approved by the owner of the information.  
Data generation, transmission, archiving and analysis of personal data within this study, 
strictly follows the current Swiss legal requirements for data protection. Prerequisite is 
the voluntary approval of the Participant given by signing the informed consent prior 
start of participation of the clinical trial.  
Individual participant medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited. Participant’s confidentiality will 
be further ensured by utilizing participant identification code numbers to correspond to 
treatment data in the computer files. 
Such medical information may be given to the participant’s personal physician or to 
other appropriate medical personnel responsible for the participant’s welfare, if the 
patient has given his/her written consent to do so. 
Data generated as a result of this study are to be available for inspection on request by 
the monitors and by the CEC. 
2.8 Early Termination of the Study  
The Sponsor-Investigator may discontinue the study prematurely according to certain 
circumstances: 
• ethical concerns, 
• insufficient participant recruitment, 
• when the safety of the participants is doubtful or at risk, respectively, 
• alterations in accepted clinical practice that make the continuation of a clinical 

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trial unwise,  
• early evidence of benefit or harm of the experimental intervention  
2.9 Protocol Amendments 
Substantial amendments (significant changes) are only implemented after approval of 
the CEC. 
Significant changes to be authorised by the CEC are the following: 
• changes affecting the participants’ safety and health, or their rights and obligations;  
• changes to the protocol, and in particular changes based on new scientific 
knowledge which concern the trial design, the method of investigation, the endpoints 
or the form of statistical analysis; 
• a change of trial site, or conducting the clinical trial at an additional site; or 
• 
a change of sponsor, coordinating investigator or investigator responsible at a trial 
site. 
Under emergency circumstances, deviations from the protocol to protect the rights, 
safety and well-being of human participants may proceed without prior approval of the 
sponsor and the CEC. Such deviations shall be documented and reported to the 
sponsor and the CEC as soon as possible. 
All Non-substantial amendments are communicated to the CEC within the Annual 
Safety Report (ASR). 

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3 INTRODUCTION 
3.1 Background and Rationale 
Damage of the neurological system, because of illness or injury, affects over a billion 
people worldwide [1].This damage can, amongst other consequences, lead to motor 
impairment, which necessitates rehabilitative treatment. Rehabilitation has been defined 
by the World Health Organization (WHO) as “active process by which those affected by 
injury or disease achieve a full recovery or, if a full recovery is not possible, realize their 
optimal physical, mental and social potential and are integrated into their most 
appropriate environment” [2]. Literature shows, that intensive training is required to 
exploit the full potential of recovery. There is in fact overwhelming evidence that more 
intensive training leads to better rehabilitation outcomes in individuals with stroke [3-14] 
and reduces hospital readmission rates [15]. However, today, clinical reality looks rather 
different. Many individuals with motor impairments are discharged from rehabilitation 
considerably short of attaining their optimal potential. Rather than receiving therapy until 
their potential is reached, they are discharged when it is considered safe by the third 
party payers [16]. Actual therapy time during a regular day at a rehabilitation hospital is 
generally very limited, mostly due to management decisions, lack of structured 
organization and inefficient use of resources [17, 18]. In four European rehabilitation 
centers, individuals with stroke received between one and three hours of therapy per 
day, while over 72% of time was spent with non-therapeutic activities [17]. This has 
consequences, as these authors also were able to show that patients in centers with 
less therapy time per day have less functional recovery than those who are treated in 
centers that provide more therapy time per day [18]. In addition, within a session of 
conventional therapy, dosage is generally rather low, even during inpatient 
rehabilitation. For example, Hayward et al. describe that the dose of activity-related arm 
training only adds up to an average of 4min and as little as 23 repetitions per therapy 
session during inpatient rehabilitation [19]. Lang et al. found an average number of 
repetitions per session of 32 for the upper extremity and of 357 for the lower extremity 
[20]. 
Individuals post stroke also make significantly less use of their upper extremities 
throughout the rest of their day during inpatient rehabilitation. While able-bodied control 
persons use their arms during 8-9hrs per day, individuals with stroke during inpatient 
rehabilitation use their more affected arm during 3.3 hrs and their less affected arm 
during 6 hrs per day [21]. This non-use leads to negative plasticity and further 
impairment [22]. 
So, while it is certainly possible to intensify therapeutic treatments during inpatient 
rehabilitation [12, 18], it is challenging for many reasons and often not done. Needless 
to say that this less than optimal amount of therapy provided results in large amounts of 
untouched recovery potential. Out of the roughly 15 million people worldwide who 
experience a stroke each year, 5 million live with permanent disability [1]. The 
Framingham study for example showed that of all stroke survivors, 20% remain 
dependent in their mobility [23]. Clearly, this dependency, as well as other under-treated 
impairments lead to tremendous costs throughout the person’s lifetime [24-27]. For 
Medicare users in the United States for example, while mean rehabilitation length of 
stay after an acute stroke was only 14.6 days, readmission rate to the hospital was 
12.7% within the first 30 days after discharge from rehabilitation [28]. In Europe, the 
total cost resulting from strokes was 37.4 billion in 2010 [29]. In Switzerland, in 2014, 

