A Prospective, Multicenter Study to Evaluate the Performance and Safety of CometTM Pressure Guidewire in the Measurement of FFR in Chinese Patients
Phase: NA
Conditions: Cardiovascular Diseases
Sponsor: Boston Scientific Corporation

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A prospective, multicenter study to evaluate the performance and 
safety of CometTM Pressure Guidewire in the measurement of 
FFR in Chinese patients 
COMET CHINA 
 
S2434 
CLINICAL INVESTIGATION PLAN 
 
 
 
 
 
 
 
Sponsored By 
BSC International Medical Trading (Shanghai) Co., Ltd, (“BSC China”) 
Part A, 2nd Floor, No.68, Rijing Road, 
WaiGaoQiao Free Trade Zone, 
Shanghai, China 200131 
 
 
 
 
 
 
 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 

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Contact Information 
Role 
Contact  
Clinical Contact 
YANG GUANGWEI 
Clinical Trial Manager  
Boston Scientific Corporation 
31F, No.763 Mengzi Road 
Shanghai 200023 
P.R.China 
Email: Guangwei.yang@bsci.com 
Mobile: 86 21 80317313 
 
LI CUIFEN 
Medical Affairs Manager 
Boston Scientific Corporation 
12F, Building 2, 16 Tianze Road  
Beijing 100125 
P.R.China 
Email:  cuifen.li@bsci.com 
Mobile: 86 10 87542962 
Coordinating Principal 
Investigator(s) 
Prof. Guo Ning 
The First Affiliated Hospital of Xi’an Jiaotong University 
Investigational Sites 
Tianjin Medical University General Hospital  
Vendors/Labs 
A list of vendors/laboratories involved in the trial is maintained 
by the sponsor. A complete listing of applicable vendors will be 
provided to investigational sites. 
Original Release: Jan, 25, 2019 
Current Version: Apr, 29, 2019  
 
 
 
 
Revision 
Version 
Protocol 
Date 
Template 
number and 
version 
Protocol 
Section 
Modified 
Summary of Changes 
 
Justification 
for 
Modification 
AA 
Jan, 25, 
2019 
90702637_Re
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N/A 
N/A 
First release 
AB 
Apr, 29, 
2019 
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Inclusion 
criteria  
Limited patient age must  less 
than or equal to 75 years 
Clear 
description  
 
 
 
Data 
collection  
Identify the data collection time 
rang after procedure  
Clear 
description  
 
 
 
 

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2 Protocol Synopsis 
A prospective, multicenter study to evaluate the performance and safety of CometTM 
Pressure Guidewire in the measurement of FFR in Chinese patients 
COMET CHINA 
Objective 
To evaluate the performance and safety of CometTM Pressure Guidewire 
in FFR (Fractional Flow Reserve) measurements in Chinese population. 
Planned 
Indication(s) for 
Use 
The CometTM Pressure Guidewire, FFR Link and iLab™ Polaris Multi-
Modality Guidance System is indicated for use to measure physiological 
parameters in the coronary and peripheral blood vessels. 
Test Device 
CometTM Pressure Guidewire, FFR Link and iLab™ Polaris Multi-Modality 
Guidance System (Boston Scientific) 
Controlled 
Device  
Pressure Wire Certus® , RadiAnalyzer® System (St. Jude Medical Systems 
AB, Uppsala, Sweden) 
Test Device Sizes 
1  iLab™ Polaris Multi-Modality Guidance System 
2  FFR Link 
3  CometTM Pressure Guidewire 
Characteristic 
Comet Pressure 
Guidewire 
Labeled diameter 
0.014” 
Wire length 
185 cm 
Flexible portion of wire 
length 
33 cm 
Tip length 
3 cm 
Tip shape 
Straight 
   
Controlled 
Device Size 
1 RadiAnalyzer® System 
2 Pressure Wire Certus® 
Characteristic 
Pressure Wire Certus 
Labeled diameter 
0.014” 
Wire length 
175 cm 
Flexible portion of wire 
length 
31 cm 
Tip length 
3 cm 
Tip shape 
Straight 
 

