Prospective Multicentre Open Clinical Study to Assess the Safety Performance and Durability of the TIES® Transcutaneous Titanium Implant in Patients Requiring a Permanent Ileostomy
Phase: NA
Conditions: Ileostomy - Stoma
Sponsor: Ostomycure AB

 
 
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TIES® C03 Study  
 
Prospective multicentre open clinical study to assess the safety 
performance and durability of the TIES® transcutaneous titanium 
implant in patients requiring a permanent ileostomy 
 
 
Protocol No 
TIES® III C03 
 
Version 
5.0  
Date 
02 Feb 2022 
Sponsor 
OstomyCure AS 
Oslo, Norway 
 
 
 
 
 
 
EXCLUSIVELY FOR CLINICAL INVESTIGATION 
 
 
 
 
 
 
 
 
This document contains confidential information and is limited in its distribution 
outside OstomyCure AS to Investigators, Ethics Committees and Competent Authorities 
only. Copying of the confidential information is not permitted without the written 
approval of the Sponsor. 
 
 
 
 
 
 
 
 
 
 

 
 
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CONFIDENTIALITY STATEMENT 
The information contained in this document, especially unpublished data, is the property of 
OstomyCure AS (the Sponsor) and therefore is confidential and may not be disclosed unless 
such disclosure is required by law or regulation. OstomyCure confidential information may be 
disclosed to the Investigator(s), potential Investigator(s) and necessary Investigator 
assistant(s) or study personnel. In any event, persons to whom the information is disclosed 
must be informed that the information is privileged or confidential and may not be further 
disclosed by them without written authorization from OstomyCure AS. These restrictions on 
disclosure will apply equally to all future information supplied to the Investigator(s), potential 
Investigator(s) and necessary Investigator assistant(s) or study personnel, which is indicated 
as privileged or confidential. 
 
 

 
 
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SPONSOR 
Person or organization that takes responsibility for the initiation and / or the implementation 
of a clinical investigation: 
Name: 
OstomyCure AS 
Address: 
Gaustadalléen 21 
0349 OSLO, Norway 
 
CLINICAL INVESTIGATION ORGANIZATION 
 

 
 
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Clinical monitor for the sponsor 
Person designated by the sponsor to verify the progress of a clinical investigation, i.e. verify 
that it is conducted, recorded and communicated according to the clinical investigation plan, 
the written procedures, the ISO 14155 standard and the applicable requirement(s): 
Name: 
Devicia AB 
Address: 
Argongatan 2C 
431 53 Mölndal 
Sweden 
Phone number: 
+46 (0)725 55 06 65 
Email: 
lars.enochson@devicia.com 
 
 
Data management centre 
Organization designated by the sponsor for the data management of the clinical 
investigation, the analysis and the data transfer to the sponsor:  
Name: 
Devicia AB 
Address: 
Argongatan 2C 
431 53 Mölndal 
Sweden  
Phone number: 
+46 (0)725 51 57 02 
Email: 
matina.starck@devicia.com 
Protocol statistician 
Name: 
Tim Farley Ph D 
Address: 
Sigma3 Services SARL Geneva Switzerland 
8 rue St Jean 
1260 Nyon, VD 
Switzerland 
Phone number 
+41 22 548 18 32 
Email: 
tim.farley@sigma3services.com 
 
 

 
 
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PROTOCOL SIGNATURE PAGE 
PROTOCOL NUMBER: TIES® C03 STUDY 
Prospective multicentre open clinical study to assess the safety 
performance and durability of the TIES®  transcutaneous titanium 
implant in patients requiring a permanent ileostomy 
 
I have read the Clinical Investigation Plan mentioned above and agree to adhere to its 
requirements. 
I have received a copy of the most current version of the Investigator’s Brochure.  
I will provide copies of the Protocol and access to all information furnished by OstomyCure 
(“Sponsor”) to the study personnel under my supervision and involved in carrying out the study. 
I will discuss this material with them to ensure that they are fully informed about the 
investigational device and the conduct of the study. 
I have read the Confidentiality Statement of this Protocol. The contents of this Protocol may 
not be used in any other clinical study and may not be disclosed to any other person or entity 
without the prior written permission of the Sponsor. The foregoing shall not apply to disclosure 
required by law or regulation, for example submission to an Ethics Committee; however, I will 
give prompt notice to the Sponsor of any such disclosure. 
 
Site Number/Name:  
____________________________________________ 
Printed Name of Investigator: 
____________________________________________ 
Date: __________________ 
Signature: 
 
Printed Sponsor Name & Title: 
____________________________________________ 
Date: __________________ 
Signature: 

 
 
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PROTOCOL SYNOPSIS 
Title: 
Prospective multicentre open clinical study to assess the safety 
performance and durability of the TIES® transcutaneous titanium 
implant in patients requiring a permanent ileostomy 
Protocol Number: TIES® III C03 
Medical Device: 
TIES® (Transcutaneous Implant Evacuation System) 
Study Design: 
 
 
This is a prospective open multi-center clinical study that evaluates the 
safety, performance and durability of the TIES® transcutaneous titanium 
implant (TIES® Port) to 12-months post implantation. A minimum of 200 
patients from up to 25 sites will be enrolled in the study.  
The study population includes patients requiring a permanent ileostomy; 
or patients with a medical need for an alternative to an existing 
conventional ileostomy, continent ileostomy or pelvic pouch. 
This protocol plans for five interim data analyses. The first two interim 
analysis are planned after collection of 8-week results from the first 5 
and of 24-week results of the first 20 subjects respectively, to review all 
available study data and to assess if there is a need to modify the study 
protocol including adjusting the collection of outcome measurements for 
performance assessment.  The third, fourth and fifth interim analyses 
will be conducted when 50, 100 and 150 subjects, respectively, have 
completed 24 weeks follow-up in order to assess the primary and 
secondary 24-week safety and performance endpoints, make a 
preliminary assessment of the types of patient with high device 
acceptability, and consider whether some of the secondary study 
instruments (e.g. Quality of Life Questionnaires) can be dropped for the 
remaining patients to simplify follow-up and reduce burden on patients 
and clinical teams. 
This study will be conducted in accordance with the Standard ISO 
14155 and other legal requirements. 
Study Objectives: The primary objective is to evaluate the safety, performance and 
durability of the TIES® system to 12 months. Quality of Life (QoL) in 
subjects implanted with TIES® device will also be assessed as a 
secondary objective. 
Study Treatment: 
Subjects who are eligible for enrolment and can tolerate surgery will 
undergo 
a 
conventional 
ileostomy 
procedure 
under 
general 
anaesthesia. and the TIES® Port is implanted transcutaneous to form 
part of the stoma. 
Revision of the implant procedure, implantation of a second implant, or 
explantation is allowed based on investigator´s assessment.  
Performance 
Evaluation 
Performance evaluation is based on subject´s assessment of 
performance as recorded on the 3-day  
 preceding each scheduled follow-up at 16, 24, 36 and 52 weeks after 
operation.  Performance evaluation applies only among subjects with 
the TIES® Port in situ.   

 
 
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Among subjects with the TIES® Port in situ,  performance  will be 
assessed according to (a) the proportion of subjects who use the 
TIES® Lid for continence control; (b) the proportion of subjects 
experiencing visible leakages around the implant; and (c) subject´s 
assessment on the ease of use of the TIES® Solution.  
Primary endpoint is absence of visible leakage or fecal staining of 
clothing at 24 weeks after implantation of the TIES® Port.   
The success criterion at 24 weeks requires at least 70% of subjects 
with the TIES® Port in situ having no visible leakage or staining of 
clothing adjacent to the implant between consecutive episodes of 
using the lid for continence control. Spillage that might occur at 
opening of the lid is not regarded as leakage. 
Secondary endpoints are  
• 
Absence of visible leakage or fecal staining of clothing at 16, 
36 and 52 weeks.   
• 
Proportion of implanted subjects using the TIES® Lid  for 
continence control at 16, 24, 36 and 52 weeks.  
• 
Subject´s assessment on the ease of use of the TIES® Lid using 
a visual analog scale 16, 24, 36 and 52 weeks after implantation.  
• 
Subject´s preference for the TIES® solution assessed at 52 
weeks.  
The subject´s assessment on the ease of use of the TIES® Lid will 
provide feedback to the manufacturer regarding future refinements of 
the TIES® solution. Information will be collected in the diary to 
understand patient´s needs as described in section 10.  
Durability 
Evaluation 
Durability of use is evaluated by the cumulative proportion of subjects 
with the TIES® Port in situ at each of the following timepoints of 8,16, 
24, 36 and 52 weeks. These are secondary endpoints.  
Durability will be computed by lifetable methods as the complement of 
the cumulative proportion of subjects in whom the TIES® Port has been 
removed or has spontaneously explanted, with subjects censored if they 
withdraw from the study with the device in situ, have insufficient follow-
up time, or the device is removed for reasons unrelated to device 
performance. 
Safety Evaluation Safety outcome measures are secondary endpoints and will be 
analysed as proportion of all implanted subjects using descriptive 
statistics. Safety information will be collected during the following 
intervals: during hospitalisation, interval from discharge to 4-weeks visit, 
interval after the 4-weeks visit including 8-weeks visit, interval after the 
8-weeks visit including 16-weeks visit, interval after the 16-weeks visit 
including 24-weeks visit, interval after the 24-weeks visit including 36-
weeks visit, and interval after the 36-weeks visit including 52-weeks 
visit.  
Secondary endpoints are: 
• 
Proportion of implanted subjects with treatment emergent 
adverse events. Treatment emergent adverse events are 
defined as events with onset during or after the implantation 

 
 
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procedure.  
• 
Proportion of implanted subjects with peristomal skin lesions will 
be evaluated using a validated 5-point scale by assessing signs 
of erythema, erosion, or papular lesions.  
• 
Proportion of implanted subjects with device-related adverse 
event.  
• 
Proportion of implanted subjects with device displacement, 
device revision or device replacement. 
Photographs of the stoma are to be taken to document the ingrowth into 
the TIES® Port, surrounding peristomal skin and position of the implant 
at 4, 8, 16, 24, 36 and 52 weeks after implantation.  
Quality of Life 
Evaluation 
Impact on quality of life will be evaluated by using two validated 
instruments EQ-5D-5L Quality of Life (QoL) questionnaire and Montreux 
Quality of Life questionnaire.  
Secondary endpoints are: 
Change in quality of life from baseline at 8, 16, 24, 36 and 52 weeks 
post implantation will be assessed among subjects with the device in 
situ. 
Participating 
Sites: 
Up to 25 sites will be enrolling in up to 6 countries in Europe and Asia.  
Study Population 
and Sample Size: 
A minimum of 200 patients will be enrolled. These patients have an 
indication for a permanent ileostomy, e.g., ulcerative colitis, familial 
adenomatous polyposis coli, or other diseases requiring elective 
colectomy; or patients with a medical need for an alternative to an 
existing conventional ileostomy or continent ileostomy or pelvic pouch. 
 
Inclusion Criteria: 
Subjects will be included if the following criteria are met: 
1) Subject has ulcerative colitis, familial adenomatous polyposis 
coli or other diseases for whom a permanent ileostomy is 
indicated; or the subject has a medical need for an alternative to 
an existing conventional end-ileostomy, continent ileostomy or 
pelvic pouch; and 
2) Patient is a male ≥18 years of age or female ≥18 years of age 
(See exclusion criterion 4 regarding female with childbearing 
potential); and 
3) Signed written informed consent has been obtained prior to any 
study- related procedure. 
Exclusion 
Criteria: 
Subjects will be excluded if any one of the following conditions exists: 
1) Concurrent gastrointestinal fistula, parastomal or incisional 
hernia, or a history of recurrent gastrointestinal fistula, recurrent 
parastomal hernia(s), and/or recurrent incisional hernia(s). 
2) Patients with undetermined colitis. 

 
 
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3) Patients with Crohn´s disease  
4) Females who are of childbearing potential and do not wish to 
use birth control measures for the duration of the study 
5) Patients receiving immunosuppressives, oncologic treatment or 
anticoagulants.  
6) Any clinically significant, abnormal, baseline laboratory result 
which in the opinion of the surgeon, affects the patient’s 
suitability for the study or puts the patient at risk if he/she 
undergoes surgery 
7) Severe illness which, in the opinion of the surgeon may put the 
patient at risk when participating in the study or may affect the 
patient’s ability to complete the study visits 
8) Condition associated with the risk of poor protocol compliance, 
e.g. alcoholism and/or drug abuse, dementia, self-destructive 
personality disorder 
9) Subjects with BMI ≤ 17 kg/m2 or BMI ≥ 33 kg/m2 
10) Participate in other clinical studies that could interfere with the 
result in the ongoing study 
Estimated 
Timelines  
Estimated duration for enrolment: 48 months  
Duration of participation for each subject:  12 months 
Total study duration: 5 years 
Clinical Study 
Organization: 
Sponsor: OstomyCure AS 
                Gaustadalléen 21                  
     0349 Oslo,  
     NORWAY 
Monitor : Devicia AB 
               Argongatan 2C 
               431 53 Mölndal 
               Sweden 
 
A Data Safety Monitoring Board will be appointed to review interim study 
results as discussed in section 9. A dermatologist will provide 
independent review of photographs of the stoma for peristomal skin 
lesions as required. 
 