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25.8% of health costs were spent on acute inpatient treatment, while only 1.7% were 
spent on inpatient rehabilitation. Outpatient physical therapy only added up to 1.4% of 
the total health costs [30].  
There is a desperate need for affordable solutions to provide our patients the intensity of 
therapy necessary to optimally exploit their potential for recovery. Finding such a 
solution must include dialog between all the stakeholders, i.e. patients, clinicians, 
technological solution providers and insurers. The Swiss Rehab Tech Initiative aims to 
do exactly that. It provides a platform where all involved parties come together. The 
initiative is now ready to test a model solution in the clinic. 
3.2 Study Intervention and Indication 
In a first step, the feasibility of the intervention aims to establish efficient settings in four 
trailblazer clinics. This will enable them to provide intensive therapy to the patients in 
accordance with the study protocol. While these settings are integrated into the clinical 
routine, we will be able to collect data to get some first insight into economic and 
functional data required to calculate changes in socioeconomic costs. 
3.3 Clinical Evidence to Date  
Suitable solutions include advanced technology, such as electromechanically assisted 
gait and arm trainers, which is one way to allow reaching high training intensities [31, 
32]. These devices take the physical burden from the therapists, thus allowing training 
duration to be limited by the patient’s capabilities rather than by exhaustion of the 
therapists. With the assistance of such devices, participants in one study performed up 
to over 600 functional arm movements per session [33]. Another study describes 
walking distances of up to 2000m (roughly 3300 steps) per session in an individual with 
spinal cord injury [34]. Technology assisted training has received considerable attention 
over the past years. This is reflected in a large number of published research studies. 
Numerous individual trials and several systematic reviews [35-38] have shown the 
positive effects of robotic assisted gait training, as well as of technology assisted 
training of the upper extremity [35, 36, 38, 39]. Cochrane Reviews showed that every 
fifth gait dependency could be prevented if patients received electromechanically 
assisted gait training in addition to their regular therapy program [40] and that 
electromechanical and robot-assisted arm training leads to improvements in activities of 
daily living and arm function [41] in individuals post stroke. Similar to physical therapy in 
general, it was also shown for technology assisted gait training that more intensive 
training programs lead to improved outcomes [42]. 
All these studies have shown that it is in fact possible to improve outcomes through 
intensifying training paradigms. 
3.4 Justification of Study Intervention 
Treatment intensification so far has often taken place within a research environment 
and with the corresponding reimbursement through grants or other sources. In order to 
show the effect under clinical every day conditions and reimbursement situations, 
efficient settings have to be integrated into rehabilitation institutes and their effect on 

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patient outcome as well as economic parameters have to be shown. Investing into new 
technologies to provide efficient settings and delivering high intensive therapy as 
requested by clinical evidence is currently the sole responsibility of healthcare 
providers. It is not reimbursed either through support of investments or reimbursement. 
Specifically with certain reimbursement models, such as diagnosis related groups, there 
is no incentive for rehabilitation institutions to invest in such therapy models and provide 
more therapy for their patients. 
3.5 Explanation for Choice of Comparator Intervention 
Not applicable, pilot study without control intervention 
3.6 Risk / Benefits  
As the technological devices under study have already been certified as medical 
devices and are currently used in involved clinics, there are no adverse risks to be 
expected. To examine the benefits of this intervention by using specific outcome 
measurements is part of this research project. Further aspects are discussed under 
point 4.4 (Safety outcomes). 
3.7 Study Population  
The study aims to target on patients with a residual hemiparesis after a cerebrovascular 
accident up to 12 month ago. The primary rehabilitation has terminated. Their general 
health conditions should be stable to allow nearly daily intensive rehabilitation. Patients 
should cognitively and educationally be able to communicate verbal and non-verbal in 
German language. Specific inclusion and exclusion criteria are specified under 7.1. 
Each involved clinical site aims to include five patients. The enrolment procedure will be 
iterative with one or two clinics starting the recruitment. A total of twenty (n=20) patients 
are aimed to be enrolled.  

