A Single-center Study on the Effectiveness and Safety of Artificial Intelligence Assisted System in Clinical Application of Endoscopic Retrograde Cholangiopancreatography
Phase: NA
Conditions: Gastrointestinal Disease, Endoscopy, Artificial Intelligence, Endoscopic Retrograde Cholangiopancreatography
Sponsor: Renmin Hospital of Wuhan University

Endoangel Study 
1 / 26 
Version 1.2/Apr13, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Development and Validation of an Artificial 
Intelligence-based Biliary Stricture Navigation 
System in MRCP-based ERCP 
 
 
Short Title：Endoangel Study 
 
 
 
 
 
 
 
 
 
NCT 
- 
Trial number 
EA-19-003 
Protocol version 
1.2 
Version date 
Apr13, 2021 
Country 
China 
Device 
EndoAngelTM 
Principal investigator 
Professor HonggangYu 
Address 
No. 99, Zhangzhidong Road, Wuchang District, Wuhan, 
Hubei. 

Endoangel Study 
2 / 26 
Version 1.2/Apr13, 2021 
 
 
Content 
1. 
Summary ................................................................................................................................... 4 
1.1. 
Time and event table ..................................................................................................... 5 
1.2. 
Flow chart ..................................................................................................................... 5 
2. 
Introduction ............................................................................................................................... 7 
3. 
Patient Selection ........................................................................................................................ 7 
3.1. 
Inclusion Criteria ........................................................................................................... 8 
3.2. 
Exclusion Criteria .......................................................................................................... 8 
3.3. 
Definition of enrollment ................................................................................................ 9 
4. 
Endpoints .................................................................................................................................. 9 
4.1. 
Primary endpoint ........................................................................................................... 9 
4.2. 
secondary endpoints ...................................................................................................... 9 
4.3. 
Safety evaluation endpoints and other secondary endpoints ......................................... 9 
5. 
Purpose and overall design...................................................................................................... 10 
5.1. 
Purpose ........................................................................................................................ 10 
5.2. 
Overall design ............................................................................................................. 10 
6. 
Study process .......................................................................................................................... 10 
6.1. 
Summary of Study Process ......................................................................................... 10 
6.2. 
Enrollment ................................................................................................................... 10 
6.2.1. 
Informed Consent ............................................................................................ 11 
6.2.2. 
Patient Selection .............................................................................................. 11 
6.2.3. 
Subject identification number ......................................................................... 12 
6.3. 
Treatment Description ................................................................................................. 12 
6.3.1. 
Patient Screening Assessments ........................................................................ 12 
6.3.2. 
Pre-procedure Management ............................................................................ 12 
6.3.3. 
Intraprocedure Management ........................................................................... 12 
6.3.4. 
Post-procedure Management ........................................................................... 13 
6.4. 
Suspension and withdrawal ......................................................................................... 13 
6.4.1. 
Pre-procedure .................................................................................................. 13 
6.4.2. 
Intraprocedure ................................................................................................. 13 
6.4.3. 
Replacement .................................................................................................... 13 
6.5. 
Randomization and Blinding ....................................................................................... 14 
6.5.1. 
Randomization Implementation ...................................................................... 14 
6.5.2. 
Blinding Implementation and Protection ........................................................ 14 
6.5.3. 
Unblinding....................................................................................................... 14 
6.6. 
Concomitant Therapy and Medication ........................................................................ 15 
7. Basis of study protocol and risk/benefit analysis .................................................................... 15 
7.1. 
Selection of endpoints ................................................................................................. 15 
7.2. 
Definition of participants ............................................................................................ 15 
7.3. 
Adverse events ............................................................................................................ 16 
7.4. 
Expected and trial-related adverse events ................................................................... 16 
7.5. 
Risk minimization ....................................................................................................... 17 
7.6. 
Related benifits............................................................................................................ 17 
7.7. 
Overall feasibility analysis .......................................................................................... 17 

Endoangel Study 
3 / 26 
Version 1.2/Apr13, 2021 
 
 
8. 
Statistical Analysis Plan .......................................................................................................... 17 
8.1. 
Statistical Analysis Plan .............................................................................................. 17 
8.2. 
Methods ....................................................................................................................... 17 
8.3. 
Hypothetical test.......................................................................................................... 17 
8.4. 
Sample Size Calculation ............................................................................................. 18 
8.5. 
Statistical analysis set .................................................................................................. 18 
9. 
Device Description .................................................................................................................. 18 
10. Abbreviation ........................................................................................................................... 18 
11. References ............................................................................................................................... 20 
12. Informed Consent Form .......................................................................................................... 21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Endoangel Study 
Version 1.2/Apr13, 2021 
 
 
 
1. Summary 
 
 
Title： 
Development and Validation of an Artificial Intelligence-based 
Biliary Stricture Navigation System in MRCP-based ERCP 
Short Title： 
EndoAngel Study 
Trial number： 
EA-19-003 
Research system 
EndoAngel 
Expected effect： 
ENDOANGEL's intended use is to instruct the direction of 
guide wire and the position of stent placement in real time. 
Primary Endpoint： 
Procedure time 
Secondary Endpoints: 
1.Intersection over union of bile duct segmentation 
2. Intersection over union of bile duct matching 
model 
 3.Success rate of stent placement 
4. Rate of adverse events 
5. Fluoroscopy time 
6. Total amount of contrast medium 
Trail design： 
Prospective, single-center, randomized controlled trial 
Participants： 
Male and female subjects aged 18 years or older will require MRCP and 
ERCP,   and   voluntarily   provide imaging data of MRCP and ERCP, and 
sign an informed consent form. 
Sample size： 
62 samples needed to be enrolled 
Study Process： Subjects who met all inclusion criteria and did not meet all exclusion criteria 
were included in the study before ERCP. All included subjects signed an 
informed consent form. Subjects will be randomized prior to the start of the 
examination to either an Endoangel-assisted experimental group or a 
control group without Endoangel assistance. The operating physician 
completed ERCP   according   to   the presence or absence of AI prompt. 
The recorder shall record procedure time, intersection over union of bile 
duct segmentation, intersection over union of bile duct matching model, 
success rate of stent placement, rate of adverse events, fluoroscopy time and 
total amount of contrast medium etc. Follow-up will be performed for one 
week after the end of examination. The end time of follow-up is the 
end time of study. And the results are sent to an independent data 
analysis team for review. 
 
