Multicenter Clinical Trial for the Evaluation of Safety and Effectiveness of Endorail in Patients With Long-lasting Colonoscopy
Phase: NA
Conditions: Colonoscopy, Incomplete Colonoscopy
Sponsor: Endostart srl

Endorail 
 
Protocol v 1.1, 24.10.2022 
 
 ______________________________________________________________________________________________________________  
 
Code: CO-09-A02 
Confidential  
 1/52  
Version: 1.00 
Effective date: December 18th, 2020  
 
 
 
Clinical Study Protocol  
 
Multicenter clinical trial for the evaluation of safety and effectiveness of Endorail in patients with 
long-lasting colonoscopy 
  
 
 
Study acronym  
Endorail   
Sponsor 
Endostart s.r.l., Via delle Regioni 265, 50052 Certaldo (FI), 
Italy 
Investigational Product: 
Endorail Set and Endorail System 
Protocol Version and Date: 
V 1.1, Date:  24 October2022 
 
 
CONFIDENTIAL 
The information contained in this document is confidential and the property of the sponsor. The information may not 
- in full or in part - be transmitted, reproduced, published, or disclosed to others than the applicable Competent Ethics 
Committee(s) and Regulatory Authority(ies) without prior written authorisation from the sponsor except to the extent 
necessary to obtain informed consent from those who will participate in the study. 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 2/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Sponsor Signature Page(s)  
 
Study Title:  Multicenter clinical trial for the evaluation of safety and effectiveness of Endorail 
in patients with long-lasting colonoscopy 
 
 
 
 
Endostart s.r.l. has approved the protocol version 1.1 dated 24 October 2022 
 
Printed name of Sponsor Representative: Alessandro Tozzi 
 
 
Date 
 
Signature 
 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 3/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Principal Investigator: 
I have read and understood this protocol entitled “Multicenter clinical trial for the evaluation of 
safety and effectiveness of Endorail in patients with long-lasting colonoscopy” and agree to 
conduct the study as set out in this study protocol, ICH-GCP E6 guidelines or ISO 14155 standard 
and the local applicable regulations. I will provide all study personnel under my supervision with 
all information provided by the Sponsor and I will inform them about their responsibilities and 
obligations. 
 
Site Humanitas Research Institute, Rozzano, Milan, Italy 
 
Principal Investigator Prof. Alessandro Repici, Department Director and Head of Operative Unit 
of Gastroenterology and Digestive Endoscopy  
 
 
 
Date 
 
Signature 
 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 4/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Additional Trial Personnel/Site Information 
 
Sponsor authorized representative  
 
Name/title: 
Dr. Alessandro Tozzi, Endostart s.r.l. 
Address: 
Via delle Regioni 265, 50052 Certaldo (FI), 
Italy 
Phone: +39 3387717731 
Certified electronic mail: 
euroendoscopy@pec-it 
E-mail: a.tozzi@endostart.com 
Safety desk (SAE Reporting) 
Name/title: 
Dr. Alessandro Tozzi, Endostart s.r.l. 
Address: 
Via delle Regioni 265, 50052 Certaldo (FI), 
Italy 
Phone: +39 3387717731 
Certified electronic mail: 
euroendoscopy@pec-it 
E-mail: a.tozzi@endostart.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 5/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
TABLE OF CONTENTS 
 
STUDY SYNOPSIS .................................................................................................................................. 8 
ABBREVIATIONS................................................................................................................................. 14 
STUDY SCHEDULE ............................................................................................................................. 16 
1. 
BACKGROUND AND RATIONALE ............................................................................................. 17 
1.1 
Aim .............................................................................................................................................. 17 
1.2 
Background and Rationale .......................................................................................................... 17 
1.2.1 Optical colonoscopy ............................................................................................................ 17 
1.2.2 Incomplete colonoscopy ..................................................................................................... 17 
1.2.3 Long lasting colonoscopy .................................................................................................... 17 
1.2.4 Complications in colonoscopy ............................................................................................. 18 
1.2.5 Looping ............................................................................................................................... 18 
1.2.6 Endorail and Looping .......................................................................................................... 18 
1.3 
Investigational Product Description ............................................................................................. 19 
1.3.1 Endorail Intended Use/Indications for Use ......................................................................... 19 
1.3.2 Principles of Operation and Technological Characteristics ................................................ 19 
1.4 
Clinical Evidence to Date ............................................................................................................ 20 
1.5 
Study rationale ............................................................................................................................ 21 
1.6 
Explanation for choice of comparator .......................................................................................... 21 
1.7 
Risks / Benefits ............................................................................................................................ 21 
1.8 
Justification of choice of study population ................................................................................... 22 
2. 
STUDY OBJECTIVES .................................................................................................................... 23 
2.1 
Primary Objective ........................................................................................................................ 23 
3. 
STUDY ENDPOINTS .................................................................................................................... 23 
3.1 
Primary Endpoints: ...................................................................................................................... 23 
4. 
STUDY DESIGN ............................................................................................................................ 24 
4.1 
General study design and justification of design ......................................................................... 24 
4.2 
Methods of minimizing bias ......................................................................................................... 24 
4.3 
Eligibility criteria ........................................................................................................................... 24 
4.4 
Recruitment and screening ......................................................................................................... 26 
4.5 
Criteria for withdrawal / discontinuation of participants ............................................................... 26 
4.6 
Premature Stopping of the Trial .................................................................................................. 27 
4.7 
Replacements ............................................................................................................................. 27 
5. 
STUDY INTERVENTION ............................................................................................................ 28 
5.1 
Identity of Investigational Products (medical device) .................................................................. 28 
5.2 
Experimental Intervention (treatment/medical device) ................................................................ 29 
5.2.1 Treatment with the investigational device ........................................................................... 30 
5.2.2 Control Intervention (Clinical Practice)................................................................................ 30 
5.2.3 Packaging, Labelling and Supply ........................................................................................ 30 
5.2.4 Handling .............................................................................................................................. 30 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 6/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
5.2.5 Storage Conditions.............................................................................................................. 30 
5.3 
Administration of experimental and control interventions ........................................................... 31 
5.3.1 Experimental Intervention ................................................................................................... 31 
5.3.2 Compliance with study intervention .................................................................................... 31 
5.4 
Data Collection and Follow-up for withdrawn participants .......................................................... 32 
5.5 
Lost to Follow-up ......................................................................................................................... 32 
5.6 
Trial specific preventive measures .............................................................................................. 32 
5.7 
Concomitant Interventions (treatments) ...................................................................................... 32 
5.7.1 Permitted Medicines............................................................................................................ 32 
5.7.2 Prohibited Medicines ........................................................................................................... 33 
5.7.3 Other Interventions.............................................................................................................. 33 
5.7.3.1 
Special Precautions ....................................................................................................... 33 
5.7.3.2 
Management of Specific Adverse Events or Adverse Medical Device Reactions .............. 33 
5.7.3.3 
Medical Care of Subjects after End of Trial .................................................................... 33 
5.8 
Medical Device Accountability ..................................................................................................... 33 
5.9 
Return or Destruction of Medical Device..................................................................................... 33 
6. 
STUDY ASSESSMENTS ................................................................................................................. 34 
6.1 
Assessments of Endpoints .......................................................................................................... 34 
6.1.1 Assessment of primary Endpoints ...................................................................................... 34 
6.1.2 Assessments in participants who prematurely stop the study ............................................ 34 
6.2 
Procedures at each visit .............................................................................................................. 34 
6.2.1 Treatment Visit - Visit 1 (Day 1) .......................................................................................... 34 
6.2.2 Phone follow-up - Visit 2 (Day 7 ± 1) .................................................................................. 35 
7. 
SAFETY .......................................................................................................................................... 36 
7.1 
Medical Device – Class I ............................................................................................................. 36 
7.1.1 Definition of (Serious) Adverse Events and other safety related events ............................ 36 
Health hazards that require measures: ................................................................................................. 38 
Findings in the trial that may affect the safety of study participants, and which require preventive or 
corrective measures intended to protect the health and safety of study participants. .......................... 38 
7.2 
Method of Recording and Assessing Adverse Events ................................................................ 38 
7.2.1 Intensity of an adverse event .............................................................................................. 38 
7.2.2 Outcome .............................................................................................................................. 38 
7.2.3 Medical Device Incidents .................................................................................................... 39 
7.2.4 Reporting of (Serious) Adverse Events and other safety related events ............................ 39 
7.3 
Follow up of (Serious) Adverse Events ....................................................................................... 40 
8. 
STATISTICAL METHODS ............................................................................................................ 41 
8.1 
Hypothesis ................................................................................................................................... 41 
8.2 
Determination of Sample Size ..................................................................................................... 41 
8.3 
Statistical criteria of termination of trial ....................................................................................... 42 
8.4 
Planned Analyses ........................................................................................................................ 42 
8.4.1 Datasets to be analysed, analysis populations ................................................................... 43 
8.4.2 Interim analyses .................................................................................................................. 43 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 7/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
8.5 
Handling of missing data and drop-outs...................................................................................... 43 
9. 
QUALITY ASSURANCE AND CONTROL ................................................................................... 44 
9.1 
Data handling and record keeping / archiving ............................................................................. 44 
9.1.1 Case Report Forms ............................................................................................................. 44 
9.1.2 Specification of source documents ..................................................................................... 45 
9.1.3 Record keeping / archiving ................................................................................................. 46 
9.2 
Data management ....................................................................................................................... 46 
9.2.1 Data Management System ................................................................................................. 46 
9.2.2 Data security, access and back-up ..................................................................................... 46 
9.2.3 Analysis and archiving ........................................................................................................ 46 
9.2.4 Electronic and central data validation ................................................................................. 46 
9.3 
Monitoring .................................................................................................................................... 47 
9.4 
Audits and Inspections ................................................................................................................ 47 
9.5 
Ethical considerations ................................................................................................................. 47 
9.5.1 Ethics Committee (EC) and Competent Authority (CA) ...................................................... 47 
9.6 
Ethical conduct of the trial ........................................................................................................... 48 
9.6.1 Informed Consent ................................................................................................................ 48 
9.7 
Confidentiality, Data Protection ................................................................................................... 48 
10. INSURANCE ................................................................................................................................. 49 
11. PUBLICATION AND DISSEMINATION POLICY ...................................................................... 49 
REFERENCES ...................................................................................................................................... 50 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 8/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
STUDY SYNOPSIS  
 
Sponsor  
Endostart s.r.l., Via delle Regioni 265, 50052 Certaldo (FI), 
Italy 
Study Title 
Multicenter clinical trial for the evaluation of safety and 
effectiveness of Endorail in patients with long-lasting 
colonoscopy    
 
Study Acronym 
Endorail 
Protocol Version and Date: 
V1.1 
Date: 24th October 2022 
Clinical Phase: 
Post-market 
Background and Rationale: 
This clinical trial is intended to expand the clinical 
knowledge base about safety and efficacy of Endorail in 
facilitating colonoscopy completion in patients with long 
lasting colonoscopy. 
Reported incomplete colonoscopy rates range from 4% to 
25%.  While international guidelines recommend a rate of 
less than 10% for diagnostic colonoscopies, the risk is at 
least 20% in the more challenging subset of patients 
characterized by long-lasting procedures. 
A colonoscopy can be defined as “long-lasting” when 
caecal intubation time is longer than 10 minutes. As data 
from literature shows that about 80% of all diagnostic 
colonoscopies are typically completed in less than 10 
minutes, the long-lasting colonoscopy subset represents 
approx. 20% of the total procedures. Indeed, since nearly 
virtually all incomplete colonoscopies are also long-lasting, 
the risk of incompleteness in this subset of patients 
increases nearly five-fold (i.e., for a 5x increase, the lower 
bound of the rate increases from 4% to 20%) [1]. 
Endorail is intended to facilitate the positioning of a 
standard colonoscope. One of the main advantages of this 
device is that it can be used “as needed” during the 
procedure to prevent incomplete procedures without 
requiring any “preloading” ahead of time. This makes 
Endorail particularly indicated for patients in which caecal 
intubation time gets longer and the risk of incompletion 
increases. 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 9/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Objective(s): 
Primary Objectives:  
Efficacy (Timeframe: day 1): To validate the efficacy of 
Endorail in long-lasting colonoscopies by reaching a 
colonoscopy incompletion rate minor or equal to 10%. 
 
AND 
Safety (Timeframe: day 1 to day 7): To validate the safety 
of Endorail in long-lasting colonoscopies by demonstrating 
that colonoscopy serious adverse events are not increased 
using the device (i.e., in particular the absence of device-
related serious adverse events). 
Endpoint(s) 
Efficacy: 
The primary efficacy endpoint is the percentage minor or 
equal to 10% of incomplete long-lasting colonoscopies 
(colonoscopy is defined completed when caecal intubation 
is achieved) 
 
AND 
 
Safety: 
Medical adverse events and medical device adverse events 
will be collected during the study. The primary safety 
endpoints are:  
The absence of device-related serious adverse events. 
 
AND 
 
The evaluation of the equality or reduction of the adverse 
events rates compared to colonoscopies without Endorail.  
The adverse events assessed are: 
• Occurrence of general adverse events and medical 
device incidents; 
• Occurrence 
of 
specific 
adverse 
events: 
gastrointestinal bleedings, intestinal perforation, 
mucosal petechiae and abdominal pain. 
 
Study design: 
Multi Centre, Post Market, Single-Arm, Open-Label, 
Interventional Study  
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 10/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Inclusion / Exclusion criteria: 
Inclusion Criteria 
1. Patients of both sexes aged between 22 – 75 years 
(inclusive); 
2. Outpatients undergoing long-lasting diagnostic or 
surveillance colonoscopy; long-lasting colonoscopy 
is defined as follows: colonoscopy completion 
(caecal intubation) not achieved after 10 minutes 
from endoscope insertion through the anal canal; 
3. Patients have given a written informed consent for 
participation in the study at the time of enrolment 
or before.  
4. Patients able to understand the full nature and the 
purpose of the investigation, including possible 
risks and side effects, able to cooperate with the 
Investigator and to comply with the requirements 
of the entire investigation based on Investigator’s 
judgement. 
 