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4 STUDY OBJECTIVES  
4.1 Overall Objective 
This feasibility project aims to establish an efficient setting for intensive rehabilitation 
with new technology in four trailblazer clinics. This will enable them to provide intensive 
therapy to the patients in accordance with the study protocol. If this setting is integrated 
into the clinical routine, we will be able to collect data to get some first insight into 
economic and functional data required to calculate changes in socioeconomic costs. 
4.2 Primary Objective 
Develop and investigate the feasibility of a rehabilitative training program adopting new 
technologies, which focuses on scientifically based intensity and efficiency.  
4.3 Secondary Objectives 
Describe economic costs of the program. 
Document and evaluate functional changes in response to the training. 
4.4 Safety Objectives 
All medical devices will be used as indicated. Involved physiotherapists will be trained in 
using the devices and supervising the training. Every clinic has its emergency plan, 
which will be applied in case of need 
Participants will be supervised permanently during the intervention. No adverse events 
(AE) or serious adverse events (SAE) are expected to occur. However, participating 
subjects might complain about tiredness or muscle soreness due to the intensive 
intervention, which will be recorded on the case report form (CRF).  
All adverse (AE) and serious adverse events which will be defined later (Point 10) 
whether related or unrelated will be recorded in the case report form (CRF). The CEC 
will be informed of any SAE within 15 days. 
4.5 Primary Outcome 
The primary outcome is to assess the feasibility of planned trainings. Every training and 
training day will be described in terms of 
• devices used,  
• duration of training,  
• training mode (passive, active or resistive) and 
•  feedback given by the device. 
 
The specific interest is the adherence of the patients: 
• to planned trainings in terms of planned vs. actually performed training-days and 
training intensity.  

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• the subjectively perceived effort by the patients to perform the trainings will be 
recorded on a visual analogue scale (VAS).  
• the subjectively perceived effectiveness will be recorded by using the “Patients 
Global Impression of Change” = PGICS) 
4.6 Secondary Outcomes 
Secondary outcomes are patient-related outcomes:  
• generic functional and specific functional performance, focusing on upper and/or 
lower extremity and measured by rater observing patients during standardized tests. 
The tests used will be listed later at point 9.2 by the “Functional independence 
measurement” (FIM) 
• specific functional assessments of the upper AND/OR lower extremity 
o Stroke impact scale (SIS) 
• upper extremity: 
o Fugl-Meyer test 
o Box and Block test 
• lower extremity: 
o Functional ambulation categories (FAC) 
o Comfortable walking speed (10m Walk test= TMT) 
o Chedoke-McMaster Stroke Assessment Measure (CMSA), the walking index 
o Berg Balance scale (BBS) 
• health-related quality of life (EQ-5D) 
 
• Cost elements and structures for cost description analysis 
o quantities and prices of inputs (staff, technologies, infrastructure) 
o intensity of use of new rehabilitation technologies  
o h/day, h/week, time of the day 
o description of operational procedures 
o patient(device)/therapist ratio 
o identification of main drivers for increasing efficiency 
o efficiency gains 
o current reimbursement 
o future reimbursement possibilities and models 
4.7 Safety Outcomes 
Participating patients will be monitored constantly by attending physiotherapists. The 
ratio of patient to therapist will be between 1:1 and 3:1. Physiotherapists are specially 
trained in the use of the devices and in life saving measures. Only patients regarded 
“stable” by their physician to conduct the program will be included.  
The subjectively perceived effort by the patient and during the training will be noted on 
the CRF. Heart rate frequency and blood pressure can be monitored if necessary. 

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5 STUDY DESIGN AND COURSE OF STUDY 
5.1 General Study Design and Justification of the Design 
Since the aim of this feasibility study is the development and validation of a new 
treatment program and not yet, the investigation of effectiveness while controlled with a 
current state of the art intervention, no control group will be included. A longitudinal 
single group design has been chosen. Blinding of therapists and patients is accordingly 
not possible. Blinding of assessment cannot be guaranteed, due to logistical reasons 
and as assessments are either self-conducted or by attending therapists, who are 
trained in doing so. 
5.2 Study Duration and Study Schedule 
The duration of this study is planned to be 30 months (i.e. 2.5 years). The completion 
depends on the rate of recruitment.  
 
Clinics start recruitment at different dates. 
Clinic 
Start of recruitment 
Klinik Lengg 
01.11.208 
Reha Rheinfelden 
01.11.2018  
Kliniken Valens 
01.11.2018 
Rehaklinik Zihlschlacht 
01.11.2018  
 
Project and study schedule 
 
Project months 
WP 
1 2 3 
4 
5 
6 7 8 9 10 11 12 13 14 15 16 17 
1 Set-up of infrastructure and 
processes 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
2 Patient trainings/-assessments 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
3 Analysis/ Dissemination 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
4 Communication 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
5 Project management 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Milestones 
Funding acquired 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KEK Approval 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
First patient, first visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Interim Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Last patient, last visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Final Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.3 Methods of Minimizing Bias  
Not applicable as no control intervention will be conducted, no randomization and/or 
blinding for the study design can be applied. Clinics will undertake measures to 
minimize tester bias. 