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Study Design 
A prospective, open-label, multi-center study designed to validate the 
agreement of CometTM Pressure Guidewire and Pressure Wire Certus® in 
FFR measurements 
Study 
Population 
Patient with stable angina or any form of non-ST elevation acute coronary 
syndrome, who are scheduled for diagnostic angiography and pressure wire 
assessment, and signed the informed consent, will be screened for 
enrollment in this study. 
Planned Number 
of Subjects 
100 paired measurements from up to 50 subjects  
Planned Number 
of Sites/ 
Countries 
At least 2 sites in China 
Follow-up 
Schedule 
Subject follow-up will end at hospital discharge post FFR measurement 
Study Duration 
18 months  
Primary 
endpoint 
Acceptable agreement between CometTM Pressure Guidewire and Pressure 
Wire Certus® in FFR measurements 
Secondary 
endpoint 
Safety endpoints: 
• 
Pressure wire-related death 
• 
Pressure wire-related cardiac tamponade 
• 
Pressure wire fracture 
• 
Pressure wire-related unanticipated adverse event (UADE) 
Method of 
Assigning 
Patients to 
treatment 
Patients who sign the Ethics Committee-approved Informed Consent 
Form (ICF), and have met all inclusion criteria and none of the 
exclusion criteria, are eligible to be enrolled in the clinical study. All 
eligible subjects will receive FFR measurements simultaneously by 
both CometTM Pressure Guidewire and pressure wires Certus®. 
For the two pressure wires which should be passed the target lesion 
first, each site will be provided a randomized digital table with a 1:1 
ratio at target vessel level. 
Medication 
treatment 
1) Maximal hyperemia will be induced by intravenous adenosine-5’-
triphosphate (ATP) via the median cubital vein. 
2) Subjects will receive routine drug treatment required for diagnostic 
angiography and PCI according to the standard clinical practice in 
China. 
✓ FFR 
FFR system set-up 

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Measurement 
method 
✓ Set up both FFR systems according to their respective DFUs 
FFR measurement: based on the current FFR guidelines in China*, 
following steps of FFR measurement are required:  
1) The two sensors of Comet wire and Certus wire should be placed at 
same location – 3 to 5cm distal to the target lesion.  
2) Coronary infusion of Nitroglycerine prior to pressure measurement. 
3) Both baseline Pd/Pa will be recorded. 
4) Maximal hyperemia will be induced by intravenous adenosine-5’-
triphosphate (ATP) via the median cubital vein. 
5) FFR values measured by both systems should be recorded during 
hyperemia for each target lesion.                
6) After FFR measurement, withdraw the pressure wire and record 
‘Pd/Pa’ when the sensor is at the tip of guiding catheter for calculating 
the drift. (Drift is equal to the observed ‘Pd/Pa’ minus 1) 
 
Special requirement 
Revascularization decision-making is based on FFR value achieved 
by Pressure Wire Certus®.  
*The Chinese expert consensus on the clinical application of coronary fractional flow 
reserve Chinese Journal of Cardiology. 2016,44(4):292-297. 
Inclusion Criteria General Inclusion Criteria: 
 
Patient  must be at least 18 years old and less than or equal to 75 years 
of age 
 
Patient or his/her legally-authorized representative agrees to sign the 
EC-approved ICF prior to the procedure 
 
Patient with stable angina or any form of non-ST elevation acute 
coronary syndrome and is clinically indicated of intra-coronary 
diagnostic angiography and FFR assessment 
Angiographic Inclusion Criteria: 
 
Moderate stenosis (30% to 70% diameter stenosis by visual estimation) 
is detected at diagnostic angiography  
Exclusion Criteria General Exclusion Criteria: 
 
Patients unable to provide informed consent 
 
Patients in pregnant state 
 
Known renal insufficiency or failure (serum creatinine level of > 2.5 
mg/dL, or on dialysis)  
 
Allergy to the contrast  
 
Significant arrhythmia, such as II degree or above of 
atrioventricular block, Sick sinus syndrome, ventricular tachycardia 
 
Spastic bronchial asthma 
 
ST elevationacute coronary syndrome 
 
Hemodynamic instability 
 
Contraindications to nitroglycerin or ATP 
 
Current participation in another investigational drug or device clinical 
study that may affect the FFR measurements 
Angiographic Exclusion Criteria: 
 
Chronic total occlusion (CTO) lesion 
 
Severe vessel tortuosity at the stenotic segments 

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 
Culprit vessel of non-ST-segment elevation acute myocardial infarction 
Statistical Test 
Method 
Bland-Altman plot will be used to assess the agreement between 
CometTM Pressure Guidewire and Pressure Wire Certus® in FFR 
measurements. 
Sample Size 
Parameters 
 
Pre-defined agreement limits = [-0.08, 0.08] 
 