4 / 26 

Endoangel Study 
 
 
 
 
 
1.1. Time and Event Tables 
 
 
Events 
Screening period （ d 
-30~-1） 
The day of ERCP(d 0） Follow up (d 1-14) 
Informed Consent 
X 
Basic characteristics 
X 
Medical 
history/surgical 
history 
X 
Inclusion/Exclusion 
Criteria 
X 
Random 
X 
ERCP 
X 
Concomitant 
treatment 
X 
X 
Concomitant 
medication 
X 
X 
Adverse Events 
X 
X 
Research completed 
X 
 
 
1.2. Flow chat 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5/ 26 
 
Safety incidents shall be evaluated and reported according to the quality 
management measures for clinical trials of medical devices 
Security 
Images of MRCP and ERCP were 
collected retrospectively 
Meeting the Inclusion and not 
meeting exclusion Criteria？ 
Artificial intelligence devices were studied and tested to build ERCP 
and MRCP bile duct segmentation models 
Quit 
No
The doctors mark the bile ducts of images 
Sign the informed consent 
Patients requiring ERCP were 
prospectively collected 

Endoangel Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6/ 26 
Yes
A free MRCP in prone position was added before ERCP, and 
a round box with a diameter of 2mm filled with water was 
pasted next to the patient's spine at the level of angulus 
inferior scapulae as a reference. (It does not affect the normal 
MRCP of patients) 
A sheet metal with a diameter of 2mm was pasted 
at the same area during ERCP as a reference. (It 
does not affect the normal ERCP of patients) 
According to the reference, the bile duct of MRCP 
was automatically matched to ERCP by the 
artificial intelligence assisted system, and the bile 
duct matching model was constructed 
Evaluate the accuracy of the bile duct matching 
model by comparing the bile ducts generated by 
matching model and those of ERCP 
Clinical trials were designed to verify the effectiveness 
and safety of bile duct matching model in providing 
navigational cues to endoscopists 
Research completed 
Patients with malignant hilar biliary obstruction 
requiring ERCP stent implantation were 
prospectively collected 
Meeting the Inclusion and not 
meeting exclusion Criteria？ 
 
Quit 
Yes
No
Record procedure time, success rate of stent 
placement, rate of adverse events, fluoroscopy time 
and total amount of contrast medium 
Randomization 
Experimental group 
Control group 

Endoangel Study 
7 / 26 
Version 1.2/Apr13, 2021 
 
 
 
2. Introduction 
 
Biliary stricture can be divided into benign biliary stricture and malignant biliary stricture, 
and malignant hilar biliary obstruction is the one of the common cause. 1Since there is no specific 
early screening method for malignant hilar biliary obstruction at present and most patients have no 
obvious clinical symptoms in the early stage, most patients are already in the advanced stage when 
they are first diagnosed. 2Advanced malignant hilar biliary obstruction cannot undergo resection 
surgery, whose first choice for the treatment is palliative endoscopic biliary drainage. Biliary 
drainage can relieve jaundice, pruritus and other symptoms due to cholestasis.3 However, before 
the narrow segment was placed the stent, the contrast agent could not pass through the narrow 
segment and the bile duct above the narrow segment could not be seen. So it was difficult for 
doctors to determine the direction of the guide wire and the position of the stent. In addition, 
indiscriminate application of the contrast agent may cause outflow obstruction leading to infection. 
However, there is no relevant research to solve these problems. 
 
MRCP is the preferred examination method of pancreatic and bile duct diseases. 4,5Therefore, 
MRCP should be routinely performed before patients are treated with ERCP. At present, MRCP is 
in supine position, and ERCP is in prone position. Different positions lead to differences in the 
morphology of MRCP and the bile duct on ERCP. So preoperative MRCP in supine position has 
limited role in advising physicians on the morphology of the bile duct. Therefore, MRCP in the 
prone position is more favorable for endoscopists to perform ERCP. 
 
In recent years, deep learning algorithms have been continuously developed and increasingly 
mature. They have been gradually applied to the medical field. 6Computer vision is a science that 
studies how to make machines "see". Through deep learning, camera and computer can replace 
human eyes to carry out machine vision such as target recognition, tracking and measurement. 7-
9Interdisciplinary cooperation in the field of medical imaging and computer vision is also one of 
the research hotspots in recent years. At present, it is mainly applied to the automatic identification 
and detection of lesions and quality control, and has achieved good results. It can assist doctors to 
find lesions, make disease diagnosis and standardize doctors' operations, so as to improve the 
quality of doctors' operations. 10-15With mature technical support, it has a good prospect and 
application value to develop endoscopic operating system for lesion detection and quality control 
based on artificial intelligence methods such as deep learning. 
 
In this study, the investigators proposed an artificial Intelligence-based Biliary Stricture 
Navigation System in MRCP-based ERCP, which can instruct the direction of guide wire and the 
position of stent placement in real time. 
 