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6 STUDY POPULATION 
Four rehabilitation centres located across the German speaking area of Switzerland will 
participate in this project. 
 
Klinik Lengg, Zurich 
The Klinik Lengg has a workload of 250-stroke patients a year. All patients fulfilling the 
inclusion criteria will be asked for participation. 
 
Reha Rheinfelden 
The Reha Rheinfelden has a workload of approximately 400 ischaemic and 
haemorrhagic stroke patients as in-and outpatients a year, which will recruited via direct 
contact, clinic’s database, and flyer distributed in-house. 
 
Kliniken Valens 
Kliniken Valens treated approximately 460 ischaemic and 150 haemorrhagic stroke in-
patients a year, who will be approached by a research assistant to check their eligibility 
while entering the clinical site for inpatient rehabilitation. 
 
Rehaklinik Zihlschlacht 
The Rehaklinik Zihlschlacht has a yearly workload of approximately 300 stroke patients; 
some of them will be treated after discharge in the clinic’s outpatient setting. Study 
personnel will approach patients regarded eligible for further evaluation. 
 
Each site aims to include five patients leading to 20 patients in total. Study sites are 
entering the study consecutively and according to their personnel capacity. 
6.1 Eligibility Criteria 
6.1.1 Inclusion Criteria 
Patients fulfilling all of the following inclusion criteria can be enrolled in the study 
• Adult patients with residual hemiparesis after cerebrovascular accident 
• Up to 12 months after the event 
• Primary rehabilitation terminated 
• Able to cognitively comprehend the aim of the project 
o At least 22 points in the Montreal Cognitive Assessment (MoCA) 
• General health condition allows for intensive rehabilitative training with limited 
supervision i.e. clearance and prescription of responsible physician 
• Understand written and spoken German language 
6.1.2 Exclusion Criteria 
The presence of any one of the following exclusion criteria will lead to exclusion of the 
participant: 
 
▪ Patients with any signs and symptoms showing that the participant is unwilling to 
participate in the study will result in the patient being excluded from participation 
▪ Any medical condition preventing participation such as 

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o Severe respiratory disease 
o Severe OR unstable cardio-circulatory conditions 
o Orthopaedic conditions, especially in extremities targeted for rehabilitation 
such as 
▪ fixed joint contractures limiting range of motion  
▪ non-consolidated fractures 
o Neuro-psychological conditions including cognitive deficits limiting 
communication or non-cooperation like (self-) aggressive behaviour 
o Infections or inflammatory diseases, like osteomyelitis 
 
▪ Specific absolute contraindication for the training with any of the respective 
devices: 
o Improper fit of the device, including its harness to relevant extremity(ies) 
o Contraindicated training position (standing, sitting) 
 
Device specific contraindications will be respected and will lead to the exclusion of the 
device for that patient.  
 
The choice of the device is dependent by the patient’s goal, primary impaired limb, and 
availability at the study site. Comparison of devices is not intended, but to measure the 
feasibility of their intensive use. 
 
 
Devices from Hocoma AG Switzerland HocomaProducts 
•  
Lokomat 
•  
Erigo 
•  
Andago 
•  
Armeo (Boom, Senseo, Spring, Power) 
•  
Valedo Motion 
 
Devices from Tyromotion Austria Tyromotion 
•  
Amadeo 
•  
Myro 
 
Devices from other manufacturers 
• Devices from NuStep: NuStep 
• The Bi-Manu-Trainer by Reha Stim: Bi-Manu-Trainer  
• The EksoGT by EkSo Bionics, USA: Ekso GT 
• The Float by Lutz Medical Engineering, Switzerland: The Float 
• Devices from Reck MOTOmed: MOTOmed 
• Allegro Medical device by Dynamic devices: Dynamic Devices 
 
Physicians, not participating in the study, safeguard patient interest and insures proper 
medical care at every clinical site. 

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6.2 Recruitment and Screening 
Eligible in-and or outpatients attending at each clinic and fulfilling the inclusion criteria 
will be screened by trained medical personal at each site.  
The screening procedure of each participating clinic has been described before (point 
6.1).  
6.3 Assignment to Study Groups  
NA, every patient will be assigned to the intervention under study. 
6.4 Criteria for Withdrawal/ Discontinuation of Participants 
Patients not willing to adhere to the protocol will not be included. For included patients 
who, while having already attended some session but are not able to complete the six 
weeks program within the intensity planned, a tailored reduction of intensity in terms of 
days, hours per days and/or sessions per day is considered. A maximum training break 
of 7 days is foreseen 
Patients who withdraw before the start of the study will be replaced.  