Expected paired mean difference = 0.0013  
 
Expected paired standard deviation (SD) = 0.03 
 
Two-sided significance level=5% (alpha) 
 
Power > 80% 
 
A minimum of 100 paired measurements* from 50 patients are needed 
for this study 
 
*Lu MJ, Zhong WH, Liu YX, Miao HZ, Li YC, Ji MH (2016) Sample size for 
assessing agreement between two methods of measurement by Bland-Altman 
method.  The International Journal of Biostatistics 12: issue 2 (8pp) 
Acceptable 
criteria 
Agreement between the two methods of measurement will be confirmed if 
both conditions are met: 
1) The mean paired difference is within +/- 0.005 # 
2) The limits of agreement (defined as the mean observed difference +/- 
1.96* observed SD) is within the pre-defined agreement limits of [-0.08, 
0.08] # 
 
# Nick Curzen, Rod Stables. Randomised Comparison of Simultaneous Data from 
two Different Pressure Wires: the COMET trial(NCT02578381) 

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3 Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2 
PROTOCOL SYNOPSIS .........................................................................................................3 
3 
TABLE OF CONTENTS .........................................................................................................7 
2.1. Table of Figures .....................................................................................................10 
2.2. Table of Tables ......................................................................................................10 
4 
INTRODUCTION.................................................................................................................12 
4.1 
Background ............................................................................................................12 
4.1.1  preclinical study ............................................................................................13 
4.1.2 
Clinical trial ..............................................................................................14 
4.2 
Study Rationale .....................................................................................................15 
5 
DEVICE DESCRIPTION ......................................................................................................16 
5.1 
Test devices ............................................................................................................16 
5.2  CONTROLLED DEVICE .......................................................................................................18 
6 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................18 
6.1  study objectives ........................................................................................................18 
6.2  Study endpoints ........................................................................................................18 
7 
STUDY DESIGN .................................................................................................................19 
7.1 
Scale and Duration ................................................................................................19 
7.2 
Treatment Assignment ..........................................................................................20 
7.2.1 
Treatment and Control ..............................................................................20 
7.3 
Justification for the Study Design ........................................................................20 
8 
SUBJECT SELECTION ........................................................................................................21 
8.1 
Study Population and Eligibility ..........................................................................21 
8.2 
Inclusion Criteria ..................................................................................................21 
8.3 
Exclusion Criteria .................................................................................................21 
9 
SUBJECT ACCOUNTABILITY .............................................................................................22 
9.1 
Point of Enrollment ...............................................................................................22 
9.2 
Withdrawal ............................................................................................................22 

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9.3 
End-of-Study Definition........................................................................................22 
9.4 
Enrollment controls ..............................................................................................23 
10 STUDY METHODS .............................................................................................................23 
10.1 Data Collection ......................................................................................................23 
10.2 Study Candidate Screening ..................................................................................25 
10.3 Informed Consent..................................................................................................25 
10.4 Screening (Up to 14 days prior to index procedure) ..........................................25 
10.5   Required Concomitant Medications ...................................................................25 
10.5.1   Prior and post to the index procedure ........................................................26 
10.5.2   In the Catheterization Laboratory ..............................................................26 
10.6   Enrollment & Index Procedure ...........................................................................26 
10.6.1FFR measurements ...............................................................................................26 
10.6.2 End of the Index Procedure ................................................................................27 
10.7 Post-Procedure / Pre-Discharge ...........................................................................27 
10.8 Study Completion ..................................................................................................27 
10.9 Source Documents .................................................................................................27 
11 STATISTICAL CONSIDERATIONS ......................................................................................28 
11.1 Endpoints ...............................................................................................................28 
11.1.1 
Primary Endpoint ......................................................................................28 
11.1.1.1 Sample Size ..............................................................................28 
11.1.1.2 Statistical Methods ...................................................................28 
11.1.2 
Safety Endpoints .......................................................................................28 
11.2 General Statistical Methods .................................................................................28 
11.2.1 
Analysis Sets .............................................................................................28 
11.2.2 
Control of Systematic Error/Bias ..............................................................28 
11.2.3 
Number of Subjects per Investigative Site ...............................................29 
11.3 Data Analyses ........................................................................................................29 
11.3.1 
Other Endpoints/Measurements ................................................................29 
11.3.2 
Interim Analyses .......................................................................................29 
11.3.3 
Subgroup Analyses ...................................................................................29 
11.3.4 
Multivariable Analyses .............................................................................29 
11.3.5 
Other Analyses ..........................................................................................29 
11.3.6 
Changes to Planned Analyses ...................................................................29 
12 DATA MANAGEMENT .......................................................................................................30 