3. Patient Selection 
 
Male and female subjects aged 18 years or older will require MRCP and ERCP, and   
voluntarily   provide imaging data of MRCP and ERCP, and sign an informed consent form. 
Patients not meeting the inclusion criteria or meeting exclusion criteria will not be considered 
for participation in the study. Patients who met all criteria and singed informed consent may be 
excluded from the study due to: 
• Endoscopists’ professional advices/medical reasons (only under very limited conditions to avoid 
researcher bias). 

Endoangel Study 
8 / 26 
Version 1.2/Apr13, 2021 
 
 
• Withdraw informed consent. 
 
3.1. Inclusion criteria 
 
All patients meeting the following criteria will be considered for participation in the study: 
1.Bile duct segmentation model 
1) Male or female aged 18 or above;  
2) Who needs ERCP, MRCP and its related tests are needed to further define the characteristics of 
digestive tract diseases；  
3) The images of MRCP and ERCP are clear;  
4) Able to read, understand and sign informed consent;  
5) The investigator believes that the subject can understand the process of the clinical study and is 
willing and able to complete all the study procedures and follow-up visits and cooperate with the 
study procedures. 
 
2.Bile duct matching model 
In addition to the criteria mentioned in the bile duct segmentation model, the bile duct matching 
model should also meet the following criteria: 
1) Able to complete MRCP in prone position; 
2) Bile ducts are almost completely visible in MRCP and ERCP. 
 
3.Clinical trials 
In addition to the criteria mentioned in the bile duct segmentation model, the clinical trials should 
also meet the following criteria: 
1) Able to complete MRCP in prone position; 
2) Patients requiring biliary drainage by ERCP due to malignant hilar biliary obstruction. 
 
3.2. Exclusion criteria 
 
All patients meeting the following criteria will not be considered for participation in the study: 
1.Bile duct segmentation model and bile duct matching model 
1) Has participated in other clinical trials, signed the informed consent and was in the follow-up period 
of other clinical trials;  
2) Drug or alcohol abuse or psychological disorder in the last 5 years;  
3) Patients in pregnancy or lactation; 
4) The investigator considers that the subjects were not suitable for MRCP, ERCP and related tests;  
5) A high-risk diseases or other special conditions that the investigator considers inappropriate for the 
subject to participate in a clinical trial. 
 
2.Clinical trials 
In addition to the criteria mentioned in the above, the clinical trial must not meet any of the following 
criteria: 
1) Previous gastrectomy; 
2) Stent replacement; 
3) Pyloric or duodenal obstruction. 
 
 

Endoangel Study 
9 / 26 
Version 1.2/Apr13, 2021 
 
 
3.3. Definition of enrollment 
 
After participants signed informed consent, they were randomized before ERCP. The 
randomization time was the enrollment time, and was recorded in CRF. 
 
4. Endpoints 
 
4.1. Primary Endpoint 
 
1) Procedure time: It was the time of performing ERCP. 
 
4.2. Secondary Endpoints 
 
1) Intersection over union of bile duct segmentation: It was the ratio of union and intersection of bile 
ducts predicted by artificial intelligence devices and actual bile ducts 
2) Intersection over union of bile duct matching model: It was the ratio of union and intersection 
between the bile ducts generated by the AI device and the actual bile ducts in ERCP 
3) Success rate of stent placement: It was calculated by dividing total number of patients with stent 
placement by the number of successful patients. 
4) Rate of adverse events: It was calculated by dividing the total number of patients undergoing stent 
placement by the number of patients who experienced adverse events. 
5) Fluoroscopy time: It was the sum of the total X ray fluoroscopy time during the whole procedure. 
6) Total amount of contrast medium: It was the total amount of contrast medium during the whole 
procedure. 
 
4.3. Safety evaluation endpoints and other secondary endpoints 
 
Adverse events shall be determined according to the definition in the code for the quality 
management of adverse events of medical devices. The following types of adverse events should 
be recorded and calculated in the hospital history and CRF. According to the CRF table, the 

Endoangel Study 
10 / 26 
Version 1.2/Apr13, 2021 
 
 
occurrence time, starting and ending time, intervention measures and treatment results should be 
filled in when recording. The severity should be referred to the previous literature and CTCAE 5.0 
standard. 
 
5. Purpose and overall design 
 
5.1. Purpose 
 
The purpose of this study is to develop an artificial intelligence-based biliary stricture 
navigation system in MRCP-based ERCP, which can instruct the direction of guide wire and the 
position of stent placement in real time. 
 
5.2. Overall design 
 
This is a prospective, single-center, randomized controlled trial study. 
 
6. Study process 
 
6.1. Summary of Study Process 
 
• If the patient meets the inclusion criteria, the patient is invited to participate in the study and then 
the informed consent procedure for the clinical trial is applied. 
• Assess patients’ eligibility based on the inclusion/exclusion criteria. 
• If the patient meets the inclusion/exclusion criteria, information prior to ERCP will be collected 
• If the patient is enrolled, he will be randomized 
• ERCP is performed after informed consent. Any intraoperative adverse events are recorded on 
the CRF for submission and subsequent analysis. 
• Follow-up will be performed from the postoperative to the study completion, as detailed in the 
time and event table. 
 
6.2. Enrollment 
 
Only after patients signed the informed consent, can the research-related procedures be conducted. 