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7 STUDY INTERVENTION 
7.1 General Information 
7.1.1 Study Intervention 
• Series of tailored rehabilitative training with the use of new technology which provide 
feedback and allow for a targeted and intensive and dense training. 
• With supervision based on patients preconditions and therapy device (e.g. patient/ 
therapist ratio= 3/1). 
• A training series lasts four weeks and comprises 3-5 training-days per week. 
Maximum training break of 7 days. Five sessions of training with duration of 45 min 
per session, and up to four hours each day are foreseen.  
• The training can take place in an outpatient or inpatient setting. 
• Training will be organized in individual one-to-one or group sessions. 
7.2 Administration of Study Intervention  
7.2.1 Study Intervention  
Interventions will be applied and supervised according to the needs, aims and planned 
interventions (devices used) for each patient individually. Adaptations to a minimum 
program as outlined under 6.4. can be made.  
7.2.2 Control Intervention 
n.a. 
7.3 Compliance with Intervention 
For every patient a CRF including a trainings and intervention plan will be completed. 
This plan includes measurements to adherence to the intervention plan. The trainings 
plan will be made in advance and in collaboration by both patient and therapist, 
including all scheduled days and sessions (devices). Patients not able or willing to fulfil 
the minimum program outlined before (6.4) will be excluded.  
7.4 Data Collection and Follow-up for Withdrawn Participants  
Data of all included patients will be analyzed. A follow-up is not planned. 
7.5 Concomitant Intervention(s) 
All co-interventions such as medication used or other therapies visited during the trial 
will be recorded. 
All concomitant and/or rescue interventions or treatment(s) will be recorded in the CRF. 

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8 STUDY PROCEDURES 
8.1 Study Flow Diagram 
 
 
 
 
Baseline assessment 
Screening 
Fail inclusion criteria 
Meet exclusion criteria 
Refuse to participate 
Excluded 
> 1 week training 
break  
Intervention 
4 weeks of tailored interventions  
Post-training assessment 
•
Intervention-related outcomes 
•
Patient-related outcomes 
•
Costs-specific outcomes 

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8.2 Assessments of Outcomes  
8.2.1 Assessment of Primary Outcome (daily) 
The primary outcome is to assess the feasibility of planned trainings. Every training and 
training day will be described in terms of 
• device used,  
• duration of training 
• training mode (passive, active or resistive) 
• feedback given 
 
The specific interest is the adherence of the patients 
• to planned trainings in terms of planned vs. actually performed training-days and 
training intensity.  
• The subjectively perceived effort by the patients to perform the trainings will be 
recorded on a visual analogue scale (VAS).  
• The subjectively perceived effectiveness will be recorded by using the “Patients 
Global Impression of Change” = PGICS) 
 
The primary outcomes will be assessed at each intervention day. Either during the 
training, at the end of each training or at the end of each training day. The PCICS will be 
assessed at the end of the whole intervention. 
8.2.2 Assessment of Secondary Outcomes (Baseline and end of study) 
Secondary outcomes are patient-related outcomes are: 
• generic functional performance measured by the “Functional independence 
measurement” (FIM) 
• specific functional assessments of the upper AND/OR lower extremity 
• Stroke impact scale (SIS) 
• Upper extremity: 
o Fugl-Meyer test 
o Box and Block test 
• Lower extremity: 
o Functional ambulation categories (FAC) 
o Comfortable walking speed (10m Walk test= TMT) 
o Chedoke-McMaster Stroke Assessment Measure (CMSA), the walking index 
o Berg Balance scale (BBS) 
• Health-related quality of life (EQ-5D) 
 
Patient-related outcomes will be assessed after the last training session. These 
outcomes will be assessed at baseline and at the end of the intervention by raters 
observing the patient during aforementioned tests. During final assessment, raters will 
be kept blind to the baseline values. 
 