Exclusion Criteria 
1. Body mass index (BMI) > 30 kg/m2; 
2. Outpatients undergoing colonoscopy for colorectal 
cancer screening or therapeutic indication; 
3. Patients in class >2 physical status of the 
classification system of American Society of 
Anesthesiologists; 
4. Any contraindications to colonoscopy;  
5. Any contraindications to sedation; 
6. Known allergy or hypersensitivity to any of the 
elements of the Endorail Set (e.g.: iron); 
7. Patients with permanently or semi-permanently 
implanted 
medical 
devices, 
e.g. 
orthopedic 
implants, 
trauma 
fixation 
devices, 
cardiac 
pacemakers, implantable cardioverter defibrillator, 
drug pumps, neurostimulators, vascular stents, 
cochlear implants, aneurysm clip); 
8. Presence of dense diverticulosis; 
9. Presence of diverticulitis; 
10. Presence of ferromagnetic foreign body; 
11. Presence of large abdominal hernias; 
12. Urgent colonoscopy. 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 11/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 
13. Presence of severe thrombocytopenia; 
14. Presence of severe granulocytopenia; 
15. Presence of severe coagulopathy; 
16. Presence of peritonitis; 
17. Presence of colonic wall ischemia or necrosis or 
injured mucosa;; 
18. Presence of peritoneal carcinomatosis; 
19. Boston Bowel Preparation Scale <2 in at least one 
of the colonic segments; 
20. Presence of obstructing masses and strictures of 
the colon; 
21. History of total or subtotal colectomy; 
22. Presence of angulated and fixed colon curves; 
23. Pregnant or breast-feeding women; 
24. Patient unable to provide the signed informed 
consent, uncooperative patient or patient unlikely 
to comply with the protocol or unable to 
understand the nature, scope and possible 
consequences of the study; 
25. Presence of any other reason that, in the opinion of 
the investigator, prevents the subject from 
participating in the study or compromises the 
subject safety; 
26. Concomitant participation in 
other clinical 
investigations or participation in the evaluation of 
any investigational product/device in the 30 days 
before this study or previous participation in the 
same investigation; 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 12/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Measurements and procedures: 
Methodology: 
Outpatients of both sexes, aged between 22 and 75 years 
(inclusive), undergoing to diagnostic o surveillance 
colonoscopy, who have signed a written informed consent 
and a caecal intubation time greater than 10 minutes (long-
lasting colonoscopy), will take part in the study. 
The study plan will include a screening/baseline/treatment 
visit (Visit 1/Day 1), during which the colonoscopy will be 
performed with the investigational medical device 
Endorail, if long-lasting;  
AND 
a phone follow-up visit (Visit 2), scheduled 7 (± 1) day after 
treatment for patients treated with Endorail.  
Since only patients with long-lasting colonoscopy will be 
actually enrolled (i.e., Endorail will be used during the 
colonoscopy only when the intubation time is longer than 
10 minutes), about 80% of patients who signs the informed 
consent will likely not be enrolled. 
 
Study Product 
Endorail Set and Endorail System (Endostart s.r.l., 
Certaldo, Firenze, Italy) are the investigational medical 
devices to be used in this study. 
Endorail is composed of the following two CE marked 
medical devices: 
- Endorail Set (including Endorail Balloon Guide, and 
Endorail Solution Syringe, Endorail Powder and Spike)  
- Endorail System (including Endorail Handpiece and 
Endorail Cart).   
Sample size calculation: 
With a significance level α of 5%, assuming a proportion of 
outcome of 10.1%, 85 patients allow to test with a power 
of 80% the H0: p ≥ 20% vs H1: p < 20%, where 20% is 
the estimated percentage of incomplete procedure from 
literature.  
The chosen number is then increased by 10% to account 
for possible drop-out (e.g., cases to be discarded, losses to 
follow-up, etc.), resulting in 85/0.90 = 95 patients to be 
actually enrolled. 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 13/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Study Duration: 
Enrollment period: approximately 8 months; 
Follow up: 1 week; 
One single procedure (long-lasting colonoscopy). 
 
Study Schedule: 
Month/Year of First-Patient-In (planned): September 
2022 
Month/Year of Last-Patient-Out (planned): June 2023 
Study Centre(s): 
Multi-center study:  Conducted in Italy, Belgium and 
Germany. 
Statistical Considerations: 
A single-arm trial will be carried out to evaluate the safety 
and the completion rate in long-lasting colonoscopies 
conducted with Endorail. 
All data obtained in this study and documented in the 
eCRFs will be listed and summarized as appropriate: 
• 
for quantitative variables: standard quantitative 
statistics 
(N, 
mean, 
standard 
deviation, 
median, 
interquartile range, minimum and maximum);  
• 
for qualitative variables: frequency distribution 
[number of non-missing observations (N) and percentages 
(%)]. 
A statistical test will be performed to assess the significant 
difference with respect to the threshold.  
The number of adverse events (AEs) – related or not to the 
medical device – and the number and proportion of 
patients with at least one AE will be presented.  
The frequency of occurrence of specific adverse events 
(gastrointestinal bleedings, intestinal perforation, mucosal 
petechiae, abdominal pain) will be presented by means of 
default descriptive statistics. 
Analyses will be carried out using R Statistical (Foundation 
for Statistical Computing, Vienna, Austria). 
 
GCP Statement: 
This study will be conducted in compliance with the 
protocol, the ICH-GCP E6 or ISO 14155 (as far as 
applicable), 21 CFR 812.28 as well as all applicable 
regulatory requirements.  
 
 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 14/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 
ABBREVIATIONS 
AE 
Adverse Event  
ADE 
Adverse Device Event 
ASADE 
Anticipated Serious Adverse Device Effect 
BMI 
Body Mass Index 
CA 
Competent Authority  
CEC 
Competent Ethics Committee 
CFR 
Code of Federal Regulations 
CIP 
Carbonyl Iron Particles 
CRF 
Case Report Form  
eCRF 
Electronic Case Report Form  
DD 
Device Deficiency 
DRM 
Data Reviewed Meeting 
DSUR 
Development safety update report 
EBG 
Endorail Balloon Guide 
EC  
Endorail Cart 
EH 
Endorail Handpiece  
EP 
Endorail Powder 
ESS 
Endorail Solution Syringe 
FDA 
Food and Drug Administration 
FIM 
First In Man  
GCP 
Good Clinical Practice  
GI 
Gastro-Intestinal 
IB 
Investigator’s Brochure 
Ho 
Null hypothesis 
H1 
Alternative hypothesis 
ICD 
Implantable Cardioverter Defibrillator 
ICE 
Integrated Clinical trial Environment 
IIT 
Investigator-initiated Trial 
ISO 
International Organisation for Standardisation 
ITT 
Intention to treat 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 15/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
MD 
Medical Device  
PI 
Principal Investigator  
PT 
Preferred Term 
PP 
Per- Protocol 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Event  
SDV 
Source Data Verification  
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SPC 
Summary of product characteristics 
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
TMF 
Trial Master File  
USADE 
Unanticipated Serious Adverse Device Effect 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 16/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 STUDY SCHEDULE 
 Table 1 – Study Schedule of Assessments  
 
 
Screening/Baseline/ 
Treatment with Endorail 
System 
Phone Follow-up 
Visit 
Visit 
V1 
V2 
Day 
1 
7 ± 1 
Informed consent 
X 
 
Demographic data 
X 
 
Medical history 
X 
 
Concomitant treatments 
X 
X 
Physical examination 
X 
 
Vital signs pre-procedure 
X 
 
Inclusion/exclusion criteria 
X 
 
Use of sedation 
X 
 
Colonoscopy with Endorail  
X 
 
Local (intraprocedure) adverse events 
X 
 
Vital signs after procedure 
X 
 
Colonoscopy completion 
X 
 
General/specific adverse events 
X 
X 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 17/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 
1. BACKGROUND AND RATIONALE  
1.1 
Aim 
The aim of this study is to test the safety and efficacy of the Endorail in ensuring low incompletion 
rate in long-lasting colonoscopies. 
 
1.2 
Background and Rationale 
1.2.1 
Optical colonoscopy 
Optical colonoscopy represents the diagnostic and therapeutic gold standard for colonic diseases 
[23]. 
1.2.2 
Incomplete colonoscopy 
A colonoscopy can be defined as incomplete when the endoscopist cannot reach the last segment 
of the colon called caecum. In particular a colonoscopy is incomplete when the endoscopist feels 
that it is not useful anymore to continue the procedure and make further efforts [15]. Because 
neoplasms or other pathologies may occur in any part of the colon, it is essential to complete 
colonoscopy and also explore the right segments. In case the caecum is not reached, the 
endoscopist always recommends to complete the examination with a second procedure. The 
completion is usually performed with virtual colonoscopy or deep sedation colonoscopy possibly 
with a more experienced endoscopist. However, it was found that about 30% of patients with 
incomplete colonoscopy after one year from the examination have not carried out any 
complementary investigation yet. The execution of a complementary examination entails an 
increase in overall costs for both the health care system and the patient [4]. In fact, the latter will 
have to carry out the intestinal preparation and undergo further invasive procedure. The cost of 
the complementary procedure may fluctuate from 250 to 1,000 Euros in relation to the type of 
procedure [22]. 
Thus, caecal intubation is one of the main goals of colonoscopy and represents a diagnostic quality 
indicator. International guidelines recommend caecal intubation rates ≥90% for all colonoscopies 
in daily clinical practice and ≥95% in screening programs. Reported incomplete colonoscopy rates 
range from 4% to 25%. Caecal intubation fails in 4-10% of cases in tertiary referred centres), instead 
in national surveys colonoscopies are incomplete in 10-25% of cases [25][21][27][1].  
1.2.3 
Long lasting colonoscopy 
A colonoscopy can be defined as difficult or long-lasting when caecal intubation time is longer 
than 10 minutes. Long lasting colonoscopies are cause of stress and delays in the workflow. 
Moreover, longer procedures are characterized by more traumatic manoeuvres, increased pain and 
discomfort, higher sedation requirements and higher risk of severe complications such as 
cardiorespiratory events and bowel perforation. 
As data from literature shows that about 80% of all diagnostic colonoscopies are typically 
completed in less than 10 minutes, the long-lasting colonoscopy subset represents approx. 20% of 
the total procedures. Indeed, since nearly virtually all incomplete colonoscopies are also long-
lasting, the risk of incompleteness in this subset of patients increases nearly five-fold (i.e., for a 5x 
increase, the lower bound of the rate increases from 4% to 20%) [1][7][17][20].  

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 18/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
1.2.4 
Complications in colonoscopy 
Severe complications such as cardiorespiratory events and bowel perforation, although rare, can 
develop during colonoscopy [10]. Serious gastrointestinal events; myocardial infarction; stroke; 
pneumonia occurrence rates in screening or surveillance colonoscopy are 47 persons, 4 persons, 7 
persons and 10 persons per 100’000, respectively [30]. 
1.2.5 
Looping 
One of the main risk factors for incomplete colonoscopy is colon loop formation [1] Moreover, 
looping can make colonoscopy a time-consuming procedure requiring manoeuvres that demand a 
significant amount of training.  
The frequency of occurrence of loops during endoscopy is high and may reach proportions of 80- 
90% of cases of endoscopy [5][12]. 
Looping is the process where the scope tip does not progress forward when the endoscopist pushes 
the scope into the patient, but rather the mid-section of the scope bows out, resulting in stretching 
of the colon. If the endoscope is being inserted into the colon by simply pushing it forward and 
steering the tip, the shaft pushes against the colonic wall until the colon and its surroundings 
provide sufficient counter pressure to force the shaft to bend. In practice, this means that the colon 
is often stretched substantially. This frequently leads to formation of loops in the flexible 
endoscope shaft and colon, which can hinder further advancement of the tip [32][9]. The 
functionally necessary flexibility and length of the scope shaft and the floppy nature of the colon 
and its attachments may prohibit reaching the cecum and visualizing the entire colon 
[2][8][13][19][24][3][16]. 
Abdominal pain is mainly due to the traction on the mesenteries exerted by the colonoscope with 
the intent to solve eventual loops. Moreover, such manoeuvres enhance the risk of colon 
perforation, discomfort, undue pain and longer recovery time [12]. Sedation is often used to 
prevent pain. Studies using magnetic endoscopic imaging correlated that looping in the sigmoid 
colon causes significant pain that can alter colonoscopy outcomes [28]. Most of the forces are 
exerted on colonic walls whilst the instrument is looping [9]. The colon is rarely perforated by the 
tip of the colonoscope. Perforations usually occur when the endoscopist is pushing the 
colonoscope to get around a curvature. The curvature expands more and more as the colonoscope 
is being pushed in without advancing the tip, and suddenly, the outer wall of the colonoscope splits 
from the expanding loop [32] 
It is important for endoscopists to pay attention to loops and to straighten the instrument by 
adequate endoscopic techniques such as hooking, torque, jiggling, pull back, and suctioning excess 
air. However, these techniques are not easy to be managed and demand a significant amount of 
training [18][1]. 
 
1.2.6 
Endorail and Looping 
The first generation of Endorail has been tested in 2020 in a first in human clinical trial called 
ESPILOT2019H. This clinical trial provided first clinical data about safety and efficacy of Endorail. 
In particular this trial showed that Endorail is able to facilitate loop resolution. The current study 
has been conceived considering that Endorail should allow to facilitate colonoscopy completion. 
Long-lasting colonoscopies represents a challenging subset of patients with higher risk of 
incomplete colonoscopy. Our study is intended to demonstrate the efficacy and safety of the 
Endorail in ensuring that incompletion rate, even in long-lasting colonoscopies, is lower than the 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 19/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
10% threshold as recommended by international guidelines. 
 