Endoangel Study 
11 / 26 
Version 1.2/Apr13, 2021 
 
 
 
6.2.1. Informed Consent 
 
According to the Helsinki Declaration, patients are not allowed to participate in the study 
without adequate informed consent. The principal investigator is responsible for ensuring that no 
patient was enrolled in the study without adequate informed consent. Failure to obtain informed 
consent and failure to document this process is considered a violation of the Helsinki Declaration 
and the study protocol. 
All informed consent documents (ICDs) must be approved by ethics. Patient’s informed 
consent requires documentary record on the informed consent by himself in his primary language. 
 
The investigator or trained designated person performs a preliminary screening to determine 
if the patient generally meets the eligibility criteria for the study. If yes, the investigator or trained 
designee should recommend the patient to participate in the study. If the patient agrees to 
participate, they will need to sign an informed consent document. 
 
The investigator or trained designated person should confirm that the subject understands the 
following points in the study: 
• The purpose of research, 
• Potential risks or adverse events, 
• Potential risks or adverse events directly related to participating the research, 
• The likelihood of failure, 
• Research requirements include follow-up visits, 
• All rights of the subject as a participant in the clinical study. 
 
After explaining the purpose of the study, the investigator or trained designee should answer 
any questions from the subject. If the subject agrees to participate, his or her wishes must be 
recorded by signing and dated on the EC-approved ICF, and the document should be signed and 
dated by the patient receiving the informed consent. 
After successful completion of the informed consent process, the investigator or trained 
designated person will assess the eligibility of patients based on the protocol. 
 
6.2.2. Patient Selection 
 
All patients who underwent ERCP, agreed to use EndoAngel and generally meet the study 
requirements were screened based on the inclusion/exclusion criteria. Patients who passed the 
screening were enrolled and recorded in the subject screening and enrollment tables. There is no 
bias in the choice of the enrolled subjects. The date of screening, the results (enrolled or not), and 
the primary reason for not selecting subjects (such as not meeting inclusion criteria, or not 
interested in participating in the study) will be recorded. 
 
After the patients are enrolled, the research center should complete the preoperative study 
data collection. 

Endoangel Study 
12 / 26 
Version 1.2/Apr13, 2021 
 
 
It is desirable to be able to collect complete data for all enrolled patients, without who 
withdrawal from the study. 
 
6.2.3 Subject identification number 
 
Patients were numbered after signing informed consent. 
 
The subject number begins with EA as a fixed number and is numbered starting from 0001 at 
the time of signing the informed consent. For example, the first patient who signed the informed 
consent was EA0001, and the second one was EA0002. 
 
Once the subject identification number is assigned, the number is not reusable. 
 
6.3 Treatment Description 
 
This section applies to individuals who have signed an approved informed consent and have 
been identified as eligible to participate in this study on the basis of the inclusion and exclusion 
criteria. This section introduces the preoperative, surgical and postoperative management of 
subjects in detail. 
 
6.3.1 Patient Screening Assessments 
 
1） History 
2） Physical examination 
3） Hematuria pregnancy test (if required) 
 
6.3.2 Pre-Procedure Managements 
 
1） Fasting for 6 hours and water deprivation for 2 hours before examination 
2） Routine stomach preparation. 
3） Psychological counseling. 
4） Performing routine anesthesia for painless gastroscopy patients. 
 
6.3.3 Intraoperative Managements 
 
1） Patient position: prone position with appropriate restraint. 
2） Insertion route: according to the actual situation of the subject, usually through the esophagus 
3） Routine observation 

Endoangel Study 
13 / 26 
Version 1.2/Apr13, 2021 
 
 
 
6.3.4 Post-operative Managements 
 
1） Postoperative routine nursing 
2） The anesthetized subjects were observed until they woke up, and the ordinary subjects were 
observed until they left the endoscopic room.  
3） Record complications (if any). 
 
6.4 Suspension and withdrawal 
 
Patients who were screened and confirmed to be eligible for the study, signed the informed 
consent and completed the randomization were considered as enrolled. If serious program 
deviation, withdrawal, or death occurs, the subject study is considered to be suspended. If the 
subject discontinues the study after obtaining informed consent, the data before the 
discontinuation will still be included in the study-related analysis. 
 
6.4.1Pre-Procedure 
 
In any time during the study period, even before ERCP, participants could withdraw their 
informed consent whenever necessary. Researchers can withdraw participants before surgery 
according to safety considerations in the inclusion and exclusion criteria. 
 
6.4.2 Intraprocedure 
 
For safety reasons, the investigator may have the subject quit during the procedure. For 
example, the patient is not suitable for receiving the instrument for the study or the endoscopists 
do not use the specified instrument for any reason. If the following serious cases occur, please 
withdraw during the operation: 
1） Perforation 
2） Bleeding 
3） Allergy to narcotic drugs 
4） Unable to complete ERCP due to obstruction or other reasons 
 
6.4.3 Replacement 
 
Subject will be deemed to have commenced the study upon completion of the informed 
consent process, and any subject who has been discontinued prior to or during the ERCP will not 
subsequently be replaced by other subjects. 

Endoangel Study 
14 / 26 
Version 1.2/Apr13, 2021 
 
 
 
6.5 Randomization and Blinding 
 
6.5.1 Randomization Implementation 
 
Randomization is conducted according to the study protocol, and the random contents are 
implemented in an electronic system block-randomized manner (n = 4; experimental group/control 
group = 1). Randomization prior to ERCP to decide whether to use EndoAngel. The researchers 
randomized the random results generated by the electronic system, and the generated random 
results were stored in the research center. The random time (accurate to minute), random person, 
subject number and acronym were recorded in the corresponding positions of the electronic system. 
 
