Pressure Guidewire System Multi-center, Prospective, Self-Control, Clinical Trial
Phase: NA
Conditions: Myocardial Ischemia
Sponsor: Zurich Medical Inc.

 
 
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Pressure Guidewire System Multi-center, 
Prospective, Single-subject Design Clinical Trial 
Updated document date:  July 11, 2022 
Protocol No.:WXYL-LC-2018001 
 
 
 
 
 

 
 
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Protocol No.:WXYL-LC-2018001 
 
Pressure Guidewire System Multi-center, 
Prospective, Single-subject Design Clinical Trial 
 
Name of investigational medical device:  Zurich Pressure Guidewire 
System Model100 
Management category of investigational medical device:  
Class III medical devices requiring review and approval through 
clinical trial Yes
 No
  
Predicate products within the territory of China Yes
 No
 
Clinical protocol version number:  v1.0  
Document date:  July 11th, 2018 
Investigational Site:  Fudan University Zhongshan Hospital 
Principle Investigator:  Dr. Ge Junbo 
Sponsor:  Zurich Medical Inc. 
Agent:  Shandong Visee Medical Devices Co., Ltd. 
Contract Research Organization (CRO):  Beijing Jingruitianhe Medical 
Science and Technology Development Co., Ltd. 

 
 
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Instructions for filling: 
1. 
For multi-center clinical trials, only the principal investigational 
site shall be listed on the cover, while other sites shall be listed 
in the contents of the protocol.  
2. 
For multi-center clinical trials, the coordinating investigator shall 
be filled out as the investigator on the cover.  
 
 
 
 
 
 
 
 
 
 
 

 
 
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Contents 
ABBREVIATIONS TABLE .............................................................................................................................. 9 
1 
SPONSOR INFORMATION .................................................................................................................. 18 
1.1 NAME OF THE SPONSOR .................................................................................................................................. 18 
1.2 THE ADDRESS OF THE SPONSOR ....................................................................................................................... 18 
1.3 SPONSOR’S CONTACT INFORMATION ................................................................................................................. 18 
1.4 AGENT'S NAME, ADDRESS, CONTACT DETAILS AND RELATED QUALIFICATION DOCUMENTS ................................... 18 
2 
LIST OF ALL INVESTIGATIONAL SITES AND INVESTIGATORS FOR MULTI-CENTER CLINICAL TRIALS: ...... 18 
3 
OBJECTIVE AND CONTENT OF CLINICAL TRIAL .................................................................................. 19 
3.1 OBJECTIVE ...................................................................................................................................................... 19 
3.2 CONTENT ....................................................................................................................................................... 19 
4 
BACKGROUND INFORMATION .......................................................................................................... 20 
5 
PRODUCT FEATURES, STRUCTURAL COMPOSITION, WORKING PRINCIPLE, FUNCTIONAL MECHANISM 
AND TRIAL SCOPE.............................................................................................................................. 22 
5.1 PRODUCT FEATURES ........................................................................................................................................ 22 
5.2 PRODUCT STRUCTURAL COMPOSITION, WORKING PRINCIPLE, FUNCTIONAL MECHANISM......................................... 22 
5.2.1 
Structural Composition ................................................................................................................... 22 
5.2.2 
Working Principle and Functional Mechanism ............................................................................. 23 
5.3 TRIAL SCOPE.................................................................................................................................................... 25 
6 
PRODUCT'S INDICATION FOR USE AND CONTRAINDICATIONS, WARNING ....................................... 25 
6.1 INDICATION FOR USE ........................................................................................................................................ 25 

 
 
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6.2 CONTRAINDICATIONS ....................................................................................................................................... 25 
6.3 WARNING ...................................................................................................................................................... 25 
1) PRESSURE GUIDEWIRE SYSTEM IS INTENDED FOR SINGLE USE ONLY. ........................................................................ 25 
2) DO NOT RESTERILIZE OR REUSE. ......................................................................................................................... 25 
3) DO NOT USE IF THE ORIGINAL STERILE PACKAGE IS NOT INTACT. ............................................................................. 25 
4) INSPECT THE SYSTEM CAREFULLY PRIOR TO USE TO VERIFY THAT ALL PARTS ARE PRESENT AND UNDAMAGED. ............... 25 
5) REUSE AFTER CLEANING ATTEMPTS, RESTERILIZATION AND REPACKAGING MAY RESULT IN PATIENT/USER INFECTIONS AND 
COMPROMISED PRODUCT FUNCTIONALITY, SUCH AS INACCURATE PRESSURE SIGNALS AND INACCURATE TORQUE 
RESPONSE THEREBY EXPOSING THE PATIENT TO INCREASED RISKS FOR COMPLICATIONS/ADVERSE EVENTS. ................... 25 
6) PRIOR TO USE AND WHEN POSSIBLE DURING THE PROCEDURE, INSPECT GUIDEWIRE CAREFULLY FOR BENDS, KINKS OR 
OTHER DAMAGE. DO NOT READJUST ANY BEND OR KINK AS READJUSTMENTS MAY DAMAGE THE ELECTRICAL WIRING 
INSIDE THE GUIDEWIRE. .................................................................................................................................... 25 
7) GUIDEWIRE MUST NOT BE USED IF IT HAS BEEN DAMAGED IN ANYWAY; OTHERWISE, VESSEL/VENTRICLE DAMAGE 
AND/OR INACCURATE PRESSURE SIGNALS OR INACCURATE TORQUE RESPONSE MAY OCCUR. ..................................... 25 
8) WHEN INTRODUCING GUIDEWIRE IN A DIAGNOSTIC CASE, FLUSH THE CATHETER AND ADMINISTER AN ANTICOAGULANT 
BASED ON STANDARD OF CARE FOR CATHETERIZATION PROCEDURE OR CLOTTING MAY OCCUR................................. 25 
9) WHEN THE GUIDEWIRE IS EXPOSED TO THE VASCULAR SYSTEM, IT SHOULD BE MANIPULATED WHILE UNDER HIGH-
QUALITY FLUOROSCOPIC OBSERVATION. IF RESISTANCE IS MET DURING MANIPULATION, DETERMINE THE CAUSE OF THE 
RESISTANCE BEFORE PROCEEDING. ..................................................................................................................... 26 
10) DO NOT TORQUE GUIDEWIRE WITHOUT OBSERVING CORRESPONDING MOVEMENT OF THE TIP; OTHERWISE 
VESSEL/VENTRICLE TRAUMA MAY OCCUR............................................................................................................. 26 
11) ALWAYS ADVANCE OR WITHDRAW GUIDEWIRE SLOWLY. NEVER PUSH, WITHDRAW OR TORQUE GUIDEWIRE IF IT MEETS 
RESISTANCE. .................................................................................................................................................... 26 

 
 
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12) POSITIONING OF CATHETERS AND GUIDEWIRES IN THE VENTRICLES IS POTENTIALLY ARRHYTHMOGENIC. IT SHOULD NEVER 
BE DONE WITHOUT ECG MONITORING AND THE PRESENCE OF A FUNCTIONING DEFIBRILLATOR. .............................. 26 
13) AVOID USING GUIDEWIRE IN THE VENTRICLES IF THE PATIENT HAS A PROSTHETIC MECHANICAL VALVE. ZURICH PRESSURE 
GUIDEWIRE SYSTEM MAY BECOME TRAPPED AND DISRUPT THE FUNCTION OF THE VALVE, LEADING TO SERIOUS INJURY 
OR DEATH. ...................................................................................................................................................... 26 
14) DO NOT USE IT IN THE ELECTROSURGICAL ENVIRONMENT WHEN HIGH-FREQUENCY SURGICAL EQUIPMENT IS USED AT 
THE SAME TIME. ............................................................................................................................................... 26 
7 
OVERALL DESIGN .............................................................................................................................. 26 
7.1 TRIAL DESIGN .................................................................................................................................................. 26 
7.1.1 
Trial Objective .................................................................................................................................. 26 
7.1.2 
Selection of Trial Method and Justification..................................................................................... 27 
7.1.3 
Measures to Lessen and Prevent Bias ............................................................................................ 28 
7.1.4 
Investigational Medical Devices and Controlled Medical Devices / Control Methods................. 28 
7.1.5 
Subject Selection (including control group selection if necessary) ............................................... 33 
7.1.6 
Effectiveness evaluation methods .................................................................................................. 36 
7.1.7 
Safety Evaluation Methods ............................................................................................................. 39 
7.2 THE TRIAL PROCESS .......................................................................................................................................... 40 
7.2.1 ..................................................................................................................... THE TRIAL PROCESS
...................................................................................................................................................................... 40 
7.2.2 ..................................................................................................................... TRIAL FLOW CHART
...................................................................................................................................................................... 42 
7.2.3 ................................................................................................................. DEVICE SPECIFICATION

 
 
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...................................................................................................................................................................... 44 
7.3 MONITORING / AUDIT PLAN ............................................................................................................................. 44 
8 
STATISTICAL CONSIDERATIONS .......................................................................................................... 46 
8.1 STATISTICAL DESIGN, METHODOLOGY AND ANALYSIS PROCEDURES ...................................................................... 46 
8.1.1 ......................................................................................... STATISTICAL DESIGN (HYPOTHESIS TESTING)
...................................................................................................................................................................... 46 
8.1.2 ...................................................................................................... STATISTICAL ANALYSIS METHODS
...................................................................................................................................................................... 46 
8.1.3 .................................................................................................. STATISTICAL ANALYSIS PROCEDURES
...................................................................................................................................................................... 47 
8.2 SAMPLE SIZE CALCULATION .............................................................................................................................. 48 
8.2.1 
Total Sample Size ............................................................................................................................. 48 
8.2.2 
Number of Clinical Trial per Disease and Reasons for Determination .......................................... 49 
8.2.3 
The Maximum and Minimum Numbers of Subjects Per Clinical Trial Institution in a Multi-center 
Clinical Trial and Reasons for Determination .......................................................................................... 49 
8.3 CLINICAL TRIAL’S SIGNIFICANCE LEVEL AND POWER ............................................................................................ 49 
8.4 EXPECTED DROP OUT RATE .............................................................................................................................. 49 
8.5 CRITERIA FOR QUALIFIED/UNQUALIFIED RESULTS IN CLINICAL TRIAL ...................................................................... 50 
8.6 STANDARDS AND REASONS FOR TERMINATING CLINICAL TRIAL BASED ON STATISTICAL REASONS.............................. 50 
8.7 STATISTICAL METHODS OF ALL DATA, ALONG WITH MISSING, UNUSED, AND ERRONEOUS DATA (INCLUDING 
WITHDRAWALS) AND THE PROCESSING METHODS FOR UNREASONABLE DATA...................................................... 50 
8.8 REPORTING DEVIATION FROM THE ORIGINAL STATISTICAL PLAN ............................................................................ 51 

 
 
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8.9 STANDARDS AND REASONS FOR SELECTING SUBJECTS TO BE INCLUDED IN THE ANALYSIS ........................................ 51 
8.10 EXCLUSION OF SPECIAL INFORMATION DURING HYPOTHESIS VERIFICATION AND ITS REASONS (IF APPLICABLE) .......... 51 
9 
DATA MANAGEMENT........................................................................................................................ 52 
9.1 DATA COLLECTION .................................................................................................................................... 52 
9.2 DATA VERIFICATION AND MODIFICATION .............................................................................................. 52 
9.3 DATABASE LOCK ......................................................................................................................................... 52 
10 FEASIBILITY ANALYSIS ......................................................................................................................... 53 
10.1 PROBABILITY OF SUCCESS ANALYSIS ......................................................................................................... 53 
10.2 PROBABILITY OF FAILURE ANALYSIS .......................................................................................................... 53 
11 QUALITY CONTROL OF CLINICAL TRIALS ............................................................................................ 53 
12 ETHICAL ISSUES AND INFORMED CONSENT IN CLINICAL TRIALS ........................................................ 54 
12.1 ETHICAL CONSIDERATIONS ................................................................................................................... 54 
12.2 REVIEW AND APPROVAL OF THE TRIAL PROTOCOL .......................................................................... 54 
12.3 INFORMED CONSENT PROCESS AND INFORMED CONSENT FORM ................................................. 54 
13 PROVISIONS ON ADVERSE EVENTS AND DEVICE DEFECTS REPORTING ............................................. 55 
13.1 ADVERSE EVENTS ................................................................................................................................... 55 
13.2 SERIOUS ADVERSE EVENTS .................................................................................................................... 55 
13.3 DEVICE DEFECTS .................................................................................................................................... 55 
13.4 SERIOUS ADVERSE EVENT REPORTING PROCEDURES, CONTACT INFORMATION ........................... 56 
14 PROVISIONS ON DEVIATION FROM CLINICAL TRIAL PROTOCOL AND REVISION OF CLINICAL TRIAL 
PROTOCOL ........................................................................................................................................ 56 

 
 
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14.1 DEVIATION FROM CLINICAL TRIAL PROTOCOL ................................................................................... 56 
14.2 CLINICAL TRIAL PROTOCOL MODIFICATION PROCEDURE ................................................................. 57 
15 DIRECT ACCESS TO SOURCE DATA, FILES ........................................................................................... 57 
15.1 DEFINITION ............................................................................................................................................. 57 
15.2 PROVISIONS FOR DIRECT ACCESS TO SOURCE DATA AND FILES ...................................................... 57 
16 FINANCE AND INSURANCE ............................................................................................................... 57 
17 CONTENTS TO BE COVERED IN CLINICAL TRIAL REPORTS .................................................................. 58 
18 THE PRINCIPLE OF CONFIDENTIALITY................................................................................................. 59 
18.1PERSONAL DATA AND DATA PROTECTION......................................................................................... 59 
18.2CONFIDENTIALITY .................................................................................................................................. 59 
19 AGREEMENT ON THE PUBLICATION OF TRIAL RESULTS ..................................................................... 59 
20 RESPONSIBILITIES OF ALL PARTIES ...................................................................................................... 60 
20.1THE RESPONSIBILITIES OF THE SPONSOR .................................................................................................. 60 
20.2RESPONSIBILITIES OF INVESTIGATIONAL SITES AND INVESTIGATORS .................................................... 63 
20.3OTHER RESPONSIBILITIES BY OTHER PARTIES CAN BE FOUND IN THE CLINICAL TRIAL AGREEMENT ... 66 
REFERENCES ............................................................................................................................................ 67 
THE INVESTIGATORS STATEMENT ............................................................................................................. 68 
I AGREE: ................................................................................................................................................... 68 
 