1.3 Investigational Product Description  
Endorail is a colonoscopy add-on device developed to be used without any modification to 
colonoscopes and peripheral devices currently utilized. It is an accessory for colonoscopy aimed at 
facilitating progression of the endoscope in the large intestine. Endorail works as a magnetic anchor 
that is able to guide the colonoscope and to straighten colon curves and loops. 
A second generation of Endorail has been developed and Endorail is composed by the following 
two CE marked medical devices: Endorail Set and Endorail System. 
The reusable Endorail System consists of: 
o 
The Endorail Handpiece (EH) 
o 
The Endorail Cart (EC) 
 
The single-use Endorail Set consists of: 
o 
The Endorail Balloon Guide (EBG) 
o 
The Endorail Solution Syringe (ESS) 
o 
The Endorail Powder (EP) 
o 
Spike 
 
1.3.1 
Endorail Intended Use/Indications for Use 
Endorail is composed by the two medical devices Endorail Set and Endorail System. 
• Endorail Set is a medical device intended to facilitate the endoscope positioning during 
colonoscopy. The use of Endorail Set is closely linked to the use of the medical device 
Endorail System. 
• Endorail System is intended to attract and lock in place Endorail Balloon Guide (part of 
the medical device Endorail Set) inside the colonic lumen, in order to facilitate the 
endoscope positioning during colonoscopy. The use of Endorail System is closely linked 
to the use of the medical device Endorail Set. 
 
1.3.2 
Principles of Operation and Technological Characteristics 
For exhaustive description of the device and its usage see the Endorail Set and Endorail System 
instructions for use. 
Colonoscopy represents the gold standard procedure for colorectal cancer prevention [11]. Its 
completion maximizes the possibility of detecting tumors in all colonic segments. However, 
intubation of the cecum may be challenging due to the occurrence of loops in the colon [1]. In 
these cases, the tip of the scope cannot move forward, the endoscope increases the wide angle of 
the loop [5] and the patients can suffer intense pain [29]. While the endoscopist may try to 
straighten the scope, unfortunately this is not always easy or feasible [Error! Reference source 
not found.][1]. 
In case of long-lasting colonoscopy, the Endorail Balloon Guide can be inserted inside the 
endoscope tool channel. The balloon guide is connected at its proximal (user) end to the syringe 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 20/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
containing the Ferromagnetic Fluid which is a magnetorheological mixture composed of solid 
micrometric carbonyl iron powder particles dispersed in a hypertonic water solution of salts (NaCl 
and Sodium Citrate). 
The ferromagnetic fluid syringe needs to be prepared by the nurse according to the following steps: 
• 
the water solution of the ESS is injected in the vial containing the iron powder EP 
• 
the vial is shaken 
• 
the ferromagnetic fluid is aspirated within the syringe  
• 
the syringe filled with ferromagnetic fluid is ready to be connected with the balloon catheter 
The balloon is advanced beyond the colonoscope tip and filled with 25 mL of biocompatible 
Endorail Ferromagnetic Fluid. The operator manually performs and controls the inflation and 
deflation of the balloon through the syringe. Thus, by applying the Endorail Handpiece over the 
patient abdomen, the balloon can be magnetically anchored. The magnetic power level can be 
increased by the operator according to the patient’s body mass characteristics and the successful 
anchorage of the balloon can be visually verified by the operator through the images captured by 
the colonoscope. 
The anchored balloon guide allows to straighten the scope and thus the colon itself. As the balloon 
guide is kept in tension, its rigidity increases and works as a rail supporting the movements of the 
colonoscope. The guided colonoscope can thus be easily moved back and forward to allow better 
colonoscope positioning and colonoscopy completion. 
The Endorail Balloon Guide pulled against the colonic wall by the handpiece magnetic field works 
as a distal anchor towards which the endoscope tip is advanced and the Endorail Balloon Guide 
inflation tube serves as a guide wire that leads the endoscope as it is pushed towards the 
magnetically anchored balloon. After the Endorail is removed, the straightened colonoscope can 
be easily pushed forward to achieve colonoscopy completion as foreseen in standard endoscopic 
technique. 
The Endorail Balloon Guide does not affect the endoscope's flexibility, its field of view and the 
maneuverability of the endoscope's tip, nor does it limit the use of any standard endoscopy tools 
such as biopsy forceps, snare, needle etc. The Endorail Balloon Guide can be pulled back at any 
time during the procedure in order to allow the use of therapy tools.  
 
 
1.4 
Clinical Evidence to Date  
With the intent of providing clinical evidence to further support the safety and efficacy profile of 
the Endorail, a First-In-Man (FIM) clinical trial has been conducted. This study, named 
“ESPILOT2019H”, was initiated on February 11, 2020, and required the enrolment of a total of 
25 evaluable Italian patients undergoing elective colonoscopy. Following the enrolment of the first 
six (6) patients however, the particularly severe COVID-19 outbreak experienced in Italy forced 
an early interruption of the study recruitment by the affected medical centers. Given the great 
uncertainty about a realistic timeline for a possible study resumption, Endostart decided to 
terminate the trial on March 11, 2020. This decision was not due to the occurrence of any adverse 
events, or safety concerns, or other device-related reasons.  
All 6 patients completed the colonoscopy in the expected timeframe without any adverse event or 
complications. Five (5) of the six (6) enrolled patients completed the study according to the 
protocol. In the very first patient however, due to an error of the device technical information 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 21/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
sheet, a pediatric colonoscope was utilized with a tool channel diameter smaller than required (3.2 
mm instead of 3.7 mm), which did not allow the successful insertion of the Endorail Balloon Guide. 
For this one patient, the colonoscopy was continued and completed in the traditional manner 
without the use of the subject device. 
Following a protocol amendment, whereby the reference colonoscope channel diameter to be used 
was specified to be ≥ 3.7 mm, all loops formed in the other 5 patients were successfully resolved 
with the Endorail.  
 
1.5 
Study rationale 
By facilitating loop solving, Endorail should be able to provide several potential benefits, which 
include fewer attempts at straightening the scope, shorter duration of looping, decreased mean 
caecal intubation time, higher procedure completion rates, higher diagnostic efficiency, reduced 
health care costs, reduced stretching forces exerted on the colon walls and attachments, reduced 
risk of perforation during diagnostic colonoscopy, reduced risk of splenic injury during diagnostic 
colonoscopy, reduction of the evoked pain and patient discomfort, reduction, and in some cases 
elimination, of the need for sedation, and reduction of cardiorespiratory complications. All these 
benefits need to be demonstrated in properly designed clinical trials.  
The current study has been conceived considering that Endorail should allow to facilitate 
colonoscopy completion. Long-lasting colonoscopies represents a challenging subset of patients 
with higher risk of incomplete colonoscopy. Our study is intended to demonstrate the efficacy and 
safety of the Endorail in ensuring that incompletion rate, even in long-lasting colonoscopies, is 
lower than the 10% threshold as recommended by international guidelines. 
 
1.6 
Explanation for choice of comparator  
Caecal intubation rate is an important quality measure in colonoscopy. The completion of the 
insertion process by fully intubating the cecum allows the endoscopist to perform a complete 
examination of the colon mucosa upon withdrawal. Caecal intubation is an objective parameter 
that, according to the standard of care, should be collected during any colonoscopy. International 
guidelines recommend achieving an incompletion rate lower than 10%. This numerical target value 
is derived from historical data from clinical studies and may be used as effectiveness endpoint (See 
Section 1.4). 
Adverse events occurrence during colonoscopy is well documented in international literature and 
can be used as safety endpoint. 
Considering the extensive objective data available from literature and the standard of care, we 
believe that valid scientific evidence to determine whether there is reasonable assurance that the 
Endorail is safe and effective may come from an objective trial without matched controls.  
 
1.7 
Risks / Benefits  
Patients with long lasting colonoscopy are characterized by high risk of incomplete colonoscopy 
and adverse events. Indeed if caecal intubation time is longer than 10 minutes, it means that the 
procedure is more challenging and traumatic and more sedation is required. Endorail has been 
developed to facilitate colonoscopy completion, thus it can provide a significant benefit to this 
population. 
From a safety perspective, reassuring evidence supports the safety of magnetic devices for 
endoscopic procedures. Magnets in gastrointestinal endoscopy are involved in applications such as 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 22/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
magnetic maneuverable capsule endoscopy, magnetic foreign body removal, magnetically tracked 
enteral tube placement, compression anastomosis, magnetic anchoring, magnetic retraction, 
magnetic sphincter augmentation and magnetic tumor marking [6]. 
There have been several reports of anchoring technology in humans. Dominguez et al reported no 
magnet related complications or conversions using neodymium magnetic forceps in 40 patients 
undergoing laparoscopic cholecystectomy [10]. The Magnetic Surgical System (by Levita 
Magnetics) is indicated in the U.S. to grasp and retract the body and the fundus of the gallbladder 
in laparoscopic cholecystectomy and the liver in bariatric procedures to facilitate access and 
visualization of the surgical site.  
PUMA-G System (by CoapTech LLC) is an accessory to enteral feeding tubes that, using the 
magnetic anchoring of its balloon, enables ultrasound-based placement of percutaneous gastrostomy 
feeding tubes. In particular the balloon of the device PUMA-G System is filled with a saline solution and 
the magnetic anchoring force towards the external magnet is ensured by a small magnetic needle hosted 
within the balloon. 
Endorail magnetic balloon anchorage is exerted thanks to the Endorail Ferromagnetic Fluid which 
is a dispersion of micrometric carbonyl iron particles (CIP) in hypertonic water-based solution 
containing sodium citrate and sodium chloride. The ferromagnetic fluid contained in the syringe is 
not intended to be in contact with the patient, however the possibility of a contact has been taken 
into account. Carbonyl iron particles incorporate excellent biocompatibility and safety factors with 
their unique magnetic properties; therefore, they have been used in biomedical applications such 
as oral iron supplements for iron deficiency anemia.  
Evidences gathered in literature suggest that carbonyl iron powders possess a low potential for 
acute systemic toxicity when ingested. This is most likely related to the long solubilization process 
that they undergo into the stomach. Since such solubilization process does not take place into the 
large intestine, it is deemed unlikely for a CIP to be readily absorbed by the tissues of this body 
structure. In the case of the Endorail, it is suggested to take appropriate countermeasures to ensure 
that accidentally poured CIP is endoscopically removed as much as possible from the patient’s 
large intestine. Indeed CIP is grey and in case of leakage it is very easy to be detected. The 
endoscopist can use the colonoscope to wash the lumen and remove the iron powder in few 
minutes. These countermeasures and the low probability of absorption by the tissues of the large 
intestine are expected to contribute to a very low biological risk for the patient. 
The planned clinical investigation will assess the safety and tolerability of Endorail by collecting 
general adverse events and specific adverse events, such as gastrointestinal bleedings, intestinal 
perforation, mucosal petechiae and abdominal pain. Overall, there are no expected or unexpected 
risks or complications that may emerge from the use of the Endorail in the patient population 
selected in this investigational protocol. Therefore, it is expected that benefits from the 
participation in this investigation will outweigh the potential risks. 
 
1.8 
Justification of choice of study population  
 
The study population includes outpatients of both sexes, aged between 22 and 75 years (inclusive), 
undergoing diagnostic and surveillance colonoscopy, who have signed a written informed consent. 
The choice of study population is guided by the need to obtain a homogeneous patients’ sample 
and to collect data that are comparable with those available in the literature, allowing an accurate 
and unbiased statistical analysis. Moreover, all those conditions that could impair the patient’s 
safety have been excluded.  

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 23/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
A population between 22 and 75 years of age has been chosen since the aim is to study the Endorail 
device in the treatment of adult population; to be compliant with FDA regulation, the age of 
majority in the United States was used as reference. Moreover, since it is known in the literature 
that the occurrence of adverse events is greater in the older population, patients aged >75 years 
are excluded.  
Targeting a homogeneous population, the choice to include surveillance and diagnostic 
colonoscopies is justified by the fact that both refer to comparable guidelines and that the data in 
the literature are comparable. On the contrary, screening colonoscopies were excluded because 
they present a different completion rate than the previous two, while therapeutic colonoscopies 
present a higher risk of occurrence of adverse events.  
In conclusion, the population was chosen homogeneously in order to compare it with the data 
available in literature, to create as few confounding factors as possible and to exclude any 
conditions that might impact on patient and device safety. 
2.  STUDY OBJECTIVES  
The aim of this study is to test the safety and efficacy of Endorail in ensuring low incompletion 
rate in long-lasting colonoscopies. 
 
2.1 
Primary Objective 
Efficacy (Timeframe: day 1) 
To validate the efficacy of Endorail in long-lasting colonoscopies by reaching a colonoscopy 
incompletion rate minor or equal to 10%. 
AND 
Safety (Timeframe: day 1 to day 7) 
To validate the safety of Endorail in long-lasting, colonoscopies by demonstrating that 
colonoscopy serious adverse events are not increased using the device (i.e., in particular the absence 
of device-related serious adverse events). 
3. STUDY ENDPOINTS  
3.1 
Primary Endpoints: 
Efficacy: 
The primary efficacy endpoint is the percentage minor or equal to 10% of incomplete long-lasting 
colonoscopies (colonoscopy is defined completed when caecal intubation is achieved) 
AND 
Safety: 
Medical adverse events and medical device adverse events will be collected during the study.  
The primary safety endpoints are:  
The absence of device-related serious adverse events. 
AND 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 24/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
The evaluation of the equality or reduction of the adverse events rates compared to 
diagnostic colonoscopies without Endorail.  
The adverse events assessed are: 
• Occurrence of general adverse events and medical device incidents; 
• Occurrence of specific adverse events: gastrointestinal bleedings, intestinal perforation, 
mucosal petechiae and abdominal pain. 
4. STUDY DESIGN  
4.1 
General study design and justification of design  
The study will be conducted according to a Multi Centre, Post Market, Single-Arm, Open-Label, 
Interventional Study design, which is considered as the most appropriate for the collection of the 
clinical data about the safety and efficacy of the Endorail device in completing long-lasting 
diagnostic colonoscopy or surveillance colonoscopy. Considering that completion rate and adverse 
events occurrence are widely described in historical data from clinical studies and/or registries and 
may be used as objective for safety or effectiveness endpoints, the single-arm design can be 
considered sufficient for the aim of the study. 
Outpatients of either sex aged between 22-75 years (inclusive), undergoing elective colonoscopy 
for diagnostic or surveillance colonoscopy, who have signed a written informed consent and 
presenting caecal intubation time greater than 10 minutes, will take part in the study. The study 
plan will include a screening/baseline/treatment visit (Visit 1/Day 1), during which colonoscopy 
with the investigational medical device Endorail will be performed and a phone follow-up visit 
(Visit 2), scheduled at 7 (± 1) day after treatment with the investigational medical device Endorail. 
 