6.5.2 Blinding Implementation and Protection 
 
Subjects and evaluators are blinded according to the protocol. 
Randomization results will be kept confidential to the subjects in general. Randomization 
results are not reflected in inpatient history and other subject access documents. During and after 
the examination, study personnel should take care not to talk to the subject about the results of the 
randomization to avoid unnecessary unblinding 
The assessors are blinded, and the data analysis team and pathologists could not obtain the 
randomization results from the medical history data. 
 
6.5.3 Unblinding 
 
Uncovering or breaking the blindness means displaying the randomized results to the subjects 
or evaluators. Researchers should protect the blind method as far as possible. Uncovering the 
randomized results of a single subject may lead to the leakage of the randomized results of other 
subjects. Any leakage of the randomized results will have a significant impact on statistical 
analysis. In general, it is prudent to deal with the disclosure of blind law. In the following cases, it 
is possible to consider the disclosure of blind law: 
 
1) endangering the safety of subjects: For example, in some serious adverse events, subjects need 
to know the randomized results to inform other physicians to take appropriate emergency 
treatment. 
2) Threatening the safety of the assessor: When the assessor is facing potential safety hazards, he 
needs to know the randomization results. 
3) Compliance: For reasons of partial compliance, in certain circumstances, if the research 
instruments and cases involved in unexpected adverse events are needed, the results of 
randomization should be made public to the relevant departments or the public. 
5) Other management reasons. 

Endoangel Study 
15 / 26 
Version 1.2/Apr13, 2021 
 
 
 
6.6 Concomitant therapy and medication 
 
The concomitant treatment and concomitant medication were recorded from the time the 
subject signed the informed consent to the time the study was completed. Concomitant treatment 
and concomitant medication should be recorded in the CRF, or a clear copy of the form available 
from the research center should be kept in the CRF as research data to identify other factors 
affecting the end of the study. When recording the concomitant treatment and concomitant 
medication, the indications and the starting and ending time of use should be clearly defined, and 
the corresponding types of adverse events should be indicated for the treatment measures to cope 
with adverse events. When using a copy of the study center form, the investigator should sign the 
copy and indicate the date of review to confirm that the document is a study document. 
 
7. Basis of study protocol and risk/benefit analysis 
 
EndoAngel is used to provide assistant to monitor the operation of endoscopists, which will 
not provide diagnosis. Doctors make their own diagnosis on the basis of EndoAngel's results. The 
security of the software and the improvement of endoscopic physician's diagnosis and treatment 
level have also been confirmed in the previous feasibility study. And the patients in this study 
carry out the diagnosis and treatment according to the conventional treatment measures, which are 
formulated in accordance with the standard medical treatment procedures and do not increase the 
risk of the subjects. 
 
7.1. Selection of endpoints 
 
The primary endpoint is the procedure time.  
The secondary endpoints were:1) Intersection over union of bile duct segmentation;2) 
Intersection over union of bile duct matching model;3) Success rate of stent placement;4) Rate of 
adverse events;5) Fluoroscopy time;6) Total amount of contrast medium. 
 
Adverse events in safety indicators shall be judged in accordance with relevant regulations, 
and serious adverse events shall be recorded and reported in accordance with regulations. 
 
Other evaluations are detailed in the Case Report Form (CRF). 
 
7.2. Definition of participants 
 
Patients were included according to the indications and contraindications described in the use 

Endoangel Study 
16 / 26 
Version 1.2/Apr13, 2021 
 
 
plan. Because of practical reasons (such as younger patients, participation in a number of clinical 
studies, alcohol/drug dependence patients, and other factors that may affect the completion and/or 
reliability of gastroscopy) and ethical reasons (whether informed consent can be completed, etc.), 
the entry and discharge criteria have been reduced. 
 
7.3. Adverse events 
 
The relevant definitions of adverse events are as follows: 
 
Adverse Events (AE): Any adverse medical event, unexpected disease or injury, or adverse 
clinical manifestations (including abnormal laboratory findings) that occur in a subject, user or 
other person, whether or not associated with medical devices. 
 
Serious Adverse Events (SAE): Adverse Events with the following information: 
- causing death. 
- leading to severe deterioration of the health of the subjects, including 
- leading to life-threatening diseases or injuries, 
- Causing impairment of body structure or function. 
- Need hospitalization or extended hospitalization 
- lead to hospitalization and preventive medical or surgical intervention 
- Permanent damage to body structure or function 
- Fetal distress, fetal death or congenital abnormalities or congenital defects. 
 
Note: Hospitalization for existing conditions, or surgery required in the program, without 
serious deterioration of health status, is not considered a serious adverse event. Purposeful 
hospitalization, such as economic or reimbursement reasons, is not considered a serious adverse 
event. 
 
Unexpected adverse device response (UADE): refers to adverse events related to medical 
devices that were not previously identified in the current version of the risk analysis report in 
terms of nature, severity or incidence. The definition includes any event caused by insufficient or 
inadequate description of the use or deployment of the device. This definition includes any event 
caused by a user's error. 
 
7.4. Expected and trial-related adverse events 
 
Previous studies have shown that the expected adverse events are basically the same as the 
complications of conventional endoscopic diagnosis and treatment. 
 
The instrument used in this experiment is a medical software which is not in contact with 
human body. There is no difference between the experimental operation and the routine operation. 
The intervention measures (such as randomized process) in the experiment may slightly increase 

Endoangel Study 
17 / 26 
Version 1.2/Apr13, 2021 
 
 
the incidents of diagnosis and treatment. 
 
7.5. Risk minimization 
 
In this study, when there are bugs in the software, doctors can still operate under their own 
judgment without affecting conventional diagnostic and treatment measures, greatly reducing the 
risk of the test. 
 
7.6. Related benefits 
 
Subjects will be randomly assigned to an experimental group or a control group. And 
experimental subjects may improve the quality of ERCP. 
 