 
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Schedule of Assessments / Flow Chart: 
Parameter/ 
Examination 
Screening 
Baseline a 
Procedure 
(day 0) 
Post OP 
(Daily 
follow up c) 
Discharge 
Visit 1 at 4 
Weeks 
(+/- 7d) 
Visit 2 at 8 
weekse 
(+/- 7d) 
Visit 3 at 
16 weeks 
(+/- 7d) 
Visit 4 at 
24 weeks 
(+/- 14 d) 
Visit 5 at 
36 weeks 
(+/- 14 d) 
Visit 6 at 
52 weeks 
(+/- 14 d) 
Informed Consent 
 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Physical Examinationf  
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Dipstick urine-analysis 
 
X 
 
 
 
 
 
 
 
 
 
ECG 
 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test b 
 
X 
 
 
 
 
 
 
 
 
 
Hematology and Chemistry  
 
X 
 
 
 
 
 
 
 
 
 
Review and instruct on care of the 
stoma 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Removal of Turnbull Adaptord 
 
 
 
 
 
X 
 
 
 
 
 
Start to use TIES® Lid 
 
 
 
 
 
 
X 
 
 
 
 
Adverse Events (AE) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety evaluation 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ingrowth assessment 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Photographsg of implant, stoma and 
adjacent skin 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
QOL questionnaires 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
Performance Questionnaire (Diary 
covering one 72-hours period) 
 
 
 
 
 
 
 
X 
X 
X 
X 
Subject´s preference questionaire 
 
 
 
 
 
 
 
 
 
 
X 
a The patient will be considered as enrolled only when the consent will have been signed. All the examinations performed before the enrolment are done according to routine practice at the hospital where the study takes place. 
The baseline assessment should be performed not earlier than 12 weeks before the procedure. 
b Pregnancy test will be performed in woman of childbearing potential.  
c A follow up will be performed every day after the procedure prior to discharge from hospital. 
d Removal of Turnbull system will be performed at 4 weeks (+/- 7 days) only if it has not already detached by itself.  
eThe patient will continue to permanently use stoma bags until visit at 8 weeks for review of suitability to start using the TIES®Lid. If trimming of ileum is required, postpone use of TIES® Lid by about a week for healing. 
f Physical examination also includes weight measurement 
g At least 4 views of the stoma should be taken: horizontal, vertical frontal, verical right and vertical left. Additional views may be required if skin lesions or device displacement develop. 

 
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TABLE OF CONTENTS 
 
1. 
Introduction ..................................................................................................................... 15 
1.1. Medical need for ileostomy and burden for patients ......................................................... 15 
1.2. Transcutaneous Implant Evacuation System (TIES®) as an add-on to the stoma of 
conventional ileostomy to enable continence control ........................................................ 16 
1.3. Study rationale .................................................................................................................. 16 
1.4. Pre-Clinical Testing ........................................................................................................... 16 
1.5. Completed Clinical Studies ............................................................................................... 16 
2. 
Transcutaneous Implant Evacuation System ............................................................... 17 
2.1. Overview of the TIES system ............................................................................................ 17 
2.2. Intended use ..................................................................................................................... 20 
2.3. Manufacturing ................................................................................................................... 21 
2.4. Training ............................................................................................................................. 22 
3. 
Study Design ................................................................................................................... 22 
3.1. Rationale for the Study Design ......................................................................................... 22 
3.2. Participating Sites and Study Population .......................................................................... 23 
4. 
Study Objective and Endpoints ..................................................................................... 23 
4.1. Performance Evaluation .................................................................................................... 23 
4.2. Durability Evaluation ......................................................................................................... 24 
4.3. Safety Evaluation .............................................................................................................. 24 
4.4. Quality of Life Evaluation .................................................................................................. 24 
5. 
Subject Selection ............................................................................................................ 25 
5.1. Inclusion Criteria (IC) ........................................................................................................ 25 
5.2. Exclusion Criteria (EC) ...................................................................................................... 25 
5.3. Subject Accountability ....................................................................................................... 26 
6. 
Study Procedures and Assessments ............................................................................ 26 
6.1. Subject Identification ......................................................................................................... 26 
6.2. Screening .......................................................................................................................... 27 
6.3. Enrolment .......................................................................................................................... 27 
6.4. Informed Consent Process ................................................................................................ 27 
6.5. Baseline Visit ..................................................................................................................... 28 
6.6. TIES® Port Implantation Procedure ................................................................................... 28 
6.7. Hospital Discharge ............................................................................................................ 29 
6.8. Turnbull Adaptor Removal ................................................................................................ 29 
6.9. Follow-Up Visits ................................................................................................................ 29 
6.10. Unscheduled Visits ............................................................................................................ 31 
6.11. Follow-up treatment after end of investigation .................................................................. 31 
6.12. Photography of the stoma including the implant and peristomal skin ............................... 32 
6.13. Quality of Life (QoL) Questionnaires ................................................................................. 32 
6.14. TIES® System Performance Evaluation Questionnaire – Subject´s diary ......................... 32 
6.15. Subject´s Preference Evaluation ....................................................................................... 32 

 
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6.16. General Investigational Device Management ................................................................... 33 
6.17. Withdrawals or Discontinuation ......................................................................................... 33 
7. 
Risk-Benefit Analysis ..................................................................................................... 34 
7.1. Risks Assessment and Risk Mitigation ............................................................................. 34 
7.2. Benefit Assessment .......................................................................................................... 36 
8. 
Adverse Event Management .......................................................................................... 37 
8.1. Definitions ......................................................................................................................... 37 
8.2. Event severity .................................................................................................................... 38 
8.3. Causality relationship ........................................................................................................ 39 
8.4. Investigator Reporting Responsibilities ............................................................................. 40 
8.5. Reporting to Ethic Committee / Competent Authority ....................................................... 41 
9. 
Data safety monitoring board ........................................................................................ 41 
10. 
Statistical Considerations .............................................................................................. 41 
10.1. Objective of the study ........................................................................................................ 41 
10.2. Study design ..................................................................................................................... 42 
10.3. Study Population Definition ............................................................................................... 42 
10.4. Performance Evaluation .................................................................................................... 42 
10.5. Sample size ....................................................................................................................... 43 
10.6. Durability Evaluation ......................................................................................................... 44 
10.7. Safety Evaluation .............................................................................................................. 44 
10.8. Quality of Life Evaluation .................................................................................................. 45 
10.9. Statistical analysis ............................................................................................................. 46 
10.10. 
Additional analyses ......................................................................................... 46 
11. 
General Study Considerations ....................................................................................... 47 
11.1. Ethical and Regulatory Considerations ............................................................................. 47 
11.2. Amendments ..................................................................................................................... 48 
11.3. Protocol Deviations ........................................................................................................... 48 
11.4. Data handling and Record Keeping .................................................................................. 49 
11.5. Monitoring ......................................................................................................................... 49 
11.6. Insurance .......................................................................................................................... 49 
11.7. Publication Policy .............................................................................................................. 50 
11.8. Funding and agreements .................................................................................................. 51 
12. 
Bibliography/References ................................................................................................ 52 
13. 
Appendices ...................................................................................................................... 54 
 

 
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List of Abbreviations 
Term 
Definition 
AE 
Adverse event 
ADE 
Adverse Device Effect  
BP 
Blood Pressure 
CA 
Competent Authority 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
CV 
Curriculum Vitae 
DCF 
Data Clarification Form 
EC 
Ethics Committee 
EDC 
Electronic Data Capture System 
FIH 
First-in-Human 
GCP 
Good Clinical Practice 
HR 
Heart Rate 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
MPA 
Medical Product Agency 
NA 
Not Applicable / Not Available 
PMS 
Post Market Study 
QA 
Quality Assurance 
QC 
Quality Control 
QoL 
Quality of Life 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification 
TIES® 
Transcutaneous Implant Evacuation System  
 
 
 

 
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Glossary 
 
TIES® System 
TIES® Port, Diathermy Leveller, Dummy (Sizer), Turnbull Adaptor, 
Stabiliser, Lid and Emptying Pouch 
 
TIES® Surgical 
Aids 
TIES® Diathermy Leveller, Dummy (Sizer) and Turnbull Adaptor (a sub-
set of TIES® System used by the surgeon) 
TIES® Port 
TIES® Port is a titanium implant that is implanted transcutaneously to 
become part of the stoma. The TIES® Lid is put on the TIES® Port. 
 
 

 
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1. 
INTRODUCTION  
The Transcutaneous Implant Evacuation System (TIES®) consists of an implantable TIES® 
Port and several aids that enables continence control for patients who would otherwise need 
to wear an ileostomy bag continuously following conventional ileostomy surgery.  See section 
2 on intended use and a description of the system. 
1.1. 
Medical need for ileostomy and burden for patients 
In some patients suffering from ulcerative colitis, familial polyposis and large bowel cancer, 
medical treatment alone is not sufficient and surgery is required for partial or total removal of 
the affected organ with construction of an ileostomy.  
 
Three major types of ileostomies may be made based on individual needs as illustrated in 
Figure 1. They are (1) pelvic pouch or ileo-anal pouch where the colon is removed and a part 
of the ileum is used to form a pouch which connects to the rectum; (2) a procedure called 
continent ileostomy ad m. Kock; and (3) conventional ileostomy for patients unsuitable of (1) 
and (2), or failed ileo-anal pouch or continent ileostomy.  
 
 
Ileo-anal pouch (J, S or W 
variants) 
 
continent ileostomy (requiring 
drainage via catheter) 
 
conventional 
ileostomy 
(drainage into a stoma bag) 
 
Figure 1 Illustrations of 3 major types of ileostomies 
         
  

 
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Each of these three procedures are associated with complications and failure rates (Refer to 
Investigator´s Brochure). Known complications associated with conventional ileostomy 
include poor stoma siting, high output, ischemia, retraction, parastomal hernia and prolapse; 
with skin irritation, a common problem affecting at least 30% of patients due to exposure to 
intestinal contents or use of the stoma bags. 
Serious complications requiring reoperations can also occur, as can minor problems that will 
subject the patient to daily and nightly discomfort.  
 
 
 
 
 
1.2. 
Transcutaneous Implant Evacuation System (TIES®) as an add-on to the stoma of 
conventional ileostomy to enable continence control 
Patients with conventional ileostomy have to wear a stoma bag attached to the abdomen for 
collection of faeces continuously. Despite the availability of a large number of light weight, 
hygienic and discrete bags, many patients suffer from complications such as skin problems, 
leakage and odour, and for some the mere change of body image results in social isolation.  
The titanium Port of the Transcutaneous Implant Evacuation System (TIES®), which is the 
subject of this study, is placed onto the surgical opening or stoma after intestinal segment 
resection and provides a permanent patient-controlled continent stoma for emptying of 
intestinal wastes and reduces/ obviates the need of using a stoma bag. It is hoped that by 
eliminating seepage, odour, noise, and the need for permanently wearing stoma appliance, 
quality of life will be improved. 
 
1.3. 
Study rationale 
The TIES® System has been studied in two studies (C01 and C02) involving a total of 11 
patients and 13 implantation procedures. This study is planned to collect more data on patients 
using the TIES® System for continence control.  This study will evaluate safety, performance, 
durability and impact on quality of life in this patient population.  
While the two completed studies gave assurance on the safety and reversibility of the 
procedure, most of the enrolled subjects had complicated baseline medical histories including 
failed pelvic pouch, failed continent ileostomy or experienced complications associated with 
previous ileostomy such as parastomal hernia or granulomatous overgrowth. The subject who 
achieved the best outcome for continence control using the TIES® Port in the C02 study was 
the one subject who had not undergone previous abdominal surgery.  
In addition, based on learnings from the two previous studies, the eligibility criteria have been 
further refined in this study and clarification included in the protocol on post-implantation care 
and the adaptation period. 
1.4. 
Pre-Clinical Testing 
Development of the TIES® implant has been ongoing since 2004. Previous animal testing on 
pigs and dogs showed the growth of tissue into the implant (ref 30 Johansson ML et al). 
During these studies the method of implantation, implant design has gradually evolved and 
improved with documentation of safety and performance.  (See Investigator´s Brochure) 
1.5. 
Completed Clinical Studies 
The implantation and implantation method has been modified gradually since the first clinical 

 
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study in 2009. Based on knowledge gained from the two studies, this has led to improvements 
in both the implant, patient selection and post-implantation care.  
The two small pre-market studies on the use of the TIES® system in humans provided data on  
a total of 11 subjects who were implanted with TIES® Port. In retrospect many of the subjects 
had baseline surgical conditions that may have impacted on the final outcome from 
implantation of the Port. For example, some of the subjects had pre-existing incisional or 
parastomal hernia and the Port was explanted as part of the hernia repair procedure.  
Implants remained in situ for longer than 6 months in ten subjects, longer than 12 months in 
five subjects and over 60 months in three subjects who are still requesting supply of TIES® 
Lid from the manufactuer. One subject developed an enterocutaneous fistula and this subject 
also had a pelvic pouch removed at the same surgery for implantation of the Port, the possibility 
cannot be excluded that this surgery or the surgical staples left behind might have contributed 
to the formation of the fistula. No unanticipated serious device related adverse events were 
reported. In those subjects who were either explanted or implanted with a second Port, the 
Port could be explanted without any difficulties and conversion to a conventional ileostomy 
could be performed without complications. This gives assurances for safety before proceeding 
with implantation in a larger group of patients, including those undergoing ileostomy for the 
first time.  (See Investigator´s Brochure) 
2. 
TRANSCUTANEOUS IMPLANT EVACUATION SYSTEM 
2.1. 
Overview of the TIES system 
2.1.1. 
Overview of the Transcutaneous Implant Evacuation System (TIES®) 
The Transcutaneous Implant Evacuation System (TIES®) is a complete method for 
constructing a stoma after intestinal segment resection. The TIES® system represents a 
concept for continent stoma creation in gastroenterological surgery. The system prevents 
seepage, and reduces or even may eliminate the need for wearing an external appliance 
(e.g. pouch/bag) on the abdomen after removal of the large intestine for collection of 
intestinal contents. 
 