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12.1 Data Collection, Processing, and Review ............................................................30 
12.2 Data Retention .......................................................................................................30 
12.3 Core Laboratories .................................................................................................30 
13 AMENDMENTS ..................................................................................................................30 
14 DEVIATIONS......................................................................................................................31 
15 DEVICE/EQUIPMENT ACCOUNTABILITY FOR PRODUCTS LABELLED INVESTIGATIONAL
 
 ..........................................................................................................................................31 
16 COMPLIANCE ....................................................................................................................32 
16.1 Statement of Compliance ......................................................................................32 
16.2 Investigator Responsibilities ................................................................................32 
16.2.1 
Delegation of Responsibility ....................................................................34 
16.3 Institutional Review Board/ Ethics Committee ..................................................34 
16.4 Sponsor Responsibilities .......................................................................................34 
16.4.1 
Role of Boston Scientific Representatives ...............................................35 
16.5 Insurance ................................................................................................................35 
17 MONITORING ....................................................................................................................36 
18 POTENTIAL RISKS AND BENEFITS ...................................................................................36 
17.1 Anticipated Adverse Events Associated with the Study Device and Procedure
 .................................................................................................................................36 
17.2 Risks associated with Participation in the Clinical Study .................................37 
17.3 Possible Interactions with Concomitant Medication .........................................37 
17.4 Risk Minimization Actions ...................................................................................37 
17.5 Anticipated Benefits ..............................................................................................37 
17.6 Risk to Benefit Rationale ......................................................................................37 
18 SAFETY REPORTING .........................................................................................................37 
18.1 Reportable Events by investigational site to Boston Scientific .........................37 
18.2 Definitions and Classification...............................................................................38 
18.3 Relationship to Study Device(s) or Procedure or Required Medications during 
the Procedure .........................................................................................................40 
18.4 Investigator Reporting Requirements .................................................................43 
18.5 Boston Scientific Device Deficiencies ...................................................................45 

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18.6 Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators .......45 
19 INFORMED CONSENT ........................................................................................................45 
20 COMMITTEES ...................................................................................................................47 
20.1 Safety Monitoring Process ....................................................................................47 
20.2 Executive Committee ............................................................................................47 
21 SUSPENSION OR TERMINATION........................................................................................47 
21.1 Premature Termination of the Study ..................................................................47 
21.1.1 
Criteria for Premature Termination of the Study ......................................47 
21.2 Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC /REB Approval ......................................................................................48 
21.3. Requirements for Documentation and Subject Follow-up ................................48 
21.4 Criteria for Suspending/Terminating a Study Site ............................................48 
22 PUBLICATION POLICY ......................................................................................................48 
23 BIBLIOGRAPHY .................................................................................................................49 
24 ABBREVIATIONS AND DEFINITIONS .................................................................................50 
24.1 Abbreviations.........................................................................................................50 
24.2 Definitions ..............................................................................................................52 
 
 
2.1. Table of Figures 
Figure4.1- 1 Observed delta .................................................................................................... 15 
Figure 5.1- 1 Comet Pressure Guidewire ................................................................................ 16 
Figure 5.1- 2  FFR Link .......................................................................................................... 17 
Figure 5.1- 3 System set-up .................................................................................................... 17 
Figure 7.1- 1 Study design ...................................................................................................... 20 
 
2.2. Table of Tables 
Table 5-1: Comet Pressure Guidewire Description ................................................................ 16 
Table 8.2-1: Inclusion Criteria ................................................................................................ 21 
Table 8.3-1: Exclusion Criteria ............................................................................................... 22 

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Table 10.1-1: Data Collection Schedule ................................................................................. 24 
Table 18.2-1: Safety Definitions ............................................................................................. 38 
Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 41 
Table 18.4-1: Investigator Reporting Requirements ............................................................... 43 
Table 24-1: Abbreviations ...................................................................................................... 50 

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4 Introduction 
4.1  Background 
Although angiography is an established invasive approach for assessment of coronary artery 
disease (CAD), its ability to evaluate the functional significance of stenosis is limited [1,2].  
Fractional flow reserve (FFR) technology is based on the concept that the functional 
significance of a lesion; i.e., whether the lesion can cause ischemia, can provide information 
as to whether the lesion should be treated. The functional significance of a lesion in the case 
of FFR is determined based on the pressure drop across the lesion. Pressure is measured at 
the descending aorta (Pa) and distal to the lesion (Pd). The ratio of Pd/Pa is known as FFR 
value. FFR value provides information on the functional significance of coronary artery 
stenosisand can be used as a diagnostic tool, to facilitate its treatment decision-making.  
 