Cost elements and structures for cost description analysis 
• quantities and prices of inputs (staff, technologies, infrastructure) 
• intensity of use of new rehabilitation technologies  
o h/day, h/week, time of the day 
• description of operational procedures 

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o patient(device)/therapist ratio 
• identification of main drivers for increasing efficiency 
• efficiency gains 
• current reimbursement 
o future reimbursement possibilities and models 
 
Secondary outcomes will be assessed at baseline and at the end of the intervention by 
raters observing the patient during aforementioned tests. During final assessment, 
raters will be kept blind to the baseline values.  
8.2.3 Assessment of Safety Outcomes 
8.2.3.1 
Serious Adverse Events  
Recording of serious adverse event (SAE) information, what information needs to be 
collected: time of onset, duration, resolution, action to be taken, assessment of intensity, 
relationship with study treatment; refer to Section 9 for SAE definition and procedures; 
define specific process to ask the participant at the visits about adverse events, 
collection of spontaneous reports.  
8.2.3.2 Laboratory Parameters 
NA 
8.2.3.3 Vital Signs 
Patient self-perceived effort during each training session as expressed by a VAS will be 
recorded. 
8.2.4 Assessments in Participants who prematurely Stop the Study 
Project investigators at each site will contact patient who withdrew from the study. 
Patients will be asked for reasons of withdrawal  
8.3 Procedures at each training day 
At each training day, the participant and responsible physiotherapist will plan the 
program of the day according to the training plan (CRF page 53). During each training 
bloc a physiotherapist will supervise the patient. Intervention-related outcomes will be 
completed after or during each training bloc and at the end of each training day.  
8.3.1 Screening Visit  
During the screening procedure, eligibility criteria will be checked by study personnel at 
each clinic and informed consent will be obtained.  
8.3.2 Baseline Visit 
During the initial visit, patient related outcomes will be obtained.  
For every patient a trainings- and intervention plan (CRF page 53ff) will be established.  

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8.3.3 Start of training 
In the beginning of each training day, patient and therapist will plan the day including 
sessions, and devices to be used.  
8.3.4 End of study 
After the intervention will end, and patient-related outcomes will be obtained either by 
self-report or measured by an observer. 

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9 SAFETY  
During the entire duration of the study, all serious adverse events (SAEs) that may be 
causally related to the study intervention are collected and documented in source 
documents. Reportable events are recorded in the case report form (CRF). Study 
duration encompassed the time from when the participant signs the informed consent 
until the last protocol-specific procedure has been completed, including a safety follow-
up period.  
9.1 Definitions 
Adverse events 
Adverse events (AEs) are defined as any untoward medical occurrence in a patient or 
clinical investigation participant after the intervention and which does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any favorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the intervention, whether or not related to the intervention. 
An AE may also consist of a new disease, an exacerbation of a pre-existing illness or 
condition, a recurrence of an intermittent illness or condition, a set of related signs or 
symptoms, or a single sign or symptom. 
 
Serious Adverse Event 
A serious adverse event is defined as any event which 
• requires inpatient treatment not envisaged in the protocol or extends a current 
• hospital stay; 
• results in permanent or significant incapacity or disability; 
• is life-threatening or results in death; or 
• causes a congenital anomaly or birth defect. 
9.2 Recording and Assessment of Serious Adverse Events 
The investigator has the responsibility for SAE identification, documentation, and 
assessing the causal relationship study intervention. 
All SAEs will be fully documented in the appropriate CRF. For each SAE, the 
investigator will provide the onset, duration, treatment required, outcome and action 
taken with regard to the study intervention.  
The assessment by the investigator with regard to the study intervention relation is done 
according to the following definitions: 
Unrelated 
• The event started in no temporal relationship to the medical 
intervention applied and  
• The event can be definitely explained by underlying diseases or 
other situations. 
Related 
• The event started in a plausible temporal relationship to the 
medical intervention applied and  
• The event cannot be definitely explained by underlying diseases or 
other situations. 

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9.3 Reporting of Serious Adverse Events 
If, in the course of a clinical trial, serious adverse events occur in participants in 
Switzerland, and it cannot be excluded that the events are attributable to the intervention 
under investigation, the investigator must report these events: 
• to the sponsor within 24 hours after they become known; and 
• to the CEC within 15 days. 
 
Safety and protective measures 
If immediate safety and protective measures have to be taken during the conduct of 
this clinical trial, the investigator must notify the CEC of these measures, 
and of the circumstances necessitating them, within 7 days. 
 
Annual Safety Report  
All SAEs will be summed up in the annual safety report (ASR) and submitted to the 
CEC. ASR shall contain:  
• A summary of events including severity and causal relationship to the intervention 
and on the safety of participants. 
• The accompanying letter provided with the Annual Safety Report should contain a 
short summary of the status of the clinical trial in Switzerland (number of centers 
open/closed, number of patients recruited/recruitment closed, and number of SAEs). 
9.4 Follow up of (Serious) Adverse Events 
Participants terminating the study (either regularly or prematurely) with 
• reported ongoing SAE, or 
• any ongoing AEs of laboratory values or of vital signs being beyond the alert limit 
will return for a follow-up investigation. This visit will take place up to 30 days after 
terminating the treatment period. Follow-up information on the outcome will be recorded 
on the respective SAE page in the CRF. 
Follow-up investigations may also be necessary according to the investigator’s medical 
judgment even if the participant has no SAE at the end of the study. However, 
information related to these investigations does not have to be documented in the CRF 
but must be noted in the source documents. 