The TIES® system is composed of the TIES® Port, TIES® Surgical Aids, TIES® Stabiliser and 
TIES® Lid and Emptying Pouch. Only the TIES® Port is implanted. The three TIES® Surgical 
Aids are tools used at the surgical procedure to optimise the surgical procedure. They 
comprise of Diathermy Leveller to guide optimal depth for the Port, Dummy (Sizer) to verify 
suitable fit and the TIES® Turnbull Adaptor clipped onto the cylinder top of the Port for use 
during the ingrowth period. The TIES® Stabiliser is placed under the TIES® Turnbull Adaptor 
and is used to secure the port above the skin during healing. The TIES® Turnbull Adaptor is 
removed when the intestine has grown enough into the implant if it has not already detached 
by itself. The TIES® Stabiliser is left longer until the TIES® Lid can be used from about 2 
months after the implant procedure. 
 
An overview of the system and the products is included below in Figure 2.  
  

 
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Figure 2 TIES system overview 
2.1.2. 
Description of the components of the TIES® system 
 
TIES® Port (Figure 3) is a titanium implant that is implanted transcutaneously and anchored 
in the subcutaneous fat and penetrates the skin. The ileum is attached through the implant to 
create a stoma. The implant is manufactured by laser melting of medical grade titanium 
powder. The Port comprises five functional sections: Cylinder Top, Upper Ingrowth Zone, 
Subdermal Ingrowth Zone, Anchor & Cylindrical Scaffolding and two technical features: Lid 
Groove and Turnbull Adaptor Notch as shown in Figure 3 below. The Anchor is an integrated 
disc that secures the implant in the subcutaneous fatty tissue. TIES® Port is supplied sterile 
in a single use sterile bag and must be implanted using sterile technique.  
  
TIES® Port 
 
1. Cylinder Top 
2. Lid Groove 
3. Turnbull Adaptor Notch 
4. Anchor 
5. Upper Ingrowth Zone 
6. Subdermal Ingrowth Zone 
7. Cylindrical Scaffolding 
Port  
(Implantable) 
Dummy 
(Sizer) 
Diathermy 
Leveller 
Stabiliser 
Turnbull 
Adaptor 
TIES System  
Lid 
Class IIb 
Class I 
Class IIa 
Professional user  
Patient 
Class I 
Class IIa
Class IIa
Emptying 
Pouch 
Class I 
2 
3 
7 
6 
4 
1 
5 

 
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Figure 3 TIES Port 
TIES® Surgical Aids consist of three simple aids that optimize the surgical procedure for the 
TIES® Port. 
 
TIES® Diathermy Leveller (Figure 4) is an optional support 
plate against the skin that is snap-locked onto the 
diathermy electrode when making a circular incision for the 
Anchor in the sub-cutis. This is to ensure that the incision 
is at the optimum depth (8 mm) and is fully level relative to 
the skin. The Diathermy Leveller also contains a fixture that 
ensures that the diathermy electrode point can be bent at 
approximately 90° at the correct place. It is supplied sterile 
in a single use sterile bag and must be used using sterile 
technique.  
 
 
Figure 4 Diathermy Leveller 
TIES® Dummy, or Sizer, (Figure 5) is used to verify that the 
ileum will fit well with the Port. It is supplied sterile in a 
single use sterile bag and must be used using sterile 
technique.  
 
 
Figure 5 TIES Dummy (Sizer) 
TIES® Turnbull Adaptor (TA) (Figure 6) is an applicator that 
is positioned (clipped) on to the Cylinder Top of the Port. 
The TA is used to flip the end part of the intestine over its 
edge and suture the intestine to the outer circumference of 
the TA. TIES® Turnbull Adaptor is supplied sterile in a 
single use sterile bag and must be used using sterile 
technique.  
 
 
Figure 6 Turnbull Adaptor 
 
TIES® aids to be used after surgery 
TIES® Stabiliser (Figure 7) is used to secure the Port and to 
provide support above skin level during the in-growth 
period. It consists of a pair of Spacers used together with a 
Locking Ring as shown in fig 5. It is affixed to the Port after 
surgery is completed, fitting into the Lid Groove on the 
Cylinder Top of the Port. TIES® Stabiliser is supplied clean 
and disinfected but not sterile. It is handled in a non-sterile 
environment and is re-usable. It can be rinsed in tap water 
but will withstand household detergents. It can also be 
soaked in 70 % alcohol. The TIES® Stabiliser should be 
replaced every week.  
 
Figure 7 TIES Stabiliser 
 

 
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TIES® Lid (Figure 8) is a removable cap attached to 
TIES® Port. It is used to achieve a continent stoma after 
the ileum has grown into the implant and healed 
completely. The Lid has an integrated emptying hole 
that can be opened to empty the stoma without 
removing the Lid. 
 
TIES® Lid is re-usable and can be cleaned in the same 
way 
as the Stabiliser.  
 
Replace the Lid every week.  
 
Figure 8 TIES Lid 
TIES Emptying Pouch (figure 9) is a dedicated 
accessory to the Lid, used when emptying the intestinal 
content. The pouch is placed over the Lid, with the 
connector fitting into the groove around the base of the 
Lid. The pouch has a tear-off base for simple conversion 
into an open-ended sleeve, allowing for emptying either 
into the pouch or directly into the toilet.  
 
The Emptying Pouch is intended for single use. 
 
Figure 9 
TIES Emptying Pouch 
 
 
Refer to the TIES® Surgical Procedure Manual and the TIES® User Care Manual in the 
appendix for further explanations and instructions (See Appendices). 
2.2. 
Intended use 
The objective for TIES® is to provide a continent, sanitary, odourless system to be used in 
various patient groups investigated in previous studies: 
• 
Patients with diseases such as ulcerative colitis, familial adenomatous polyposis coli, 
multiple colonic cancers or other diseases requiring elective colectomy followed by a 
permanent ileostomy, ileo rectal anastomosis or ileal pouch-anal anastomosis. 
• 
Patients with a failing conventional ileostomy, continent ileostomy, ileo-rectal 
anastomosis or ileal pouch-anal anastomosis. 
Patients with Crohn’s disease will not be enrolled in the trial.  
The implant or TIES® Port is used to construct a stoma by implantation in the abdominal wall, 
penetrating the skin, and is anchored in the dermal and subcutaneous tissues. The ileum outlet 
is passed through the implant. The internal mesh structure in the TIES® Port implant facilitates 
a biological attachment of the bowel segment to the implant. The Turnbull Adaptor is clipped 
on the cylinder top of the TIES® Port. It is used during the first weeks to provide optimum in-
growth conditions by securing the ileum above the TIES® Port. The Stabilizer is positioned 
around the implant in order to secure the implant and provides support above skin level during 
the in-growth period. 

 
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During the first weeks, patients will have to use standard stoma bags. Below is a drawing 
(Figure 10) of a cross section of abdominal wall displaying the TIES® Port connected to a 
conventional ileostomy stoma. 
 
Figure 10  Cross-section showing the ileum connected to the TIES Port (no Lid attached).  
After about four weeks the intestine has grown enough into the implant for the Turnbull Adaptor 
to be removed, if the Turnbull Adaptor has not already detached by itself from the stoma.  
The part of the intestine protruding outside the implant has now started to wizen and, if 
necessary, is trimmed away by the surgeon in a simple procedure if required and the intestine 
will now reside permanently just at the top of the implant. 
Once the implant is healed and fully integrated into the tissue, the top of the implant can be 
closed with a TIES® Lid. The TIES® Lid has an integrated emptying hole which can easily be 
opened and closed. Together with a TIES Emptying Pouch, this allows for the system to be 
emptiedin a soil-free procedure.  
    
 
 
Figure 11 The ileostomy is being emptied with an irrigation sleeve. 
2.3. 
Manufacturing 
The manufacturing of the Port is subcontracted by OstomyCure AS to 3DSystems, an 
ISO13485 approved medical device subcontractor.  The TIES® Port is sterilized with steam 
sterilisation by autoclaving. Please refer to the Investigators Brochure for more detailed 
manufacturing information of all system parts. 

 
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2.4. 
Training 
The Sponsor is responsible for providing site personnel with the information and training they 
need to conduct the study properly. Study-specific training and education is required for all site 
staff with roles in this trial. The Sponsor is responsible for maintaining documentation of 
attendance at each of the training sessions provided.   
The Sponsor personnel will provide training and technical support on the TIES® System and 
procedure to the Investigator and other health care personnel as needed before and during 
procedure and testing required by the protocol. In addition, the Sponsor personnel may 
perform certain activities to ensure study quality. These activities may include the following. 
§ 
Observing testing or medical procedures to provide information relevant to protocol 
compliance 
§ 
Reviewing collected data and study documentation for completeness and accuracy on 
the performance of the procedure 
3. 
STUDY DESIGN 
This is a multi-center, open study that evaluates the safety, performance and durability of the 
TIES® transcutaneous titanium implant to 12-months post implantation.  
This study will be conducted in accordance with the Standard ISO 14155 and other legal 
requirements. 
3.1. 
Rationale for the Study Design 
As discussed previously, there are currently 3 different surgical approaches for patients 
requiring a permanent ileostomy, namely pelvic pouch, continent ileostomy and conventional 
ileostomy. The choice of the procedure is based on individual needs. The TIES® system offers 
a unique function in that the TIES® Port allows the use of a TIES® Lid to control intestinal 
emptying as required, as an alternative to using stoma bag to collect waste continuously from 
conventional ileostomy. It is also indicated as a treatment for patients with failed pelvic pouch 
or continent ileostomy. A single arm study is appropriate in this context. 
The TIES® Port is implanted transcutaneously so that it becomes part of the stoma to a 
conventional ileostomy.  A pre-requisite for success is to engage only surgeons who are skilled 
in performing ileostomy.  
The study population includes patients with ulcerative colitis, familial adenomatous polyposis 
coli, other diseases requiring elective colectomy with a permanent ileostomy, or patients 
requiring a permanent ileostomy; or patients with a medical need for an alternative to an 
existing conventional ileostomy, continent ileostomy or pelvic pouch.  
Only limited conclusions on outcomes can be drawn from the two previous studies because 
most enrolled subjects were converted from pelvic pouch, continent ileostomy or had 
complications associated with previous conventional ileostomy. It is relevant to study more 
patients who have not undergone previous complicated abdominal surgeries. By enrolling 200 
subjects,  this gives an opportunity to enrol patients undergoing ileostomy for the first time 
without needing conversion from pelvic pouch, continent ileostomy or pre-existing ileostomy 
complicated by incisional or parastomal hernia. 
The objective of the study is to collect data to evaluate the safety, performance, durability of 
the implant and impact on quality of life in a group of subjects needing a permanent ileostomy 