7.7. Overall feasibility analysis 
 
EndoAngel is an independent system including both software and computer hardware, which 
can monitor image data 24 hours a day. The system is not invasive. The overall operability is 
strong. 
 
8. Statistical Analysis 
 
8.1. Statistical Analysis Plan 
 
Data management and statistical analysis were implemented by Renmin Hospital of Wuhan 
University. 
 
8.2. Methods 
 
Continuous variables should be described by number of subjects, mean, standard deviation, 
median, minimum and maximum. The classification variables are summarized by frequency and 
percentage. 
 
8.3. Hypothetical test 
 
The main assumptions are: 
1.The use of EndoAngel can reduce the operation time of ERCP; 
2.The use of EndoAngel can improve the success rate of stent placement; 
3. The use of EndoAngel can reduce the rate of adverse events; 
4. The use of EndoAngel can reduce the fluoroscopy time; 
5. The use of EndoAngel can reduce the total amount of contrast medium. 

Endoangel Study 
18 / 26 
Version 1.2/Apr13, 2021 
 
 
 
8.4. Sample Size Calculation 
 
We mainly studied the effect of EndoAngel on the quality of ERCP for physicians. Therefore, 
data collection and analysis were conducted for the main effect. It is expected that a total of 62 
subjects will be enrolled. Assuming the operation time of ERCP in experimental group is 43.9±11.56 
minutes, the operation time of ERCP in control group is 35 minutes. Bilateral significance level 5% 
(alpha =5%), assurance 80% (beta =20%), shedding rate 10%, Expected to enroll 62 patients in total. 
 
8.5. Statistical analysis set 
 
All patients who met the inclusion and exclusion criteria were considered eligible for 
recruitment. 
The two analysis sets in this study are defined as follows: 
• The full analysis set (FAS) population analysis set will contain all eligible cases and shedding 
cases, but does not include culling cases. 
• The Compliance (PP) population analysis set will include all subjects in the FAS analysis set 
with no significant deviation from the program. 
Intention-to-treat and conformity analysis sets should be used to analyze the primary efficacy 
endpoints. The main analysis will be based on the PP analysis set. FAS analysis was regarded as 
supportive analysis. 
 
9. Device Description 
 
EndoAngel 
Version: EA 2301 
 
10. Abbreviations 
 
Abbreviations 
Full Name 
Chinese 
AE 
Adverse Event 
不良事件 
CFDA 
China Food and Drug Administration 
国家食品药品监督管理总局 
CNDA 
China National Drug Administration 
国家食品药品监督管理总局 
CRF 
Clinical Record File 
病例报告表 
CTCAE 
Common Terminology Criteria for Adverse Events 
不良事件常规评价标准 
EC 
Ethical Committee 
伦理委员会 
ICD 
Informed Consent Document 
知情同意文件 
ICF 
Informed Consent Form 
知情同意书 

Endoangel Study 
19 / 26 
Version 1.2/Apr13, 2021 
 
 
 
ITT 
Intention to Treat 
意向治疗分析集 
PP 
Per Protocol 
符合方案集 
SAE 
Serious Adverse Event 
严重不良事件 
ERCP 
Endoscopic Retrograde Cholangiopancreatography 
经内镜逆行性胰胆管造影术 
MRCP 
Magnetic Resonance Cholangiopancreatography 
磁共振胰胆管造影 

Endoangel Study 
20 / 26 
Version 1.2/Apr13, 2021 
 
 
 
11. References 
 
1.  Tantau, A. I. et al. Extrahepatic cholangiocarcinoma: Current status of endoscopic approach and 
additional therapies. World J Hepatol 13, 166-186, doi:10.4254/wjh.v13.i2.166 (2021). 
2.   Balasubramanian, B. et al. Co-Clinical Trials: An Innovative Drug Development Platform for 
Cholangiocarcinoma. Pharmaceuticals (Basel) 14, doi:10.3390/ph14010051 (2021).  
3. Squadroni, M. et al. Cholangiocarcinoma. Crit Rev Oncol Hematol 116, 11-31, 
doi:10.1016/j.critrevonc.2016.11.012 (2017). 
4.  Solonitsyn, E. & Dechêne, A. Diagnostic Approach to Suspected Perihilar Malignancy. Visc 
Med 37, 3-9, doi:10.1159/000513950 (2021). 
5.   Boškoski, I. et al. Personalized Endoscopy in Complex Malignant Hilar Biliary Strictures. J 
Pers Med 11, doi:10.3390/jpm11020078 (2021). 
6.   Jones, O. T. et al. Artificial Intelligence Techniques That May Be Applied to Primary Care 
Data to Facilitate Earlier Diagnosis of Cancer: Systematic Review. J Med Internet Res 23, e23483, 
doi:10.2196/23483 (2021). 
7.  Topol, E. J. High-performance medicine: the convergence of human and artificial intelligence. 
Nat Med 25, 44-56, doi:10.1038/s41591-018-0300-7 (2019). 
8.   Suzuki, K. Overview of deep learning in medical imaging. Radiol Phys Technol 10, 257-273, 
doi:10.1007/s12194-017-0406-5 (2017). 
9.   Castiglioni, I. et al. AI applications to medical images: From machine learning to deep learning. 
Phys Med 83, 9-24, doi:10.1016/j.ejmp.2021.02.006 (2021). 
10.  Gong, D. et al. Detection of colorectal adenomas with a real-time computer-aided system 
(ENDOANGEL): a randomised controlled study. Lancet Gastroenterol Hepatol 5, 352-361, 
doi:10.1016/s2468-1253(19)30413-3 (2020). 
11.  Zhou, J. et al. A novel artificial intelligence system for the assessment of bowel preparation 
(with video). Gastrointest Endosc 91, 428-435.e422, doi:10.1016/j.gie.2019.11.026 (2020). 
12. Chen, D. et al. Comparing blind spots of unsedated ultrafine, sedated, and unsedated 
conventional gastroscopy with and without artificial intelligence: a prospective, single-blind, 3-
parallel-group, randomized, single-center trial. Gastrointest Endosc 91, 332-339.e333, 
doi:10.1016/j.gie.2019.09.016 (2020). 
13.  Wu, L. et al. Randomised controlled trial of WISENSE, a real-time quality improving system 
for monitoring blind spots during esophagogastroduodenoscopy. Gut 68, 2161-2169, 
doi:10.1136/gutjnl-2018-317366 (2019). 
14.  Wu, L. et al. A deep neural network improves endoscopic detection of early gastric cancer 
without blind spots. Endoscopy 51, 522-531, doi:10.1055/a-0855-3532 (2019). 
15.  Huang, L. et al. Intelligent difficulty scoring and assistance system for endoscopic extraction 
of common bile duct stones based on deep learning: multicenter study. Endoscopy, doi:10.1055/a-
1244-5698 
(2020).