Abbreviations table 

 
 
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Abbreviations 
Full name in English 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
AO 
Aortic output 
AST 
Aspartate Aminotransferase 
ATP 
Adenosine Triphosphate 
AUC 
Area Under Curve 
BUN 
Blood Urea Nitrogen 
CAD 
Coronary Artery Disease 
CFDA 
China Food and Drug Administration 
CK 
Creatine Kinase 
CK-MB 
Createine Kinase-MB 
CR 
Creatinine 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
FAS 
Full Analysis Set 
FFR 
Fractional Flow Reserve 
FFRPW 
Fractional Flow Reserve Pressure Wire 
FFRWS 
Fractional Flow Reserve Wire System 
FPR 
False Positive Rate 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICA 
Invasive Coronary Angiography 

 
 
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Abbreviations 
Full name in English 
in. 
inch 
ITD 
Intention To Diagnostic 
kg 
kilogram 
min 
minute 
mm 
millimeter 
mmHg 
millimeter(s) of mercury 
NPV 
Negative Predictive Value 
NYHA 
New York Heart Association 
Pa 
Arterial Pressure 
Pd 
Distal Coronary 
PPV 
Positive Predictive Value 
PLT 
Platelets 
ROC 
Receiver Operating Characteristic 
PPS 
Per Protocol Set 
RBC 
Red Blood Count 
SAE 
Serious Adverse Event 
SAS 
Statistical Analysis System 
SOP 
Standard Operating Procedure 
SS 
Safety Set 
cTNI 
cTroponin I 
cTNT 
cTroponin T 
TPR 
True Positive Rate 

 
 
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Abbreviations 
Full name in English 
ug 
Microgram 
WBC 
White Blood Count 

 
 
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Protocol Summary 
Protoc
ol 
Name 
Pressure guidewire system multi-center, prospective, single-subject 
design clinical trial 
Objecti
ve 
To Evaluate the effectiveness and safety of Zurich Medical's 
pressure guidewire system (including guidewire with high-fidelity 
sensors and a unique paired portable display unit), which is used 
to measure the coronary artery blood fractional flow reserve (FFR) 
to diagnose coronary artery disease, and to direct a catheter 
through a blood vessel. 
Study 
Device 
Names 
Investigational device: 
pressure guidewire system (including wire with high-fidelity 
sensor strains and unique paired portable display 
units) 
Model:100 
Sponsor: Zurich Medical Inc. 
Agent: Shandong Visee Medical Devices Co., Ltd. 
 
Control group device:  
pressure guidewire 
Model: C12008 
Manufacturer: St. Jude Medical, China Agent: St. Jude Medical 
(Shanghai) Co., Ltd. 
Registration license number: 
20143775272 
Analyzer Express 
Model:12711 
Manufacturer: St. Jude Medical, China Agent: St. Jude Medical 
(Shanghai) Co., Ltd. 
Registration license number: 
2013
3211615 
Indicati
on For 
Use 
For patients who need coronary angiographic examination and 
coronary interventional treatment, pressure guidewire system is 
indicated to calculate the patient's blood fractional flow reserve 
(FFR), and to assist the physicians to make clinical decisions.  

 
 
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Trial 
Design 
This clinical trial uses a multi-center, prospective, single-subject 
design trial method, using St. Jude Medical's pressure guidewire 
and Analyzer Express as a control device. The subjects who met 
the criteria for this study will be registered with the central 
registration system after enrollment. The subject’s fractional flow 
reserve of coronary artery stenosis will first be measured using 
investigational device and recorded, and then measured using 
control device and recorded. The safety follow-up period is 48 
hours. 
Numb
er of 
centers 
Trial is expected to be held simultaneously at 5 centers in mainland 
China.  
Sample 
size 
300 
Trial 
duratio
n 
The overall duration of clinical trials includes the time of signing 
of clinical trial site’s agreements with all participating hospitals, 
the time of review and approval of the ethnic committee 
meeting and the post-meeting opinion rectification, filing time, 
the trial kickoff, the enrollment and the subject's FFR 
measurement, the data collection, statistics, summary report 
writing time, etc., and is expected to be 2 years. 
Inclusio
n 
Criteria 
1） Age 18 to 75 years old, gender-unrestricted, non-pregnant 
female; 
2） Understand and be willing to sign an informed consent form; 
3） Diagnosed with coronary heart disease; 
4） Intrusive ICA and FFR measurement are needed; 
5） Visual coronary angiography showed at least one moderate 
stenosis lesion (diameter stenosis of 30% - 70%) on the coronary 
artery with diameter ≥ 2.5mm 
Exclusi
on 
Criteria 
1） Patient who do not understand or are unwilling to sign an 
informed consent form; 
2） Has a history of myocardial infarction; 
3） Patient with other serious diseases are not suitable for 
clinical trials, such as a complex congenital heart disease history, 

 
 
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severe heart failure(NYHA cardiac function level IV), long QT 
syndrome, severe hypertension, Severe asthma, severe chronic 
obstructive pulmonary disease, liver and kidney dysfunction and 
other serious infections and critical illnesses; 
4） Coronary intervention surgery contraindications; 
5） Patient with ATP contraindications (ATP contraindications: 
sinus syndrome, sinus insufficiency and the elderly with cautious 
use or no use); 
6） The clinical manifestations of patients show acute instability, 
including acute chest pain (sudden appearance), cardiogenic 
shock, unstable blood pressure (systolic pressure less than 
90mmHg), severe congestive heart failure or acute pulmonary 
edema; 
7） The angiography shown or suspect of thrombosis; 
8） The angiography shown or suspect of dissection; 
9） Left main coronary artery disease, target blood vessels with 
severe curvature or calcification lesions, total occlusion; 
10）There are any other factors that the investigator considers 
unsuitable for inclusion or completion of this study. 
Primary 
Effectiv
eness 
Endpoi
nt 
Diagnostic consistency rate: When the measurement of control 
device is positive (FFRPW ≤ 0.80) or negative (FFRPW > 0.80), 
investigational device is also positive (FFRWS ≤ 0.80) or negative 
(FFRWS > 0.80). 
Each subject will be considered a research unit (for patients with 
multiple lesions, the method of converting the results of multiple 
lesions into patient level is defined in the statistical analysis plan), 
and the coronary artery FFRPW measured by control device will 
be taken as reference. 
Second
ary 
Effectiv
1) The sensitivity and specificity of the investigational device 
used to diagnose coronary heart disease: Taking the subject 
as the research unit, the sensitivity and specificity of 

 
 
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eness 
Endpoi
nt 
investigational device for diagnosis of coronary heart disease 
will be calculated. FFRPW of coronary artery measured by 
control device will be used as the reference and FFRPW ≤ 
0.80 as positive threshold  
2) Positive predictive value, negative predictive value and area 
under working characteristic curve: Taking subjects as 
research units, FFRPW measured by Control Device as 
reference, and FFRPW < 0.80 as positive threshold, the positive 
predictive value, negative predictive value and area under 
ROC curve (AUC) of investigational device for diagnosis of 
coronary heart disease will be calculated. 
3) Passing-Bablok Regression Analysis: Taking the blood vessel as 
the research unit, Passing-Bablok regression analysis will be 
used to analyze the FFRWS value of coronary artery measured 
by the investigational device and the FFRPW value of coronary 
artery measured by the control device. 
4) Bland-Altman Deviation Analysis: Taking the blood vessel as 
the research unit, Bland-Altman deviation analysis will be 
used to analyze the FFRWS value of coronary artery measured 
by the investigational device and the FFRPW value of coronary 
artery measured by the control device. 
5) Pearson linear correlation analysis: Taking the blood vessel as 
the research unit, Pearson linear correlation analysis will be 
used to analyze the FFRWS value of coronary artery measured 
by the investigational device and the FFRPW value of coronary 
artery measured by the control device. 
6) Device success rate: Taking the blood vessel as the research 
unit, Effective FFRWS and FFRPW readings will be used as the 
criteria to judge the success rate of the devices, and the 
success rate of the investigational device and the control 
device will be compared. 
Safety 
The occurrence of adverse events and device defects will be 

 
 
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Endpoi
nt 
used as a safety evaluation index. 
 

 
 
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1 
SPONSOR INFORMATION 
1.1 
Name Of The Sponsor 
Zurich Medical Inc. 
1.2 
The Address Of The Sponsor 
2405 Xenium Lane N, Plymouth, MN 55441 USA 
1.3 
Sponsor’s Contact Information 
Phone:001-651-571-0020 
 
Email:info@zurichmed.com 
1.4 
Agent's Name, Address, Contact Details and Related Qualification 
Documents 
Agent Name: Shandong Visee Medical Devices Co., Ltd. 
Address: 10 Junshan Road, Chucun Town, Torch High-Tech Industrial 
Development Zone in Weihai City, Shandong Province 
Contact: Tel: 0631-5716452 Fax: 0631-5621156 
2 
LIST OF ALL INVESTIGATIONAL SITES AND INVESTIGATORS FOR MULTI-CENTER 
CLINICAL TRIALS: 
Investigational Site 
Code 
Name of investigational site 
Investigators 
01 
Fudan University Zhongshan Hospital 
Ge Junbo 
02 
The First Hospital of Lanzhou University 
Zhang Zheng 
03 
The First Affiliated Hospital of XiAn 
Jiaotong University 
Yuan Zuyi 
04 
The People’s Hospital of Liaoning 
Province 
Li Zhanquan 

 
 
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05 
Remin Hospital of Wuhan University 
People's Hospital 
Jiang Xuejun 
 
3 
OBJECTIVE AND CONTENT OF CLINICAL TRIAL 
3.1 Objective 
To Evaluate the effectiveness and safety of Zurich Medical's pressure guidewire system 
(including guidewire with high-fidelity sensors and a unique paired portable display unit), 
which is used to measure the coronary artery blood fractional flow reserve (FFR) to 
diagnose coronary heart disease, and  to direct a catheter through a blood vessel. 
Including: 
Effectiveness: Coronary artery Fractional Flow Reserve(FFR) measured by control 
device, St. Jude Medical’s Pressure Guidewire and Analyzer Express (FFRPW) will be used as 
a reference to evaluate FFR measured by Investigational device, the Zurich Medical 
pressure guidewire system (including wire with high-fidelity sensor strains and unique 
paired portable display units) (FFRws)’s efficacy to diagnose coronary artery disease via 
diagnostic consistency, sensitivity, specificity, positive predictive value, negative predictive 
value, and Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC). 
Meanwhile, Passing-Bablok regression analysis, Bland-Altman deviation analysis and 
Pearson correlation analysis of the FFRpw and FFRws will be used to evaluate the success 
rate of the investigational device. 
Safety: The adverse events and device defects that occur during Zurich Medical's 
pressure guidewire system measurement of coronary arterial FFRws will be mainly 
evaluated. 
3.2 Content 
This clinical trial is designed as a multi-center, prospective, single-subject design trial. The 
investigational device is Zurich Medical Pressure Guidewire System (including wire with 
high-fidelity sensor strains and unique paired portable display units) and the control device 
is St. Jude Medical’s FFR measuring device, Pressure Guidewire and Analyzer Express. The 
subjects who met the criteria for this study will be registered by login to the central 
registration system after enrollment, and the investigational device will first be used to 

 
 
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measure the fractional flow reserve of coronary stenosis lesions, and then the 
measurement of the same lesions by using the control device will be recorded, and 
followed with a 48hr post operation follow-up. Control device’s FFR (FFRpw) will be used 
as a reference to statistically analyze Investigational device’s diagnostic accuracy, sensitivity, 
specificity, positive predictive values, negative predictive values, and the Area Under the 
Curve (AUC) of Receiver Operating Characteristic (ROC). FFRws and FFRpw will be used to 
analyze the consistency, also Passing-Bablok regression analysis, Bland-Altman deviation 
analysis, and Pearson correlation analysis of the FFRpw and FFRws will be used to evaluate 
the success rate of the device. Through above analysis, the effectiveness of diagnosis 
coronary artery disease by using Zurich Medical’s pressure guidewire system to measure 
fractional flow reserve (FFR) can be verified. The adverse event and device defect during 
the measurement can also be recorded. 
4 
BACKGROUND INFORMATION 
Coronary Artery Disease (CAD) is a type of coronary aortic-like plaque formation, 
vascular cavity stenosis as a pathological basis, a disease that causes clinical symptoms due 
to the imbalance of myocardial ischemia and oxygen supply in the corresponding 
coronary artery supply area. In the past, coronary artery angiography (Invasive Coronary 
Angiography, ICA) was considered the "gold standard" for the diagnosis of coronary heart 
disease. However, it can only make a morphological subjective evaluation of the coronary 
artery and cannot carry out functional evaluation. Dr. Pijls and others in 1993 put forward 
that functional indicator of stenosis through the fractional flow reserve (FFR) for the 
evaluation of vascular stenosis, to some extent, make up for the deficiency of coronary 
artery angiography. When there is a stenosis lesion in the coronary arteries, the ratio of the 
maximum blood flow to the corresponding heart muscle area range of blood supplied by 
the target arteries measured by pressure guide is obtained by FFR. In a normal coronary 
physiological state, the FFR value is1.0, which is not affected by changes in hemodynamic 
parameters such as heart rate, blood pressure, and myocardial systolic rate.  
Subsequently, Dr. Pijls, among others, conducted FFR measurements on 45patients to 
assess the severity of coronary stenosis leading to myocardial ischemia, use FFR<0.75 as a 
positive threshold, the results show FFR for diagnosing coronary artery reversibility ischemia 
has 88% Sensitivity, 100%specificity and 93% accuracy. From early DFFER study to later 
international multicenter large-sample-size FAME study, FAMEII study, and through long-
term clinical practice and research, several studies show that FFR measurements can 
accurately evaluate coronary ischemic lesions, selectively intervene positively with 
myocardial ischemic-related lesions, improve patient prognosis, reduce the incidence of 