 
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(as described in the intended use). Acceptability of the implant to study subjects is part of 
performance evaluation. Because the subject will need to use a stoma bag in the initial healing 
phase, subject´s preference for the TIES® solution for continence control versus stoma bag 
can be evaluated in this single-arm study.  
This protocol plans for five interim data analyses. The first two interim analysis are planned 
after collection of 8-week results from the first 5 and of 24-week results of the first 20 subjects 
respectively, to review all available study data and to assess if there is a need to modify the 
study protocol including adjusting the collection of outcome measurements for performance 
assessment.  The third, fourth and fifth interim analyses will be conducted when 50, 100 and 
150 subjects, respectively, have completed 24 weeks follow-up in order to assess the primary 
and secondary 24-week safety and performance endpoints, make a preliminary assessment 
of the types of patient with high device acceptability, and consider whether some of the 
secondary study instruments (e.g. Quality of Life Questionnaires) can be dropped for the 
remaining patients to simplify follow-up and reduce burden on patients and clinical teams. 
The final analysis will be carried out after the last subject has completed the 52-week 
assessment. 
3.2. 
Participating Sites and Study Population 
Up to 25 sites will be enrolling in up to 6 countries in Europe and Asia. A minimum of 200 
patients will be enrolled, with a history of ulcerative colitis, familial adenomatous polyposis 
coli, other diseases requiring elective colectomy with a permanent ileostomy, or patients with 
a failing conventional or continent ileostomy or pelvic pouch. This study population is 
representative of the devices intended target population. These patients will be followed for 
12 months after the implantation procedure.  Enrolment is expected to take approximately 48 
months due to Covid-19 
4. 
STUDY OBJECTIVE AND ENDPOINTS 
The primary objective is to evaluate the safety, performance and durability of the TIES® Port 
to 52 weeks in subjects after implantation. The secondary objective is to evaluate Quality of 
Life (QoL) in subjects implanted with the TIES® Port. 
4.1. 
Performance Evaluation 
Performance evaluation is based on subject´s assessment of performance as recorded on 
the 3-day diary preceding each scheduled follow-up at 16, 24, 36 and 52 weeks after 
operation.  Performance evaluation applies only among subjects with the TIES® Port in situ.   
Among subjects with the TIES® Port in situ,  performance  will be assessed according to (a) 
the proportion of subjects who use the TIES® Lid for continence control; (b) the proportion of 
subjects experiencing visible leakages around the implant; and (c) subject´s assessment on 
the ease of use of the TIES® Solution.  
Primary endpoint is absence of visible leakage or fecal staining of clothing at 24 weeks after 
implantation of the TIES® Port.   
The success criterion at 24 weeks requires at least 70% of subjects with the TIES® Port in 
situ having no visible leakage or staining of clothing adjacent to the implant between 
consecutive episodes of using the lid for continence control. Spillage that might occur at 
opening of the lid is not regarded as leakage. 
Secondary endpoints are  

 
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• 
Absence of visible leakage or fecal staining of clothing at 16, 36 and 52 weeks.   
• 
Proportion of implanted subjects using the TIES® Lid  for continence control at 16, 24, 
36 and 52 weeks.  
• 
Subject´s assessment on the ease of use of the TIES® Lid using a visual analog scale 
16, 24, 36 and 52 weeks after implantation.  
• 
Subject´s preference for the TIES® solution assessed at 52 weeks.  
The subject´s assessment on the ease of use of the TIES® Lid will provide feedback to the 
manufacturer regarding future refinements of the TIES® solution. Information will be collected 
in the diary to understand patient´s needs as described in section 10.  
4.2. 
Durability Evaluation 
Durability of use is evaluated by the cumulative proportion of subjects with the TIES® Port in 
situ at each of the following timepoints of 8,16, 24, 36 and 52 weeks. These are secondary 
endpoints.  
Durability will be computed by lifetable methods as the complement of the cumulative 
proportion of subjects in whom the TIES® Port has been removed or has spontaneously 
explanted, with subjects censored if they withdraw from the study with the device in situ, 
have insufficient follow-up time, or the device is removed for reasons unrelated to device 
performance.  
4.3. 
Safety Evaluation 
Safety outcome measures are secondary endpoints and will be analysed as proportion of all 
implanted subjects using descriptive statistics. Safety information will be collected during the 
following intervals: during hospitalisation, interval from discharge to 4-weeks visit, interval after 
the 4-weeks visit including 8-weeks visit, interval after the 8-weeks visit including 16-weeks 
visit, interval after the 16-weeks visit including 24-weeks visit, interval after the 24-weeks visit 
including 36-weeks visit, and interval after the 36-weeks visit including 52-weeks visit.  
Secondary endpoints are: 
• 
Proportion of implanted subjects with treatment emergent adverse events. Treatment 
emergent adverse events are defined as events with onset during or after the 
implantation procedure.  
• 
Proportion of implanted subjects with peristomal skin lesions will be evaluated using a 
validated 5-point scale by assessing signs of erythema, erosion, or papular lesions.  
• 
Proportion of implanted subjects with device-related adverse event.  
• 
Proportion of implanted subjects with device displacement, device revision or device 
replacement. 
Photographs of the stoma are to be taken to document the ingrowth into the TIES® Port, 
surrounding peristomal skin and position of the implant at 4, 8, 16, 24, 36 and 52 weeks after 
implantation.  At least 4 views are to be taken: horizontal, vertical frontal, vertical right and 
vertical left. Additional views may be required if skin lesions or device displacement develop. 
4.4. 
Quality of Life Evaluation 
Impact on quality of life will be evaluated by using two validated instruments EQ-5D-5L Quality 
of Life (QoL) questionnaire and Montreux Quality of Life questionnaire.  

 
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Secondary endpoints are: 
Change in quality of life from baseline at 8, 16, 24, 36 and 52 weeks post implantation will be 
assessed among subjects with the device in situ. 
5. 
SUBJECT SELECTION 
A minimum of 200 patients will be enrolled. These patients have an indication for a permanent 
ileostomy, e.g., ulcerative colitis, familial adenomatous polyposis coli, or other diseases 
requiring elective colectomy; or patients with a medical need for an alternative to an existing 
conventional ileostomy or continent ileostomy or pelvic pouch. 
5.1. 
Inclusion Criteria (IC) 
Subjects will be included if the following criteria are met: 
1) Subject has ulcerative colitis, familial adenomatous polyposis coli or other diseases for 
whom a permanent ileostomy is indicated; or the subject has a medical need for an 
alternative to an existing conventional end-ileostomy, continent ileostomy or pelvic 
pouch; and 
2) Patient is a male ≥18 years of age or female ≥18 years of age (note exclusion criterion 
4 regarding female with childbearing potential); and 
3) Signed written informed consent has been obtained prior to any study- related 
procedure. 
5.2. 
Exclusion Criteria (EC) 
Subject will be excluded if any one of the following conditions exists: 
1) Concurrent gastrointestinal fistula, parastomal or incisional hernia, or a history of 
recurrent gastrointestinal fistula, recurrent parastomal hernia(s), and/or recurrent 
incisional hernia(s). 
2) Patients with undetermined colitis. 
3) Patients with Crohn´s disease 
4) Females who are of childbearing potential and do not wish to use birth control 
measures for the duration of the study 
5) Patients receiving immunosuppressives, oncologic treatment or anticoagulants. 
6) Any clinically significant, abnormal, baseline laboratory result which in the opinion of 
the surgeon, affects the patient’s suitability for the study or puts the patient at risk if 
he/she undergoes surgery 
7) Severe illness which, in the opinion of the surgeon may put the patient at risk when 
participating in the study or may affect the patient’s ability to complete the study visits 
8) Condition associated with the risk of poor protocol compliance, e.g. alcoholism and/or 
drug abuse, dementia, self-destructive personality disorder 
9) Subjects who are underweight or obese with BMI ≤ 17 kg/m2 or BMI ≥ 33 kg/m2 
10) Participate in other clinical studies that could interfere with the result in the ongoing 
study 

 
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5.3. 
Subject Accountability 
5.3.1. 
Enrolled subjects 
 
The point of enrolment is the time at which, following recruitment, a subject signs and dates 
the informed consent to agree to participate in the clinical investigation. Subject for whom 
consent was not obtained prior to participation in the study will not be considered enrolled. 
No data from subject who has not provided signed informed consent will be included in any 
analysis.  
 
5.3.2. 
Screen failures  
 
A screen failure is a subject who does not meet all eligibility criteria and therefore will not be 
enrolled into the study and no informed consent form will be signed. A screening log will 
contain information on all subjects screened identified by the Subject Identification number. 
For screened failures, the eligibility criterion/ criteria that are not met will be recorded. 
 
5.3.3. 
Treated Subjects 
An enrolled subject who meets all eligibility criteria, and has been implanted with the TIES® 
Port will be followed in accordance with the protocol requirements. 
Any enrolled subject in whom the TIES® Port implantation procedure is attempted but not 
successfully implanted will be followed for 6 months after the implantation procedure and 
then exit the study. 
5.3.4. 
Withdrawal 
Early termination of study participation will be documented for patients that have signed an 
informed consent form and who exited for any of the following reasons: 
• 
Subject for whom the implantation procedure has been attempted but cannot 
completed, for example, due to technical reasons. (These subjects will be followed for 
six months.) 
• 
Subject who are explanted. (These subjects will be followed for six months.) 
• 
Subject no longer wishes to continue with the study follow-up. No further follow up 
applies. 
• 
Investigator believes it is the best medical interest of the subject to discontinue study 
participation due to safety reasons. (These subjects will be followed until study 
procedure related adverse events have resolved.) 
• 
Death of the subject. 
No additional subjects will be recruited to compensate for subjects who withdraw or are 
withdrawn from the study. 
6. 
STUDY PROCEDURES AND ASSESSMENTS 
6.1. 
Subject Identification 
Each subject will be given a Subject Identification Number for tracking purposes from 
screening, enrolment and throughout study participation. Use of a Subject Identification 

 
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Number is intended to assure confidentiality for subjects. Subject numbers will be issued 
chronologically by the EDC following signed informed consent. 
6.2. 
Screening 
At the screening visit, each potential subject will be allocated a Subject Identification Number 
for tracking purposes and it is intended to assure confidentiality for subjects. 
A full medical history including concomitant medications and physical examination will be 
performed in accordance with standard of care. Subjects will be assessed according to the 
eligibility criteria. They will not undergo any tests or procedures that are study specific and 
are not standard clinical practice.  
 
The screening visit may be combined with the baseline visit.  
 
Subjects who do not meet the eligibility criteria are regarded as screen failures. A screening 
log should be kept and will be a record on all subjects screened identified by the Subject 
Identification number. For screened failures, the eligibility criterion/ criteria that are not met 
should be recorded. 
6.3. 
Enrolment 
Only subjects who meet the eligibility criteria will be approached to participate in the study. 
Subjects are enrolled into the study after providing signed informed consent to participate in 
the study.    
6.4. 
Informed Consent Process 
The Informed Consent Form can only be used after the clinical investigation has been fully  
approved by the Competent Authority and Institution’s Ethics Committee (EC). The Sponsor 
or their CRO representative should be informed on the approved Informed Consent form 
before it is implemented in the study.  
When the Investigator has determined the eligibility of a specific subject to enter this study, 
the Investigator will provide an informed consent form to the subject. The Investigator or 
designee will discuss and explain the clinical investigation with the subject as following: 
• 
include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• 
avoid any coercion of or undue influence of subjects to participate, 
• 
not waive or appear to waive subject’s legal rights, 
• 
use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• 
provide ample time for the subject to consider participation and ask questions if 
necessary, 
• 
ensure important new information is provided to new and existing subjects throughout the 
clinical study. 
 
The Investigator will obtain a signed informed consent form from the subject before 
performing the TIES® implant procedure or any protocol-specific tests. The Investigator will 
provide subjects with a copy of their signed informed consent form. The Investigator will 
provide new information to new and existing subjects.  
The Investigator will maintain a copy of the EC-approved Informed Consent Form along with 
a copy of each subject’s signed Informed Consent Form in a designated study file.   

 
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6.5. 
Baseline Visit 
The baseline visit may be combined with the screening visit. A full medical history including 
concomitant medications and physical examination will be performed in accordance with 
standard of care. Subjects will be assessed according to the eligibility criteria. They will not 
undergo any tests or procedures that are study specific and are not standard clinical practice 
until informed consent has been provided.  
 
Each subject will be given a Subject Identification Number for tracking purposes and it is 
intended to assure confidentiality for subjects. 
After confirming that all the inclusion and exclusion criteria are met, Informed consent will be 
discussed. 
 
The following examinations are regarded as part of pre-operative assessment and the results 
are to be recorded in the medical case notes in accordance with requirements of the 
institution where the surgical procedure will be performed: 
• 
Demographics, medical history and concomitant medications 
• 
Physical examination  
• 
Pregnancy test in woman of childbearing potential 
• 
Pre-operative ECG  
• 
Hematology and Chemistry  
• 
Dipstick urine analysis  
• 
Assessment by the stoma/research nurse and siting of stoma if required 
 
The following information will be collected in the case report forms (CRFs): 
• 
Demographics  
• 
Medical history including indications for ileostomy and previous surgeries 
• 
Concomitant medications 
• 
Document in CRFs if the following procedures have been performed and any 
abnormal findings: physical examination, pre-operative ECG, hematology and 
chemistry tests, dipstick urine analysis 
• 
Record if pregnancy test has been performed and the result 
• 
Record if assessment by the stoma/research nurse has been performed and any 
abnormal findings 
• 
Quality of Life (QoL) Questionnaire/s 
6.6. 
TIES® Port Implantation Procedure 
 
Detailed instructions on implanting the TIES® Port and on connecting the distal ileum to the 
TIES® Port can be found in the Surgical Procedure Manual (see Appendix).  
6.6.1. 
Subject Preparation 
The subject will be prepared for the implantation surgery, per the Surgical Procedure Manual 
(see Appendix), and per the hospital’s standard for ileostomy surgeries including siting of the 
stoma prior to surgery. 
6.6.2. 
Implantation Procedure  
Performance on the implantation procedure will be captured as well as any Adverse Events 
(AE) that occurred during the procedure. A list of the TIES®surgical aids used should be 
recorded. Any changes in the doses or discontinuation of concomitant medications will also 
be documented.  