Tonino PA, et al[2] found angiography is inaccurate in assessing the functional significance 
of a coronary stenosis when compared with the FFR, not only in the 50% to 70% category 
but also in the 70% to 90% angiographic severity category. Among all stenosis with an 
angiographic severity of 50% to 70%, 65% were functionally nonsignificant and 35% were 
functionally significant by the FFR. Even in more severe stenosis between 71% and 90% 
angiographic stenosis severity, 20% of the lesions did not induce reversible myocardial 
ischemia as established by a FFR value above the ischemic threshold. Therefore, in patients 
with multivessel CAD, whether or not taking into account clinical data, one cannot rely on 
the angiogram to identify ischemia-producing lesions.  
 
Tonino PA et al[3] also demonstrated the importance of FFR in patients with multivessel 
coronary disease undergoing revascularization in the FAME (Fractional Flow Reserve 
Versus Angiography for Multivessel Evaluation) study. This prospective, multicenter, 
international trial randomly assigned 1005 patients with multivessel coronary artery disease 
to either PCI guided by FFR (PCI if FFR ≤0.8)  or by angiography alone. As compared with 
the standard strategy of PCI guided by angiography, FFR guided PCI significantly reduced 
the rate of the primary composite end point of death, myocardial infarction, and repeat 
revascularization at 1 year (18.3% in the angiography group and 13.2% in the FFR group, P 
= 0.02). 
 
Subsequently, the FAME 2 clinical trial [4] was designed to test whether optimal medical 
therapy alone was superior to FFR-guided PCI plus optimal medical therapy in patients with 
stable coronary disease. Recruitment was halted early in this prospective, multi-center, 
international trial of 1220 patients (of whom 888 underwent randomization) due to an early 
finding of a significant difference between the groups in the primary endpoint event (death 
from any cause, myocardial infarction, or unplanned hospitalization leading to urgent 
revascularization). The PCI group had a primary event at a rate of 4.3% as compared with the 
medical therapy group that had an event rate of 12.7% (HR with PCI: 0.32; 95% CI: 0.19–
0.53; p < 0.001). Of note, a lower rate of urgent revascularization in the PCI group drove this 

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difference (1.6 vs 11.1%; HR: 0.13; 95% CI: 0.06–0.30; p < 0.001). Recently, the 2-year 
results of FAME 2 showed similar primary endpoint trajectories (8.1% event rate for the PCI 
group vs 19.5% event rate for the medical therapy group; HR: 0.39; 95% CI:0.26–0.57; p < 
0.001), driven by urgent revascularization (4.0% in the PCI group vs 16.3% in the medical 
therapy group; HR: 0.23; 95% CI: 0.14–0.38; p < 0.001)[5]. 
 
FFR has been also shown to be an effective method for guiding revascularization in other 
studies [6–10]. Therefore, it has received a class IA recommendation from the European 
Society of Cardiology for identifying hemodynamically relevant coronary lesions when 
evidence of ischemia is not available and a class IIA recommendation from the American 
College of Cardiology for the assessment of angiographic intermediate coronary lesions (50-
70% diameter stenosis) and for guiding revascularization decisions in patients with CAD 
[11,12].  
4.1.1  preclinical study 
1）A preclinical study (91050762) was conducted to assess Comet thrombogencity. The 
purpose of the study was to evaluate the thrombogenic potential risk of a the Comet Pressure 
Guidewire compared to the Kinetix Guidewire under non-anticoagulated conditions in the 
common swine model.  
 