4.2 
Methods of minimizing bias  
The following measures have been implemented in order to minimize avoid/bias: 
• New technology bias is minimized through an adequate and thorough training to the 
endoscopist; 
• Low statistical bias is minimized through an adequate estimate of the number of patients 
in the treatment group as compared to the state of the art; 
• 
Multicentric study to minimize usability bias. 
 
4.3 
Eligibility criteria  
Inclusion Criteria 
1. Patients of both sexes aged between 22 – 75 years (inclusive); 
2. Outpatients undergoing long-lasting diagnostic and surveillance colonoscopy; long-lasting 
colonoscopy is defined as follows: colonoscopy completion (caecal intubation) not 
achieved after 10 minutes from endoscope insertion through the anal canal; 
3. Patients have given a written informed consent for participation in the study at the time 
of enrolment or before;  
4. Patients able to understand the full nature and the purpose of the investigation, including 
possible risks and side effects, able to cooperate with the Investigator and to comply with 
the requirements of the entire investigation based on Investigator’s judgement. 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 25/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Exclusion Criteria 
1. Body mass index (BMI) > 30 kg/m2; 
2. Outpatients undergoing colonoscopy for colorectal cancer screening or therapeutic indication;  
3. Patients in class >2 physical status of the classification system of American Society of 
Anaesthesiologists; 
4. Any contraindications to colonoscopy;  
5. Any contraindications to sedation; 
6. Known allergy or hypersensitivity to any of the elements of the Endorail Set (e.g.: iron); 
7. Patients with permanently or semi-permanently implanted medical devices, (e.g. orthopedic 
implants, trauma fixation devices, cardiac pacemakers, implantable cardioverter defibrillator, 
drug pumps, neurostimulators, vascular stents, cochlear implants, aneurysm clip); 
8. Presence of dense diverticulosis 
9. Presence of diverticulitis 
10. Presence of ferromagnetic foreign body; 
11. Presence of large abdominal hernias; 
12. Urgent colonoscopy; 
13. Presence of severe thrombocytopenia; 
14. Presence of severe granulocytopenia; 
15. Presence of severe coagulopathy; 
16. Presence of peritonitis; 
17. Presence 
of 
colonic 
wall 
ischemia 
or 
necrosis 
or 
injured mucosa; ; 
18. Presence of peritoneal carcinomatosis; 
19. Boston Bowel Preparation Scale <2 in at least one of the colonic segments; 
20. Presence of obstructing masses and strictures of the colon; 
21. History of total or subtotal colectomy. 
22. Presence of angulated and fixed colon curves; 
23. Pregnant or breast-feeding women; 
24. Patient unable to provide the signed informed consent, uncooperative patient or patient 
unlikely to comply with the protocol or unable to understand the nature, scope and possible 
consequences of the study; 
25. Presence of any other reason that, in the opinion of the investigator, prevents the subject from 
participating in the study or compromises the subject safety 
26. Concomitant participation in other clinical investigations or participation in the evaluation of 
any investigational product/device in the 30 days before this study or previous participation in 
the same investigation; 
27. Urgent colonoscopy. 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 26/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
4.4 
Recruitment and screening  
Before starting the recruitment, each investigator must be familiar with the device under 
investigation. 
If the Investigator has never used the Endorail device, he/she should perform at least three 
colonoscopy procedures with Endorail. To assess the performance case, the Investigator should 
sign  a self-declaration titled “ Performance case declaration” stating that the three cases have been 
duly performed in compliance with Protocol requirement.  
Before any screening procedure all patients must sign a written informed consent for the study.  
The following logs must be maintained at each study site and kept in the Investigator Site File: a 
“Subject Screening Log\Enrolment Log”, to document the identification of subjects who enter 
screening and to document chronological enrolment of patients, a “Subject Identification List” for 
all subjects registered to maintain the correlation with the patient's full identification data (name, 
surname - confidential).  
Eligible patients who have provided written informed consent to study participation and that satisfy 
all inclusion criteria and none of the exclusion criteria both detailed in Section 4.3, will be enrolled 
in the clinical study.  
Eligibility will be determined by the investigator basing on standard colonoscopy clinical history 
and colonoscopy indication. Enrolment will be completed during colonoscopy if caecal intubation 
time is longer than 10 min. 
When the investigator registers in the eCRF the enrolment of a new patient, the eCRF will assign 
a 4-digit identification number to each patient included in the investigation. The patient number 
will be sequentially assigned to each patient who signs the informed consent, starting from 0001 . 
If a subject discontinues from the study, the patient number will not be re-used, and the subject 
will not be allowed to re-enter the study. Moreover, to distinguish the patient number of different 
sites involved in the clinical trial, the 4 digit patient number will be preceded by a 2-digit site number. 
Before the study initiation, the Sponsor will assign to each participating site its unique 2-digit site 
number.  
 
4.5 
Criteria for withdrawal / discontinuation of participants 
Patients have the right to withdraw from the investigation at any time for any reason including 
personal reasons (consent withdrawal). The Investigator also has the right to withdraw any patient 
from the investigation if he/she deems this appropriate and in the best interest of the patients.  
Possible reasons to discontinue a patient from the study include: 
• Patients’ withdrawal of consent for study participation;  
• Adverse events (AEs): occurrence of unexpected symptoms during the study, whose 
intensity or specific treatments require the discontinuation of the colonoscopy with the 
investigational product. The reason of discontinuation must be recorded in the medical 
records and in the eCRF. If necessary, patients will be given an appropriate symptomatic 
treatment that will be recorded in the medical records and in the eCRF, together with the 
outcome and the duration of the AE. In case of serious adverse reactions to the 
investigational device, the study sponsor must be advised within 24 hours and all 
procedures for the reporting of serious adverse events (SAEs) will be made effective;  

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 27/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
• Protocol violation: at least one of the conditions that represent any of the exclusion criteria 
(refer to Section 4.3). The reason of discontinuation must be recorded in the medical 
records and in the eCRF;  
• The Investigator considers the study procedure discontinuation as appropriate, in the best 
interest of the patient;  
• The Sponsor will terminate the study for any reason (refer to Section 4.6);  
• Patient dies during the study: the reason and the date of death will have to be recorded in 
the medical records and in the eCRF, together with the Investigator’s opinion on the 
correlation between the cause of death and the investigational product.  
Should a patient decide to withdraw from the study, all efforts will be made to complete and report 
the observations as thoroughly as possible. A complete final evaluation at the time of the 
withdrawal (study end-point) should be performed, and a clear, univocal explanation of the reason 
why the subject is withdrawn from the study should be reported in the medical record.  
  
4.6 
Premature Stopping of the Trial 
Both the Sponsor and the Principal Investigator reserve this right to terminate the investigation at 
any time. The Sponsor has the right to terminate the participation of the participant site at any time, 
for any reason, including but not limited to the following: 
• The information on the investigational products leads to doubt as to the benefit/risk ratio; 
• Patient enrolment is unsatisfactory and the patient recruitment lags behind the prospected 
timetable by more than 50%;  
• The Principal Investigator has received from the Sponsor all investigational medical 
products, means and information necessary to perform the clinical study and has not 
included any patient after a reasonable period of time mutually agreed upon;  
• Non-compliance of the Principal Investigator or Sub-investigators, delegated staff with any 
provision of the clinical study protocol, and breach of the applicable good clinical practice 
(GCP) requirements. In any case the Sponsor will notify the Principal Investigator of its 
decision by written notice. 
• In particular, when 38 patients (40% of the sample size) and 57 patients (60% of the sample 
size) are reached, the significance will be tested. If significance is found, the trial can be 
terminated with the patients already collected. 
 
4.7 
Replacements 
Patients who withdraw the informed consent before the completion of the procedure can be 
replaced by newly recruited patients. Similarly, for patients who are found to be lost to follow-up 
following the procedure completion and therefore cannot be reached by phone for the scheduled 
follow-up visit (Visit 2) a second and third attempt should be made after the second and third 
week; if the patient is still untraceable it can also be replaced by newly recruited patients (See section 
5.5). 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 28/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
5. STUDY INTERVENTION  
5.1 
Identity of Investigational Products (medical device)  
  
Endorail (Endostart s.r.l., Certaldo, Firenze, Italy) is the investigational medical device used in this 
study. For an extensive description of the device, please see the instruction for use. 
The Endorail is composed by the following two CE marked medical devices: 
• 
The reusable Endorail System, which consists of: 
o 
The Endorail Handpiece (EH) 
o 
The Endorail Cart (EC) 
• 
The single-use Endorail Set, which consists of: 
o 
The Endorail Balloon Guide (EBG) 
o 
The Endorail Solution Syringe (ESS) 
o 
The Endorail Powder (EP) 
o 
Spike  
Endorail Balloon Guide (EBG) 
EBG is an on-demand disposable balloon catheter that can be inserted through the instrument 
channel of the colonoscope. EBG includes the balloon and the inflation tube. The balloon is elastic 
and is placed at the distal end of the catheter and its maximal capacity is 25 mL. The user may 
operate and control the inflation and deflation of the balloon through the syringe containing 
Endorail Ferromagnetic fluid connected at the proximal end of the catheter.  
The balloon can be advanced ahead of the endoscope tip or pulled back through pushing/pulling 
action on the inflation tube at its proximal side, outside the patient's body. The EBG can be pulled 
back at any time during the procedure in order to allow the use of other endoscopic accessories.  
 
Endorail Solution Syringe (ESS)  
ESS included in the Endorail Set is disposable and intended for-single use. The syringe is prefilled 
with a hypertonic water-based saline solution with high sodium citrate and sodium chloride 
concentrations.  
 
Endorail Powder (EP) 
Endorail Powder is a 50 mL vial containing dry carbonyl iron powder.  
 
Spike 
The spike is a tool required for piercing the vial and inject the saline solution in the vial.  
 
Endorail Ferromagnetic Fluid Syringe (EFFS) 
Before using Endorail the saline solution contained in the syringe need to be mixed with the iron 
powder. For this purpose, the ESS is connected with the spike and the spike is connected with EP. 
After that the saline solution has been mixed with the iron powder, at the end of the preparation 
phase, the syringe is filled with a water dispersion of iron micrometric particles called Endorail 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 29/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Ferromagnetic Fluid.  
Endorail Handpiece (EH)  
Endorail handpiece (EH) contains a powerful permanent magnet. The handpiece is reusable and 
allows both the safe use of the magnet and the regulation of the magnetic field exerted on the filled 
balloon. EH is used during the procedure to magnetically anchor the balloon filled with 
ferromagnetic fluid. 
Thanks to a screw-like mechanism the magnet can be moved inside the handle. There are 5 
different magnet positions that correspond to 5 different levels of magnetic field intensity. The 
first level is the weakest and is called MIN Level. The fifth level is the most powerful one and also 
the most dangerous. For safety reasons EH should be always used and stored carefully following 
the instruction for use. EH misuse can cause severe adverse events both for patients and users. 
The magnetic field can interfere with other ferromagnetic objects or electronic devices. 
Endorail Cart (EC) 
Endorail Cart is used for the storage and transportation of Endorail Handpiece. It is composed by 
a case and a base with wheels. The case is provided with a shield for magnetic fields to avoid 
accidental interferences between the magnet and other ferromagnetic objects or electronic devices. 
 
5.2 
Experimental Intervention (treatment/medical device) 
 
Endorail is a colonoscopy add-on device developed to be used without any modification to 
colonoscopes. Endorail is an accessory to an endoscope and is intended to facilitate positioning of 
a standard colonoscope during endoscopy of the large intestine. Endorail works as a magnetic 
anchor that is able to guide the colonoscope and to straighten colon curves and loops. 
In case caecal intubation time is longer than 10 minutes, the balloon is inserted in the 
endoscope tool channel, advanced beyond the colonoscope tip and filled with 25 mL of 
biocompatible Endorail Ferromagnetic Fluid. The operator manually performs and controls the 
inflation and deflation of the balloon through the syringe. Thus, by applying the Endorail 
Handpiece over the patient abdomen, the balloon can be magnetically anchored. The magnetic 
power level can be increased by the operator according to the patient’s body mass index and the 
successful anchorage of the balloon can be visually verified by the operator through the endoscopic 
images. 
For achieving the optimal effectiveness, anchorage should be performed in any colon segments 
proximal to the sigmoid colon (descending colon, transverse colon, ascending colon, caecum and 
colon curves). 
The anchored balloon guide allows to straighten the scope and thus the colon itself. As the balloon 
guide is kept in tension, its rigidity increases and works as a rail supporting the movements of the 
colonoscope. The guided colonoscope can thus be easily moved back and forward to allow better 
colonoscope positioning and colonoscopy completion. 
The Endorail Balloon Guide pulled against the colonic wall by the handpiece magnetic field works 
as a distal anchor towards which the endoscope tip is advanced and the Endorail Balloon Guide 
inflation tube serves as a guide wire that leads the endoscope as it is pushed towards the 
magnetically anchored balloon. After the Endorail is removed, the straightened colonoscope can 
be easily pushed forward to achieve colonoscopy completion as foreseen in standard endoscopic 
technique. 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 30/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
The Endorail Balloon Guide does not affect the endoscope's flexibility, its field of view and the 
manoeuvrability of the endoscope's tip, nor does it limit the use of any standard endoscopy tools 
such as biopsy forceps, snare, needle etc. The Endorail Balloon Guide can be pulled back at any 
time during the procedure in order to allow the use of other endoscopic accessories. 
EBG is a disposable device however it can be used up to three times in the same patient. For 
detailed description of the procedure, see the instruction for use of Endorail Set and Endorail 
System. 
 