 
 
21 
 
major cardiovascular events. In 2014, Clinical guidelines for myocardial blood 
reconstructive published by the European Society of Cardiology categorized FFR as IA 
class，highest recommendation level for when ischemic-related blood vessels are not 
clear. In 2016, Chinese guidelines for the intervention treatment of coronary arteries 
suggest for patients with stable coronary heart disease with no evidence of ischemia and 
with angiography show of stenosis of 50% -90% lesion perform FFR assessment. The 
suggestion comes with IA class, the highest level of the class.  
Current FFR device for intravascular measurements has multiple independent 
components and bulky monitors, and there has been a need to improve. The high cost of 
the capital equipment and associated high maintenance costs hinder the spread and 
adaptation of FFR technology, which is not conducive to the selection and effective 
evaluation of PCI surgical treatment, and thus to the effective conservation of medical 
resources and the reduction of national health insurance expenditure.  
Zurich Medical invented the device for intravascular measurements in 2013, which is the 
device and method for intravascular diagnostics. The device comprises a pressure 
guidewire and a display unit. The pressure guidewire consists of a core wire and a sensor 
arranged in the distal end of the core wire. The display unit includes a processor and 
display screen and can receive communication signals from the pressure guidewire. The 
display unit is configured to use the processor to perform the calculation based on the 
communication signal received from the pressure guidewire and is configured to display 
information on the display screen based on the calculation. The display unit can be 
configured to be disposed of after a predetermined number of uses or after a 
predetermined period of use. Based on the above invention, the "pressure guidewire 
system" of medical device devices consists of a self-contained sensor guidewire and a 
portable processor display unit for measuring the physiological parameters of the coronary 
artery and peripheral blood vessels and the heart, and can also direct the catheter through 
the blood vessels.  
Zurich Medical's Pressure Guidewire System, which cleverly combines pressure 
guidewire and processor display unit, uses high-tech sensors to accurately measure blood 
pressure and offers a variety of options for one or more measurements. Through high-
precision low drift pressure detection algorithm, non-electro cardioid heartbeat pressure 
sensing algorithm and low false positive heartbeat detection filtering algorithm, the blood 
fractional flow reserve is calculated, and the intuitive display is made in a timely and 
accurate manner through self-contained portable display unit, which is convenient for 
doctors to use, easy to operate and with high accuracy. Because there is no need to use 
any external equipment, ensuring safety and effectiveness at the same time, greatly reduce 
the cost of surgery, reduce the financial burden of patients, is beneficial for the adaptation 
of FFR technology at all levels of hospitals, and more conducive to the national health 
insurance system to save resources.  

 
 
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5 
PRODUCT FEATURES, STRUCTURAL COMPOSITION, WORKING PRINCIPLE, 
FUNCTIONAL MECHANISM AND TRIAL SCOPE 
5.1 Product Features 
The product is a pressure wire system with self-contained sensor guide and portable 
processor display unit, it can complete blood pressure measurement without the need for 
any external device and able to operate independently. The fractional flow reserve (FFR) is 
calculated through an innovative software design that includes precise algorithms, real-time 
display of results, greatly facilitate the doctor's operation in the process. Self-contained all-in-
one product, small size, easy to operate, no need to buy any external equipment. The 
product offers two pressure measurement methods, including the AO method and the 1-
sensor method, which allows doctors to use different pressure measurement methods to 
ensure the smooth operation and patient safety according to the actual situation of the 
patient and the operation.  
5.2 
Product Structural Composition, Working principle, Functional Mechanism 
5.2.1 Structural Composition 
The Pressure Guidewire System Model 100 consists of a 0.014” (0.36 mm) diameter, 
180 cm long Guidewire with a high-fidelity sensor located immediately beyond the 3 
cm shapeable radiopaque tip and a uniquely paired Portable Display (Figure 1). The 
signals from the sensor can be used to measure blood pressures and estimations of 
Fractional Flow Reserve (FFR). The Guidewire is connected to the Portable Display via 
the Handle. The distal end has hydrophilic coating. The Portable Display also has an AO 
cable that may be used to connect to the Zurich Medical Accessory Cable for AO 
pressure signal. 
 
Figure 1: Pressure guidewire system 

 
 
23 
 
5.2.2 Working Principle and Functional Mechanism 
Fractional Flow Reserve (FFR) based on the principle of anatomy and functional 
regulation of coronary artery circulation defined as the ratio of the maximum blood flow 
to the myocardium of the epicardial stenosis coronary artery and the maximum blood 
flow to the myocardium when the same coronary artery is healthy. It’s equivalent to the 
average pressure of the distal-end of stenosis during a hyperemia state (Pd) and the 
average aortic pressure during hyperemia state (Pa) (Figure2).  Clinically using vessel 
dilator to induce hyperemia in myocardium, can reduce cardiac microcirculation 
resistance small enough and become negligible and constant, at this time the 
myocardial blood flow is only affected by perfusion pressure, so that the reduction of 
perfusion pressure in the hyperemia state can be equivalent to the degree of 
narrowness as the heart muscle blood flow is reduced.  
 
 
 
 
Figure 2: The basic principles of calculating fractional flow reserve (FFR)  
The product can measure FFR using the conventional AO method, as shown in 
Figure3.  
FFR: Fractional Flow Reserve 
Assess whether stenosis causes myocardial ischemia 
The gold standard for clinical assessment whether the stent 
implantation is necessary 
FFR = Pd / Pa (during hyperemia ) 
FFR>0.8  
 
No interventional treatment required 
0.75 < FFR ≤ 0.8  
Doctor's assessment 
FFR ≤ 0.75   
Interventional treatment (implant stent) 

 
 
24 
 
 
Figure 3: AO Method Real-Time Data Screen 
In addition to being able to measure FFR using the above conventional AO 
method, the pressure guidewire system also provides an innovative1-sensor method for 
FFR measurement, i.e. measuring at different parts of the vessel using the same sensor. 
Using the same sensor to measure in different parts of the blood vessel, is more 
accurate and reduce the error that can be generated by using two sensors. FFR value is 
automatically calculated and displayed by the precise algorithm provided by the 
portable display unit in real time. The innovative1-sensor measurement as shown in 
Figure 4: 
 
导丝-手柄连接状
态 
电池状态  
实时FFR 
实时导丝平均压力 
 动作状态 
图表刻度 
导丝压力信号
号轨迹（黄） 
保存的近端平
均压力（红） 

 
 
25 
 
Figure 4:1-Sensor Method Real-Time Data Screen 
5.3 
Trial Scope 
The pressure guidewire system is used to measure coronary blood pressure during 
diagnostic angiography and/or interventional procedure. The FFR value is automatically 
calculated by an accurate algorithm provided by the portable display unit in real time to 
support assessment of ischemic conditions in myocardial lesions.  
6 
PRODUCT'S INDICATION FOR USE AND CONTRAINDICATIONS, WARNING 
6.1 
Indication for use 
For patients who need coronary angiographic examination and coronary 
interventional treatment, pressure guidewire system is indicated to calculate the patient's 
fractional flow reserve (FFR), and to assist the physicians to make clinical decisions.  
6.2 
Contraindications 
The Pressure Guidewire System is contraindicated for use in the cerebral vasculature. 
6.3 
Warning 
1) Pressure Guidewire System is intended for single use only. 
2) Do not resterilize or reuse. 
3) Do not use if the original sterile package is not intact. 
4) Inspect the system carefully prior to use to verify that all parts are present and 
undamaged. 
5) Reuse after cleaning attempts, resterilization and repackaging may result in 
patient/user infections and compromised product functionality, such as inaccurate 
pressure signals and inaccurate torque response thereby exposing the patient to 
increased risks for complications/adverse events. 
6) Prior to use and when possible during the procedure, inspect Guidewire carefully 
for bends, kinks or other damage. Do not readjust any bend or kink as 
readjustments may damage the electrical wiring inside the Guidewire. 
7) Guidewire must not be used if it has been damaged in anyway; otherwise, 
vessel/ventricle damage and/or inaccurate pressure signals or inaccurate torque 
response may occur. 
8) When introducing Guidewire in a diagnostic case, flush the catheter and 

 
 
26 
 
administer an anticoagulant based on standard of care for catheterization 
procedure or clotting may occur. 
9) When the Guidewire is exposed to the vascular system, it should be manipulated 
while under high-quality fluoroscopic observation. If resistance is met during 
manipulation, determine the cause of the resistance before proceeding. 
10) Do not torque Guidewire without observing corresponding movement of the tip; 
otherwise vessel/ventricle trauma may occur. 
11) Always advance or withdraw Guidewire slowly. Never push, withdraw or torque 
Guidewire if it meets resistance. 
12) Positioning of catheters and guidewires in the ventricles is potentially 
arrhythmogenic. It should never be done without ECG monitoring and the 
presence of a functioning defibrillator. 
13) Avoid using Guidewire in the ventricles if the patient has a prosthetic mechanical 
valve. Zurich Pressure Guidewire System may become trapped and disrupt the 
function of the valve, leading to serious injury or death. 
14) Do not use it in the electrosurgical environment when high-frequency surgical 
equipment is used at the same time. 
7 Overall Design 
7.1 Trial Design 
This study is multi-center, prospective, single-subject design clinical trial.  Subjects 
that signed Informed Consent form (ICF) which was approved by the Ethics Committee 
(EC) will enter selection process. Subjects that meet all inclusion criteria and do not meet 
any of the exclusion criteria, are considered eligible to enroll in the clinical trial.  
Coronary angiography is performed on subjects. The investigators combine 
angiographic images and subject’s inclusion/exclusion criteria to confirm if the subject 
meets the trial requirements. The subjects who met the criteria for this study will be 
registered by login to the central registration system after enrollment, and the 
investigational device will first be used to measure the fractional flow reserve of 
coronary stenosis lesions, and then the measurement of the same lesions by using the 
control device will be recorded, and followed with a 48hr post operation follow-up. The 
investigational device measure FFR using the innovative 1-sensor method according to 
the product Instructions for Use (IFU), and the control device measure FFR through the 
conventional AO method according to the product Instructions for Use (IFU). 
7.1.1 Trial Objective 

 
 
27 
 
To Evaluate the effectiveness and safety of Zurich Medical's pressure guidewire 
system (including guidewire with high-fidelity sensors and a unique paired portable 
display unit), which is used to measure the coronary artery blood fractional flow reserve 
(FFR) to diagnose coronary heart disease, and the effectiveness and safety of  to direct a 
catheter through a blood vessel. Including: 
Effectiveness: Coronary artery Fractional Flow Reserve(FFR) measured by control 
device, St. Jude Medical’s Pressure Guidewire and Analyzer Express (FFRpw) will be used 
as a reference to evaluate FFR measured by Investigational device, the Zurich Medical 
pressure guidewire system (including wire with high-fidelity sensor strains and unique 
paired portable display units) (FFRws)’s efficacy to diagnose coronary artery disease via 
diagnostic consistency, sensitivity, specificity, positive predictive values, negative predictive 
value, and Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC). 
Meanwhile, Passing-Bablok regression analysis, Bland-Altman deviation analysis and 
Pearson correlation analysis of the FFRpw and FFRws will be used to evaluate the success 
rate of the investigational device. 
Safety: The adverse events and device defects that occur during Zurich Medical's 
pressure guidewire system measurement of coronary arterial FFRws will be mainly 
evaluated. 
7.1.2 Selection of Trial Method and Justification 
The nature of this clinical study is medical device registration clinical validation.  
Therefore, it is necessary to comply with the relevant regulations such as the “Provisions 
for Medical Device Registration” and the “Quality Management Practice for Clinical Trials 
of Medical Devices” promulgated by the CFDA.  
7.1.2.1 Reason for selection of the control group 
After searching the China Food and Drug Administration (CFDA) medical device 
database, St. Jude Medical's Pressure Guidewire and Analyzer Express are listed as CFDA 
approved products. The selection of the control device for this trial is based on the 
following: 
(1) The basic principle and the indication for use of the control device are the same 
as those of the investigational device; 
(2) The control device has been on the market in China and has a wide clinical use, 
with good clinical effectiveness and safety. 
7.1.2.2 Reasons for the selection of the trial population 
 
According to the investigational device’s indication for use, the trial population 
selected in this clinical trial is to perform coronary angiography to determine the 

 
 
28 
 
degree of stenosis. Such trial population satisfies the relevant range of indication for 
use and is representative. 
7.1.2.3 Reason for the selection of the endpoints 
The primary effectiveness endpoint is the diagnostic consistency of FFRWS, for 
diagnosis of coronary heart disease measured by Zurich Medical’s Pressure Guidewire 
System. 
7.1.3 Measures to Lessen and Prevent Bias 
This clinical trial will use the following methods to lessen bias in trials. 
Multi-center: Case samples from multiple centers are more representative than 
single centers, preventing systemic errors in a single center from biasing the trial results, 
and obtained conclusions are more credible. To reduce the operational differences 
between the investigational sites, investigators should be trained by uniform standard, 
and clear evaluation criteria should be adopted for the effectiveness indicators and 
safety indicators. 
Control: This study is a single-subject design clinical trial. Subjects use 
investigational device then control device to complete FFR measurements, preventing 
factors that may affect efficacy judgment. 
Investigator Training: Before the clinical trial begins, the auditor and the head of 
investigational site will provide training for investigators, so investigators will gain 
understanding and become familiar with the investigational device. Investigators 
should also have grasp on all new findings during the clinical trial that’s related to the 
investigational device. 
Clinical Trial Monitoring: Develop inspection plan. Sponsor appoints auditors to 
conduct regular on-site audit of investigational sites, ensure that all content of the 
research program is strictly observed, and the original data is checked for consistency 
with the contents on the EDC. 
7.1.4 Investigational Medical Devices and Controlled Medical Devices / 
Control Methods 
The ICA examination performed by qualified interventional cardiologist. After the 
informed consent form is signed, coronary angiography will be taken from different 
positions via standard operating procedures. After enrollment, and registration in the 
central registration system, investigator will first use investigational device to perform FFR 
measurement, then use control device to remeasure FFR of the same vessel. The interval 
between two measurements should be greater than 3 minutes. The pressure guidewire 