During the explantation of the test devices, no thrombus was observed on any of the test 
devices and no occlusions of the arteries were observed. During the explantation of the 
control devices minimal thrombus was observed on one of the control devices. No occlusions 
of the arteries were observed. Images were obtained of each treatment site and device. The 
limited necropsies for both animals no thromboembolisms were present in the heart or lungs. 
Based on the results of this study, the Comet Pressure Guidewire (test) had similar 
thromboresistance characteristics compared to the Kinetix Guidewire (control). 
2）A GLP in vivo preclinical study was conducted to evaluate acute performance of the 
Comet Pressure Guidewire using a series of performance characteristics and evaluated acute 
pressure measurements (Pd) using the iLab™ Polaris Multi-Modality Guidance System and 
Comet Pressure Guidewire compared to invasive aortic blood pressure (Pa) in the vasculature 
of a swine model. 
Test Articles met the acceptance criteria of a pressure accuracy specification Pd – Pa ≤ 8 
mm Hg. This acceptance criteria is derived from IEC 60601-2-34: 2011 accuracy 
specification of ± 4 mmHg for each System (i.e., Invasive blood pressure monitor (Pa) and 
iLab™ Polaris Multi-Modality Guidance System with Comet Pressure Guidewire (Pd)). 
Considering that each system has an accuracy requirement of ± 4 mmHg, the combined 
tolerance is ± 8 mmHg.  
The absence of adverse events and the acceptable delivery and performance of the device 
support the safety and performance of the Comet Pressure Guidewire and iLab Polaris. 

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4.1.2 Clinical trial 
The COMET Trial [13] assessed diagnostic and drift performance of FFR devices in a 100-
patient randomized controlled trial (RCT) that compared the Comet Pressure Guidewire to 
the Pressurewire Certus ( St. Jude) by allocating patients to simultaneous paired readings 
using three groups (Comet-Comet [n=37], Certus-Certus [n=34], Comet-Certus [n=35]). The 
COMET trial was conducted at two sites in the United Kingdom. For each vessel, four 
pressure readings were taken with the pressure wires in the same position: equalization at the 
guide tip catheter; baseline Pd/Pa in the distal vessel; FFR in the target measurement site (at 
steady state maximum hyperemia using intravenous adenosine); and final Pd/Pa at the guide 
catheter tip (to measure drift). Drift estimations were made in 142 vessels for Comet Pressure 
Guidewire and 137 for Pressurewire Certus. 
 
No significant difference in the performance between the two pressure wires was observed. 
The absolute magnitude of the difference between the measurements of the Comet Pressure 
Guidewire and the Pressure wire Certus is no different than the magnitude of difference 
between two measurements of Pressure wire Certus, with a Comet-Certus median difference 
of 0.01(n=108 paired readings) and Certus-Certus median difference of 0.015 (n=90 paired 
readings; p=0.61 for difference between the two groups). See Figure4.1- 1 for graphs of 
paired readings.  In addition, both the Comet Pressure Guidewire and Pressure wire Certus 
exhibit a small degree of drift that is not significantly different from the other (Comet median 
drift = 0.02, standard deviation 0.039; Certus median drift = 0.02, standard deviation 0.031; 
p=0.14). 
 

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Figure4.1- 2 Observed delta 
Observed Delta in FFR Reading in Comet-Comet (top), Comet-Certus(middle), and Certus-
Certus (bottom) Groups 
 
4.2    Study Rationale 
The objective of this study is to evaluate the performance and safety of CometTM Pressure 
Guidewire in FFR (Fractional Flow Reserve) measurements in Chinese population in order to 
support the regulatory submission in China. 
 
 

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5 Device Description 
5.1   Test devices 
5.1.1 Comet Pressure Guidewire  
The Comet Pressure Guidewire is a single use, hydrophilic-coated, steerable wire with a 
custom optical cable. A pressure sensor is mounted approximately 3 cm from the distal end 
of the radiopaque and shapeable straight tip. For product specifications, including wire 
diameter, length, and radiopaque tip length, please refer to the product labeling/DFU.   
The Comet Pressure Guidewire is indicated to direct a catheter through a blood vessel and to 
measure physiological parameters in the coronary blood vessels.  
 
Figure 5.1- 1 Comet Pressure Guidewire 
 
The characteristics of the Comet Pressure Guidewire are described in Table 5-1. 
Table 5-1: Comet Pressure Guidewire Description 
Characteristic 
Description 
Labeled diameter 
0.014” 
Wire length 
185 cm 
Flexible portion of wire length 
31 cm 
Tip length 
3 cm 
Tip shape 
Straight 
 
5.1.2 FFR link 
FFR Link: The FFR Link (see Figure 5.1- 2 transmits aortic (Pa) and distal (Pd) blood 
pressure under the control of the Polaris software or Hemodynamic System with Licensed 
FFR Calculation Module. The FFR Link is a hardware module that is installed with either an 
existing or a new iLab Polaris system. In this use scenario, the FFR Link can be used to 
obtain the pressure measurement from the Comet Pressure Guidewire and provide an analog 
Pd out signal. 