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10 STATISTICAL METHODS  
10.1 Hypothesis 
Not applicable, as this study is a feasibility study. Determination of Sample Size  
Twenty patients, five at each site are planned to be enrolled. A sample size calculation 
is not applicable for this feasibility study.  
10.3 Planned Analyses  
The analysis of intervention-related outcomes is primarily regarded descriptive.  
For patient-related outcomes parametrical and/or non-parametrical univariate 
statistics for pre-to post changes will be used. 
 
10.3.1 Primary Analysis 
Intervention-related outcomes: Absolute and relative frequency together with 
parameters of central tendency and spread will be derived for any devices used, 
duration of intervention per day, per session, per device. This applies analogously for 
training and feedback modes used and for self-perceived exertion rates. Adherence 
rates will examined by using Chi-Square statistics.  
10.3.2 Secondary Analyses 
For patient related outcomes pre-post analysis will be performed by parametrical or 
non-parametrical univariate tests. Subgroup analysis for upper and or lower extremity 
will be done. 
 
For Cost elements and cost description analysis, descriptive analysis will be performed 
including costs for technology, staff and infrastructure. Efficiency gains and suitable 
reimbursement models will be calculated.  
 
10.3.3 Interim Analyses 
n.a. 
10.3.4 Safety Analysis 
n.a. 
10.3.5 Deviation(s) from the Original Statistical Plan  
n.a. 
10.4 Handling of Missing Data and Drop-Outs  
Primary analysis is according to intention to treat – and all patients will be included. 
 

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For secondary analysis, all participants with equal or less than seven days training 
break of the planned training will be included only.  
 
Analysis of drop-outs will be carried out to find reasons or barriers (CRF) that might 
explain why sticking to the treatment plan was not possible, whether related or 
unrelated to the intervention.  

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11 ELIGIBILITY OF THE PROJECT SITE(S) 
Four rehabilitation centres located across the German speaking area of Switzerland will 
participate in this project. 
 
Klinik Lengg, Zurich 
The Klinik Lengg has a workload of 250-stroke patients a year. All patients fulfilling the 
inclusion criteria will be asked for participation. 
 
Reha Rheinfelden 
The Reha Rheinfelden has a workload of approximately 400 ischaemic and 
haemorrhagic stroke patients as in-and outpatients a year, which will recruited via direct 
contact and flyer distributed in-house. 
 
Kliniken Valens 
Kliniken Valens treated approximately 460 ischaemic and 150 haemorrhagic stroke in-
patients a year, who will be approached by a research assistant to check their eligibility 
while entering the clinical site for inpatient rehabilitation. 
 
Rehaklinik Zihlschlacht 
The Rehaklinik Zihlschlacht has a yearly workload of approximately 300 stroke patients; 
some of them will be treated after discharge in the clinic’s outpatient setting. Study 
personnel will approach patients regarded eligible for further evaluation. 
 
Each site aims to include five patients leading to 20 patients in total. Study sites are 
entering the study consecutively and according to their personnel capacity. Each site 
aims to include five patients leading to 20 patients in total. Study sites are entering 
the study consecutively and according to their personnel capacity.  

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12 DATA QUALITY ASSURANCE AND CONTROL 
The Sponsor-Investigator will provide all study sites with case report forms and written 
instructions. All study sites ensure that the trial is conducted and data are generated, 
documented (record), and reported in compliance with the protocol, GCP, and 
applicable regulatory requirement(s). 
Monitoring and Audits will be conducted during the course of the study for quality 
assurance purposes. 
12.1 DATA HANDLING AND RECORD KEEPING 
The study will strictly follow the protocol. If any changes become necessary, they must 
be laid down in an amendment to the protocol. All amendments of the protocol must be 
signed by the Sponsor-Investigator and if essential submitted to CEC.  
12.1.1 Case Report Forms  
The investigators will use paper case report forms (CRF), one for each enrolled study 
participant, to be filled in with all relevant data pertaining to the participant during the 
study. All participants who either entered the study or were considered not eligible or 
were eligible but not enrolled into the study additionally have to be documented on a 
screening log. The investigator will document the participation of each study participant 
on the Enrolment Log.  
CRFs will be kept current to reflect participant status at each phase during the course of 
study. Participants must not to be identified in the CRF by name. Appropriate coded 
identification (e.g. SRTI_ClinicCode_Number) must be used.  
It must be assured that any authorized person, who may perform data entries and 
changes in the CRF, can be identified. A list with signatures and initials of all authorized 
persons will be filed in the study site file and the trial master file, respectively. 
The investigators assure to perform a complete and accurate documentation of the 
participant data in the CRF. All data entered into the CRF from original questionnaires 
and assessment sheets will also be available in the individual participant file either as 
print-outs or as notes taken by either the investigator or another responsible person 
assigned by the investigator.  
Essential documents will be retained for at least 10 years after the regular end or a 
premature termination of the respective study (KlinV Art. 45).  
Any patient files and source data will be archived for the 10 years at each study site.  
12.1.2 Specification of Source Documents 
The following documents are considered source data, including but not limited to: 
• SAE worksheets 
• Case report forms 
 