 
 
29 
 
and catheter should be flushed with saline. Nitroglycerin to be used to eliminate 
coronary artery spasm, and ATP are to be infused through the central vein (intermediate 
elbow or femoral vein) at 140-180 μg·kg-1·min-1 to place the coronary vessels in 
hyperemia state. FFR measurements should be performed by qualified, experienced, 
and trained physicians, primarily focus on stenosis that shows moderately stenotic 
lesions (diameter stenosis 30% - 70%) in vessels that’s ≥ 2.5 mm in diameter. The FFR 
results from the investigational device and the control device are not be used as a 
reference basis for further stent therapy. See operational instruction below: 
DIRECTIONS TO USE ZURICH PRESSURE GUIDEWIRE SYSTEM 1-SENSOR METHOD TO 
TAKE MEASUREMENTS: 
1
 Open the package using sterile techniques 
2
 Fill the coil with saline solution, using the flush port 
3
 Soak Guidewire in saline until calibration is complete 
4
 Gently detach the portable display unit from the tray 
5
 Carefully wipe and dry the proximal end of Guidewire and insert into Handle (see Figure 1 
for proximal end location of Guidewire) 
6
 Open the portable display unit by lifting the screen. This turns on the portable display unit 
 
7
 Verify the Guidewire -handle connection status icon is 
displayed in the upper left 
corner to confirm the correct connection 
 
8
 Ensure the tray containing the Guidewire is at the same height as the patient´s heart 
9
 Press the button 
 once for calibrating the system to zero atmospheric pressure (the 
 

 
 
30 
 
button is on the back of the screen).  
 will be displayed in the action state box at 
bottom center of the display 
 
 
 
10
Carefully remove the Guidewire from the package coil 
WARNING: Guidewire is a delicate instrument and should be handled carefully. Bending 
or excessive force during removal from packaging tray may damage the guidewire.  
CAUTION: 
If recalibration is necessary during the case, remove Guidewire from the body 
and follow the RESET procedure after step 20.  
NOTE: After calibration, the Guidewire may be disconnected from the Portable Display for 
ease of advancement. 
11
Engage the guiding catheter using standard practice and flush the catheter with sterile 
saline solution 
WARNING:  When introducing the Guidewire, confirm that the catheter tip is free within 
the vessel lumen and is not touching the vessel wall. Failure to do so may result in vessel 
trauma upon Guidewire exit of the catheter. Use the radiopaque marker of the catheter 
to confirm position. 
12
Carefully insert the distal tip of the guidewire into the hemostatic valve of the Y connector. 
Advance Guidewire out of the guiding catheter and steer Guidewire to a location just 
proximal to the lesion of interest 
13
Pull back the insertion tool out of the hemostatic valve and tighten the hemostatic valve 
14
If the Guidewire has been detached from the Portable Display, carefully wipe and dry the 
proximal end and reconnect it now with the Handle. Verify the connection by checking for 
 in the upper left corner of the display 
15
If estimating FFR, induce maximum hyperemia using standard clinical practice 
CAUTION: Failure to achieve maximum coronary and myocardial hyperemia may result in 
invalid FFR. 
16
Save the pressure proximal to the lesion of interest by pressing and holding the BUTTON 
 until 
 is displayed in the action status box. At this point RELEASE the BUTTON 
   
17
Advance Guidewire across the lesion and perform pressure measurement 

 
 
31 
 
WARNING: Observe all Guidewire movements. Whenever Guidewire is moved or torqued, 
the tip movement should be examined under fluoroscopy. 
WARNING: Torque Guidewire against resistance or repeated attempts to cross a total 
vessel occlusion may cause damage and/or fracture, which may lead to a portion of 
Guidewire separating from the tip. 
CAUTION: Do not measure pressure when the sensor element of Guidewire is in sharp 
curves, since this might result in pressure artifacts. 
NOTE: When a position of interest is difficult to reach, Guidewire may be disconnected 
from the Portable Display for easier use. Carefully wipe and then dry the male 
connector before reconnecting to Handle. 
 
 
Diagram 3: Live Data Screen 1-Sensor Method 
18
Double-click the BUTTON 
 to begin recording an episode. 
 will display in the 
action status box; 
19
Press the 
 BUTTON again to once to end recording an episode. The data review screen 
of the episode will appear on the display. The two lowest FFR values will be displayed 

 
 
32 
 
 
20
Press the BUTTON 
 again once to return to live data screen; 
WARNING: Excessive manipulation when sensor element or tip of Guidewire is located in 
sharp bend may cause damage or tip fracture. If the guiding catheter is in an anatomically 
severe or sharp bend, for example a tortuous subclavian artery or adjacent vessel position, 
the junction between the shaft and the flexible distal section of the wire, 31 cm from the 
tip, may be vulnerable to kinking or fracture. 
DIRECTIONS TO RESET 
NOTE: If for any reason, the Portable Display needs to be reset and returned to out-of-
the-box settings, do the following  
1. Press and hold the BUTTON 
 for more than 5 seconds until the RESET screen 
appears 
 
2. Press the BUTTON 
 again to confirm reset to out of the box settings 
3. If an inadvertent BUTTON 
 press for more than 5 seconds occurs, wait until the 
countdown clock reaches 0 and the portable display will return to the screen before 
the reset mode is activated 
WARNING: Recalibration is required following RESET. Remove Guidewire from the body 
and follow the instructions above to calibrate. 
  
Use St. Jude Medical 's Fractional Flow Reserve (FFR) Measuring Device to Measure FFR: 
1
 Connect the power cord, connect the aortic pressure input cable, and turn on the 
Analyzer Express 
2
 Select or create a new patient 
3
 Engage the guiding catheter in accordance with standard procedures and flush the 

 
 
33 
 
guiding catheter 
4
 Place the AO sensor at the same height as the patient's heart, connect the pressure 
sensor to the air (through the atmosphere), and zero the aortic pressure; 
5
 Open the pressure guide wire package and leave the pressure guide wire in the tray 
6
 Fill the packaging coil with heparin saline through the innermost rinse port of the 
packaging coil 
7
 Connect the pressure guidewire to the Analyzer Express, and zero the pressure 
guidewire 
8
 Gently remove the pressure guidewire from the packaging coil 
9
 Insert the pressure guidewire into the guiding catheter and advance the pressure 
guidewire until the pressure sensor just outside of the guiding catheter 
10
 Equalize the Pd and Pa values 
11
 Push the pressure guidewire to the distal end of the lesion and record the vessel and 
position 
12
 Record the resting Pd/Pa through the pressure guidewire 
13
 Use standard catheter laboratory procedures for administer nitroglycerin, then 
adenosine from the vein to achieve hyperemia 
14
 Record the FFR value through pressure guidewire 
15
 Retract the pressure guidewire until the sensor just outside of the guiding catheter, the 
pressure wire position is similar to the position during the equalization of Pa and Pd 
earlier, and verify that the difference between the aortic mean pressure (Pa) and the 
pressure guidewire reading of mean pressure (Pd) is within ±3 mmHg. ; 
16
 Repeat the step 6 -- 11 to measure other lesions 
17
 Remove the pressure guidewire from the body 
7.1.5 Subject Selection (including control group selection if necessary) 
(1) Inclusion Criteria 
Patients must meet all the following inclusion criteria to qualify for enrollment: 
1
 Age 18 to 75 years old, gender-unrestricted, non-pregnant female; 
2
 Understand and be willing to sign an informed consent form; 
3
 Diagnosed with coronary heart disease; 

 
 
34 
 
4
 Intrusive ICA and FFR measurement are needed; 
5
 Visual coronary angiography showed at least one moderate stenosis lesion (diameter 
stenosis of 30% - 70%) on the coronary artery with diameter ≥ 2.5mm 
(2) Exclusion Criteria 
Patients meet any of the following criteria is not qualified for enrollment: 
1
 Patient who do not understand or are unwilling to sign an informed consent 
form; 
2
 Has a history of myocardial infarction; 
3
 Patient with other serious diseases are not suitable for clinical trials, such as a 
complex congenital heart disease history, severe heart failure(NYHA cardiac 
function level IV), long QT syndrome, severe hypertension, Severe asthma, 
severe chronic obstructive pulmonary disease, liver and kidney dysfunction and 
other serious infections and critical illnesses; 
4
 Coronary intervention surgery contraindications; 
5
 Patient with ATP contraindications (ATP contraindications: sinus syndrome, sinus 
insufficiency and the elderly with cautious use or no use); 
6
 The clinical manifestations of patients show acute instability, including acute 
chest pain (sudden appearance), cardiogenic shock, unstable blood pressure 
(systolic pressure less than 90mmHg), severe congestive heart failure or acute 
pulmonary edema; 
7
 The angiography shown or suspect of thrombosis; 
8
 The angiography shown or suspect of dissection; 
9
 Left main coronary artery disease, target blood vessels with severe curvature or 
calcification lesions, total occlusion; 
10
 There are any other factors that the investigator considers unsuitable for 
inclusion or completion of this study. 
(3) Standards and procedures for terminating trial / trial treatment 
Subject may withdraw from the trial at any time during the trial without any reason; and 
after signing of the informed consent form, subject can still choice not to participate in any trial 
procedures (by doing so it’s equivalent to withdraw the consent). If after signing the informed 
consent form, the subject chooses not to participate in the trial, investigator must be informed. 
But no matter what happens, the subject has the right to continue to receive other standard 
treatments. 

 
 
35 
 
 
The investigators can also withdraw subjects from the trial based on medical 
judgment at any time. 
1) Criteria for the subject to be withdrawn from the trial: 
The subject meets any of the following and trail stops: 
➢ 
The subject withdrew his/her informed consent 
➢ 
The investigator believes that there are any safety reasons (adverse events or 
serious adverse events) 
➢ 
The investigators believe that subject has poor compliance with trial protocol 
2) Criteria for terminating the trial: 
➢ 
Sponsor requests to terminate the trial 
➢ 
The regulator or the relevant department of the administration requests the 
termination of the trial 
➢ 
For the purpose of protecting subject rights and interests, the investigators 
believe that the subject should terminate the trial 
➢ 
Subject death 
3) Elimination Criteria: 
➢ 
After enrollment, subject found to not meet the inclusion criteria, or meet 
exclusion criteria 
➢ 
Serious breach of protocol (confirmed by the principal investigator). 
(4) Enrollment Time 
Before the selection, subject’s consent and signed informed consent form required 
1) 
Subject’s general information, past medical and disease history, examination of 
combined drug use 
2) 
Physical examination, vital signs, clinical diagnosis 
3) After coronary angiography, the investigators combined with angiographic images 
and subject inclusion/exclusion criteria to determine whether to use the control 
device and the investigational device to determine identified lesion’s FFR, if the 

 
 
36 
 
inclusion criteria are met, and no exclusion criteria are met, subject will then be 
selected for the trail and the time will be recorded for enrollment. 
(5) The Expected Overall Duration of Clinical Trial and Rational 
The overall duration of clinical trial, including the time of signing clinical trial agreement in all 
trial hospitals, ethical committee approval and post-conference rectification, filing time, trial 
initiation, patient enrollment, and FFR procedure time, collection, statistics, and summary of trial 
data, report creation time, etc., is expected to be 2 years. 
(6) The expected duration of each subject's participation 
Considering that the time of enrollment and the operation time are the same 
day, the subjects are required to complete the informed consent form signing, vital 
signs, physical examination, medical history investigation, and clinical diagnosis 
within one week before enrollment. Each trial subject's participation time is set at the 
end of the visit from the time the subject signs an informed consent form, and the 
expected duration of each subject's participation is no more than 9 days, based on the 
number of visits set by the clinical trial program.  
(7) Number of subjects required for clinical trials 
A total of 300 subjects are planned for this trial. Through the results of 
angiographic images and inclusion/exclusion criteria, investigator will confirm if the 
subject met the trial requirements and those meets all the qualifications will be 
enrolled. After enrollment and logged into the central registration system, subject’s 
FFR measurements were performed using a control device after the investigational 
device to assess the Fractional Flow Reserve of the coronary artery stenosis 
7.1.6 Effectiveness evaluation methods 
7.1.6.1 Description of effectiveness parameters 
(1) Primary effectiveness endpoint: 
Diagnostic consistency rate in the diagnosis of coronary heart disease with investigational 
device and control devices: Each subject will be considered as a research unit (for patients 
with multiple lesions, the method of converting the results of multiple lesions into patient 
level is defined in the statistical analysis plan), and the coronary artery FFRPW measured by 
control device will be taken as reference, when the measurement of control device is 

 
 
37 
 
positive (FFRPW ≤ 0.80) or negative (FFRPW > 0.80), the investigational device is also positive 
or negative. 
(2) Secondary effectiveness endpoint 
➢ 
The sensitivity and specificity of the investigational device used to diagnose coronary 
heart disease: Taking the subject as the research unit, the sensitivity and specificity of 
investigational device for diagnosis of coronary heart disease will be calculated. 
FFRPW of coronary artery measured by control device will be used as the reference 
and FFRPW ≤ 0.80 as positive threshold.  
➢ 
Positive predictive value, negative predictive value and area under working 
characteristic curve: Taking subjects as research units, FFRPW measured by control 
device as reference, and FFRPW < 0.80 as positive threshold, the positive predictive 
value, negative predictive value and area under ROC curve (AUC) of investigational 
device for diagnosis of coronary heart disease will be calculated.  
➢ 
Passing-Bablok Regression Analysis: Taking the blood vessel as the research unit, 
Passing-Bablok regression analysis will be used to analyze the FFRWS value of 
coronary artery measured by the investigational device and the FFRPW value of 
coronary artery measured by the control device. 
➢ 
Bland-Altman Deviation Analysis: Taking the blood vessel as the research unit, Bland-
Altman deviation analysis will be used to analyze the FFRWS value of coronary artery 
measured by the investigational device and the FFRPW value of coronary artery 
measured by the control device. 
➢ 
Pearson linear correlation analysis: Taking the blood vessel as the research unit, 
Pearson linear correlation analysis will be used to analyze the FFRWS value of coronary 
artery measured by the investigational device and the FFRPW value of coronary artery 
measured by the control device.  
➢ 
Device success rate: Taking the blood vessel as the research unit, effective FFRWS and 
FFRPW readings will be used as the criteria to judge the success rate of the devices, 
and the success rate of the investigational device and the control device will be 
compared.  
7.1.6.2 Methods and time selection for evaluating, documenting and analyzing 
effectiveness parameters 
(1) Primary effectiveness endpoint: the consistency rate in the diagnosis of coronary heart 
disease with investigational device and control device.  
At Visit 2(FFR-ICA examination), record coronary artery FFRWS measured by 
investigational device and coronary artery FFRPW measured by control device. After all 
subjects completed the Visit 2, taking the subject as the research unit, the consistency 