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Figure 5.1- 3  FFR Link  
 
5.1.3  iLab™ Polaris Multi-Modality Guidance System 
The iLab Polaris Multi-Modality Guidance System is an upgrade to the iLab Ultrasound 
Imaging System to add a Fractional Flow Reserve (FFR) modality to the existing ultrasound 
imaging modality (IVUS). 
The iLab Polaris System is designed to provide both ultrasound imaging and fractional flow 
reserve modalities. Only one modality can be used at a time and are independent of one 
another. 
The system set up shall follow the instructions in the DFU. And the connection is shown 
in the Figure 5.1- 4. 
 
Figure 5.1- 5 System set-up 
 

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5.2  Controlled device 
5.2.1  PressureWire Certus  
 
 
PressureWire Certus is a 0.014’’ guidewire with an integrated sensor element at the tip to 
enable measurements of physiological parameters. Pressurewire is available in different 
lengths. Please refer to the label for information about pressureWire length and thermos 
compatibility. 
5.2.2 RadiAnalyzer System 
RadiAnalyzer is a diagnostic computer designed to compute, record and display information 
from PressureWire and other external transducers.  
6 Study Objectives and Endpoints  
6.1  study objectives 
The primary objective of this study is to evaluate the performance and safety of CometTM 
Pressure Guidewire in FFR (Fractional Flow Reserve) measurements in Chinese population. 
6.2  Study endpoints 
6.2.1  The primary efficacy endpoint: 
The primary efficacy endpoint is the acceptable agreement between CometTM Pressure 
Guidewire and Pressure Wire Certus® in FFR measurements. 
 
Notes 
Agreement between the two methods of measurement will be confirmed if both conditions 
are met: 
• The mean paired difference is within +/- 0.005 13 
• The limits of agreement (defined as the mean observed difference +/- 1.96* observed SD) 
is within the pre-defined agreement limits of [-0.08, 0.08] 13 
 
6.2.2  The Secondary endpoint: 

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The safety endpoint is the rate of following major adverse events: 
• 
Pressure wire-related death 
• 
Pressure wire-related cardiac tamponade 
• 
Pressure wire fracture 
• 
Pressure wire-related unanticipated adverse event (UADE)  
7 Study Design 
The COMET China study is a prospective, open-label, multi-center study designed to 
validate the agreement of CometTM Pressure Guidewire and Pressure Wire Certus® in FFR 
measurements. Patient with stable angina or any form of non-ST elevation acute coronary syndrome, 
who are scheduled for diagnostic angiography and pressure wire assessment, and signed the 
informed consent, will be screened for enrollment in this study. 
7.1 Scale and Duration 
The COMET China trial will be conducted in at least 2 sites in Mainland China with planned 
enrollment of up to 50 subjects. 
The study is planned to have approximately 6 months of enrollment.  
All subjects will be screened according to the protocol inclusion and exclusion criteria. All 
eligible subjects will receive Pd/Pa and FFR measurements simultaneously by both CometTM 
Pressure Guidewire and pressure wires Certus®. For the two pressure wires which should be 
passed the target lesion first, each site will be provided a randomized digital table with a 1:1 
ratio at target vessel level. Subject follow-up will end at hospital discharge post FFR 
measurement. 
The study will be considered complete after all subjects have discharged from hospital, or 
withdrawn from the trial (due to death or having been lost to follow-up).   
  

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Figure 7.1- 1 Study design 
7.2 Treatment Assignment 
Patients who sign the Ethics Committee-approved Informed Consent Form (ICF), and have 
met all inclusion criteria and none of the exclusion criteria, are eligible to be enrolled in the 
clinical study. All eligible subjects will receive Pd/Pa and FFR measurements simultaneously 
by both CometTM Pressure Guidewire and pressure wires Certus®. For which wire should be 
passed the target lesion first, randomization will be performed as described in chapter 7.1. 
 
7.2.1 Treatment and Control 
Subjects enrolled in this clinical trial will not be randomized, and there is no control group in 
this study. All the patients will receive measurements by both CometTM Pressure Guidewire 
and pressure wires Certus® at the same time. For which wire should be passed the target 
lesion first, each site will be provided a randomized digital table with a 1:1 ratio at target 
vessel level. 
7.3  Justification for the Study Design 
The Comet Pressure Guidewire received FDA clearance on 06-Oct-2015 and CE Mark on 