5.2.1 
Treatment with the investigational device 
Each procedure is performed by an experienced endoscopist. If possible, the entire procedure will 
be video recorded. Sedation will be performed by an anaesthesiologist or an endoscopist according 
to standard of care.  
A standard colonoscope with instrument channel diameter bigger or equal than 3.7 mm will be 
used for colonoscopy.  
Endorail will be used only in case caecal intubation time is longer than 10 minutes. For detailed 
description of the device and the procedure, see the instruction for use. 
5.2.2 Control Intervention (Clinical Practice)  
This clinical trial has no prospective control group; results about primary endpoints for efficacy 
and safety will be compared with the standard clinical practice and international guidelines 
reference values (Section 1.6). 
5.2.3 Packaging, Labelling and Supply   
The investigational medical device Endorail Set and Endorail System are produced and packaged 
by Endostart s.r.l., Via delle Regioni 265, 50052 Certaldo (FI), Italy. Endostart s.r.l. will also supply 
the investigational medical devices to the investigational study sites.  
The labelling of the investigational device Endorail will be performed by Endostart s.r.l. in 
accordance with the ISO 14155 guideline for medical devices and to all the local requirements.  
5.2.4 Handling 
The Principal Investigator will be responsible for the correct storage and use of the investigational 
medical devices, as well as of its accountability (usage and returning). The site staff can be delegated 
by the Principal Investigator to the abovementioned activities.  
The Sponsor of the study will be responsible for the distribution of the investigational medical 
devices to the site involved in the investigation.  
At the end of the investigation, the unused investigational medical devices will be returned to the 
Sponsor for reconciliation. 
5.2.5 Storage Conditions  
No specific storage conditions are required for the use of the investigational medical device 
Endorail, which should be stored at room temperature. 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 31/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
5.3 
Administration of experimental and control interventions  
5.3.1 
Experimental Intervention  
Endorail is a colonoscopy add-on device developed to be used without any modification to 
colonoscopes. Endorail is an accessory to an endoscope and is intended to facilitate positioning of 
a standard colonoscope during endoscopy of the large intestine. Endorail works as a magnetic 
anchor that is able to guide the colonoscope and to straighten colon curves and loops. 
The procedure can be summarised according to the following description. 
In case caecal intubation time is longer than 10 minutes, the balloon is inserted in the endoscope 
tool channel, advanced beyond the colonoscope tip and filled with 25 mL of biocompatible 
Endorail Ferromagnetic Fluid. The operator manually performs and controls the inflation and 
deflation of the balloon through the syringe. Thus, by applying the Endorail Handpiece over the 
patient abdomen, the balloon can be magnetically anchored. The magnetic power level can be 
increased by the operator according to the patient’s body mass index and the successful anchorage 
of the balloon can be visually verified by the operator through the endoscopic images. 
For achieving the optimal effectiveness, anchorage should be performed in any colon segments 
proximal to the sigmoid colon (descending colon, transverse colon, ascending colon, caecum and 
colon curves). 
The anchored balloon guide allows to straighten the scope and thus the colon itself. As the balloon 
guide is kept in tension, its rigidity increases and works as a rail supporting the movements of the 
colonoscope. The guided colonoscope can thus be easily moved back and forward to allow better 
colonoscope positioning and colonoscopy completion. 
The Endorail Balloon Guide pulled against the colonic wall by the handpiece magnetic field works 
as a distal anchor towards which the endoscope tip is advanced and the Endorail Balloon Guide 
inflation tube serves as a guide wire that leads the endoscope as it is pushed towards the 
magnetically anchored balloon. After the Endorail is removed, the straightened colonoscope can 
be easily pushed forward to achieve colonoscopy completion as foreseen in standard endoscopic 
technique. 
The Endorail Balloon Guide does not affect the endoscope's flexibility, its field of view and the 
manoeuvrability of the endoscope's tip, nor does it limit the use of any standard endoscopy tools 
such as biopsy forceps, snare, needle etc. The Endorail Balloon Guide can be pulled back at any 
time during the procedure in order to allow the use of other endoscopic accessories. 
EBG is a disposable device however it can be used up to three times in the same patient. For 
detailed description of the procedure, see the instruction for use of Endorail Set and Endorail 
System. 
 
5.3.2 Compliance with study intervention  
Each enrolled patient will be contacted by telephone (V2, see Section 6.2.2) 7 days after the 
procedure to evaluate the occurrence of general and specific adverse events from the previous visit. 
To improve the adherence to the follow up, the investigator will recommend the commitment of 
each participant in concluding the study schedule. 
 
In case the patient does not respond at the scheduled phone visit, a second attempt should be tried 
one week after V2 and, in case he/she is still untraceable, he/she will be re-contacted two weeks 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 32/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
after V2. In case the contact is still unsuccessful, the patient will be defined as lost to follow up as 
indicated in Section 5.5. 
5.4 
Data Collection and Follow-up for withdrawn participants  
If study intervention is permanently discontinued, the participant will remain in the study to be 
evaluated for the efficacy and safety of the patient following Endorail procedure up to 7 days after 
the discontinuation, except in the case of participant death.  
If a patient decides to withdraw the informed consent, this process will happen through a specific 
communication from the patient to the medical doctor; the physician will report the patient 
decision in the medical record. If the patient decides to withdraw before the procedure completion, 
no other data will be collected. If the patient decides to withdraw after the procedure, only the 
safety and efficacy information will be collected to evaluate the safety of the patient following 
Endorail procedure, up to 7 days after the colonoscopy. 
 
 
Upon withdrawal of consent, the patient can:  
- 
request that his/her previously collected data are deleted  
OR 
 
- 
accept the retention of the data collected up to the moment of withdrawal.  
Since the withdrawal of consent is communicated to the investigator, it will be the investigator who 
will register the withdrawal in eCRF specifying whether to delete or not all the previously collected 
data. Moreover, as far as possible, the Investigator will complete the End of Study Visit eCRF page. 
The Investigator should try to ascertain the reason(s) for withdrawal while fully respecting the 
patient’s rights. 
 
5.5 
Lost to Follow-up 
A participant will be considered lost to follow-up if the study site is unable to contact him/her. In 
case of missed phone contact, the investigator or designee must make every effort to reach the 
participant (i.e., three phone calls). Should the participant continue to be unreachable up to 14 days 
after the scheduled phone follow-up visit (V2), after at least three contact attempts, he/she will be 
considered to have withdrawn from the study. 
 
5.6 
Trial specific preventive measures 
No specific preventive measures other than those indicated in the exclusion criteria (Section 4.3) 
are foreseen. 
 
5.7 
Concomitant Interventions (treatments)  
5.7.1 
Permitted Medicines  
Participants will be allowed to use any concomitant medication necessary for the treatment of pre-
existing concomitant pathologies or for intercurrent diseases, provided that they do not interfere 
with the parameters under investigation.  
As anticipated in Section 5.2.1, sedation will be performed by an anaesthesiologist or an 
endoscopist according to standard of care.  

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 33/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 
5.7.2 Prohibited Medicines  
No prohibited concomitant treatments are currently defined. 
 
5.7.3 Other Interventions 
The patient preparation to colonoscopy will be performed according to standard practice used in 
the investigational study site.  
5.7.3.1 
Special Precautions  
Not applicable. No special precautions other than those detailed in Section 5.2 will be implemented. 
5.7.3.2 
Management of Specific Adverse Events or Adverse Medical Device 
Reactions  
Specific adverse events will include gastrointestinal bleedings, mucosal petechiae, intestinal 
perforation and abdominal pain. However, these specific adverse events are general potential 
adverse events that might occur during colonoscopy. No specific adverse events (AEs) or adverse 
device effects (ADEs) are described with the use of the investigational product due to the low risks 
associated with the medical device under study.  
5.7.3.3 
Medical Care of Subjects after End of Trial  
No specific requirements for medical care of subjects after the end of the trial will be implemented. 
 
5.8 
Medical Device Accountability  
After receipt of the investigational products supplies, the Principal Investigator or his deputy will 
conduct an inventory and subsequently fill-in and sign the investigational product Delivery Form 
called “Device Accountability Log”. The Principal Investigator or his deputy, will keep an 
investigational product inventory and accountability records. 
The Principal Investigator will keep the investigational products in a locked and secure storage 
facility, accessible only to those individuals authorised by the Principal Investigator himself.  
 
5.9 
Return or Destruction of Medical Device  
At the conclusion of the study, a final investigational product inventory will be performed, and the 
unused investigational products will be returned to the Sponsor together with an investigational 
product Return Form accurately filled-in and signed by the Principal Investigator or his deputy. If 
any supplies are missing, this must be specified within the Return Form together with an 
explanation for the discrepancy. 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 34/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
6. STUDY ASSESSMENTS 
6.1 
Assessments of Endpoints 
The primary endpoint is the evaluation of the efficacy and safety of Endorail in patients undergoing 
long-lasting colonoscopies.  
 
6.1.1 
Assessment of primary Endpoints  
The efficacy endpoint is measured at V1 as the successful completion of the long-lasting 
colonoscopy (Colonoscopy completion is defined as the caecal intubation). 
 
The safety endpoint is evaluated throughout the entire study duration by collecting the medical 
adverse events and the medical device adverse events.  
 
Adverse events  
Definitions, coding, methods of collection of adverse events and medical device incidents are 
described in detail in Section 7.1.1. Special attention will be given to the following specific adverse 
events: gastrointestinal bleedings, intestinal perforation, mucosal petechiae and abdominal pain.  
 
Vital signs 
The following vital signs will be assessed before and after the procedure (Section 5.2): 
• Blood pressure and heart rate will be measured before the procedure; 
• Blood pressure and heart rate will be measured at approximately 30 minutes after 
completing the procedure. 
6.1.2 
Assessments in participants who prematurely stop the study 
Considering the brevity of the follow up period, at the moment of the withdrawn communication 
the patient will be asked for safety information about the concomitant treatments and the 
occurrence of any adverse event.  
 
6.2 
Procedures at each visit 
The study plan scheduled examinations and procedures are summarised in Table 1. The study plan 
will include a screening/ treatment visit (Visit 1 - Day 1), during which the colonoscopy with the 
investigational medical device Endorail will be performed. A phone follow-up visit (Visit 2) will be 
scheduled 7 (± 1) days after treatment with the investigational medical device Endorail. 
6.2.1 
Treatment Visit - Visit 1 (Day 1)  
Potential participant patients, prospectively attending the investigational study to undergo 
colonoscopy, will be informed, orally and in writing, about the scope of the study, the relevant 
procedures, the nature of the risks related to the study, and they will be asked to sign and date the 
written Informed Consent Form.  
After the correct obtaining of the Informed Consent, the following assessments and procedures 
will be performed during Visit 1 (Day 1):  

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 35/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
• 
Demographic data (age, sex, race) will be recorded;  
• 
A detailed medical history, with special attention to previous history of diverticular disease, 
hysterectomy, gastrointestinal surgery, implantable devices will be recorded in the patient’s 
medical record and in the appropriate section of the eCRF;  
• 
All concomitant medications being taken by the patient, including treatments administered in 
the last 4 weeks, will be checked and will be recorded in the patient’s medical records and in 
the appropriate section of the eCRF;  
• 
A general physical examination will be performed. The physical examination will include an 
examination of head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, 
genitourinary, gastrointestinal, skeletal, and neurological systems. Any identified abnormality 
should be recorded in the patient’s medical records and in the eCRF;  
• 
Height, weight, BMI; 
• 
Vital signs (blood pressure, heart rate) will be measured and will be recorded both in the 
patient’s medical record and in the appropriate section of the eCRF; 
• 
Inclusion/exclusion criteria will be reviewed and eligible patients will be included in the study;  
• 
Pre-procedure sedation will be performed according to the standard of care;  
• 
Procedure for colonoscopy will be started;   
• 
Caecal intubation time will be recorded; 
• 
Colonoscopy will be performed and completed according to procedures detailed in Section 
5.2.;  
• 
In case caecal intubation time is longer than 10 minutes, the patients can be enrolled. 
• 
The occurrence of local (intra-procedure) adverse events (i.e. gastrointestinal bleeding, 
intestinal perforation, presence of mucosal petechiae and abdominal pain) will be checked and 
(if any) will be recorded in the patient’s medical records and in the appropriate section of the 
eCRF; 
• 
At the end of the colonoscopy, successful or failed caecal intubation will be recorded in the 
patient’s medical record and in the appropriate section of the eCRF; 
• 
Vital signs (blood pressure and heart rate,) will be measured approximately 30 minutes after 
completing the procedure and will be recorded in the patient’s medical record and in the 
appropriate section of the eCRF;  
• 
The occurrence of general and specific adverse events from obtainment of Informed Consent 
Form will be checked and (if any) will be recorded in the patient’s medical records and in the 
appropriate section of the eCRF;  
• 
Patient will be discharged and an appointment will be taken for the phone follow-up visit, 
scheduled after 7 (± 1) days from the procedure. 
 
6.2.2 Phone follow-up - Visit 2 (Day 7 ± 1)  
• All concomitant medications being taken by the patient will be checked and, in case of changes 
from the baseline/treatment visit, will be recorded in the patient’s medical records and in the 
appropriate section of the eCRF;  
• The occurrence of general and specific adverse events from the previous visit will be checked 
and (if any) will be recorded in the patient’s medical records and in the appropriate section of 
the eCRF; Visit 2 (phone follow-up visit) will represent the conclusion of patient’s participation 
in the study. 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 36/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
7. SAFETY  
Complete and accurate data on all adverse events (AEs) experienced for the duration of the study 
reporting period will be reported on an ongoing basis in the AE forms of the eCRF.  
It is important that each AE report includes a description of the event, its expectedness, whether 
it is considered serious, its duration (onset and resolution dates), its intensity, its relationship to the 
medical device, any other potential causality factors, any action taken and its outcome.  
Note: After completion of the investigation, the Sponsor will continue to have an obligation to 
report serious and treatment-related AEs affecting the investigation subjects.  
Refer to Section 7.1.4 for procedures of reporting of serious adverse events (SAEs), devices 
deficiencies (DD) and medical device incidences. 
 