 
 
38 
 
rate of investigational device for diagnosis of coronary heart disease will be calculated 
based on FFRWS measured by investigational device. FFRPW of coronary artery measured 
by control device will be used as the reference and FFRPW ≤ 0.80 as positive threshold.  
Diagnostic consistency rate = (true positive + true negative) / (positive + negative); 
Positive and negative respectively correspond to the results of the control device assay 
(positive when FFRPW≤0.80, negative when FFRPW>0.80), true positive refers to that 
when investigational device is also positive at the same time as control device is positive 
(FFRPW≤0.80 and FFRWS≤0.80, true negative refers to that when control device is 
negative and investigational device is also negative (FFRPW>0.80 and FFRWS>0.80).  
(2) Secondary effectiveness endpoint: 
➢ Sensitivity and specificity of investigational device in the diagnosis of coronary heart 
disease: 
At Visit 2(FFR-ICA examination), record the coronary artery FFRWS measured by 
investigational device and the coronary artery FFRPW measured by control device. After 
all subjects completed the visit 2, taking the subject as the research unit, the sensitivity 
and specificity of investigational device for diagnosis of coronary heart disease will be 
calculated based on FFRWS measured by investigational device. FFRPW of coronary artery 
measured by control device will be used as the reference and FFRPW ≤ 0.80 as positive 
threshold.  
Sensitivity = True Positive / Positive; 
Specificity = True Negative / Negative; 
➢ Positive predictive value, negative predictive value and area under the working 
characteristic curve in the diagnosis of coronary heart disease with investigational device: 
At Visit 2(FFR-ICA examination), record the coronary artery FFRWS measured by 
investigational device and the coronary artery FFRPW measured by control device. 
After all subjects completed the Visit 2, taking the subject as the research unit, the 
positive predictive value, negative predictive value and area under the working 
characteristic curve of investigational device for diagnosis of coronary heart disease 
will be calculated based on FFRWS measured by investigational device. FFRPW of 
coronary artery measured by control device will be used as the reference and FFRPW ≤ 
0.80 as positive threshold.  
Positive predictive value (PPV) = true positive / (true positive + false positive); 
Negative predictive value (NPV) = true negative / (true negative + false negative); 
ROC curve drawing and AUC calculation: In a two-dimensional coordinate map, set 
the horizontal x-axis to false positive rate (False Positive Rate, FPR), vertical y-axis is set to 
true positive (True Positive Rate, TPR). The FFRWS measured by the investigational 

 
 
39 
 
device can be obtained from a TPR and FPR based on its performance on the test 
sample, adjust the diagnostic threshold for FFRWS, get a series of points that are 
connected in turn (including (0,0) and (1,1) the two points),it is called the ROC Curve 
of FFRWS. As the name implies, the value of the AUC is the area below the ROC curve. 
Curve drawing is done by using MedCalc software.  
➢ Passing-Bablok Regression Analysis: After all subjects completed Visit 2(FFR- ICA 
examination), taking the blood vessel as the research unit, using FFRWS value of coronary 
artery measured by the investigational device as the vertical y-axis, and the FFRPW value 
of coronary artery measured by the control device as the horizontal x-axis to perform 
Linear regression analysis and record regression analysis equation, slope and intercept. 
 
➢ Bland-Altman Bias Analysis: After all subjects completed Visit 2(FFR- ICA examination), 
taking the blood vessel as the research unit, Bland-Altman deviation analysis will be used 
to analyze the FFRWS value of coronary artery measured by the investigational device and 
the FFRPW value of coronary artery measured by the control device, and draw deviation 
map. In the two-dimensional rectangular coordinates of Bland-Altman deviation map, the 
horizontal x-axis of abscissa represents the average FFR of each lesion vessel measured by 
two devices, and the vertical y-axis of ordinate represents the difference of FFR of each 
lesion vessel measured by two devices. 
 
➢ Pearson Linear Correlation Analysis: After all subjects completed Visit 2 (FFR-ICA 
examination), taking the blood vessel as the research unit, Pearson linear correlation 
analysis will be used to analyze the FFRWS value of coronary artery measured by the 
investigational device and the FFRPW value of coronary artery measured by the control 
device, and the correlation coefficient and P value will be recorded.. 
 
➢ Device success rate: After all subjects completed the visit 2(FFR-ICA examination), taking 
the blood vessel as the research unit, use the effective FFRWS and FFRPW readings as the 
criteria for the success of the use of the device to calculate the success rate of the 
investigational device and the control device. Compare differences in device success 
rates between groups.  
7.1.7 Safety Evaluation Methods 
7.1.7.1 Description of Safety Parameters 
The occurrence of adverse events and device defects is used as a safety 

 
 
40 
 
evaluation index. 
7.1.7.2 Methods and Time Selection for Evaluating, Documenting, and 
Analyzing Safety Parameters 
Adverse events were closely observed and evaluated during the screening 
period and in the trial. Adverse events that need to be recorded are recorded 
in the adverse event log. Record the time, occurrence, measures, and results of 
device defects. 
7.2 The Trial Process 
7.2.1 The Trial Process 
Patients who are eligible for this clinical trial will complete screening and 
enrollment after Visit 1 and Visit 2, and each subject who meets the inclusion criteria 
and does not meet any of the exclusion criteria will undergo a series of study visits, 
including Visit 1 (screening period, -7-0 days), Visit 2 (FFR-ICA examination), and visit 
3 (48 hours post-surgery follow up). The specific visit process is described as follows: 
7.2.1.1 Visit 1(Screening Period, -7 – 0 days) 
Subject selection is according to the inclusion and exclusion criteria. This visit needs to 
complete the following: 
1. Subjects will sign an informed consent form; 
2. Demographic Information: record the subject's gender, age (date of birth), ethnicity, 
height, weight and other information; 
3. Complete Medical History: inquire and record the subject's past illness, surgical 
history, current medical history, etc.; 
4. Pregnancy Check-up: complete urine pregnancy test, and if positive, complete 
blood pregnancy test for confirmation; 
5. Combined medications: record drug use that may affect device use evaluation; 
6. Laboratory examination: including blood routine, liver function, kidney function, 
myocardial enzyme, etc.; 
7. Vital signs: record subject's systolic pressure, diastolic pressure and heart rate; 
8. Inclusion/Exclusion Criteria: complete the inclusion criteria item 1 to 4, and exclusion 
criteria item 1 to 4 and item10; 

 
 
41 
 
9. Adverse Events: record adverse events that occurred during screening process.  
7.2.1.2 Visit 2 (FFR - ICA examination) 
On the day of the operation after the ICA examination, subjects will be selected again based 
on the inclusion and exclusion criteria. This visit includes: 
1. Inclusion/Exclusion Criteria: complete the inclusion criteria item 5, and exclusion 
criteria item 5 to 9; 
2. Vital signs: record subject's systolic pressure, diastolic pressure and heart rate; 
3. Device information: distribute device, record device information; 
4. Investigational device coronary artery FFR value: record the position of the blood 
vessel, record the FFR value measured by the investigational device; 
5. Investigational device success rate: using effective FFR readings as a success 
criterion, record the success rate of the investigational device; 
6. Control group device coronary artery FFR value: record the position of the blood 
vessel, record the FFR value measured by the control device; 
7. Control group device success rate: using effective FFR readings as a success 
criterion, record the success rate of the control device; 
8. Adverse Events: record all adverse events that occurred during subject's FFR -ICA 
examination; 
9. Device Defects: record device defects that occurred during the use of 
devices; 
10. Combined medications: record the combined drugs used during the trial.  
7.2.1.3 Visit 3 (48 hours post-surgery follow up)  
1. Laboratory examination: within 48 hours after the procedure, complete the 

 
 
42 
 
laboratory examination, including blood routine, liver function, kidney function, 
myocardial enzyme, etc. 
2. Vital signs: including systolic pressure, diastolic pressure and heart rate; 
3. Adverse Events: record all adverse events that occurred during subject's FFR -
ICA examination; 
4. Device Defects: record device defects that occurred during the use of 
devices; 
5. Combined medications: record the combined drugs used during the trial.  
7.2.2 Trial Flow Chart 
 
Visit 1 
Visit 2 
Visit 3 
Procedure Name 
Screening 
period 
(-7 – 0 days) 
FFR - ICA 
Examination 
Follow 
(48 hours post- 
surgery follow 
up) 
Sign Informed Consent Form 
Ⅹ 
 
 
Demographic Information 1 
Ⅹ 
 
 
Complete Medical History 2 
Ⅹ 
 
 
Pregnancy Check-up 
Ⅹ 
 
 
Laboratory Examination 3 
Ⅹ 
 
X7 
Inclusion /Exclusion Criteria 
X4 
X5 
 

 
 
43 
 
 
Visit 1 
Visit 2 
Visit 3 
Procedure Name 
Screening 
period 
(-7 – 0 days) 
FFR - ICA 
Examination 
Follow 
(48 hours post- 
surgery follow 
up) 
Vital Signs 6 
Ⅹ 
Ⅹ 
Ⅹ 
Device Information 
 
Ⅹ 
 
Investigational Device Coronary Artery 
FFR Value 
 
Ⅹ 
 
Investigational Device Success Rate 
 
Ⅹ 
 
Control Group Device Coronary Artery 
FFR value 
 
Ⅹ 
 
Control Group Device Success Rate 
 
Ⅹ 
 
Adverse Events 
Ⅹ 
Ⅹ 
Ⅹ 
Device Defects 
 
Ⅹ 
Ⅹ 
Combined Medications 
Ⅹ 
Ⅹ 
Ⅹ 
Note: 
1. 
Demographic Information: including gender, age (date of birth), ethnicity, height, weight, etc. 
2. 
Complete medical history: inquire and record the subject's past illness, surgical history, current medical 
history, etc. 
3. 
Laboratory examination: including blood routine (RBC, WBC, PLT), liver function (ALT, AST), kidney function 
(BUN, CR), myocardial enzyme (cTNT) / cTNI, CK, CK-MB). The laboratory will accept examination results 
within 7 days of the signing of the informed consent.  
4. 
Visit1Inclusion/ Exclusion Criteria: complete the inclusion criteria item 1 to 4, and exclusion criteria item 1 to 

 
 
44 
 
4 and item10; 
5. 
Visit 2 Inclusion/ Exclusion Criteria: complete the inclusion criteria item 5, and exclusion criteria item 5 to 9 
6. 
Vital signs: record subject's systolic pressure, diastolic pressure and heart rate  
7. 
Visit 3 Laboratory examination completed within 48 hours of surgery. If the cTNT / cTNI and CK-MB exceed 
the upper limit of normal by 5 times within 48 hours after surgery; if the blood routine and liver and kidney 
abnormalities are clinically significant within 48 hours after surgery, and the baseline corresponding 
examination item is normal or abnormal and it has no clinical significance, review and follow up until 
abnormalities have no clinical significance. 
7.2.3 Device Specification 
For the use of the investigational device, the sponsor provides the product’s 
Instruction For Use or User Manual and the Investigator’s Brochure and 
conducts sufficient operation training for all the medical staff involved in the trial 
during the trial preparation phase to ensure operators are proficient in operating 
the device. 
7.3 Monitoring / Audit plan 
Pre-Trial monitoring is mainly divided into: distribution of investigational device to 
clinical trial sites, preparation of research documents, trial personnel and trial 
training; In-Trial monitoring is mainly divided into: subjects screening, informed 
consent, and regular visits, documents to be submitted to the hospital and ethics 
committee, and monitoring of adverse events; Post-Trial monitoring (or before 
the termination of the trial) is mainly divided into: recovery of investigational 
devices, EDC data challenge, confirmation of trial document integrity, Ethics 
Committee notification, AE and SAE review, closure of sites, clinical trial statistical 
analysis report and clinical report. 
The auditor should undergo the necessary training, be familiar with the Good 
Clinical Practice for Medical Device and relevant regulations. Also, be familiar 
with the non-clinical aspects of investigational devices in the trial, as well as the 
clinical aspects of other similar devices, and clinical trial protocol and related 
documents. 
Each clinical site is visited/inspected at least 2-4 times per week, and the frequency of 
audits is appropriately increased according to the enrollment situation.  
The auditor shall follow the GCP principles and supervise the conduct of clinical 
trials to ensure that clinical trials are strictly implemented according to the 
protocol.  The trial data is true, complete and accurate. Specific responsibilities 

 
 
45 
 
include: 
(1) Confirm prior to trial start that the investigational site has the appropriate conditions, 
including staffing and training, laboratory equipment in good working 
conditions, estimated a sufficient number of subjects, participating investigators 
are familiar with the trial requirements; 
(2) Whether the investigational sites and investigators comply with the approved clinical 
trial protocol, the Good Clinical Practice for medical device and the relevant 
regulations before, during and after the trial; 
(3) Confirm that each subject signed an informed consent form prior to 
participating in the trial. Be aware of subject’s inclusion criteria and the 
progress during the trial. Tests that have not been conducted by the 
investigators, unconducted examination, and whether errors or omissions are 
corrected should be clearly and truthfully recorded. Confirm revised informed 
consent form is resigned by subjects prior to the end of follow up visit.  
 (4) Confirm that all case report forms are correctly filled out and consistent with 
the original data. All errors or omissions have been corrected or noted and 
signed and dated by the investigator. The disease type, the total number of 
cases and the gender, age, and treatment result of each case should be 
confirmed and recorded; 
(5) Document subjects who withdrawal from the study or is non-compliance with 
the requirements of the informed consent form. Discuss the situation with the 
investigator; 
 (6) Confirm that all adverse events and device defects should be recorded, and 
serious adverse events and major device defects that may cause serious 
adverse events are reported and recorded within the specified time; 
(7) Responsible for monitoring the supply, storage, use, maintenance and 
handling of medical device samples after the trial; 
(8) Ensure that the relevant equipment is regularly maintained and calibrated and 
documented during clinical trials; 
(9) Ensure that investigators receive the latest version of all documents related to 
clinical trials; 
(10) After each audit, a written report shall be sent to the sponsor and 
investigational site. The report shall state the name of the auditor, the date of 
the audit, the location of the audit, the content of the audit, the name of the 
investigator, the completion of the project, problems, conclusions, and 
corrections to errors, omissions, etc. 