 
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6.6.3. 
Post operation care 
The patient will be followed up daily before their discharge for the stoma/device and general 
health condition, as follows: 
• 
Adverse Event and safety evaluation  
• 
Changes in concomitant medications  
• 
Cleaning procedure according to patient’s needs (the same as used in conventional 
ileostomies) will be performed; the stabilizer can be left in place during cleaning. 
6.6.4. 
Bail Out Procedure (if applicable) 
All bailout procedures, that is, conversion to a conventional ileostomy, and all adverse events 
associated with the procedure should be documented. 
 
Refer, also, to section 6.16.2 on explant procedure. 
6.7. 
Hospital Discharge  
Before discharge from the hospital, the following study assessments/activities will be 
performed: 
• 
Examination of the subject and the stoma  
• 
Photographs of the stoma and adjacent skin 
• 
Adverse Event evaluation  
• 
Record any changes in concomitant medications  
• 
Cleaning procedure, according to schedule will be performed; 
• 
Instructions provided to the patients on care of the stoma.  
o A patient´s guide on care of the implant and use of the TIES® Lid  for the first 
16 weeks after implantation is included in the Appendix.  
6.8. 
Turnbull Adaptor Removal 
The Turnbull Adaptor will be removed at 4 weeks (+/- 7 days) if it has not already detached 
from the stoma. The patient will continue to use a stoma bag for several weeks after that time 
until the stoma is sufficiently healed to allow introduction of the TIES® Lid and subsequent 
regular use of the TIES®Lid. 
6.9. 
Follow-Up Visits 
Follow-up visits for this study are planned at 4, 8, 16, 24, 36 and 52 weeks after the 
implantation procedure. They are named consecutively from Visit 1 to Visit 6. All visits are 
office visits except for Visit 5 at 36 weeks and Visit 6 at 52 weeks that can be conducted via 
video-conferencing if the subject is unable/unwilling to make the journey. The subject will be 
instructed to take photographs and forward these to the site. An office visit might still be 
carried out depending on the assessment during the video-conference.  
Unscheduled office visits can be carried out if there is a medical need. 
For subjects who require a second implant, the timing of the follow-up visits will commence 
after the new implantation procedure. 
For subjects who require a revision of the implant, the timing of the follow-up visits may or 
may not  need to be readjusted following the revision procedure, based on the assessment 
by the investigator.  
Photographs showing the implant and peristomal skin will be taken to as study 
documentation at every follow-up visit as described below in section 6.12.  

 
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The following assessments/activities will be performed at follow-up visits. 
6.9.1. 
Visit 1 at 4 weeks (+/- 7 days) at the office 
o Physical examination including evaluation of ingrowth into the stoma 
o Inspect healing around the stoma and implant 
o Review and instruct on care of the stoma  
o Removal of Turnbull Adaptor if it has not already detached from the stoma 
(see Surgical Procedure Manual, in Appendix) 
o Adverse event and safety evaluation 
o Concomitant medications review 
o Photographs of the implant, stoma and adjacent skin 
6.9.2. 
Visit 2 at 8 weeks (+/- 7 days) at the office 
o Physical examination including evaluation of ingrowth into the stoma 
o Evaluate if the healing around the implant is sufficient for start of TIES® Lid 
use 
§ 
Trimming of excess intestinal tissue to about 5 mm above the top of 
the cylinder of the Port if required 
§ 
If trimming is performed, postpone start of use of TIES® Lid by one 
week for healing 
o Review and instruct on care of the stoma  
o Adverse event and safety evaluation 
o Concomitant medications review 
o Photographs of the implant, stoma and adjacent skin 
o Complete EQ-5d and Montreux Quality of Life Questionnaires  
o Provide instructions on the 72-hour subject´s diary to be completed prior to 
the next visit 
6.9.3. 
Visit 3 at 16 weeks (+/- 7 days) at the office 
o Physical examination including evaluation of ingrowth into the stoma 
o Review and instruct on care of the stoma  
o Adverse event and safety evaluation 
o Concomitant medications review 
o Photographs of the implant, stoma and adjacent skin 
o Review if the required 72-hour subject´s diary has been completed and 
provide the subject a new diary to complete prior to the next visit 
o Review if the required EQ-5d and Montreux Quality of Life Questionnaires 
have been completed  
6.9.4. 
Visit 4 at 24 weeks (+/- 14 days) at the office 
o Physical examination including evaluation of ingrowth into the stoma 

 
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o Review and instruct on care of the stoma  
o  Adverse event and safety evaluation 
o Concomitant medications review 
o Photographs of the implant, stoma and adjacent skin 
o Review if the required 72-hour subject´s diary has been completed and 
provide the subject a new diary to complete prior to the next visit 
o Review if the required EQ-5d and Montreux Quality of Life Questionnaires 
have been completed  
6.9.5. 
Visit 5 at 36 weeks (+/- 14 days) at the office or via video-conferencing 
o Physical examination including evaluation of ingrowth into the stoma 
o Review and instruct on care of the stoma  
o Adverse event and safety evaluation 
o Concomitant medications review 
o Photographs of the implant, stoma and adjacent skin 
o Review if the required 72-hour subject´s diary has been completed and 
provide the subject a new diary to complete prior to the next visit 
o Review if the required EQ-5d and Montreux Quality of Life Questionnaires 
have been completed  
6.9.6. 
Visit 6 at 52 weeks (+/- 14 days) at the office or via video-conferencing 
o Physical examination including evaluation of ingrowth into the stoma 
o Review and instruct on care of the stoma  
o Adverse event and safety evaluation 
o Concomitant medications review 
o Photographs of the implant, stoma and adjacent skin 
o Review if the required 72-hour subject´s diary has been completed and 
provide the subject a new diary to complete prior to the next visit 
o Review if the required EQ-5d and Montreux Quality of Life Questionnaires 
have been completed  
o Complete subject´s preference questionnaire 
6.10. 
Unscheduled Visits  
Subject may contact the investigator or the stoma/research nurse at any time outside of the 
scheduled follow-up visits.  If there is a need for an unscheduled visit, for example, to 
evaluate adverse events, this should be documented in the case report forms. 
6.11. 
Follow-up treatment after end of investigation 
The investigation sponsor will provide explantation of the device during the clinical 
investigation if necessary (see Explantation procedure, below). At the end of the 
investigation, subjects have the right to choose whether to retain the device or to have the 
device removed. The same applies should the investigation be temporarily halted, or early 
terminated. The decision will be made in accordance with the investigator and based on 

 
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investigator judgement. If the subject keeps the device in place, the subject will be followed 
up by his/her general stoma team per standard stoma care and standard care for a non CE-
marked device outside the investigation.  
6.12. 
Photography of the stoma including the implant and peristomal skin 
Photographs should be taken to show extent of ingrowth into the implant and around the 
implant at every visit and as needed if any complications develop. The photographs should 
include the peristomal skin, particularly if peristomal skin lesions are noted or suspected. The 
subject identification number, the view and the Visit number are to be included in the 
photographs.  
 
The following views are required: 
1. Horizontal view with the subject in the supine position: 
• 
“Horizontal View (HV)” – photograph of the implant and peristomal skin from 
above; 
2. 3 Vertical views with the subject standing upright:  
• 
Vertical frontal view (FV) – photograph of the implant and peristomal skin taken 
from the front,  
• 
Vertical right view (RV)- photograph of the implant taken from the right, and, 
• 
Vertical left view (LV)– photograph of the implant taken from the left.  
 
The photographs are to be uploaded into the electronic case report form system. Care 
should be taken so that the identity of the subject is not disclosed in the photographs. The 
files should be labelled by renaming the image file using the following convention study 
comprising of number_subject ID_photograph view_visit number, eg TIESIIIC03_9901_RV_4 
weeks. 
A printed copy of the photographs should be kept as part of medical records at the site and 
these should be labelled by the subject number, the view and the Visit number. 
 
6.13. 
Quality of Life (QoL) Questionnaires  
Quality of Life questionnaires will be provided to the subjects, with instructions on how and 
when the questionnaires should be completed at baseline and from Visit 2 onwards. The QoL 
questionnaires can be completed either prior to the visit or during the office visit.  These 
questionnaires can be filled in on the internet or on paper.  Those QoL questionnaires 
include: 
• 
EQ-5d quality of Life Questionnaire   
• 
Montreux Quality of Life Questionnaire (specific to stomas) 
See Appendix for more details on the QoL questionnaires.  
6.14. 
TIES® System Performance Evaluation Questionnaire – Subject´s diary 
A TIES® System Performance Evaluation Questionnaire will be provided to the subjects in 
the form of a 72-hour diary, with instructions on how and when the questionnaire should be 
completed per the study visit schedule.  See Appendix for more details.  
6.15. 
Subject´s Preference Evaluation 
A Subject´s preference questionnaire will be provided to the subjects to respond to at the last 
study visit at 52 weeks. Appendix for more details.  

 
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6.16. 
General Investigational Device Management  
6.16.1. 
Device Accountability 
A device accountability log for the TIES® Port and all appliances used shall be kept for this 
study. Lot numbers must be included in the accountability log. A copy of the completed 
accountability log will be kept on site for traceability for all subjects, including early 
terminations. Access to device is restricted to delegated staff in the investigation. Unused 
and expired devices will be returned to Sponsor at the end of the investigation. 
6.16.2. 
Explant Procedure (if applicable) 
If the TIES® Port must be removed, it can be done using standard surgical procedures.  
Should there be a reason for explanting the implant and/or the surrounding tissue, it shall be 
removed in a manner that causes minimal damage to both the implant and the tissues. It is 
particularly important that implant surfaces and adjacent tissues are kept intact. 
See the Surgical Procedure Manual (Appendix) for further detail. 
Information on the explant procedure must be documented in source notes and captured in 
the Case Report Form on “Explant procedure”.  
All explanted devices must be immediately put into neutral buffered 10% formalin for tissue 
fixation and returned to the sponsor OstomyCure for evaluation.   
6.17. 
Withdrawals or Discontinuation 
6.17.1. 
Lost to Follow-Up Subject 
A subject will be considered “lost to follow-up” and terminated from the study when all of the 
following criteria have been met. 
• 
Failure to complete 3 consecutive visits without due cause (after 30 days) 
• 
Documentation of 3 unsuccessful attempts, one of which must be in written 
communication, by the Investigator or his/her designee to contact the subject or next 
of kin 
• 
A communication from the Investigator to Sponsor reporting subject as lost to follow up 
• 
Subjects lost to follow up will still require management of their stoma and they will be 
in contact with their standard stoma team for the continuing management of their 
stoma. 
6.17.2. 
Withdrawal  
Subjects may withdraw from the study at any time, with or without reason and without 
prejudice to further treatment. Withdrawn subjects will not undergo any additional study 
follow-up. The reason for withdrawal will be recorded (if given) in all cases of withdrawal. The 
investigator may discontinue a subject from participation in the study if the investigator feels 
that the subject can no longer fully comply with the requirements of the study or if any of the 
study procedures are deemed potentially harmful to the subject. No new data will be 
collected after withdrawal from the study. Data that have already been collected on 
withdrawn subjects will be retained and used for analysis, unless disallowed by national or 
local regulations. 
6.17.3. 
Unplanned pregnancy 
In the event that any subject becomes pregnant during the study, the pregnant subject will be 
withdrawn from the study. The optimal way to handle the implant will be reviewed on a case 
by case basis involving the investigator, obstetrician and the subject. No new data will be 
collected after withdrawal from the study. Data that have already been collected on 

 
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withdrawn subjects will be retained and used for analysis, unless disallowed by national or 
local regulations. 
6.17.4. 
Study Completion 
All subjects will be evaluated at discharge from hospital, 4 weeks, 8, 16, 24, 36 and 52 
weeks post implantation procedure. A subject’s participation in the study will be considered 
complete after the 52-week visit. 
7. 
RISK-BENEFIT ANALYSIS 
7.1. 
Risks Assessment and Risk Mitigation 
7.1.1. 
Risks Associated with ileostomy 
Creation of a stoma is a well-established surgical technique and should only be carried out 
by a surgeon experienced in this procedure. The risks are well known and are reported in the 
published literature. They can be discussed according to time to onset. As a consequence of 
the complications listed below, the patient may require medical or surgical intervention, 
including re-operation. 
 