Endoangel Study 
21 / 26 
Version 1.2/Apr13, 2021 
 
 
 
Informed Consent Form 
 
 
“Development and Validation of an Artificial Intelligence-
based Biliary Stricture Navigation 
System in MRCP-based ERCP” 
Informed Consent Form for clinical study subjects 
 
 
Informed Consent Form: Information page 
 
 
Release date: 1.2,13 April 2021 
Principal investigator: Yu Honggang 
Dear sir / Madam, 
We will invite you to participate in a clinical study “Development and Validation of an 
Artificial Intelligence-based Biliary Stricture Navigation System in MRCP-based ERCP”. During 
this study, we will use a new ERCP-assisted system which do not interfere the physician's original 
observations and procedures. 
Before you decide whether to participate in the study, please read the following as carefully 
as possible to help you understand the study and why it was conducted, the procedure and duration 
of the study, the potential benefits or risks of participating in the study. If you wish, you can 
discuss it with your family or friends, or ask your doctor for an explanation to help you make a 
decision 
1. Background and Purpose 
Biliary stricture can be divided into benign biliary stricture and malignant biliary stricture, 
and malignant hilar biliary obstruction is the one of the common cause. Since there is no specific 
early screening method for malignant hilar biliary obstruction at present and most patients have no 
obvious clinical symptoms in the early stage, most patients are already in the advanced stage when 
they are first diagnosed. Advanced malignant hilar biliary obstruction cannot undergo resection 
surgery, whose first choice for the treatment is palliative endoscopic biliary drainage. Biliary 
drainage can relieve jaundice, pruritus and other symptoms due to cholestasis. However, before the 
narrow segment was placed the stent, the contrast agent could not pass through the narrow segment 
and the bile duct above the narrow segment could not be seen. So it was difficult for doctors to 
determine the direction of the guide wire and the position of the stent. In addition, indiscriminate 
application of the contrast agent may cause outflow obstruction leading to infection. However, 
there is no relevant research to solve these problems. 
 

Endoangel Study 
22 / 26 
Version 1.2/Apr13, 2021 
 
 
MRCP is the preferred examination method of pancreatic and bile duct diseases. Therefore, 
MRCP should be routinely performed before patients are treated with ERCP. At present, MRCP is 
in supine position, and ERCP is in prone position. Different positions lead to differences in the 
morphology of MRCP and the bile duct on ERCP. So preoperative MRCP in supine position has 
limited role in advising physicians on the morphology of the bile duct. Therefore, MRCP in the 
prone position is more favorable for endoscopists to perform ERCP. 
 
In recent years, deep learning algorithms have been continuously developed and increasingly 
mature. They have been gradually applied to the medical field. Computer vision is a science that 
studies how to make machines "see". Through deep learning, camera and computer can replace 
human eyes to carry out machine vision such as target recognition, tracking and measurement. 
Interdisciplinary cooperation in the field of medical imaging and computer vision is also one of the 
research hotspots in recent years. At present, it is mainly applied to the automatic identification 
and detection of lesions and quality control, and has achieved good results. It can assist doctors to 
find lesions, make disease diagnosis and standardize doctors' operations, so as to improve the 
quality of doctors' operations. With mature technical support, it has a good prospect and 
application value to develop endoscopic operating system for lesion detection and quality control 
based on artificial intelligence methods such as deep learning. 
 
In this study, the investigators proposed an artificial Intelligence-based Biliary Stricture 
Navigation System in MRCP-based ERCP, which can instruct the direction of guide wire and the 
position of stent placement in real time. 
2. Who can participate in the study 
2.1. Bile duct segmentation model 
1) Male or female aged 18 or above;  
2) Who needs ERCP, MRCP and its related tests are needed to further define the characteristics of 
digestive tract diseases；  
3) The images of MRCP and ERCP are clear;  
4) Able to read, understand and sign informed consent;  
5) The investigator believes that the subject can understand the process of the clinical study and is 
willing and able to complete all the study procedures and follow-up visits and cooperate with the 
study procedures. 
 
2.2. Bile duct matching model 
In addition to the criteria mentioned in the bile duct segmentation model, the bile duct matching 
model should also meet the following criteria: 
1) Able to complete MRCP in prone position; 
2) Bile ducts are almost completely visible in MRCP and ERCP. 
 