 
 
46 
 
8 Statistical Considerations 
8.1 Statistical Design, Methodology and Analysis Procedures 
8.1.1 Statistical Design (Hypothesis Testing) 
This clinical trial is intended to use a prospective, multi-center, single-subject 
target value design. The main purpose is to evaluate diagnostic consistency rate 
in diagnosing coronary heart disease by FFRWS measured by investigational 
device, using FFRPw as the gold standard. Each subject in the clinical trial will 
provide a pair of test results from both the investigational device and the control 
device (FFRWS and FFRPw), and the degree of agreement between the two will 
be used to evaluate the investigational device’s performance, using the control 
product’s result as the “gold standard” in the process of comparison 
(FFRPW≤0.80 as positive，FFRPW>0.80 as negative), evaluating the primary 
evaluation index ie. accuracy in coronary heart disease diagnosis, applying target 
values comparison to ensure FFRWS ‘s result satisfies clinical application 
requirements, the corresponding statistical hypothesis testing is: 
0
1
0
0
:
:
p
p
p
p
T
T




 
pT represents the investigational device’s accuracy in diagnosing coronary heart 
disease, p0 represents the target value. 
8.1.2 Statistical Analysis Methods  
（1 ）Descriptive Analysis: Describing qualitative data with frequency and 
composition ratio description; describing quantitative data with mean, standard 
deviation, maximum, minimum, median, interquartile range, 25th percentile, and 
75th percentile. 

 
 
47 
 
（2 ）Baseline demographics statistical analysis: Mainly based on descriptive 
analysis, comparing subgroups that may be involved, use likelihood ratio χ2 test 
between qualitative groups, use Fisher’s exact test when more than 25% of cell 
frequencies are less than 5; conduct group T-test between normally distributed 
quantitative datasets; apply Wilcoxon Rank Sum test between non-normally 
distributed quantitative datasets.  
（3）Efficacy analysis: All subjects undergoing a study product review will be 
included in the analysis (according to the Intention To Diagnostic (ITD)), for the 
primary efficacy index, in addition to the point estimate for coronary heart disease 
diagnosis accuracy, the asymptotic normal method and the exact probability 
method would also be used to make estimates in the 95% confidence interval, 
comparing the lower bound of the confidence interval with a target value to 
determine whether the investigational device satisfies clinical application 
requirements. 
（4 ）Safety evaluation: Adverse events are described by the number and 
frequency of adverse events; meanwhile, the specific performance, the severity, 
and the relationship with investigational device of all adverse events will be 
described in detail.  
（5）For primary evaluation indicators, statistical analysis will be conducted with 
a one-tailed 0.025 significance level, other indicator statistical analysis will be 
conducted with a two-tailed 0.05 significance level (unless stated otherwise). 
Statistical analysis is done with SAS®9.4 statistics software. 
  
8.1.3 Statistical Analysis Procedures 
Relevant steps in statistical analysis will refer to the provisions of ICH E9 and the 
relevant guidelines in the “Guidelines for Biostatistics in Clinical Trial” promulgated 
by the China Food and Drug Administration (CFDA). Meanwhile, all statistical 
analysis procedures are carried out in strict accordance with the Standard 
Operating Procedures (SOP) established by the Medical Statistics Department of 
the National Center for Cardiovascular Diseases. 

 
 
48 
 
8.2 Sample Size Calculation 
8.2.1 Total Sample Size 
A total of 300 patients is planned to be enrolled in this study. Such sample size is 
determined by a combination of the research hypotheses and the estimates of 
expected efficacy, calculated according to statistical principles. The calculation of 
sample size is based on the primary endpoint, i.e., the accuracy in coronary heart 
disease diagnosis. 
Based on literature reports and clinical experiences, the hypothesized coronary 
heart disease diagnosis accuracy of the investigational device is set at 83%, while 
the evaluation standard, i.e., the target value is set at 75%, considering a one-tailed 
0.025 significance level and that the maximum drop out rate does not exceed 
10%, calculated based on statistics principles, a sample size of 300 provides over 
90% confidence, to prove that the performance of the investigational device 
meets clinical trial requirements (exceeding target value). From clinical experiences, 
the proportion of patients with positive (FFRPW ≤ 0.80) and negative (FFRPW > 
0.80) in the target population is approximately 1:2, test subjects will be included 
in a continuous selection process until the total sample size is met. Required 
sample size calculation is: 
(
)
(
)


(
)
 
1
1
2
0
2
1
0
0
1
p
p
p
p
p
p
n
T
T
T
−
−
+
−
=
−
−




 
In the equation,  represents the coronary heart disease diagnosis accuracy in the 
test group,   presents the target value;   represents the quantile corresponding 
to a normal distribution,   represents the statistical test’s probability for type I 
error, use 0.025 here, and  represents the test’s probability for type II error, use 
0.2 for calculation (corresponding to the 80% power). 
In addition to the above sample size estimation for the primary endpoint, this 
clinical trial offers respective statistical considerations for the secondary endpoint. 
Referencing the target population’s positive to negative proportion and the total 
sample size of 300, in the continuous selected sample, about 100 subjects are 
tested positive by FFRPW≤0.80, while about 200 subjects are tested negative by 
FFRPW＞0.80. Based on literature reports, set the results from the control device 
as the gold standard, the sensitivity of the investigational device compared to it is 
around 86%; the specificity of the investigational device compared to it is around 
78%; under the premise that  statistical test’s two-tailed 0.05 significance level, 

 
 
49 
 
current number of positive cases (100) can ensure the error between the 
sensitivity and the true value of FFRWS is no more than 6.8% (the estimated 
accuracy is ±6.8%); number of negative cases (200)  can ensure the error 
between the specificity and the true value of FFRWS is no more than 5.7% (the 
estimated accuracy is ±5.7%); when the observed sensitivity or specificity of FFRWS 
is higher than the hypothesized, the estimation accuracy will be further improved..  
8.2.2 Number of Clinical Trial per Disease and Reasons for Determination 
This clinical trial has tough restrictions on the inclusion/exclusion criteria for 
selected subjects, it can be considered that the current clinical trial is only conducted 
for a single indication subject, the above 300 subjects belong to the same disease 
and will not be further divided. 
8.2.3 The Maximum and Minimum Numbers of Subjects Per Clinical Trial 
Institution in a Multi-center Clinical Trial and Reasons for Determination 
This clinical trial will take place simultaneously in multiple clinical trial institutions, 
in theory, the number of centers to be grouped will be evenly distributed to ensure 
maximum representation. But considering the feasibility and progress of selection, 
the number of enrollment for each institution will be adjusted according to situations. 
To ensure the balance of each center’s selection scale, the final size for any one 
specific institution will not exceed 50% of the total sample size. 
8.3 Clinical Trial’s Significance Level and Power 
In this clinical trial, the significance level for the statistical analysis is set at two-
tailed 5% (unless specified), the test’s power is about 90% (only for primary evaluation 
indexes).  
8.4 Expected Drop Out Rate 
In the sample size design process, the maximum drop out rate during the clinical 
trial is expected to be 10%, such drop out rate includes all reasons that prevent a 
subject from being selected for primary analysis, usually referred to serious violations 
of clinical trial protocols as determined by researchers (influencing the primary 
efficacy analysis). Possible scenarios include: a subject does not meet the inclusion 
criteria, or meets the exclusion criteria; a subject did not use any test-related products; 
a subject used third-party products outside of clinical trial or such. All of the above 
will be included in the total drop out rate.  

 
 
50 
 
8.5 Criteria for Qualified/Unqualified Results in Clinical Trial 
To determine whether a clinical trial result is qualified or not from a statistical 
standpoint, it is to test the result with the initial hypothesis testing. For this clinical trial, 
the primary index is the accuracy in coronary heart disease diagnosis, the test results 
and the preset target values could be compared to determine if the investigational 
device meets the requirements for clinical application.  
In summary, the determination will be based on the comparison between the 
investigational device’s accuracy in coronary heart disease diagnosis and the preset 
target value. If the result shows: the lower bound of the 95% confidence interval for 
the investigational device’s accuracy in coronary heart disease diagnosis is greater 
than 75% (the preset target value), then a positive result is obtained, therefore 
proving the investigational device meets the requirements for clinical application. 
8.6 Standards and Reasons for Terminating Clinical Trial Based on Statistical 
Reasons 
This clinical trial does not have preset interim analysis and corresponding 
standards for early termination, thus it is not applicable here. All statistical analysis will 
be performed after the data has been collected, cleaned, and finally locked in. 
8.7 Statistical Methods of All Data, Along With Missing, Unused, and 
Erroneous Data (Including Withdrawals) and the Processing Methods for 
Unreasonable Data 
The statistical analysis processes (procedures) are carried out in strict accordance 
with the Standard Operating Procedures (SOP) established by the Medical Statistics 
Department of the National Center for Cardiovascular Diseases. Details can be 
referred to related documents.  
To account for possible missing data in clinical trials, the missing primary 
endpoint index will be carried over during analysis, the specific carry over procedure 
will be outlined in the statistical analysis plan, if there exists any missing results, it will 
be treated as inconsistent in the consistency evaluation. No carry-over processing will 
be done on other missing index, analysis will be performed on observed data.  
Erroneous and unreasonable data will be cleaned in the data cleansing process 
before statistical analysis. The information of subjects who withdrew from clinical 
trials will still be included in the final statistical analysis. The specific reasons for 

 
 
51 
 
withdrawal of  each subject will be described in the statistical report, the missing 
primary index caused by early withdrawal will be carried over following the above 
missing value processing method. 
8.8 Reporting Deviation from the Original Statistical Plan 
The statistical analysis plan needs to be confirmed by the sponsor and the main 
investigator, and to be finalized before the locking of database. Prior to finalization, 
adjustments could be made on the initial analysis plan according to the actual 
situation during clinical trials. In principle, the main analytical principles, methods, and 
analysis set will not be modified, and all adjustments will be recorded. 
8.9 Standards and Reasons for Selecting Subjects to be included in the 
Analysis 
Statistical analysis will be performed upon the following demographics, 
demographic categorization will be done prior to the statistical analysis, the analysis 
population in this clinical trial includes: 
Full Analysis Set (FAS): collection of subjects selected based on the Intention To 
Diagnostic (ITD) principles, refers to the dataset of all subjects who participated in the 
research and used the investigational device.  
Per Protocol Set (PPS): the subgroup of the subjects who completed the trial, 
excluding those who seriously violated the procedure (refers to the trial subjects who 
violated the selection standard or the exclusion standard, or those lost during the 
trial). 
Safety Set (SS): Use the same definition method as the Full Analysis Set (FAS), 
therefore the Safety Set will not be defined separately in the analysis. 
The analysis of primary efficacy index will be performed on the Full Analysis Set 
(FAS) and the Per Protocol Set (PPS); in addition, all baseline demographic data and 
secondary efficacy analysis will be performed on the Full Analysis Set (FAS), the safety 
evaluation will also be performed on the Full Analysis Set (FAS). 
8.10 
Exclusion of Special Information during Hypothesis Verification and 
Its Reasons (If Applicable) 
Not applicable. 

 
 
52 
 
9 DATA MANAGEMENT 
The collection of clinical data was done by using an Electronic Data Capture (EDC) 
system. The EDC system has undergone rigorous testing and fully meets the requirements 
of ”Good Clinical Practice for Medical Device” and ”Clinical Trial Data Management Technical 
Guidelines”. Before the system is officially launched, it is necessary to conduct training tests 
on relevant users to ensure that the system meets the test requirements. After the official 
launch, the relevant personnel will get the account number and password. The account is 
bound to the user's role and permissions. The account information must be properly kept. 
The account information must not be shared with others or exercise tasks for others. 
9.1 DATA COLLECTION 
EDC transfers data directly from the client terminal to the server side over the Internet. 
Without filling out a paper case report form, investigators can complete data collection by 
entering the source data directly into the EDC system. Investigators are responsible for the 
quality of the data entered to ensure the authenticity and integrity of the data. The EDC 
system provides interface printing, allowing investigators to print information on electronic 
case reports as needed.  
9.2 DATA VERIFICATION AND MODIFICATION 
The EDC system provides both online and offline verification methods. When the 
investigator enters abnormal data, the EDC system issues a real-time warning to remind the 
investigator to check the data. The data administrator performs a logical check on the data 
held by the server and issues the wrong data in the form of manual challenge through EDC. 
Investigators need to answer questions posted. The auditor needs to periodically remind and 
assist the investigator to answer the questions and ensure that each question is handled 
correctly. The system will record all the questions and the corresponding answers. 
9.3 DATABASE LOCK 
When all data entry is completed and submitted, all questions are answered, the 
system enters the soft lock state. The statistician will generate a blind audit report based on 
this database. If the confirmation data requires no more modified, the sponsor, the data 
management person in charge, and the statistical person in charge must sign the database 
lockout form, and the data administrator will complete the database lock operation 
according to this form. The locked database must not be modified again. If there is an error 
affecting the main efficacy index or safety indicator, the sponsor, the data management 
person in charge, and the statistical person in charge must confirm the unlocking 

 
 