Complications with onset within 30 days following ileotomsy 
• 
High output leading to dehydration/electrolyte abnormalities  
• 
Ischemia/necrosis of the stoma  
• 
Edema and venous congestion of stoma  
• 
Retraction of stoma  
• 
Technical complications 
• 
Risk of recurrence in patients with Crohn’s disease  
 
Complications with onset after 30 days following ileotomsy 
• 
Peristomal skin complications  
• 
Retraction of stoma  
• 
Parastomal Hernia  
• 
Mucocutaneous separation  
• 
Peristomal pyoderma gangrenosum  
• 
Stenosis  
• 
Intestinal obstruction  
• 
Technical complications  
• 
Peristomal suppuration and fistula formation – Crohn´s disease is associated with a 
higher risk. 
• 
Recurrence of disease activity in patients with Crohn’s disease  
7.1.2. 
Risks Associated with the procedure of Implantation of the TIES® Port 
Potential risks associated with implantation of the TIES® Port are described here, note that 
some of these complications are known complications of ileostomy. As a result of the 
complications listed below, the patient may require medical or surgical intervention, including 
re-operation and/or removal or replacement of the TIES® Port. 
• 
Redness at the operation site 
• 
Pain 

 
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• 
Allergic reaction (including to medications, anaesthesia or device materials) 
• 
Infection 
• 
Device misplacement or displacement 
• 
Enterocutaneous fistula 
• 
Perforation of the intestine during insertion of ileum through implant 
• 
Contamination of implant with intestinal content during surgery 
• 
Narrow passage caused by irritated or swollen intestine 
• 
Occlusion, sub-occlusion and constipation 
• 
Parastomal/incisional hernias 
 
7.1.3. 
Possible Risks Related to the TIES® Port, including Functional Risks 
 
7.1.3.1 
Titanium as a biocompatible material 
The titanium used to manufacture the implant is a medically approved material that has been 
used in surgery for more than 30 years. Titanium is recognized to be non-allergenic. Various 
tests in line with regulatory standards have been performed during the development to 
ensure bio-compatibility of the TIES® Port with human tissue. 
7.1.3.2 
Potential risks post-surgery 
It is important to maintain the TIES® Port in place during the healing period to facilitate tissue 
ingrowth into the implant in the abdominal wall and avoid applying any stress to the TIES® 
Port. Possible risks that may arise include: 
• 
Insufficient ingrowth of soft tissue into the TIES® Port to ensure a leak-free system  
• 
Leakage of intestinal liquid between the device and the skin due to: 
o Ileum retraction 
o Too early use of the TIES®Lid 
o Trauma 
o Other factors 
o External violence - skin or body injuries caused by the protruding part of the 
implant getting caught or by violent accidents 
7.1.3.3 
Actions required if ingrowth is insufficient 
Should the system show incomplete ingrowth inside or outside or being harmed in a way or 
other over time, it should be “put to rest”. The usage of the TIES® Lid should be stopped for 
a few weeks to give the biological system time to adjust to the situation and come to a new 
balance; the ingrowth of the skin and the intestinal serosa and mucosa tends to adjust by 
itself. 
7.1.4. 
Possible Risks Associated with the Post-Operative Care of the TIES® Port 
All post-operative stoma care procedures are standard procedures and are not expected to 
add any additional risk. There are no additional risk-baring procedures planned in the study 
(e.g. CT-Scan, X-rays). 
 
Warnings and Precautions are included in the Surgical Procedure Manual and in the User 
Care Manual (see Appendix). 
7.1.5. 
Possible Risks and Side Effects Associated with Medication 
The patients may continue to take their usual medication as required.  There is no additional 
medication required for the TIES® Port implantation procedure, other than that usually used 
to perform a common end ileostomy.  

 
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There is no known incompatibility between the TIES® System and any medication. 
7.1.6. 
Risks Mitigations 
Risk mitigation in this study will be accomplished through the following actions: 
• 
Clear definition of inclusion/exclusion criteria to ensure only appropriate subjects are 
enrolled, in line with contraindications listed in the Surgical Procedures Manual 
• 
Ensuring that treatment and follow-up of the subject is consistent with current medical 
practices 
• 
Selection of investigators who are experienced and skilled in performing ileostomy 
procedures 
• 
Completion of training of site personnel by the Sponsor  
• 
Performing all procedures in accordance with the Surgical Procedure Manual and User 
Care Manual 
• 
Device training to the patient, per the User Care Manual 
• 
Advise the patient on good care of the stoma and regular review by Stoma/ Research 
nurse 
• 
Advise the patient on specific dietary measures to avoid excessive output 
• 
Use of only soft catheter and soluble gel for intestinal emptying (flushing), to avoid 
occlusion, sub-occlusion and constipation 
• 
Continuous safety review processes  
 
7.1.7. 
Residual risks 
There are known long-term risks associated with ileostomy. These include peristomal skin 
complications, retraction of stoma, incisional or parastomal hernia, mucocutaneous 
separation, intestinal obstruction, infection, fistula formation, or recurrence of the background 
disease. The presence of the implant is unlikely to alter the occurrence of these conditions 
and they can be treated using standard medical practice. It is expected that the study 
subjects will be followed up life-long in clinics specialised in care of stoma patients.  
 
7.2. 
Benefit Assessment 
7.2.1. 
Potential Benefits of the TIES® System 
• 
Patient controlled continent ileostomy 
• 
Fewer or no stoma bags needed 
• 
Better quality of life (ability to travel, better social integration) 
• 
Facilitated manipulation (clean and comfortable evacuation) 
• 
Facilitated body hygiene 
• 
No skin irritation resulting from stoma fixation device  
• 
A leak-free system – “accidents” becoming a non-issue 
7.2.1. 
Risks to Benefit Rationale 
The product development and risk management activities for the TIES® System were 
performed while considering the essential requirements of the European Medical Device 
Directive (MDD) 93/42/EEC. Pre-clinical testing was performed using animal models and in 
vitro testing, before conducting clinical investigations in human subjects. Ostomycure AS has 
established manufacturing controls following the requirements of ISO 13485.   

 
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The potential risks outlined above will be mitigated by proper patient selection, the attention 
given to the choice of investigational sites, the expertise of the investigators and surgeons, 
regular review by  stoma/research nurse, and the training that will be provided to all involved 
study personnel, and to the patients.  
It is noted that following any explantation/removal of the device, the patient can revert to use 
of ileostomy bags without any added risks.  
The potential benefits of the system outweigh the potential risks, supporting use of the TIES® 
System in this study. 
8. 
ADVERSE EVENT MANAGEMENT 
Subjects will be carefully monitored during the study for possible adverse events (AEs) from 
the time the subject signs the Patient Informed Consent form to the completion of their 
participation in the study. Any AE observed will be fully investigated by the Investigator and 
classified in line with the definitions of the ISO14155:2011 as described below. 
8.1. 
Definitions 
Adverse Event (AE): 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the investigational medical device 
NOTE 1 This definition includes events related to the investigational medical device or the 
comparator. 
NOTE 2 This definition includes events related to the procedures involved. 
NOTE 3 For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
Treatment emergent adverse events are adverse events with onset at or following the 
implantation procedure for the purpose of this study. 
Serious Adverse Event (SAE): 
Adverse event that: 
a) led to death, 
b) led to a serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) hospitalization or prolongation of existing hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
c) led to foetal distress, foetal death or a congenital abnormality or birth defect 
NOTE Planned hospitalization for a pre-existing condition, or a procedure required by the 
Clinical Investigation Plan, without serious deterioration in health, is not considered a serious 
adverse event. 

 
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Device Deficiency: 
Inadequacy of an investigational medical device related to its identity, quality, durability, 
reliability, safety or performance. This may include malfunctions, use error, or inadequacy in 
the information supplied by the manufacturer. 
Adverse Device Effect (ADE): 
Adverse event related to the use of an investigational medical device 
NOTE 1 This definition includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, implantation, installation, operation, 
or any malfunction of the investigational medical device. 
NOTE 2 This definition includes any event resulting from a use error or from intentional 
misuse of the investigational medical device. 
Serious Adverse Device Effect (SADE): 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event 
Unanticipated Serious Adverse Device Effect (USADE): 
Serious adverse device effect which by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report. 
NOTE Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report. 
Use error: 
Act or omission of an act that results in a different medical device response than intended by 
the manufacturer or expected by the user. 
NOTE 1 Use error includes slips, lapses, and mistakes. 
NOTE 2 An unexpected physiological response of the subject does not in itself constitute a 
use error. 
Malfunction: 
Failure of an investigational medical device to perform in accordance with its intended 
purpose when used in accordance with the instructions for use or CIP. 
8.2. 
Event severity  
Event severity is classified as follows: 
Mild: awareness of a sign or symptom that does not interfere with the patient’s usual activity 
or is transient, resolved without treatment and with no sequelae 
Moderate: interferes with the patient’s usual activity and/or requires symptomatic treatment 
Severe: symptom(s) causing severe discomfort and significant impact on the patient’s usual 
activity and requires treatment 

 
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8.3. 
Causality relationship 
The investigator will assess the causality of all adverse events in relation to the research, i.e., 
the relationship between the AE / SAE and the investigational treatment or any other study-
related procedures. 
Each SAE will be classified according to five different levels of causality: 
1) Not related: relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to or of similar 
devices and procedures; 
- the event has no temporal relationship with the use of the investigational device or the 
procedures; 
- the serious event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or increase of the 
level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the device or 
procedure; 
- the serious event can be attributed to another cause (e.g. an underlying or concurrent illness/ 
clinical condition, an effect of another device, drug, treatment or other risk factors); 
- harms to the subject are not clearly due to use error; 
- In order to establish the non-relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious event. 
2) Unlikely: the relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be obtained. 
3) Possible: the relationship with the use of the investigational device is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). Cases were 
relatedness cannot be assessed or no information has been obtained should also be classified 
as possible. 
4) Probable: the relationship with the use of the investigational device seems relevant and/or 
the event cannot be reasonably explained by another cause, but additional information may 
be obtained. 
5) Causal relationship: the serious event is associated with the investigational device or with 
procedures beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or of similar 
devices and procedures; 
- the event has a temporal relationship with investigational device use/application or 
procedures; 
- the event involves a body-site or organ that 

 
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- the investigational device or procedures are applied to; 
-  the investigational device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the response 
pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment) have been adequately ruled out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the investigational device used for diagnosis, 
when applicable 
- In order to establish the relatedness, not all the criteria listed above might be met at the same 
time, depending on the type of device/procedures and the serious event.  
8.4. 
Investigator Reporting Responsibilities 
The investigator should report to the sponsor the following events, whether expected or not, 
in the corresponding CRF form, with the exception of AEs / SAEs detected before the 
patients has signed the patient consent form.   
- 
AE 
- 
SAE 
- 
Device Deficiencies that did not but might have led to a SAE if: 
o Suitable action has not been taken or 
o Intervention had not been made or 
o If circumstances had been less fortunate 
- 
New findings/updated in relation to already reported events 
If an AE / SAE is present at the beginning of study prior to the subject providing signed 
consent to participate in the study, only its worsening should be reported. 
The investigator will document all AEs on the Adverse Event Form, including (at a minimum) 
a description of the event, date of onset, severity, relationship to the investigational device 
and/or procedure, required interventions, duration, and outcome. The investigator will 
monitor all AEs until they are resolved, determined to be a chronic condition or the subject is 
lost to follow-up. The investigator will report all AEs regardless of whether it is anticipated or 
unanticipated and regardless of classification, seriousness, intensity, outcome or causality. 
All Serious Adverse Events including all device deficiencies that could have led to a SAE 
should be reported to the Sponsor within 24 hours of awareness of an event via the Adverse 
Event electronic Case Report Form in the study’s electronic database, as that will trigger an 
immediate e-notification to the Sponsor and Devicia. All device deficiencies should also be 
reported without unjustified delay.  
If the e-CRF is unavailable, notification to the sponsor can be made by email and the email 
address is TIESstudy@ostomycure.com 

 
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The investigator must ensure that all additional relevant information (i.e., radiology reports,  
hospitalization reports indicating the SAE) that becomes available is also forwarded to the 
sponsor immediately after the initial notification and the information should be de-identified. 
8.5. 
Reporting to Ethic Committee / Competent Authority 
Depending on the local requirements or following agreement between both parties, the 
sponsor or the principal investigator will be responsible for performing safety reporting to the 
Ethics Committee according to the relevant local regulatory requirements.    
Devicia will be responsible for reporting to the National Competent Authority according to 
national requirements and in line with MEDDEV 2.7/3. 
The sponsor must report to the national Competent Authorities where the clinical 
investigation has  commenced: 
 
• 
a SAE which indicates an imminent risk of death, serious injury, or serious illness and 
that requires prompt remedial action for other patients/subjects, users or other 
persons11 or a new finding to it: immediately, but not later than 2 calendar days after 
awareness by sponsor of a new reportable event or of new information in relation with 
an already reported event. 
• 
any other reportable events as described in section 8.1 or a new finding/update to it: 
immediately, but not later than 7 calendar days following the date of awareness by the 
sponsor of the new reportable event or of new information in relation with an already 
reported event. 
9. 
DATA SAFETY MONITORING BOARD 
An independent committee comprised of experts in the field of gastroenterology or colorectal 
surgery will review all the safety and performance data on at least 2 occasions during the 
study: 
(1) The first review will take place after the first 5 subjects have been implanted and the 
fifth subject has been followed to 8 weeks. The purpose of the review of data to 8 weeks 
is to make recommendations if changes to the study design would be required.  This 
meeting should be held about 4 weeks after the data becomes available. 
(2) The second review is planned after collection of 24-week results from the first 20 
subjects to review if further modification to the collection of outcome measurements for 
performance assessment would be required. 
In the event of reports of unexpected adverse events, an independent expert will review 
these unexpected adverse events and making assessment in regards of the seriousness and 
relationship to the device. 
10. STATISTICAL CONSIDERATIONS  
10.1. 
Objective of the study 
This is a single-arm prospective multi-center clinical study to evaluate the safety, 
performance, durability of TIES® Port in patients who require permanent ileostomy as its 

 
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primary objective, and assessment of impact on quality of life in the implanted patients as its 
secondary objective. Acceptability of the TIES® solution for patients will is part of assessment 
of performance. 
 