2.3. Clinical trials 
In addition to the criteria mentioned in the bile duct segmentation model, the clinical trials should 
also meet the following criteria: 
1) Able to complete MRCP in prone position; 
2) Patients requiring biliary drainage by ERCP due to malignant hilar biliary obstruction. 
 
3. Who can not participate in the study 
3.1. Bile duct segmentation model and bile duct matching model 

Endoangel Study 
23 / 26 
Version 1.2/Apr13, 2021 
 
 
1) Has participated in other clinical trials, signed the informed consent and was in the follow-up period 
of other clinical trials;  
2) Drug or alcohol abuse or psychological disorder in the last 5 years;  
3) Patients in pregnancy or lactation; 
4) The investigator considers that the subjects were not suitable for MRCP, ERCP and related tests;  
5) A high-risk diseases or other special conditions that the investigator considers inappropriate for the 
subject to participate in a clinical trial. 
 
3.2. Clinical trials 
In addition to the criteria mentioned in the above, the clinical trial must not meet any of the following 
criteria: 
1) Previous gastrectomy; 
2) Stent replacement; 
3) Pyloric or duodenal obstruction. 
 
4. What would you need to do 
Patients need to prepare for ERCP routinely, fasting for at least 6 hours and water 
deprivation for at least 2 hours before the procedure. Patients undergoing painless operation 
receive general anesthesia, while patients undergoing general operation do not need it. If you are 
assigned to the experimental group, the endoscopists will be assisted by EndoAngel, which can 
instruct the direction of guide wire and the position of stent placement in real time. If you are 
assigned to the control group, the endoscopist performs ERCP routinely without special prompts. 
You are equally likely to be in the above two groups. 
 
5. Benefits 
You will be randomized into the experimental group and the control group. The endoscopists 
in the experimental group will be assisted by EndoAngel, which can assist in instructing the 
direction of guide wire and the position of stent placement in real time. Patients who have access 
to the ERCP with EndoAngel will likely have fewer surgical times, higher surgical success rates, 
and lower incidences of adverse events. 
 
6. Adverse events 
The adverse events are basically the same as the complications of conventional endoscopic 
diagnosis and treatment. Participants in this study do not increase other additional risks. 
 
7. Related fees 
Routine MRCP and ERCP for your clinical examination items, the cost of your own. 
Additional MRCP in prone position is free.  
 
8. Personal Information 
During the MRCP and ERCP process, your electronic images and case information will be 

Endoangel Study 
24 / 26 
Version 1.2/Apr13, 2021 
 
 
collected and preserved in the hospital. Your doctor, the researcher, will be given access to this 
electronic information for scientific research. Your personal identity will not be disclosed in any 
public report of the results of the relevant research and development. We will do everything 
within the law to protect the privacy of your personal medical data. 
 
9. For more information 
You can ask any question about this study at any time. 
Your doctor will give you his or her phone number so that he or she can answer your 
questions 
Your doctor will keep you informed if there is any important new information during the 
course of the study that may affect your willingness to continue participating in the study. 
 
10. Participation and withdrawal are voluntary 
Participation in the study is entirely up to you. You may refuse to participate in the study or 
withdraw from the study at any time during the course of the study. You will not be discriminated 
against or retaliated against for refusing to participate in the study. Your medical treatment and 
entitlements will not be affected. 
Your doctor or researcher may suspend your participation at any time in the best interest of 
you. 
If you withdraw from the study for any reason, you may also be required to undergo a 
laboratory and physical examination if your doctor deems it necessary. 
If you choose to participate in this study, we hope that you can adhere to the completion of the 
entire research process. 
11. Others 
Participating in this study is up to you. You can discuss it with your family or friends before 
making a decision. 
Before you decide to participate in the study, ask your doctor as many questions as you can 
about the study until you have a complete understanding of it. 
Thank you for reading this. If you decide to participate in the study, please tell your doctor, he 
or she will arrange for you to participate in all matters related to the study.  
Please keep this information. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Endoangel Study 
25 / 26 
Version 1.2/Apr13, 2021 
 
 
 
Informed Consent Form: Information page 
Name of Clinical Research Project: Development and Validation of an Artificial 
Intelligence-based Biliary Stricture Navigation System in MRCP-based ERCP 
Research physician commitment: 
As a research physician, I confirmed that I had clearly explained to the subject 
the details of this trial, including their rights and possible benefits and risks, and gave 
them a signed copy of my informed consent. 
Name：＿＿＿＿＿＿＿ 
Date: ＿＿＿＿＿＿
Contact：＿＿＿＿＿＿＿ 
 
Subject commitment: 
I have read and understood the introduction to this study on the informed consent 
page, and have had the opportunity to ask questions. I understand the research 
physician's explanation. 
I am aware of the risks and benefits of participating in this study. I am aware that 
participation in the study is voluntary, and I am sure that there has sufficient time to 
consider and volunteer for the trial. I can always ask my doctor for more information, 
and I can always withdraw from the study without discrimination or retaliation, and 
without prejudice to medical benefits and entitlements. 
I also knew that if I dropped out of the study, I would tell my doctor and 
complete the physical and chemical tests. If I need to take any other medication for 
my illness, I will consult with my doctor in advance or tell him the truth afterwards. 
I agree□ or refuse□ Use my medical records for any other study. 
I agree to participate in the study and promised to follow the doctor's advice to 
the best of my ability. I will receive a signed and dated copy of the Informed Consent 
Form. 
Name：＿＿＿＿＿＿＿ 
Date: ＿＿＿＿＿＿＿ 
Contact：＿＿＿＿＿＿＿ 

Endoangel Study 
26 / 26 
Version 1.2/Apr13, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
-End-