53 
 
modification and sign the database unlocking form. The data administrator will modify the 
error data and perform quality control according to the reason of the unlocking. After the 
error is revised, the sponsor, the data management person in charge, and the statistical 
person in charge are required to sign the database lockup form again. 
10 FEASIBILITY ANALYSIS 
10.1 
PROBABILITY OF SUCCESS ANALYSIS 
A series of tests and researches have been carried out during the development of this 
product, including laboratory bench tests, animal studies, and human factors research etc. 
The company has established a strict quality system, established design control procedures 
for design and development, and formed documents to implement planning and control 
of the product design and development process. The product has passed the type testing 
of Shanghai Medical Device Quality Supervision and Inspection Center of the China Food 
and Drug Administration (CFDA) and has been strictly tested before leaving the factory. 
There will be no defective products.  In addition, the control device has been approved 
for marketing in the country. In this trial, the investigator will enroll subjects who meet the 
trial requirements based on the indication for use of the investigational device. The study 
design meets CFDA requirements. 
10.2 
PROBABILITY OF FAILURE ANALYSIS 
The main causes of treatment failure or poor performance may be related to 
the following factors: 1) accuracy and proficiency of the operation; 2) inaccurate 
understanding of indications for use and contraindications; 3) product defects 
specifically due to manufacturing. 
In addition to the above reasons, there may be other unpredictable risks (such 
as wire breakage) in this trial, leading to trial failure. However, by following this 
protocol, conduct procedure at a trial institution, adhering to the subjects’ inclusion 
criteria, and closely monitoring the physical condition of the subjects during the 
procedure can minimize the risk. 
11 QUALITY CONTROL OF CLINICAL TRIALS 
During the trial, sponsor assigned auditors will conduct on-site audit to ensure 
that all aspects of the protocol are strictly followed, and trial documents are filled 
out correctly. Investigators must undergo unified training so to perform recording 
and judgment criteria with consistency. The entire trial should be carried out under 
strict operational standard. The investigator should fill in the requirements 

 
 
54 
 
according to the medical report form, truthfully, in detail, and carefully record the 
contents of the EDC to ensure that the case report form is complete, true and 
reliable. All observations and findings in clinical trials should be verified to ensure 
data reliability and to ensure that conclusions from clinical trials are derived from 
raw data. There are corresponding data management measures in the clinical trial 
and data processing stages.  
The original information from this trial, including signed informed consent, 
products distribution records, relevant laboratory inspection reports, auxiliary 
examination reports, case records and other relevant records, shall be kept at the 
investigational site’s related hospital for 10 years after the end of the clinical trial.  
The Sponsor shall keep the clinical trial data until this product is no longer on the 
market. 
12 ETHICAL ISSUES AND INFORMED CONSENT IN CLINICAL TRIALS  
12.1 
ETHICAL CONSIDERATIONS 
This clinical trial complies with the requirements of the Helsinki Declaration of 
the World Medical Assembly and relevant Chinese regulations, and shall, in 
accordance with the requirements of the CFDA Order No.25, pass the ethical audit 
of the investigational site and protect the rights of the subjects of the clinical trial in 
accordance with the ethical principles stipulated therein, safety and health, as well 
as privacy.  
12.2 
REVIEW AND APPROVAL OF THE TRIAL PROTOCOL 
Clinical trial protocol must be submitted to the medical Ethics Committee of the 
investigational site hospital for approval prior to initiate the clinical trial.  During the 
clinical trials, if the protocol is revised, it shall be implemented only after obtaining 
written approval from the Ethics Committee. 
12.3 
INFORMED CONSENT PROCESS AND INFORMED CONSENT FORM 
The Ethics Committee must approve the drafted ICF. The sponsor provides ICF 
to each investigational site. To meet specific requirements, the investigational site 
may modify ICF. Each investigational sites present sponsor with a copy of the ICF 
approved by the Ethics Committee, as well as a copy of the renewal and permission 
for the duration of the trial. The original signed and dated ICF by subject is kept by 
the investigational site for audit and a copy will be given to the subject.  
Whenever new information that may affect the patient's consent is obtained, 

 
 
55 
 
ICF (and any other written information provided to the subject) is updated. Any 
such amendments or updates must be reviewed and approved by the Ethics 
Committee before made available to the subjects. 
13 PROVISIONS ON ADVERSE EVENTS AND DEVICE DEFECTS 
REPORTING 
13.1 
ADVERSE EVENTS 
Definition: Adverse Events (AE), are adverse medical events that occur during 
clinical trials, whether or not is related to investigational devices.  
Grade: 
Mild:  
Subject can tolerate, does not affect diagnosis and treatment, do not 
requires special treatment, no impact on the subject's health. 
Medium:  Subject can not tolerate, and requires special treatment, direct 
impact on the subject's health. 
Severe:  
Endangers subject's life, results in death or disability, requires 
emergency treatment. 
13.2 
SERIOUS ADVERSE EVENTS 
A serious adverse event is a death or serious deterioration of health during a 
clinical trial, including a fatal illness or injury, a permanent defect in the body's 
structure or function, a need for hospitalization or prolonged hospitalization (Except 
for those who are hospitalized for medical insurance reimbursement, elective 
surgery, routine treatment of the disease under study or previous diseases without 
deterioration of the condition, and who are not hospitalized for emergency 
treatment only, they are recorded in the original medical case report, and no 
serious adverse events are reported.), medical or surgical intervention to avoid 
permanent defects in the body structure or physical function; causes fetal distress, 
fetal death or congenital abnormalities, congenital defects and other events.  
13.3 
DEVICE DEFECTS 
Device defects refer to under normal use of medical device presents the 
unreasonable risks that may endanger health and life, such as mislabeling, quality 
problems, malfunctions and so on. 

 
 
56 
 
The investigator shall record all adverse events and device defects during the 
clinical trial, and jointly analyze the causes of the events with sponsor, form a 
written analysis report includes opinions on continuing, suspending or terminating 
the trial, The report shall be submitted by the medical device clinical trial 
management department of the investigational site to its Ethnic Committee for 
review. 
13.4 
SERIOUS ADVERSE EVENT REPORTING PROCEDURES, CONTACT 
INFORMATION 
All adverse events that occur during the clinical trials must be truthfully 
recorded in the adverse event table. The investigators should give targeted 
treatment and follow-up on adverse events until symptoms disappear or the 
symptoms stabilize. 
In the case of serious adverse events in clinical trials, the investigator shall 
immediately take appropriate treatment measures on the subjects, and report in 
writing to the clinical investigational site’s medical device clinical trial management 
department, and notify the sponsor in writing. The medical device clinical trial 
management department shall report in writing within 24 hours to the appropriate 
ethics committee, the competent department of food and drug supervision and 
administration and the health and family planning authorities of the province, 
autonomous region or municipality directly under the central government where 
the investigational site is located. In the case of a death, investigational site and 
investigator should provide the Ethics Committee and the sponsor with all the 
information they need.  
For serious adverse events and device defects that potentially lead to serious 
adverse events, the sponsor shall report to the food and drug regulatory authority 
and the health and family planning authorities within 5 working days, and shall 
inform the other investigational sites and investigators, and through medical device 
clinical trial management department to inform investigational site ethics committee 
in a timely manner.  
14 PROVISIONS ON DEVIATION FROM CLINICAL TRIAL PROTOCOL AND 
REVISION OF CLINICAL TRIAL PROTOCOL 
14.1 
DEVIATION FROM CLINICAL TRIAL PROTOCOL 
The investigator is responsible that protocol is not deviated without prior 

 
 
57 
 
notice to the implementer and without the approval of the sponsor, and that all 
actions are in full compliance with all regulation and procedures established by the 
Ethics Committee. Without the written approval of the sponsor, the investigator 
may not deviate from clinical trial protocol for any reason, except in case of medical 
emergency to protect subject’s life, physical health, or to avoid significant harm to 
the subject. If this happens, the investigator must immediately notify the sponsor. All 
protocol deviations must be reported to the sponsor. 
14.2 
CLINICAL TRIAL PROTOCOL MODIFICATION PROCEDURE 
The deviation of the clinical plan should be reviewed on a regular basis to 
determine whether a revision of the protocol or termination is necessary. All 
revisions to the protocol must be agreed by both the sponsor and the investigators 
of the investigational sites. The reasons for the revision should be recorded. 
When investigational sites and investigators changed from the original list, 
changes can proceed without a formal amendment. The sponsor maintains an 
updated list and provides it when needed, but the final report must include the final 
list of investigational sites and investigators. 
15 DIRECT ACCESS TO SOURCE DATA, FILES 
15.1 
DEFINITION 
Source data is the original record of clinical findings, observations, and other 
activities in clinical trials that can be used for clinical trial reconstruction and 
evaluation.  
    Source files are printed files, visual files, or electronic files that contain source 
data.  
PROVISIONS FOR DIRECT ACCESS TO SOURCE DATA AND FILES
The investigator shall truthfully and accurately record and preserve the source 
data and source documents from the clinical trial, and accept audit by auditors 
authorized by sponsor and regulatory authorities. 
16 FINANCE AND INSURANCE 
Before the subjects of this trial are enrolled, the sponsor, investigational sites 
and investigator shall handle the trial design, the quality control of the trial, the 
division of responsibilities in the trial, the costs associated with the clinical trial 

 
 
58 
 
undertaken by the agent, and the possible injury treatment during the trial. A 
written agreement was reached on principles and so on. 
This trial stipulates that the sponsor shall bear the cost of treatment and the 
corresponding financial compensation for subject who suffers injury or death 
related to the clinical trial, except for the damage caused by the fault of the 
investigational site and its medical staff during the medical treatment. The sponsor 
has purchased the medical device clinical trial liability insurance for this trial, and the 
relevant expenses are paid preferentially to commercial insurance. Sponsor will 
cover the portion of compensation that’s not covered by insurance. 
17 CONTENTS TO BE COVERED IN CLINICAL TRIAL REPORTS 
The clinical trial report follows the relevant requirements of the "Good Clinical 
Practice for Medical Device" and is written with reference to the "Clinical Trial Report 
Template for Medical Devices", which includes but is not limited to:  
（1
General information; 
（2
Summary; 
（3
Introduction; 
（4
Objective; 
（5
Overall Design; 
（6
Content; 
（7
General Clinical Information; 
（8
Investigational Devices and Control Devices / Control Methods for Diagnosis 
and Treatment methods; 
（9
Statistical Design; Method and Analysis Procedures 
（10
Clinical Evaluation Criteria; 
（11
The Organizational Structure of Clinical Trials; 
（12
Ethic Issues; 
（13
Results of Clinical Trials; 
（14
Adverse Events and Treatment; 
（15
Analysis and Discussion of Clinical Trial Results, Indication for Use, 
Contradiction and Warnings; 
（16
Conclusions of Clinical Trials; 
（17
Problems and Suggestions for Improvement; 

 
 
59 
 
（18
List of Investigators; 
（19
Other Information Requiring Clarification; 
（20
Investigator and Clinical Trial Site Opinions 
18 THE PRINCIPLE OF CONFIDENTIALITY 
18.1 
PERSONAL DATA AND DATA PROTECTION 
All data obtained in clinical trials are protected. Investigators must not disclose 
patient's name and other personal data (excluding date of birth/age and gender). 
It is important to ensure that the EDC or other documents (ex: report on special 
findings) transmitted to the National Cardiovascular Center do not contain patient 
name, but only the patient’s registration number (patient number, date of birth, 
and/or registration number). 
Similarly, statistical storage and evaluation can only be performed under the 
patient registration number. Only the investigator can identify the patient's 
name/other personal details by registration number. 
During clinical trial, if patient's name needs to be identified for medical reasons, 
all relevant personnel are obliged to keep it confidential. 
Personal data storage and process should comply with data protection laws 
18.2 
CONFIDENTIALITY 
All persons involved in this clinical trial should treat the objective and content 
of this clinical trial and its results as confidential. 
The investigators shall keep all the information provided by the sponsor 
confidential and safe. 
Ownership of all documents, test data and results of this clinical trial belongs to 
Zurich Medical, and no party is allowed to disclose this clinical trial related 
information without the written permission from the sponsor.  
19 AGREEMENT ON THE PUBLICATION OF TRIAL RESULTS 
The result of this trial will be used by the sponsor for CFDA product registration 
and approval. Before the sponsor obtains CFDA product approval, the investigators 
of each investigational site may not publish any articles based on the clinical trial. To 
publish article, sponsor's written consent must be obtained. After sponsor obtained 

 
 
60 
 
CFDA’s product approval, the investigator of each investigational site may publish 
the article individually, but the data and results of the published article must be 
consistent with the final clinical report and investigational site report, and sponsor 
must be notified in writing. 
20 RESPONSIBILITIES OF ALL PARTIES 
20.1 
THE RESPONSIBILITIES OF THE SPONSOR 
（1
The sponsor is responsible for initiating, applying, organizing and supervising 
clinical trials, and is responsible for the authenticity and reliability of clinical trials. 
 
（2
The sponsor is responsible for organizing the development and revision of the 
investigator's manual, clinical trial protocol, informed consent form, case report 
form, relevant standard operating procedures and other relevant documents, 
and is responsible for organizing the training needed for clinical trials. 
 
（3
The sponsor shall select the investigational sites and its investigators from 
qualified healthcare institutions according to the characteristics of the 
investigational device used in the trial. Prior to signing the clinical trial 
agreement, sponsor should provide the investigational site and investigators 
with the latest investigator's manual and other relevant documents for their 
decision on whether they can undertake the clinical trial. 
 
The investigator's manual should include the following information: 
1) 
General information of the sponsor and the investigator;   
2) 
Investigational devices summary  
3) 
Rationale for the intended use and clinical trial design  
（4
The sponsor shall not exaggerate the mechanism and efficacy of investigational 
devices used in the clinical trial. 
 
（5
During the clinical trial process, when the sponsor receives important 
information affecting clinical trial, the investigator's manual and related 
documents shall be promptly revised and submitted to the Ethics Committee for 
review and approval through the investigational site clinical trial management 
department. 
 