For patients who require a permanent ileostomy, the current available alternatives for 
emptying of ileal contents are (1) attaching a stoma bag to the end-ileostomy; (2) surgery to 
create a pelvic pouch through an ileo-anal anastomosis; and (3) surgery to create a continent 
ileostomy. All of these procedures are associated with complications and failure rates.  
 
The TIES® solution is intended as an alternative to stoma bags in patients requiring end-
ileostomy so that the patient has control over emptying of intestinal wastes and to minimise 
the need to wear stoma bags for collection and emptying of intestinal wastes. This is 
achieved by putting a TIES® Lid  on the TIES® Port to control emptying of intestinal waste 
through the Port, instead of letting the waste emptiy continuously into a stoma bag. In 
addition, the TIES® solution can also be an option for patients who cannot tolerate use of 
stoma bags due to complications, failed continent ileostomy or failed pelvic pouch.  
10.2. 
Study design  
This protocol plans for five interim data analyses during the course of this open study. The 
first two interim analyses are planned after collection of 8-week results from the first 5 and of 
24-week results of the first 20 subjects, respectively,  to review all available study data and to 
assess if there is a need to modify the study protocol including adjusting the collection of 
outcome measurements for performance assessment.  The third, fourth and fifth interim 
analyses will be conducted when 50, 100 and 150 subjects, respectively, have completed 24 
weeks follow-up in order to assess the primary and secondary 24-week safety and 
performance endpoints, make a preliminary assessment of the types of patient with high 
device acceptability, and consider whether some of the secondary study instruments (e.g. 
Quality of Life Questionnaires) can be dropped on the remaining patients to simplify follow-up 
and reduce burden on patients and clinical teams. 
10.3. 
Study Population Definition 
The study population is defined according to the Intent-to-Treat principle. All enrolled 
subjects will be taken into consideration in the reported results, without any planned 
exclusion. 
10.4. 
Performance Evaluation 
The subject is assumed to empty the “bowels” about 6 times per day. 6-months is chosen as 
the time point for primary endpoint assessment because the subject is expected to be familiar 
with the use of the TIES® Lid  as well as study procedures at that time. 
• 
By analysing the frequency of use of the TIES® Lid  versus the use of stoma bags in 
individual subjects, this gives an assessment of the usefulness and acceptability of the 
TIES® solution.    
• 
Leakage around the stoma between emptying is to be assessed. For a conventional 
end-ileostomy, the peristomal skin is often in contact with the intestinal contents and at 
least 30% of the patients reported skin problems based on the literature. For patients 
with pelvic pouch, perfect continence is achieved in less than 80% of patients. 
Performance evaluation is based on subject´s assessment of performance as recorded on 
the 3-day diary preceding each scheduled follow-up at 16, 24, 36 and 52 weeks after 

 
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operation.  Performance evaluation applies only among subjects with the TIES® Port in situ.   
Among subjects with the TIES® Port in situ,  performance  will be assessed according to (a) 
the proportion of subjects who use the TIES® Lid for continence control; (b) the proportion of 
subjects experiencing visible leakages around the implant; and (c) subject´s assessment on 
the ease of use of the TIES® Solution.  
Primary endpoint is absence of visible leakage or fecal staining of clothing at 24 weeks after 
implantation of the TIES® Port.   
The success criterion at 24 weeks requires at least 70% of subjects with the TIES® Port in 
situ having no visible leakage or staining of clothing adjacent to the implant between 
consecutive episodes of using the lid for continence control. Spillage that might occur at 
opening of the lid is not regarded as leakage. 
Secondary endpoints are  
• 
Absence of visible leakage or fecal staining of clothing at 16, 36 and 52 weeks.   
• 
Proportion of implanted subjects using the TIES® Lid  for continence control at 16, 24, 
36 and 52 weeks.  
• 
Subject´s assessment on the ease of use of the TIES® Lid using a visual analog scale 
16, 24, 36 and 52 weeks after implantation.  
• 
Subject´s preference for the TIES® solution assessed at 52 weeks.  
The subject´s assessment on the ease of use of the TIES® Lid will provide feedback to the 
manufacturer regarding future refinements of the TIES® solution. Information will be collected 
in the diary to understand patient´s needs and the number of stoma bags used as described 
in section 10.  
10.5. 
Sample size 
The purpose of the study is to assess the durability and performance of the TIES® Port over 
one year. The table below shows the power to demonstrate non-inferiority to within 10% of 
the target 24-week performance criterion of 70% of subjects with the device in situ 
experiencing no leakage (i.e. lower two-sided 95% confidence limit no less than 60%) 
according to the true proportion and number of assessable subjects. 
 
True proportion experiencing 
no leakage at 24 weeks 
200 
subjects 
180 
subjects 
160 
subjects 
140 
subjects 
120 
subjects 
 
 70% 
87% 
83% 
79% 
73% 
67% 
71% 
93% 
90% 
87% 
82% 
76% 
72% 
97% 
95% 
92% 
89% 
83% 
73% 
99% 
98% 
96% 
93% 
89% 
74% 
99% 
99% 
98% 
97% 
94% 
75% 
100% 
100% 
99% 
98% 
97% 
 

 
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There will be sufficient power with the planned 200 subjects to demonstrate non-inferiority of 
the TIES® Port with respect to the primary performance criterion (efficacy when device used 
as intended), if at least 80% of subjects are evaluable at 24 weeks (i.e. with at least 160 
subjects).  If the true proportion of patients experiencing no leakage is higher than the expected 
minimum of 70% there will be sufficient power to demonstrate non-inferiority even with fewer 
than the expected proportion of evaluable subjects at 24 weeks.   
10.6. 
Durability Evaluation 
Durability of use is evaluated by the cumulative proportion of subjects with the TIES® Port in 
situ at each of the following timepoints of 8,16, 24, 36 and 52 weeks. These are secondary 
endpoints.  
Durability will be computed by lifetable methods as the complement of the cumulative 
proportion of subjects in whom the TIES® Port has been removed or has spontaneously 
explanted, with subjects censored if they withdraw from the study with the device in situ, 
have insufficient follow-up time, or the device is removed for reasons unrelated to device 
performance.  
10.7. 
Safety Evaluation 
Safety outcome measures are secondary endpoints and will be analysed as proportion of all 
implanted subjects using descriptive statistics. Safety information will be collected during the 
following intervals: during hospitalisation, interval from discharge to 4-weeks visit, interval after 
the 4-weeks visit including 8-weeks visit, interval after the 8-weeks visit including 16-weeks 
visit, interval after the 16-weeks visit including 24-weeks visit, interval after the 24-weeks visit 
including 36-weeks visit, and interval after the 36-weeks visit including 52-weeks visit.  
Secondary endpoints are: 
• 
Proportion of implanted subjects with treatment emergent adverse events. Treatment 
emergent adverse events are defined as events with onset during or after the 
implantation procedure.  
• 
Proportion of implanted subjects with peristomal skin lesions will be evaluated using a 
validated 5-point scale by assessing signs of erythema, erosion, or papular lesions.  
• 
Proportion of implanted subjects with device-related adverse event.  
• 
Proportion of implanted subjects with device displacement, device revision or device 
replacement. 
Photographs of the stoma are to be taken to document the ingrowth into the TIES® Port, 
surrounding peristomal skin and position of the implant at 4, 8, 16, 24, 36 and 52 weeks after 
implantation.  At least 4 views are to be taken: horizontal, vertical frontal, vertical right and 
vertical left. Additional views may be required if skin lesions or device displacement develop. 
The adverse events complicating end-ileostomy, continent ileostomy and pelvic pouch are 
well described in the literature. Adverse events known to complicate end-ileostomy include 
peristomal skin problems, infection, abscess, entero-cutaneous fistula, necrosis, stenosis, 
prolapse, retraction, parastomal hernia, incisional hernia, obstruction to emptying of intestinal 
contents. That said, the exact incidences are unknown because many reports are 
retrospective and the experience of the site may influence the outcomes.  
All adverse events, device-related complications and device deficiencies or malfunctions 
described in section 4 will be fully summarized. Adverse events are to be assessed for 
seriousness and causality. 

 
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For all definitions indicated in section 10.1, the total number of adverse events, percentage of 
subjects with at least one given adverse event (AE, ADE, SAE, SADE, USADE) will be 
reported in summary tables. Moreover, description of events will be presented in listings. 
Severity and relationship will be documented for all defined adverse events (AE, ADE, SAE, 
SADE, USADE). 
10.7.1. 
Peristomal skin lesions 
Peristomal skin lesions are common and the incidences range from 20% to 50%. 
Dermatoses included irritant reactions, particularly from leakage of urine or feces and pre-
existing skin diseases, infections, allergic contact dermatitis, and pyoderma gangrenosum 
are less common. The classification of Borglund will be used to assess severity of the skin 
lesions the site. Photographs of the stoma and skin lesions will be taken as part of study 
documentation and for review by an independent panel if required. 
Classification of peristomal skin complications (Borglund et al) 
Category Criterion 
Additional explanation 
E0/P0 
No signs of irritative skin 
lesions; no obvious signs of 
erythema, erosion, or papular 
lesions 
 
E+/P0 
Mild erythematous-erosive skin 
lesions E+/P0 
This subgroup (E+) includes patients with 
dispersed 
papules 
lesions, 
and/or 
tiny, 
erythematous, macular lesions, vesicles, or 
tiny erosion.  
E++/P0 
Severe erythematous-erosive 
skin lesions. 
The E++ subgroup includes patients with 
numerous papules and/or tiny macules, 
confluent 
erythematous 
macules, 
widely 
spread erosions, excoriations, and ulcerations.  
E0/P+ 
Mild 
pseudoverrucous 
skin 
lesions 
The mild (P+) pseudoverrucous skin lesion is 
characterized by dispersed, single, eruptive, or 
partly confluent, wart-like papules, or nodules 
located on the peristomal skin close to the 
mucocutaneous lining.  
E0/P++ 
Severe pseudoverrucous skin 
lesions 
The P++ reflects severe pseudoverrucous skin 
lesions and is a confluent, elevated ostomy 
circumference close to the ostomy mucosa. 
 
10.8. 
Quality of Life Evaluation 
Impact on quality of life will be evaluated by using two validated instruments EQ-5D-5L Quality 
of Life (QoL) questionnaire and Montreux Quality of Life questionnaire.  
Secondary endpoints are: 

 
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Change in quality of life from baseline at 8, 16, 24, 36 and 52 weeks post implantation will be 
assessed among subjects with the device in situ. 
10.9. 
Statistical analysis 
Statistical analyses will be done using SAS System®, Version 9.2 or further and a complete 
statistical analysis plan will be written before the conduct of analysis. All statistical analyses 
will be made on locked databases following data clarifications resolved due to Data 
Management process. 
No replacement of missing data is planned in the statistical analysis. 
No statistical testing will be conducted for any other parameters in the study and only 
descriptive analysis will be provided to fully describe the parameters recorded. 
Continuous variables will be summarized using standard quantitative statistics: number of 
non-missing observations, mean, standard deviation, median, quartiles and range (minimum 
and maximum observed values). The number of missing observations will also be specified. 
Categorical variables will be summarized using classical frequency statistics: number of non-
missing observations and percentages by categories. Percentages will be calculated on the 
number of non-missing observations. The number of missing observations will also be 
specified. 
Durability of use will be analysed using lifetable methods to allow for censoring due to 
subject withdrawal and device removals for reasons unrelated to device performance.  
Two-sided 95% confidence intervals will be computed for all primary and secondary 
endpoints. 
A statistical analysis plan will be written to describe all derived variables used in the reporting 
(especially for all parameters to be compared in time: EQ-5d and Montreux QoL 
questionnaire) and the statistical tables and listings to be generated. 
10.10. 
Additional analyses 
10.10.1. 
Photographs of the stoma and adjacent skin 
Photographs of the stoma are to be taken to show the ingrowth into the implant and the 
peristomal skin at discharge, 4, 8, 16, 24, 36 and 52 weeks as described in section 6. 
The extent of ingrowth will be estimated using the following scale at skin/device junction and 
ileum device junction: 
1. Complete 
2. Partial 
3. None 
An independent review of skin lesions will be performed by a dermatologist if required. 
10.10.2. Use of stoma bags   
It should be noted that subjects will need to use stoma bags for at least the first 12 weeks 
until the TIES® Lid  can be used regularly, and probably also during sleep after that period. 
Information on the continuous use of stoma bags during sleep based on recall will be 
recorded in subject´s diaries at 16, 24, 36 and 52 weeks and will be presented using 
summary statistics. 