7.1 
Medical Device – Class I 
7.1.1 
 Definition of (Serious) Adverse Events and other safety related events 
 
An Adverse Event (AE) is defined as “any untoward medical occurrence, unintended disease or 
injury, or untoward clinical sign (including abnormal laboratory findings) in subjects, users or other 
persons, whether related to the investigational medical device”. 
This definition is restricted to events related to the investigational medical device and includes: 
events related to the investigational medical device, events related to the study procedures and 
events related to the device users or to other persons involved.  
An Adverse Device Effect (ADE) is defined as an AE related to the use of the medical device. 
This definition includes any AEs resulting from insufficiencies or inadequacies in the instructions 
for use, in the deployment, the implantation, the installation, the operation, or any malfunction of 
the medical device. It also includes any AE resulting from a user error or from the intentional 
abnormal use (misuse) of the investigational medical device. All ADEs will be classified as 
Serious/Non-Serious according to the categories of seriousness and as Mild, Moderate or Severe 
according to the intensity classification. In addition, the investigator will always be asked to express 
his/her judgment about the causality relationship with the medical device. 
 
Device deficiencies (DDs) are defined as any inadequacy of the medical device with respect to 
its identity, quality, durability, reliability, safety or performance, including malfunctions, use errors, 
and inadequate labelling. A malfunction is defined as a failure of the investigational medical device 
performance compared to its intended purpose, when used in accordance with the instructions for 
use or protocol. All DDs will be documented during the clinical investigation and reported to the 
Sponsor on the appropriate form.  
A device deficiency not leading to an AE but that could be the cause of a medical occurrence if 
suitable actions have not been taken, if intervention had not been made, or if circumstances had 
been less fortunate, must be reported in the same way of an adverse event.  
 
A Serious Adverse Event (SAE) is any untoward medical occurrence or effect that:  
• Results in death;  
• Is life-threatening;  

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 37/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
• Requires inpatient hospitalisation or prolongation of existing hospitalisation;  
• Results in persistent or significant disability or incapacity;  
• Is a congenital anomaly or birth defect;  
• Is an important medical event (i.e. important medical reactions that jeopardize the patient 
or may require intervention to prevent one of the other outcomes listed in the above 
definition).  
The term “life-threatening” in the definition refers to an event in which the subject was at risk of 
death at the time of the event; on the contrary, it does not refer to an event which hypothetically 
might have caused death if it was more severe.  
In addition, important medical events that may not be immediately life-threatening or result in 
death, or require hospitalisation, but that may jeopardise the patient or may require a medical 
intervention to prevent one of the other outcomes listed above, should also be considered serious. 
(ICH E2A).  
SAEs should be followed up until resolution or stabilisation. Participants with ongoing SAEs at 
the moment of their study termination (including safety visit) will be further followed up until 
recovery or until stabilisation after the study termination.  
Any adverse event which does not fall into the above-described categories is to be defined as Non-
Serious.  
Seriousness must not be confused with the intensity of the event (severity).  
Planned hospitalization for a pre-existing condition, or a procedure required by protocol, without 
serious deterioration in health, is not considered a SAE, but part of the medical history.  
 
Causal Relationship of SAE [MEDDEV 2.7/3 revision 3, May 2015]: 
A causal relationship towards the medical device or study procedure should be rated as follows: 
• Not related: The relationship to the device or procedures can be excluded. 
• 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. 
• Possible: The relationship with the use of the investigational device is weak but cannot be 
ruled out completely. Alternative causes are also possible. 
• Probable: The relationship with the use of the investigational device seems relevant 
and/or the event cannot reasonably be explained by another cause. 
• Causal relationship: The serious event is associated with the investigational device or with 
procedures beyond reasonable doubt. 
Device deficiencies that might have led to an SAE are always related to the medical device. 
 
Serious Adverse Device Effect (SADE) is an ADE that has resulted in any of the consequences 
characteristic of a SAE. All SADEs will be recorded in this study. 
An Unanticipated Serious Adverse Device Effect (USADE) is defined as a SADE which by 
its nature, incidence, severity, or outcome is not identified in the current version of the risk analysis 
report.  
An Anticipated Serious Adverse Device Effect (ASADE) is an effect which by its nature, 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 38/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
incidence, severity or outcome has been identified in the current version of the risk analysis report. 
A Device Deficiency with SAE potential is a device deficiency that might lead to a serious 
adverse event if a) suitable actions have not been taken or b) interventions have not been made or 
c) if circumstances have been less fortunate. 
Health hazards that require measures: Findings in the trial that may affect the safety of study 
participants, and which require preventive or corrective measures intended to protect the health 
and safety of study participants. 
 
7.2 
Method of Recording and Assessing Adverse Events 
It is responsibility of the Investigator to collect all AEs (both serious and non-serious) derived by 
spontaneous, unsolicited reports of subjects, by observation and by routine open questionings (e.g., 
how have you felt since I saw you last? is there anything new that you wish to discuss?). 
All Adverse Events occurring during the clinical investigation (starting from the signature of the 
informed consent and until the end of the study) must be documented in the patient’s medical 
records and in the Adverse Event forms on the eCRF, irrespectively of their classification; the 
Adverse Event forms should be completed in English, possibly writing clearly in capital letters. If 
the eCRF system is not available, the paper SAE reporting form will be filled in (in English language, 
written in clear capital letters) and reported according to the indications provided in section 7.1.4. 
For any adverse event, the following information will be recorded: description of the event, date 
of onset and date of end, intensity, correlation with investigational product, action taken and 
outcome. 
7.2.1 
Intensity of an adverse event 
Each Adverse Event will be rated on a 3-points scale of increasing intensity: 
- 
Mild: The event causes a minor discomfort, or does not interfere with daily activity of the 
patient, or does not lead to either modification of investigational product dosage or 
establishment of a correcting treatment; 
- 
Moderate: The event perturbs the usual activity of the patient and is of a sufficient severity 
to make the subject uncomfortable. Subject is able to continue in study and local or non-
invasive treatment for symptoms may be needed; 
- 
Severe: The event prevents any usual routine activity of the patient and causes severe 
discomfort. It may be of such severity to cause the definitive interruption of treatment. 
7.2.2 Outcome 
Each Adverse Event will be rated by choosing among: 
- 
Recovered/resolved; 
- 
Recovered with sequelae; 
- 
Not recovered; 
- 
Recovering; 
- 
Fatal; 
- 
Unknown. 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 39/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
7.2.3 Medical Device Incidents 
According to MEDDEV 2.12-1, Rev. 8, a medical device incident is defined as ‘any malfunction 
or deterioration in the characteristics and/or clinical performance of a device, as well as any 
inadequacy in the labelling or the instructions for use, which, directly or indirectly, might lead to 
or might have led to the death of a patient, or USER or of other persons or to a serious 
deterioration in their state of health’. A medical device incident that would require reporting 
includes: 
a) Serious public health threat: any event type which results in imminent risk of death, 
serious deterioration in state of health, or serious illness that requires prompt remedial 
action (MEDDEV 2.12-1 rev.8); 
b) Death or UNANTICIPATED serious deterioration in state of health of a subject that 
resulted in: 
1) A life-threatening illness or injury, or 
2) A permanent impairment of a body structure or a body function, or 
3) In-patient or prolonged 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) Other events: events that have an established link between the device and the event. 
 
 
7.2.4  Reporting of (Serious) Adverse Events and other safety related events 
All SAEs/SADEs and DDs that could have led to a serious adverse device effect must be reported, 
whether or not considered causally related to the medical device, or to the study procedure(s). All 
the above-mentioned events will be recorded in the eCRF no later than 24 hours after 
acknowledging the occurrence of the event. If the eCRF system is not available, the paper 
SAE/DD/Device Incidents reporting form will be filled in (in English language, written in clear 
capital letters) and must be sent via email to the Sponsor at the email address indicated below. 
Day 0 is the day the Investigator becomes aware of an event occurred to the subject, and it is used 
by the Sponsor as reference day for regulatory purposes. Each SAE and SADE must be tracked 
and assessed by the Sponsor. The Sponsor will report any SAEs/SADEs to the relevant 
Independent Ethics Committee (IEC) as required by local requirements of the committee and to 
the Competent Authority. The Sponsor will determine whether a SADE is considered 
“anticipated” or not. Each DD must be tracked and assessed by the Sponsor. Any DD that might 
have led to a SAE if suitable action had not been taken or intervention had not been made or if 
circumstances had been less fortunate will be reported to the Competent Authority.  
All SAE/DD/Device Incidents, independently of their causal relationship, must be reported 
immediately (within 24 hours) in the eCRF SAE form; if the eCRF system is not available, the 
paper reporting form must be reported immediately (within 24 hours from awareness) via email or 
Certified Electronic Mail by the Investigator or his delegated to: 
 
Dr. Alessandro Tozzi, Endostart s.r.l., Via delle Regioni 265, 50052 Certaldo (FI), Italy. 
Tel: +39 338 7717731  
Certified Electronic Mail: euroendoscopy@pec.it 
Email: a.tozzi@endostart.com and a.marsano@endostart.com 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 40/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 
Initial notification should include:  
- 
Identification of the Principal Investigator: name, address, study center, telephone number;  
- 
Study protocol number;  
- 
Subject’s identification (ID number in the study, date of birth, sex, relevant medical 
history);  
- 
Device name or code, beginning and end of treatment;  
- 
Description of event and its onset;  
-  
Measures undertaken to treat it;  
- 
Opinion of the Investigator about the relation of the event to the tested medical device. 
Subjects experiencing SAEs must be monitored until resolution, and acceptable stabilization in the 
event of chronicity.  
In the event of a death, the pathology report will be always requested.  
In case of malfunctioning of the medical device, the Investigator will immediately inform the 
Sponsor by using the same phone and email addresses specified above. The defected medical device 
will be shipped to the Sponsor, in order to allow all necessary assessments.  
In case of malfunctioning of the study medical device, the patient must not be penalized. In order 
to allow the treatment completion, a set of rescue medical device will be forwarded to each 
physician. 
Once per year for the duration of the research or on request, the Sponsor transmits a safety report 
with all the available safety information to the Competent Authority (CA) and to the sites involved. 
This report includes notably the list of all the suspected serious adverse reactions and an analysis 
of the information regarding the safety of individuals participating in the research.  
The Investigator will submit, on request, copies of all reportable SAE reports to the Ethics 
Committee concerned. Once per year for the duration of the research or on request, the 
Investigator or its delegated transmits the safety report with all the available safety information to 
the local Ethic Committee.  
 
7.3 
 Follow up of (Serious) Adverse Events 
Follow-up of SAEs/SADEs/device incidents  
• Reporting of SAEs/SADEs/device incidences from the investigational site begins from 
signing of informed consent and ends at the last study visit/last follow-up contact.  
• All new SAEs/SADEs/device incidences occurring beyond this time frame and coming to 
the attention of the investigator must be recorded only if they are considered (in the 
opinion of the Investigator) causally-related to the investigational product. Thus, only 
SAEs/SADEs/device incidences related to the investigational product will be followed 
after the Visit 2, until resolution, stabilization or patient loss at follow-up.  
• Reports of SAEs/SADEs/device incidences occurred during the study or after the site 
closure should be reported directly from the Investigator to the Sponsor Safety Contact 
see Section 7.3.4.  
• All SAEs/SADEs/device incidences should be followed-up in order to elucidate as 
completely and practical as possible their nature and/or causality. The follow-up 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 41/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
information should be submitted until resolution of all queries, clinical recovery is 
complete, laboratory results have returned to normal, until progression has been stabilized 
or until the patient is lost to follow-up. Follow-up may therefore continue after the patient 
has left the study. 
• In case of death, a comprehensive narrative report of the case should be prepared by the 
Investigator and sent to the Sponsor Safety Contact by email together with the SAE form, 
retaining a copy on site filing it in the patient folder.  
• If an autopsy is performed, copy of the autopsy report should be actively sought by the 
Investigator and sent to the Sponsor Safety Contact as soon as available, retaining a copy 
on site and filing it in the patient folder. 
8. STATISTICAL METHODS  
8.1 
Hypothesis 
This study is designed to test the null hypothesis that the proportion of ‘event’ (intended as 
procedure incomplete or serious adverse event) is equal or greater than 20%. The alternative 
hypothesis is that the proportion of ‘event’ is less than 20%. In statistical terms:  
𝐻0: 𝑝≥20% 
𝐻1: 𝑝< 20% 
 
Where: 
p = true proportion of patients with event 
  
 
8.2 
Determination of Sample Size  
Efficacy (first primary objective) will be assessed by measuring the colonoscopy completion rate 
in long-lasting procedures, which is a measurable parameter of clinical value recognized by 
international medical societies. Safety (second primary objective) will be assessed by measuring the 
rare of adverse events. They are classified into: serious gastrointestinal events; myocardial 
infarction; stroke; pneumonia. Based on the literature [30]; their occurrence rates in screening or 
surveillance colonoscopy are 47 persons, 4 persons, 7 persons and 10 persons per 100’000, 
respectively. 
These two objectives are merged in one indicator, which is equal to 1 for each subject if the 
procedure is incomplete or an adverse event occurs, and 0 otherwise. 
 
The non-completion rate of long-lasting colonoscopies conducted with Endorail is expected to be 
around 10%. This will be compared to the above-mentioned threshold of 20% for incomplete 
procedures. It should be noted that this threshold is conservative and represents the most critical 
setting for comparison with respect to the state of the art, as it is derived from the lower bound of 
the range from the literature. 
 