 
 
61 
 
（6
The sponsor shall enter into a written agreement with investigational sites  and 
investigators on the following matters: 
1) 
Conduct clinical trials in accordance with relevant laws and regulations 
and clinical trial protocol, and accept inspection, verification and audit; 
2) 
Follow data logging and reporting procedures 
3) 
Keep the basic documents relating to the trial not less than the statutory 
time until the sponsor notifies the investigational sites and the 
investigators the documents are no longer required; 
4) 
After sponsor has obtained the approval of Ethics Committee, it’s 
responsible to provide investigational devices to investigational sites and 
investigators, and ensure transport conditions, storage conditions, 
storage time, expiration date, etc. 
5) 
Investigational devices should be of good quality and covered with easy 
to identify label that reads "Trial Use", and is properly packaged and 
stored in accordance with the clinical trial protocol; 
6) 
The sponsor shall develop clinical trial quality control related standard 
operating procedures, such as the transport, reception, storage, 
distribution, treatment, recycling of investigational device, for 
investigational sits and investigators to follow.  
 
（7
The sponsor is responsible for the safety of investigational devices in clinical trials. 
When subject’s safety is of concern or that the implementation of the trial may 
alter the ethics committee's approval of the continuation of the trial, the sponsor 
shall immediately notify all investigational sites and investigators and respond 
accordingly. 
 
（8
 If the sponsor decides to suspend or terminate the clinical trial, it shall notify all 
investigational site’s medical device clinical trial management department within 
5 days and explain the reasons in writing. The clinical trial management 
department of the investigational site shall promptly notify the appropriate 
researchers and ethics committees. Suspension of clinical trials may not be 
resumed without the consent of the ethics committee. After the end of the 
clinical trial, the sponsor shall inform the food and drug supervision and 
administration department of the province, autonomous region or municipality 
directly under the Central Government in writing.  
 
（9
The sponsor shall ensure that all investigators carrying out clinical trials strictly 
follow the clinical trial protocol, and if they find that investigational sites and 
investigators do not comply with relevant laws and regulations, this clinical trial 
protocol, they shall point out and correct them in a timely manner; and if serious 
non-compliance or persistence happens, the sponsor shall terminate the clinical 

 
 
62 
 
trial and report to the food and drug regulatory departments of autonomous 
regions and municipalities directly under the Central Government where the 
investigational site located and the CFDA. 
 
（10
The sponsor shall bear the cost of treatment and the corresponding financial 
compensation for the treatment of the subject who has suffered the injury or 
death in connection with the clinical trial, except for the damage caused by the 
fault of the medical institution and its medical personnel in the medical treatment. 
 
（11
The sponsor shall assume the responsibility for supervision and inspection of 
clinical trials and select the auditor who meets the requirements to perform the 
supervision duties. The number of auditors and the number of monitors 
depends on the complexity of clinical trials and the number of clinical trial 
investigational sites.  
 
（12
The auditor shall have the corresponding professional background of clinical 
medicine, pharmacy, biomedical engineering, statistics and other relevant 
professional background, undergo the necessary training, be familiar with the 
medical device clinical trial management regulations and relevant regulations. 
Also, be familiar with the non-clinical aspects of experimental devices in the trial, 
as well as the clinical aspects of other similar devices, and clinical trial protocol 
and related documents. 
 
The auditor shall follow the standard operating procedures of the clinical trials 
for investigational devices for testing medical devices formulated by the 
sponsor, and urge clinical trial to be carried out in accordance with the 
protocol. Specific responsibilities follow the relevant national regulations and 
the requirements of the sponsor. 
 
（13
In order to ensure the quality of clinical trials, sponsors can organize auditors 
who are independent of clinical trials and have appropriate training and 
experience to audit the conducting of clinical trials and evaluate whether 
clinical trials meet the requirements of the trial protocol.  
Audit can be used as part of the sponsor's routine work on quality 
management of clinical trials, as well as to assess the effectiveness of audit 
activities, or to be carried out aiming at serious or repeated clinical trial protocol 
deviations, suspected fraud, etc. The auditor should develop a audit plan and 
audit procedure based on the importance of the clinical trial, the number of 

 
 
63 
 
subjects, the type and complexity of the clinical trial, the risk level of the subject, 
etc.  
 
（14
For serious adverse events and defects in devices that may lead to serious 
adverse events, the sponsor shall report to the food and drug regulatory 
authority and the health and family planning authorities within 5 working days 
of learning of the event, and shall inform the other investigational sites and 
investigators involved in the trial, and through investigational site’s medical 
device clinical trial management department to inform the investigational site’s 
ethics committee in a timely manner.  
 
（15
 If the sponsor adopts an electronic clinical database or a remote electronic 
clinical data system, it should ensure that the clinical data is controlled, truthful 
and form a comprehensive verification document. 
For multicenter clinical trials, the sponsor should ensure that documents are in 
place prior to the clinical trial to clearly coordinate the division of responsibilities 
between the investigators.. 
For multicenter clinical trials, the sponsor shall organize the development of 
standard operating procedures in accordance with the protocol, and organize 
operation and maintenance of investigational device training for all 
investigators, so as to ensure consistency in the implementation of clinical trial 
protocol and the use of investigational devices. 
In this multicenter clinical trial, the sponsor should ensure that the case report 
form is designed in a rigorous and reasonable manner, enabling the 
coordinating investigator to obtain all data from the investigational sites.. 
20.2 RESPONSIBILITIES OF INVESTIGATIONAL SITES AND INVESTIGATORS 
（1
Before accept to participate in the clinical trial, the investigational site shall evaluate the 
relevant resources according to the characteristics of the investigational medical device 
to determine whether to participate in the clinical trial. 
（2
The investigational site shall properly maintain the clinical trial records and basic 
documents in accordance with the agreement with the sponsor. 
（3
The investigator in charge of clinical trials shall meet the following requirements: 
1. 
In the investigational site with deputy director physician, associate professor, 
associate researcher and other deputy senior 
 professional and technical titles and qualifications;   
2. 
Have the expertise and experience required for investigational medical devices, and 
should be trained if necessary; 

 
 
64 
 
3. 
Be familiar with the requirement of the sponsor and the information and literature 
provided by the sponsor and related to the clinical trials, 
4. 
Have the ability to coordinate, to control and use the personnel and equipment to 
conduct the trial and to be able to handle adverse events and other events related 
to the investigational device; 
5. 
Be familiar with relevant laws, regulations and this protocol  
（4
Prior to a clinical trial, the medical device clinical trial management department of 
investigational site shall cooperate with the sponsor to submit an application to the 
ethics committee and submit the relevant documents in accordance with the 
provisions. 
（5
The investigators shall ensure that the relevant staffs involved in the trial are familiar with 
the principles of operation, indication for use, operating methods, installation 
requirements and technical specifications of the investigational medical device, the 
preclinical research data and safety data of the investigational medical device, and the 
prevention method for potential risks and emergency treatment methods during clinical 
trials. 
（6
The investigator shall ensure that all clinical trial subjects are fully aware of the clinical trial 
protocol, regulations, characteristics of the investigational medical device and 
responsibilities associated with the clinical trial, and that there are sufficient numbers of 
subjects who meet the inclusion criteria and that there is sufficient time during the 
agreed trial period, to safely implement and complete clinical trials in accordance with 
the relevant regulations. 
（7
The investigator shall ensure that the investigational medical device is used only by the 
subjects in the clinical trial and shall not charge any fees. 
（8
The investigator shall strictly follow the clinical trial protocol, and shall not deviate from 
the protocol or substantially change the protocol without the consent of the sponsor 
and the ethics committee, or without the approval of the China Food and Drug 
Administration in accordance with the provisions. However, in cases of immediate 
danger, such as the immediate risk of the subject, it may also be allowed to report in 
writing afterwards. 
（9
The investigators are responsible for recruiting subjects and talking to subjects or their 
guardians. It is the responsibility of the investigator to explain to the subject about the 
details of the investigational medical device and the clinical trial, and to inform the 
subject of the possible benefits and known and foreseeable risks, and to obtain an 
informed consent form signed and dated by the subject or his or her guardian.  
（10
Investigators or other persons involved in the clinical trial should not force or other 
improperly induce subject to participate in the clinical trial. 

 
 
65 
 
（11
When the investigators discover adverse events in clinical trials that are not expected 
from the investigational medical devices, they shall, together with the sponsor, modify 
the relevant contents of the informed consent form, submit to be reviewed and 
approved by ethnics committee, and have the affected subject or their guardians re-
sign the revised informed consent form. 
（12
The investigator is responsible for making medical decisions related to clinical trials, and 
when adverse events related to clinical trials occur, investigational site and investigators 
should ensure adequate and timely treatment provided to the subjects. The 
investigators shall notify the subjects once they become aware of the need for 
treatment of complications. 
（13
In the case of serious adverse events occur during clinical trial, the investigator shall 
immediately take appropriate treatment measures on the subject, and report in writing 
to the medical device clinical trial management department of investigational site and 
notify the sponsor in writing. The medical device clinical trial management department 
shall report in writing within 24 hours to the appropriate ethics committee and the 
competent department of food and drug administration and administration of the 
province, autonomous region or municipality directly under the central government 
where the investigational site is located. In the case of a death, investigational site and 
investigators should provide the ethics committee and the sponsor with all the 
information they need.  
（14
The investigator shall record all adverse events and device defects during the clinical 
trial, and jointly analyze the causes of the events with the sponsor, form a written 
analysis report, and submit opinions on continuing, suspending or terminating the trial, 
which shall be submitted by the medical device clinical trial management department of 
the investigational site to the ethics committee for review. 
（15
The investigator should file clinical data reports in accurately, completely, clearly and in a 
timely manner. The case report form is signed by the investigator, and any changes to 
the data should be signed and dated by the investigator, while the original records are 
kept and the original records should be clear and legible. 
（16
Investigational sites and investigators should ensure that the data, documents and 
records formed in clinical trials are true, accurate, clear and safe. 
（17
Investigational sites and investigators shall accept the monitoring and auditing by the 
sponsor and the supervision by Ethics Committee, and provide all required records 
relating to the clinical trial. When the food and drug administration and the department 
of health and family planning send inspectors to carry out inspections, the 
investigational site and investigators shall cooperate. 
（18
When investigational site and investigators reach a conclusion that the risk exceeds the 
likely benefit, or that results are sufficient to determine the safety and efficacy of a 

 
 
66 
 
medical device, trial needs to be suspended or terminated.  Subject shall be notified 
and properly treated and followed up, and that detailed written explanations are 
provided in accordance with report. If necessary, report to the food and drug 
administration department of the province, autonomous region or municipality.  
When investigators receive notification of trial suspension or termination from sponsor 
or ethics committee, they need to notify subjects in a timely manner and ensure that the 
subject is properly treated and followed up.  
（19
The investigational site or investigators need to report any requests from sponsor that 
violates the relevant provisions to change the clinical trial data or conclusions, to the 
provincial, autonomous region or municipality food and drug administration or to the 
China food and drug administration. 
（20
At the end of a clinical trial, the investigator should ensure that records and reports are 
completed. At the same time, the investigators should ensure that the investigational 
medical devices received are in accordance with the quantities used, discarded or 
returned, and that the remaining investigational medical devices are properly handled 
and documented. 
（21
According to the needs of clinical trials, investigators may authorize the appropriate 
personnel to recruit the subjects, communicate continuously with the subjects, record 
clinical trial data, manage investigational medical devices, etc. The investigator shall 
conduct relevant training on authorized personnel and create appropriate training 
documentations. 
20.3 OTHER RESPONSIBILITIES BY OTHER PARTIES CAN BE FOUND IN 
THE CLINICAL TRIAL AGREEMENT 
 
 

 
 
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References 
”Helsinki Declaration” 
“Regulations for the Supervision and Administration of Medical Devices” (Decree No.650 of 
State Council) 2014.06.01 
“Provisions for Medical Devices Registration” (Order No.4 of China Food and Drug 
Administration) 2014.10.01 
“Good Clinical Practice of Medical Devices” (Order No.25 China Food and Drug Administration, 
Health and Family Planning Commission of the People's Republic of China ) 2016.06.01 
“Guidelines for the Design of Clinical Trials of Medical Devices” (No. 6 of 2018) 2018.01.08 
“Provisions for Medical Device IFU and Labeling” (Order No.6 of China Food and Drug 
Administration) 2014.10.01 
“Provisions for Supervision of Medical Device Manufacture” 2014.10.01 
 
”GB/T191-2008 Packaging Storage and Transportation Graphic Mark” 2008.10.01 
”GB9706.1-2007 Medical Electrical Equipment Part1: General Requirements for Safety”  
2008.07.01 
”YY0505-2012 Medical Electrical Equipment Part 1-2: General Requirements for Safety –Collateral 
Standard: Electromagnetic Compatibility – Requirements and Tests” 2014.01.01 
”YY0783-2010 Medical Electrical Equipment Part 2-34: Particular Requirements for the Safety, 
including Essential Performance, of Invasive Blood Pressure Monitoring Equipments” 2012.06.01 
”YY0450.1-2003 Accessory Devices for Sterile Single-use Intravascular Catheters 
Part1:Introducers” 2003.09.01 
”GB/T16886.1-2011 Biological Evaluation of Medical Devices Part1: Evaluation and Testing 
within a Risk Management Process” 2011.12.01 
 
 
 

 
 
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The investigators statement 
I agree: 
1. This clinical trial will be conducted in strict accordance with the requirements of the 
Helsinki Declaration, china's existing regulations, and this trial’s protocol.  
2. Record all required data accurately in the Electronic Data Collection System (EDC) and 
complete clinical trial reports on time.  
3. Investigational medical devices are used only for this clinical trial, and the receipt and use 
of investigational medical devices are fully and accurately recorded during the clinical trial, 
and records are maintained.  
4. Allow the CRA and auditor authorized or dispatched by the sponsor, and the inspector 
from regulatory authorities, to monitor, audit and inspect the clinical trial.  
5. Strict performance of the terms of the clinical trial contract/agreement signed by the 
parties. 
I have read all the entire clinical trial protocol, including the above statement, and I agree with all 
of the above. 
Sponsor’s opinion 
Signature (stamp) 
Year /Month/Date 
Agent's opinion 
Signature (stamp) 
                                    Year /Month/Date 
Investigator’s opinion 
Signature (stamp) 
Year /Month/Date 

 
 
69 
 
Investigational site’s opinion  
Signature (stamp) 
Year /Month/Date