 
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10.10.3. Subject´s preference  
Because the subjects will need to use stoma bags continuously for at least the first 8 weeks 
and then intermittently until the TIES® Lid  can be used regularly, it is of interest to obtain 
their assessment on how the two alternatives may influence their wellbeing. Four topics from 
the 2 quality of life questionnaires have been selected for comparisons. This assessment will 
be performed at the last study visit at 52 weeks. The subjects will be asked the following 
questions about their experience with the use of the TIES® Solution compared to the 
continuous use of stoma bags.  
1. Regarding maintaining body hygiene 
a) No difference with using either stoma bags that collected waste continuously or TIES® 
Lid  for periodic emptying of waste 
b) Easier with stoma bags that collected waste continuously 
c) Easier with TIES® Lid  for periodic emptying of waste 
 
2. Regarding daily activities (e.g. work, study, housework, family or leisure activities) 
a) No difference with using either stoma bags that collected waste continuously or TIES® 
Lid  for periodic emptying of waste 
b) Easier with stoma bags that collected waste continuously 
c) Easier with TIES® Lid  for periodic emptying of waste 
 
3. How worried were you about odor from your stoma? 
a) No difference with either stoma bags that collected waste continuously or TIES® Lid  
b) Less worry with stoma bags that collected waste continuously 
c) Less worry with TIES® Lid  for periodic emptying of waste 
 
4. How worried were you about leakage from your stoma? 
a) No difference with either stoma bags that collected waste continuously or TIES® Lid  
for periodic emptying of waste 
b) Less worry with stoma bags that collected waste continuously 
c) Less worry with TIES® Lid  for periodic emptying of waste 
 
5. Would you recommend the TIES® solution to friends or family members who need to 
undergo ileostomy? 
a) No 
b) Undecided 
c) Yes 
 
11. GENERAL STUDY CONSIDERATIONS 
11.1. 
Ethical and Regulatory Considerations 
The study will be performed in accordance with the standard EN ISO 14155 on clinical 
investigations with medical devices and Ethical Principles for Medical Research Involving 
Human Subjects (Declaration of Helsinki) adopted by the 18th World Medical Assembly, 
Helsinki, Finland, 1964 and later revisions. 

 
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The clinical investigational plan, informed consent, any other specific study documents and all 
amendments to these study documents will be reviewed and approved by the Ethics 
Committees (ECs) and Competent Authority/ies (CAs) if appropriate before enrolment of any 
patient.  
Any additional requirements by the EC or CA will be followed. 
11.2. 
Amendments 
The IB, CIP, CRFs, informed consent form and other subject information, or other clinical 
investigation documents shall be amended as needed throughout the clinical investigation, 
and a justification statement shall be included with each amended section of a document. 
Proposed amendments to the CIP shall be agreed upon between the sponsor and principal 
investigator, or the coordinating investigator. The amendments to the study documents shall 
be notified to, or approved by, the EC and regulatory authorities, if required. The version 
number and date of amendments shall be documented. 
11.3. 
Protocol Deviations 
The Principal Investigator is required to conduct the study in accordance with the signed 
clinical trial agreement/investigator agreement and the clinical protocol. However in some 
situations protocol deviations will occur. 
Protocol deviations are defined as instance(s) of failure to follow, intentionally or 
unintentionally, the requirements of the CIP. Unders emergency circumstances, deviations 
from the CIP to protect the rights, safety and well-being of human subjects may proceed 
without prior approval of the sponsor and the EC. Such deviations shall be documented and 
reported to the sponsor and the EC as soon as possible. 
The Principal Investigator shall promptly report any deviations from the CIP that affects the 
rights, safety or well-being of the subject or the scientific integrity of the clinical investigation, 
including those which occur under emergency circumstances. The Principal Investigator shall 
notify the Sponsor in writing, no later than 24 hours after significant deviation from the study 
plan, to protect the life or physical wellbeing of a subject in an emergency. 
When specific tasks are delegated by the Principal Investigator, included but not limited to 
conducting the informed consent process, the Principal Investigator is responsible for providing 
appropriate training and adequate supervision of those to whom tasks are delegated. The 
investigator is accountable for regulatory deviations resulting from failure to adequately 
supervise the conduct of the clinical study.  
Protocol deviations also include, but are not limited to: 
§ 
Examinations/test/assessment not performed within the allowed follow-up window 
§ 
Required data not obtained 
The study site should report the protocol deviation on the applicable CRF page.  
Protocol deviations will be reported in progress reports to CA and EC where applicable and 
within other required timelines. 
Investigators that show continued, serious failings in adherence to the CIP, inspite of 
apropriate corrective and preventive actions will be disqualified from the study. 

 
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11.4. 
Data handling and Record Keeping 
11.4.1. 
Data Collection, Processing and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) system.  
The clinical database will reside on a production server hosted by CRFWEB eCRF provider 
Clindox. All changes made to the clinical data will be captured in an electronic audit trail and 
available for review by the Sponsor or its representative. The software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate eCRFs in compliance 
with local regulations.  
Manual and/or automatic queries will be created in the EDC system and will be issued to the 
center for appropriate response. Site staff will be responsible for resolving all queries in the 
database. 
11.4.2. 
Data Retention 
The Investigator will maintain at the investigative centre in original format all essential study 
documents and source documentation that support the data collected on the study subjects in 
compliance with ICH/GCP guidelines. Documents must be retained for at least 10 years have 
elapsed since the formal discontinuation of this study. These documents will be retained for a 
longer period by agreement with the Sponsor or in compliance with other local regulations. It 
is the Sponsor’s responsibility to inform the Investigator when these documents no longer need 
to be maintained. The Investigator will take measures to ensure that these essential 
documents are not accidentally damaged or destroyed. If for any reason the Investigator 
withdraws responsibility for maintaining these essential documents, custody must be 
transferred to an individual who will assume responsibility and the Sponsor must receive 
written notification of this custodial change.  
11.5. 
Monitoring 
Monitoring will be performed during the study according to the monitoring plan to assess 
continued compliance with the protocol and applicable regulations. In addition, the monitor 
verifies that study records are adequately maintained, that data are reported in a satisfactory 
manner with respect to timeliness, adequacy, and accuracy, and that the Investigator 
continues to have sufficient staff and facilities to conduct the study safely and effectively. The 
Investigator/institution guarantees direct access to original source documents by the Sponsor, 
their designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by the Sponsor or its designees, 
as well as inspection by appropriate regulatory authorities. It is important that the Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
11.6. 
Insurance 
Subjects who participate in this study will be insured against study related injury according to 
local regulations requirements. 
The Sponsor has issued clinical trial insurance with appropriate coverage for the continuation 
of the entire study. 

 
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11.6.1. 
Suspension or premature Termination 
The Sponsor reserves the right to suspend or terminate the study at any stage but intends to 
exercise this right only for valid scientific or administrative reasons and reasons related to 
protection of subjects.  Investigators, associated ECs, and regulatory authorities will be notified 
in writing in the event of study suspension or premature termination along with reasons for the 
actions taken/decisions made. 
Possible reasons for study suspension or premature study termination include, but are not 
limited to, the following: 
§ 
The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
§ 
An enrolment rate far below expectation that prejudices the conclusion of the study.  
§ 
A decision on the part of the Sponsor to suspend or discontinue development of the 
device. 
11.6.2. 
Criteria for Suspending/Terminating a Study Site 
The Sponsor reserves the right to stop the inclusion of subjects at a study site at any time after 
the study initiation visit if no subjects have been enrolled or if the site has multiple or severe 
protocol violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of investigator participation, all study devices and testing equipment, 
as applicable, will be returned to the Sponsor unless this action would jeopardize the rights, 
safety or wellbeing of the subjects. The EC and regulatory authorities, as applicable, should 
be notified. All subjects enrolled in the study at the site will continue to be followed per this 
protocol. The Principal Investigator at the site must make provision for these follow-up visits 
unless the Sponsor notifies the investigational centre otherwise. 
11.6.3. 
Procedure for resuming the clinical investigation after temporary suspension 
 
When the sponsor concludes an analysis of the reason(s) for the suspension, implements 
the necessary corrective actions, and decides to lift the temporary suspension, the sponsor 
shall inform the principal investigators, the ECs, and, where appropriate, the regulatory 
authority of the rationale and provide them with the relevant data supporting this decision. 
 
Concurrence shall be obtained from the ECs and regulatory authorities before the clinical 
investigation resumes. 
 
If subjects have been informed of the suspension, the principal investigator or authorized 
designee shall inform them of the reasons for resumption. 
 
11.7. 
Publication Policy 
At the end of the trial, a Clinica Investigation Report will be compiled. At the conclusion of the 
trial, a multi-centre manuscript will be prepared for submission to a peer reviewed scientific 
journal, within 6 months after database lock.  The publication of the principal results from any 
single centre experience within the trial can be initiated only after the publication of the multi-
centre results, unless a decision is made not to pursue a multicentre manuscript. Any 
exceptions to this would require the prior written approval of the Sponsor.  

 
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Investigators may publish study results, provided Sponsor receives a copy of any proposed 
oral presentation or written publication at least 10 working days in advance of submission for 
presentation or publication for review. Sponsor has the right to comment on the 
appropriateness of the data analysis and presentation. Investigator will meet with Sponsor prior 
to submission for publication for the purpose of making good faith efforts to discuss and resolve 
any issues or disagreement. Upon Sponsor’s request, Investigator shall remove from any such 
oral presentation or written publication any commercial-in confidence information.   
 
11.8. 
Funding and agreements 
This investigation is funded by OstomyCure AS. A clinical investigation agreement is set 
between the sponsor and each invetigatioal site, detailing roles and responsibilities. 

 
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12. BIBLIOGRAPHY/REFERENCES 
1. Bokey, L.E., et al., Experiments in the development of a continent ileostomy: a simplified 
technique without a reservoir in dogs. Surgery, 1981. 90(3): p. 459-63.  
2. Pemberton, J.H., et al., A continent ileostomy device. Ann Surg, 1983. 197(5): p. 61826.  
3. Salmon, R., P. Bloch, and J. Loygue, Magnetic closure of a reservoir ileostomy. Dis Colon 
Rectum, 1980. 23(4): p. 242-3.  
4. Chancellor, M., et al., Biocarbon ureterostomy device for urinary diversion. Multicenter 
clinical trial. Urology, 1989. 34(1): p. 18-21.  
5. Goligher, J.C., et al., The Erlangen magnetic colostomy control device: technique of use 
and results in 22 patients. Br J Surg, 1977. 64(7): p. 501-7.  
6. Bustamante, I., et al., [Animal studies on the construction of continent ileostomies and 
colostomies with the use of BioCarbon implants]. Chir Forum Exp Klin Forsch, 1977: p. 194-8.  
7. Kock, N.G., et al., Continent ileostomy. The present technique and long term results. Ann 
Chir Gynaecol, 1986. 75(2): p. 63-70.  
8. Kock, N.G., et al., Urinary diversion via a continent ileal reservoir: clinical results in 12 
patients. 1982. J Urol, 2002. 167(2 Pt 2): p. 1153-9; discussion 1159-60.  
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13. APPENDICES 
Appendix A: Surgical Procedure Manual  
Appendix B: User Care Manual  
Appendix C: Patient´s guide for the first 16 weeks after implantation 
Appendix D: Montreux Quality of Life Questionnaire 
Appendix E: EQ-5D-5L Quality of Life Questionnaire 
Appendix F: Subject´s Diary on Use of the Implant 
Appendix G: Subject´s Preference Questionnaire 
Appendix H: Study sites list 
 
 
Appendix 
Document name 
Sponsor 
Document number 
for English version 
Appendix A Surgical Procedure Manual 
31-5TF12033-17 
Appendix B User Care Manual 
31-5TF17062-05 
Appendix C TIES® C03 Patient´s guide for the first 
16 weeks after implantation  
73-2CL17003-03 
Appendix D TIES® C03 Subject´s Diary on Use of 
the Implant 
73-2CL17004-03 
Appendix E TIES® C03 Subject´s Preference 
Questionnaire 
73-2CL17005-01 
Appendix F TIES® C03 Montreux Quality of Life 
Questionnaire 
73-2CL17006-01 
Appendix G TIES® C03 EQ-5D-5L Quality of Life 
Questionnaire 
73-2CL17007-01