When including the safety to provide the expected value of the indicator for Endorail and the 
corresponding threshold, the above values of 10% minimally change, as the adverse event 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 42/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
occurrence rate is 0.068% (given by the sum of the occurrence of the 4 events reported above per 
100’000 persons, expressed in percentage). 
 
 
With a significance level α of 5%, assuming a proportion of outcome of 10.1%, 85 patients allow 
to test with a power of 80% the H0: p ≥ 20% vs H1: p < 20%, where 20% is the estimated 
percentage of incomplete procedure from literature. 
The chosen number is then increased by the 10% to account for possible drop-out (e.g., cases to 
be discarded, losses to follow-up, etc.), resulting in 85/0.90 = 95 patients to be actually enrolled. 
 
 
8.3 
Statistical criteria of termination of trial  
 
Interim analyses will be considered, to be able to terminate the study in advance if significance is 
found. In particular, when 38 patients (40% of the sample size) and 57 patients (60% of the sample 
size) are reached, the significance will be tested. If significance is found, the trial can be terminated 
with the patients already collected. 
 
8.4 
Planned Analyses  
 
The statistical analysis plan will be finalized before Data Base Lock and it will include a more 
technical and detailed description of the statistical analyses described in this section. This section 
is a summary of the planned statistical analyses. 
All data obtained in this study and documented in the eCRFs will be listed and summarized as 
appropriate: 
• for quantitative variables: standard quantitative statistics (N, mean, standard deviation, 
median, interquartile range, minimum and maximum);  
• for qualitative variables: frequency distribution [number of non-missing observations (N) 
and percentages (%)].  
  
A statistical test will be performed to assess the significant difference of the indicator with respect 
to the threshold and statistically prove efficacy of Endorail in long-lasting procedures. Due to the 
type of variable, the exact binomial test will be adopted. Additionally, considering as alternative 
hypothesis that the rate observed in the analyzed population is less than the respective threshold, 
the one-tailed test will be adopted. 
 
Medical adverse events and medical device adverse events will be collected during the study. 
The number of adverse events (AEs) – related or not to the medical device – and the number and 
proportion of patients with at least one AE will be presented.  
All adverse events will be tabulated by System Organ Class (SOC) and Preferred Term (PT) after 
medical coding using the Medical Dictionary for Regulatory Activities (MedDRA) thesaurus 
version 24.1. The primary SOC and the PT will be used for the analysis of the frequency 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 43/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
distribution.  
The frequency of occurrence of specific adverse events (gastrointestinal bleedings, intestinal 
perforation, mucosal petechiae, abdominal pain) will be presented by means of default descriptive 
statistics. 
 
Statistical analyses will be carried out using R Statistical Software (Foundation for Statistical 
Computing, Vienna, Austria). 
 
8.4.1 
 Datasets to be analysed, analysis populations 
• 
Screening set: will include all patients who have signed the informed consent and have been 
screened for inclusion in the study;  
• 
Intention-to-treat population (ITT): will include all enrolled patients who have started treatment 
with Endorail;  
• 
Per-Protocol (PP) population: will include all patients of the ITT who also meet all 
inclusion/exclusion criteria and who do not have any major protocol deviation, to be defined in a 
data review meeting (DRM) of the Sponsor, Contract research Organization (CRO) representatives 
and the biostatistician.  
Analysis will be performed on the ITT population and will be repeated in the PP population. The results 
obtained in the PP population will be seen as confirmative of those observed in the ITT population.  
 
8.4.2 Interim analyses 
Two interim analyses will be planned, a first when 40% of the sample size (38 patients) is reached 
and a second when 60% of the sample size (57 patients) is reached. During these interim analyses 
the significance will be tested. If significance is found, the trial can be terminated with the patients 
already collected. 
38 patients guarantee a statistical power of 80% if at least 93.9% of these are free of ‘event’ 
(intended as procedure incomplete or serious adverse event). 57 patients guarantee a statistical 
power of 80% if at least 91.8% of these are free of ‘event’. 
 
8.5 
Handling of missing data and drop-outs  
Not applicable. Missing data will not be replaced. 
 
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 44/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
9. QUALITY ASSURANCE AND CONTROL  
 
All participant data relating to the study will be recorded on eCRF. The investigator is responsible 
for verifying that data entries are accurate and correct by electronically signing the eCRF. 
 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency 
inspections 
and 
provide 
direct 
access 
to 
source 
data 
documents. 
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities, and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the monitoring plan. 
The sponsor or its designee is responsible for the data management of this study including quality 
checking of the data.  
The sponsor assumes accountability for actions delegated to other individuals (e.g. Contract 
Research Organizations). 
 
Study monitors will perform ongoing source data verification to confirm that data entered into the 
eCRF by authorized site personnel are accurate, complete, and verifiable from source documents, 
that the safety and rights of participants are being protected, and that the study is being conducted 
in accordance with the currently approved protocol and any other study agreements, ICH GCP, 
and all applicable regulatory requirements. 
 
9.1 
Data handling and record keeping / archiving  
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 25 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor.  
9.1.1 
Case Report Forms  
The study will be conducted in compliance with the dictates of the Helsinki declaration and in 
accordance with the rules of good clinical practice (Ministerial Decree of 15/07/1997 and 
subsequent 
amendments) 
as 
well 
as 
with 
the 
applicable 
regulatory 
provisions. 
Each participating center will maintain the medical records and research data of this study in an 
appropriate manner, in accordance with section 4.9 of the ICH-GCP E6, with the provisions of 
the regulatory bodies and the institution to which it belongs to ensure the protection of the 
confidentiality of the patients. As a participant in a clinical study, each center will allow staff 
authorized by the sponsor and regulatory agencies to review (and when permitted by law, to copy) 
medical records in order to check the quality of the data, for audits and for evaluations of the study 
safety and progress. 
 
Source documents are all the information, original records of clinical findings, observations, or 
other activities of a clinical study necessary for the reconstruction and evaluation of the study itself. 
Examples of these original documents and records include, but are not limited to, medical records, 
clinical charts, laboratory notebooks, memos, patient diaries or evaluation lists, data recorded by 
automated tools, copies or transcripts certified after verification that these are accurate and 
complete, microfiche, photographic negatives, microfilm or magnetic media, plates obtained with 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 45/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
x-rays, subject cards and records kept in pharmacies, laboratories, and in the technical-medical 
departments involved in the clinical study. 
 
Data collection is the responsibility of the staff at the center involved in the clinical study under 
the supervision of the center's Principal Investigator. The electronic data collection form (eCRF) 
is the main tool for collecting study data. The researcher should ensure the accuracy, completeness, 
legibility and timeliness of the data reported in the eCRF and in the same way as the other data 
reported.  
The data reported in the eCRF, which derive from source documents, must be identical to the 
original ones and where this is not the case, the discrepancy must be explained. All data requested 
by the eCRF must be registered. Any missing data must be explained. Any changes or corrections 
to a paper CRF (in case the eCRF is not available for any reason) or document must be dated, listed 
next to the initials of the compiler, explained (if necessary) and must not obscure the original data. 
The investigator should keep track of the changes and corrections made to the eCRFs. 
 
The institution should maintain the study documents as specified in the essential 
documents for conducting a clinical study (ICH-GCP E6, section 8) and as required by regulatory 
bodies and guidelines. The institution should take measures to prevent accidental 
or premature destruction of the documentation. 
 
Essential documents (written and electronic) should be kept for a period of time not less than 
twenty-five (25) years from the completion of the study, unless the Promoter provides a written 
document that allows for the disposal and conservation of data for an additional period of time 
if permitted by law, regulatory bodies and/or guidelines. 
 
The data will be inserted and managed through the use of the electronic CRF (eCRF) developed 
through the ICE platform and accessible via a specific URL address that will be provided at the 
moment of the SIV. To protect security and privacy, only authorized users will be allowed to access 
the eCRF through the use of individual access credentials (each user will be provided with unique 
username and password). The login credentials will be generated by the database administrator and 
communicated to the user via email. The user must change the password at the first access. The 
password will need to be changed every 3 months. 
 
The data collected will be pseudo anonymized; for each participating subject an alpha numeric code 
(subject code) will be generated consisting of the center code, a spacer character and the subject 
number (e.g. CTR 01-01) and the data will be stored electronically. To keep track of the association 
between the medical record and the subject code, each center will compile a study specific form, 
as indicated in section 4.4. These forms, if in hardcopy must be kept in a place with limited access 
and locked, if in electronic form, must be kept in a separate, encrypted (AES-256 encryption) and 
password protected file; these forms will never be shared with the Promoter, with the database 
administrator and not even with the study statistician.  
 
9.1.2 
Specification of source documents  
 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents, and any discrepancy must be explained. The investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical records 
must be available. 
 
The source documents for this study will be the patient’s paper medical report, where are recorded 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 46/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
all the information needed to complete the eCRF. All the information inserted in the eCRF will 
be in accordance with the paper medical report. Among the data requested from the eCRF there 
are demographic data, visit dates, participation in study and Informed Consent Forms, SAEs, AEs, 
concomitant medication, medical history, and many other results of relevant examinations.  
9.1.3 
Record keeping / archiving  
All study data must be archived for a minimum of 25 years after study termination or premature 
termination of the clinical trial. 
 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 25 years after study completion unless local regulations or 
institutional policies require a longer retention period.  
 
9.2 
Data management  
9.2.1 
Data Management System  
The CRFs in this trial are implemented electronically using a dedicated EDC system (ICE, 
Integrated Clinical Trial Environment, Advice Pharma) that fulfils the legal requirements for 
clinical trials. The EDC system is activated for the user only after successfully passing a formal test 
procedure. All data entered in the EDC are stored on a Linux server in a dedicated Oracle database.  
9.2.2 Data security, access and back-up  
The server hosting the EDC system and the database is kept in a locked server-room. Only the 
system administrators have direct access to the server. A role concept with personal passwords 
(site investigator, statistician, monitor, administrator etc.) regulates permission for each user to use 
the system and database as he/she requires.  
All data entered into the EDC are transferred to the database using Secure Sockets Layer (SSL) 
encryption. Each data point has attributes attached to it identifying the user who entered it with 
the exact time and date to ensure proper audit-trail. Retrospective alterations of data in the database 
are recorded by time, table, data field and altered value. A multi-level back-up system is 
implemented.  
9.2.3 Analysis and archiving 
At interim and final analyses, data files will be extracted from the database into statistical packages 
to be analysed. The status of the database at this time is recorded in special archive tables. The 
study database with all archive tables will be securely stored by Advice Pharma. The sponsor also 
keeps the Trial Master File and interim and final reports both in electronic and in hard copy for at 
least 25 years after trial completion. Site will archive the Investigator Site File and Source Data for 
at least 25 years after trial completion.  
9.2.4 Electronic and central data validation  
Data is checked by the EDC system for completeness and plausibility. Furthermore, selected data 
points are cross-checked for plausibility with previously entered data for that participant. In 
addition, central data reviews will be performed on a regular basis to ensure completeness of the 
data collected and accuracy of the primary outcome data. Data validation process is performed in 
accordance with the local regulations, with the FDA CFR 21 PART 11, GMP V.4 Annex 11, Data 
integrity, GAMP5 guideline and Good Practices for Computerized Systems in regulated “GXP” 
environments. Pharmaceutical Inspection Convention/Pharmaceutical Inspections Co-operation 
Scheme (PIC/S). 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 47/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 
9.3 
Monitoring  
The study will be monitored on a regular basis by the Sponsor’s adequately qualified and trained 
clinical Monitors throughout the study period to ensure the proper conduct of the clinical 
Investigation. 
The purposes of study monitoring are to verify that the rights and well-being of study subjects are 
protected, that the reported study data are accurate, complete and verifiable against the source 
documents, and that the study is conducted in accordance with the current clinical investigation 
plan, Good Clinical Practice guideline (UNI EN ISO 14155), ICH-GCP E6, 21 CFR 812.28, 
21CFR 814, 21 CFR 807, and applicable regulatory requirements. 
 
During the monitoring visits, Monitors will verify the following data, including but not limited to: 
subject informed consent, subject’s eligibility, safety data and reporting, quality of source 
documents and eCRF data against subject’s medical records. If inconsistencies are found, the 
corresponding corrections to the eCRF data will have to be made by the Investigator or designated 
person. Monitors will also check subject compliance, delegation of responsibilities within 
the Investigator’s team, relevant communications with family doctors (if any), ancillary equipment 
and facilities, etc. The Investigator and other site staff involved in the study must allocate enough 
time to the Monitor at these visits. Additionally, due to the COVID-19 pandemic, site monitoring 
visits may not be feasible; in that case, a remote monitoring strategy will be implemented. 
The Investigator agrees to allow the Sponsor’s monitors to have direct access to the study records 
for review, being understood that they are bound by professional secrecy, and that they will not 
disclose any personal identity or personal medical information.  
 
9.4 
Audits and Inspections  
Upon request by the Sponsor, on-site study audits may be conducted in order to ensure the study 
is in compliance with GCP, applicable regulatory requirements, and the clinical investigation plan. 
The auditing activities may also be conducted after study completion. 
 
 
The Investigator agrees to allow the Sponsor/auditors’ monitors to have direct access to the study 
records for review, being understood that they are bound by professional secrecy, and that they 
will not disclose any personal identity or personal medical information. 
 
Regulatory Authorities may wish to conduct on-site inspections (during the study or after its 
completion). If a Regulatory Authority notifies the Investigator of an inspection or visits the site 
unannounced for purposes of conducting an inspection, the Investigator must inform the Sponsor 
immediately. The Investigator will make every effort to facilitate the conduct of the audits and 
inspections, giving access to all necessary facilities, data and documents. 
 
Any result or information arising from the inspection will be immediately communicated by the 
Investigator to the Sponsor. The Investigator will take all appropriate measures required by the 
Sponsor to implement corrective actions for all problems found during the audits or inspections.   
 