Source data must be available at the site to document the existence of the study 
participants and substantiate the integrity of study data collected. Source data must 
include the original documents relating to the study, as well as the medical treatment 
and medical history of the participant. 

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The following information (at least but not limited to) should be included in the source 
documents 
• Demographic data (age, sex) 
• Inclusion and Exclusion Criteria details  
• Participation in study and signed and dated Informed Consent Forms  
• Visit dates  
• SAEs (related) and concomitant medication  
• Reason for premature discontinuation  
12.1.3 Record Keeping / Archiving  
All study data will be archived for a minimum of 10 years after study termination or 
premature termination of the clinical trial at each study site in a lockable and fireproof 
place. Informed consents and CRFs will be archived in separate places. Original study 
documents including any documents with personal information will be kept at the study 
site. There will be kept in fireproofed locker, accessible only by Study personnel.  
Copies of CRFs, including the clinic code will be transferred to the Sponsor investigator 
site and will be kept on a secure data pool only accessible by involved study personnel. 
The data pool will be closed after the end of the study and will by then only be 
accessible according to the separation of duties (SOD) principle. 
12.2 Data Management  
Copies of the CRF will be transferred by each site investigator and uploaded on a 
security pool at the sponsor investigators site. Original data will be kept at the clinical 
site in a lockable and fireproof place, the informed consent will be separated from other 
documents. Only study personnel involved in the clinical trial will have access to that 
security pool. No personnel data will be transferred but kept at each study site and 
separated from the CRF. Data from CRFs will be entered to electronic spreadsheets 
using double data entry and saved as raw file. During further data processing and 
analysis, edited files will be renamed with actual dates and acronyms of the responsible 
person. Original files (paper or electronic) will not be changed 
12.3 Routine Monitoring 
Monitoring visits at the investigator’s site prior to the start and during the course of the 
study will help to follow up the progress of the clinical study, to assure utmost accuracy 
of the data and to detect possible errors at an early time point. The Sponsor-Investigator 
organizes professional independent monitoring for the study.  
All original data including all patient files, progress notes and copies of laboratory and 
medical test results must be available for monitoring. The monitor will review all or a 
part of the CRF and written informed consents. The accuracy of the data will be verified 
by reviewing the above referenced documents. 

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12.4 Audits and Inspections 
A quality assurance audit/inspection of this study may be conducted by the CEC. The 
quality assurance auditor/inspector will have access to all medical records, the 
investigator's study related files and correspondence, and the informed consent 
documentation that is relevant to this clinical study. 
The investigator will allow the persons being responsible for the audit or the inspection to have 
access to the source data/documents and to answer any questions arising. All involved parties 
will keep the patient data strictly confidential. 
12.5 Confidentiality, Data Protection  
Direct access to source documents will be permitted for purposes of monitoring, audits 
and inspections to the authorities of the responsible ethical committees.  

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13 PUBLICATION AND DISSEMINATION POLICY  
After the statistical analysis of this trial, the sponsor will make every endeavor to publish 
the data in a medical journal.  

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14 FUNDING AND SUPPORT  
14.1 Funding  
This study receives funding from an anonymous Swiss Foundation. 
14.2 Other Support  
NA 

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15 INSURANCE 
Insurance is covered by “Versicherung für klinische Versuche und nichtklinische 
Versuche“ by Zürich Versicherungs-Gesellschaft AG (Policy no.: 14.237.322). 
Any damage developed in relation to study participation is covered by this insurance. So 
as not to forfeit their insurance cover, the participants themselves must strictly follow the 
instructions of the study personnel. Participants must not be involved in any other 
medical treatment without permission of the principal investigator (emergency 
excluded). Medical emergency treatment must be reported immediately to the 
investigator. The investigator must also be informed instantly, in the event of health 
problems or other damages during or after the course of study treatment. 
The investigator will allow delegates of the insurance company to have access to the 
source data/documents as necessary to clarify a case of damage related to study 
participation. All involved parties will keep the patient data strictly confidential. 
A copy of the insurance certificate will be placed in the Investigator’s Site File. 
 
 

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