 
9.5 
Ethical considerations 
9.5.1 
Ethics Committee (EC) and Competent Authority (CA) 
Before initiating the trial, the Sponsor should have written favourable opinion from the EC and 
should have notified the Ministry of Health or the Competent Authority for the trial conduction. 
All the correspondence with the EC and the Competent Authority should be retained in the 
Investigator File. 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 48/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Before implementing any protocol amendment, the EC/Competent Authority written approval 
must be obtained. The only circumstance in which an amendment may be initiated prior to EC 
approval is where the change is necessary to eliminate apparent immediate hazards to the subjects. 
In that event, the EC/Competent Authority must be notified in writing as soon as possible. 
 
9.6 
Ethical conduct of the trial 
9.6.1 
Informed Consent 
It is the responsibility of the investigator to give each patient (or the patient acceptable 
representative) full and adequate verbal and written information regarding the objective and 
procedures of the trial and the possible risks involved. The patient must be informed about his/her 
right to withdraw from trial at any time. The patient should have sufficient time and opportunity 
to enquire about details of the trial and to decide whether or not to participate in the trial.  
The patient must be made aware that he/she may refuse to join the study or may withdraw his/her 
consent at any time without prejudicing further medical care and that he/she is covered by the 
Sponsor's indemnity insurance in the event of a study related injury.  
Written subject Informed Consent Form must be approved by the EC and must be given to each 
patient before any trial-related procedure is undertaken. 
 
It is responsibility of the investigator to obtain the Informed Consent Form signed and dated by 
the patient and by the medical person conducting the Informed Consent discussion, prior to 
undertake any trial-related procedure, in accordance with the UNI EN ISO 14155 and the current 
version of the Declaration of Helsinki. One copy of the signed and dated Informed Consent Form 
should be given to the patient. The originally signed document should be archived in the 
appropriate section of the Investigator Site File. 
 
The approved patient Informed Consent Form must not be changed without prior approval by the 
Sponsor and by the EC. 
 
When new study information arises during the study, the patients still participating must be 
informed and a new Informed Consent Form or an addendum to the already signed Informed 
Consent Form must be signed and dated by the patients, after the approval by the EC. 
 
The patients must also know that their personal medical records may be reviewed in confidence 
by the Sponsor's staff or representatives and by the Ministry of Health and the EC and that every 
personal information will be collected and retained in a confidential database. 
 
If a patient becomes incompetent during the course of the trial, where it was not anticipated, legally 
acceptable representative authorization should be obtained for a subject's participation 
continuation. 
 
9.7 
Confidentiality, Data Protection  
Apart from site staff, also Sponsor/Regulatory Agency monitors, auditors or inspectors will have 
direct access to medical records and source documents for review during and after the study, being 
understood that they are bound by professional secrecy, and that they will not disclose any personal 
identity or personal medical information.  
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 49/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
10. INSURANCE  
Insurance will be provided by the Sponsor. A copy of the certificate is filed in each investigator 
site file and the trial master file. 
 
11. PUBLICATION AND DISSEMINATION POLICY  
All information obtained as a result of the study will be regarded as confidential. 
The results of the clinical study will be documented in an integrated clinical study report according 
to UNI EN ISO 14155 and to the ICH-GCP E6. 
 
The Sponsor and the Investigator(s) agree that no publications presenting or discussing data 
and/or results from this clinical study sponsored by Endostart srl. will take place until the 
the data have been interpreted, and the interim or final report has been issued. 
 
As a rule, the Sponsor is free to use the data collected in the sponsored study for world-wide 
scientific product documentation, and for publication. 
 
In general, the Sponsor has no objections if the Investigator publishes the results of the study. 
However, the Investigator is requested to provide the Sponsor with a copy of the manuscript for 
review before submitting it to the publisher with a cover letter informing the Sponsor about the 
intention to publish the study results. When permission for presentation or for publication is 
granted, Investigators, prior to submission of a manuscript or abstract to the publisher, shall 
forward a copy of said manuscript or abstract to the Sponsor who shall have 45 days to request 
any reasonable amendment thereto, which shall be taken into due account and consideration by 
the Investigator. 
 
 
The Sponsor is entitled to include, as authors of the publication, all Sponsor’s personnel who 
contributed substantially to the theoretical or experimental work and also to take part in the 
decision that establishes the order in which the authors’ names will be given. Costs for publication 
must be regulated by written agreement between the parties.  
If publication of the results of the study, either in part or in full, is prepared by the Sponsor, the 
Investigator(s) will be provided with a copy of the manuscript before the submission to the 
publisher and asked to give approval of the document. The Investigator will be asked in writing if 
he/she accepts to be included as author of the publication. Answers should be sent in writing to 
the Sponsor within a reasonable time limit (30 days). If no answer is received, it is assumed that 
the Investigator agrees to the Sponsor’s proposal.  
 
 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 50/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
 
REFERENCES  
1. ASGE Technology Committee, Trindade AJ, Lichtenstein DR, Aslanian HR, Bhutani MS, 
Goodman A, Melson J, Navaneethan U, Pannala R, Parsi MA, Sethi A, Sullivan S, Thosani 
N, Trikudanathan G, Watson RR, Maple JT. Devices and methods to improve colonoscopy 
completion (with videos). Gastrointest Endosc. 2018 Mar;87(3):625-634. doi: 
10.1016/j.gie.2017.12.011. PMID: 29454445. 
2. Ball JE, Osbourne J, Jowett S, Pellen M, Welfare MR. Quality improvement programme 
to achieve acceptable colonoscopy completion rates: prospective before and after study. 
BMJ 2004;329(7467):665-7. 
3. Bowles CJ, Leicester R, Romaya C, Swarbrick E, Williams CB, Epstein O. A prospective 
study of colonoscopy practice in the UK today: are we adequately prepared for national 
colorectal cancer screening tomorrow? Gut 2004;53(2):277-83. 
4. Brenner H, Chang-Claude J, Jansen L, Seiler CM, Hoffmeister M. Role of colonoscopy and 
polyp characteristics in colorectal cancer after colonoscopic polyp detection: a population-
based case-control study. Ann Intern Med. 2012 Aug 21;157(4):225-32. doi: 10.7326/0003-
4819-157-4-201208210-00002. PMID: 22910933. 
5. Bruce M., Choi J., Detection of endoscopic looping during colonoscopy procedure by using embedded 
bending sensors, Medical Devices: Evidence and Research, 2018:11 171–191. 
6. Cantillon-Murphy P, Cundy TP, Patel NK, Yang GZ, Darzi A, Teare JP. Magnets for 
therapy in the GI tract: a systematic review. Gastrointest Endosc 2015;82(2):237-45. 
7. Chung YW, Han DS, Yoo KS, Park CK, Patient factors predictive of pain and difficulty during 
sedation-free colonoscopy: a prospective study in Korea, Dig Liver Dis. 2007 Sep;39(9):872-6. 
8. Cotton PB, Connor P, McGee D, Jowell P, Nickl N, Schutz S, Leung J, Lee J, Libby E. 
Colonoscopy: practice variation among 69 hospital-based endoscopists. Gastrointest 
Endosc 2003;57(3):352-7. 
9. Dogramadzi S, Virk GS, Bell GD, Rowland RS, Hancock J. Recording forces exerted on 
the bowel wall during colonoscopy: in vitro evaluation. Int J Med Robot 2005;1(4):89-97. 
10. Dominitz JA, Eisen GM, Baron TH, Goldstein JL, Hirota WK, Jacobson BC, Johanson JF, 
Leighton JA, Mallery JS, Raddawi HM, Vargo JJ 2nd, Waring JP, Fanelli RD, Wheeler- 
Harbough J, Faigel DO; Standards of Practice Committee. American Society for 
Gastrointestinal Endoscopy. Complications of colonoscopy. Gastrointest Endosc 
2003;57(4):441-5. 
11. Douglas K., et al., Quality in the Technical Performance of Colonoscopy and the Continuous Quality 
Improvement Process for Colonoscopy: Recommendations of the U.S. Multi-Society Task Force on 
Colorectal Cancer, The American Journal of Gastroenterology, 2002: Vol. 97, No. 6. 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 51/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
12. Eickhoff A, Pickhardt PJ, Hartmann D, Riemann JF. Colon anatomy based on CT 
colonography and fluoroscopy: impact on looping, straightening and ancillary manoeuvres 
in colonoscopy. Dig Liver Dis 2010;42(4):291-6. 
13. Gorard DA, McIntyre AS. Completion rate to caecum as a quality measure of 
colonoscopy in a district general hospital. Colorectal Dis 2004;6(4):243-9. 
14. Guidelines of the American Society for Gastrointestinal Endoscopy (ASGE), 
Complications of colonoscopy, ASGE Technology Committee, www.giejournal.org, 2011: 
Volume 74, No. 4. 
15. Hanson ME, Pickhardt PJ, Kim DH, Pfau PR. Anatomic factors predictive of incomplete 
colonoscopy based on findings at CT colonography. AJR Am J Roentgenol. 2007 
Oct;189(4):774-9. doi: 10.2214/AJR.07.2048. PMID: 17885044. 
16. Harewood GC. Colonoscopy: Not quite the gold standard. Dig Liver Dis 2007;39(7):690-
1. 
17. Jia H, Wang L, Luo H, Yao S, Wang X, Zhang L, Huang R, Liu Z, Kang X, Pan Y, Guo 
X, Difficult colonoscopy score identifies the difficult patients undergoing unsedated colonoscopy, BMC 
Gastroenterol. 2015 Apr 9;15:46. doi: 10.1186/s12876-015-0273-7. PMID: 25886845; 
PMCID: PMC4397830. 
18. Jung Y, Lee SH. How do I overcome difficulties in insertion? Clin Endosc 2012; 45:278-
81. 
19. Lee SH, Chung IK, Kim SJ, Kim JO, Ko BM, Hwangbo Y, Kim WH, Park DH, Lee SK, 
Park CH, Baek IH, Park DI, Park SJ, Ji JS, Jang BI, Jeen YT, Shin JE, Byeon JS, Eun CS, 
Han DS. An adequate level of training for technical competence in screening and diagnostic 
colonoscopy: a prospective multicenter evaluation of the learning curve. Gastrointest 
Endosc 2008;67(4):683-9. 
20. Moon SY, Kim BC, Sohn DK, Han KS, Kim B, Hong CW, Park BJ, Ryu KH, Nam JH, 
Predictors for difficult cecal insertion in colonoscopy: The impact of obesity indices, World J Gastroenterol. 
2017 Apr 7;23(13):2346-2354. doi: 10.3748/wjg.v23.i13.2346. PMID: 28428714; PMCID: 
PMC5385401. 
21. Neerincx M, Terhaar sive Droste JS, Mulder CJ, Räkers M, Bartelsman JF, Loffeld RJ, 
Tuynman HA, Brohet RM, van der Hulst RW. Colonic work-up after incomplete 
colonoscopy: significant new findings during follow-up. Endoscopy 2010;42(9):730-5. 
22. Pyenson B, Scammell C, Broulette J. Costs and repeat rates associated with colonoscopy 
observed in medical claims for commercial and Medicare populations. BMC Health Serv 
Res. 2014 Feb 26;14:92. doi: 10.1186/1472-6963-14-92. PMID: 24572047; PMCID: 
PMC3974039. 
23. Rex DK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, Levin TR, 
Lieberman D, Robertson DJ. Colorectal Cancer Screening: Recommendations for 

Endorail 
 
Protocol v 1.1, 24 October  2022 
 
 ______________________________________________________________________________________________________________  
 
 
Code: CO-09-A02 
Confidential  
 52/52  
Version: 1.00 
Effective date: December 18th, 2020 
 
Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am 
J Gastroenterol 2017;112(7):1016-30. 
24. Rex DK, Imperiale TF, Latinovich DR, Bratcher LL. Impact of bowel preparation on 
efficiency and cost of colonoscopy. Am J Gastroenterol 2002;97(7):1696-700. 
25. Rex DK, Schoenfeld PS, Cohen J, Pike IM, Adler DG, Fennerty MB, Lieb JG 2nd, Park 
WG, Rizk MK, Sawhney MS, Shaheen NJ, Wani S, Weinberg DS. Quality indicators for 
colonoscopy. Gastrointest Endosc. 2015 Jan;81(1):31-53. doi: 10.1016/j.gie.2014.07.058. 
Epub 2014 Dec 2. PMID: 25480100. 
26. Rizek R, Paszat LF, Stukel TA, Saskin R, Li C, Rabeneck L. Rates of complete colonic 
evaluation after incomplete colonoscopy and their associated factors: a population-based 
study. Med Care. 2009 Jan;47(1):48-52. doi: 10.1097/MLR.0b013e31817d92bc. PMID: 
19106730. 
27. Sato K, Shigiyama F, Ito S, Kitagawa T, Tominaga K, Suzuki T, Maetani I. Colonoscopy 
using a small-caliber colonoscope with passive-bending after incomplete colonoscopy due 
to sharp angulation or pain. Surg Endosc. 2013 Nov;27(11):4171-6. 
28. Shah SG, Brooker JC, Thapar C, Williams CB, Saunders BP. Patient pain during 
colonoscopy: an analysis using real-time magnetic endoscope imaging. Endoscopy 
2002;34(6):435-40. 
29. Trevisani L., Zelante A., Sartori S., Colonoscopy, pain and fears: Is it an indissoluble trinomial?, 
World J Gastrointest Endosc, 2014 6(6): 227-233. 
30. Wang L, Mannalithara A, Singh G, Ladabaum U. Low Rates of Gastrointestinal and Non-
Gastrointestinal Complications for Screening or Surveillance Colonoscopies in a 
Population-Based 
Study. 
Gastroenterology. 
2018 
Feb;154(3):540-555.e8. 
doi: 
10.1053/j.gastro.2017.10.006. Epub 2017 Oct 12. PMID: 29031502. 
31. Waye JD, Rex DK, Williams CB. Colonoscopy: Principles and Practice. Oxford, U.K.: 
Blackwell, 2003. 
32. Waye JD. Difficult colonoscopy. Gastroenterol Hepatol (N Y) 2013;9(10):676-8.