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10-Feb-2016.  FDA clearance for the FFR Link was received on 06-Oct-2015 and CE Mark  
in December 2015. Date of CE Mark for iLab Polaris Multi-Modality Guidance System 
(IVUS and FFR Modality): Dec 2015. 
This trial is designed to evaluate the performance and safety of CometTM Pressure Guidewire 
in FFR (Fractional Flow Reserve) measurements compare to PressureWire Certus in Chinese 
population.  
Subjects will receive routine drug treatment required for diagnostic angiography and PCI 
according to the standard clinical practice in China. And FFR measurement will be based on 
the current FFR guidelines in China. 
8 Subject Selection  
8.1  Study Population and Eligibility  
Patient with stable angina or any form of non-ST elevation acute coronary syndrome, who are 
scheduled for diagnostic angiography and pressure wire assessment, and signed the informed 
consent, will be screened for enrollment in this study. Clinical and angiographic inclusion 
and exclusion criteria for the COMET China trial are included in Section 8.2 and Section 8.3 
respectively.  Prior to enrollment in the trial, a subject should meet all of the clinical and 
angiographic inclusion criteria and none of the exclusion criteria. 
8.2 Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8.2-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion (see Section 8.3) is 
met.  
Table 8.2-1: Inclusion Criteria 
Inclusion 
Criteria 
General Inclusion Criteria: 
 
Patient must be at least 18 years old and less than or equal to 75 years of age 
 
Patient or his/her legally-authorized representative agrees to sign the EC-
approved ICF prior to the procedure 
 
Patient with stable angina or any form of non-ST elevation acute coronary 
syndrome and is clinically indicated of intra-coronary diagnostic angiography 
and FFR assessment 
Angiographic Inclusion Criteria: 
Moderate stenosis (30% to 70% diameter stenosis by visual estimation) is detected 
at diagnostic angiography 
 
 
 
8.3 Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 8.3-1) cannot be included in this 
study or will be excluded from this clinical study. 
 

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Table 8.3-1: Exclusion Criteria 
Exclusion 
Criteria 
General Exclusion Criteria: 
 
Patients unable to provide informed consent 
 
Patients in pregnant state 
 
Known renal insufficiency or failure (serum creatinine level of > 2.5 mg/dL, 
or on dialysis)  
 
Allergy to the contrast  
 
Significant arrhythmia, such as II degree or above of atrioventricular block, 
Sick sinus syndrome, ventricular tachycardia 
 
Spastic bronchial asthma 
 
ST elevation coronary syndrome 
 
Hemodynamic instability 
 
Contraindication to nitroglycerin or ATP 
 
Current participation in another investigational drug or device clinical study 
that may affect the FFR measurements 
Angiographic Exclusion Criteria: 
 
CTO lesion 
 
Severe vessel tortuosity at the stenotic segments 
 
Culprit vessel of non-ST-segment elevation acute myocardial infarction 
 
9 Subject Accountability 
9.1 Point of Enrollment 
 Subject, who has signed the IRB/IEC-approved study ICF, and has met all inclusion criteria 
and none of the exclusion criteria, will be considered eligible to be enrolled in the trial. 
Enrollment occurs at the time of advancement of either CometTM Pressure Guidewire or 
PressureWire Certus® into the guide catheter. 
9.2 Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
shall be accounted for and documented. If a subject withdraws from the clinical 
investigation, the reason(s) of withdrawal shall be recorded. If such withdrawal is due to 
problems related to investigational device safety or performance, the investigator shall ask 
for the subject’s permission to follow his/her status/condition outside of the clinical study.   
 
9.3 End-of-Study Definition  
The clinical trial is considered completed when the last participant’s discharge from hospital 
post FFR measurement.  

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9.4 Enrollment controls 
Up to 50 subjects are needed to provide 100 paired measurements for assessing the primary 
endpoint. The enrollment cap for each participating center is 35 subjects.  
10 Study Methods 
10.1 
Data Collection 
The data collection schedule is shown in Data Collection Schedule

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Table 10.1-1: Data Collection Schedule 
Procedure/Assessment 
Screening 
(≤ 14 days prior to index 
procedure) 
Enrollment 
Index Procedure 
Pre-hospital Discharge 
In-person Visit 
X 
X 
X 
X 
Informed Consent process, including 
informed consent signature date 
X 
 
 
 
Demographics (including date of birth, 
gender, and race and ethnicity) 
X 
 
 
 
Physical Assessment, including weight, 
height and blood pressure 
X 
 
 
 
Medical History (including, concomitant 
diseases, concomitant medication and 
medical treatments) 
Xd 
Xd 
Xd 
Xd 
12-lead ECG  
X 
 
 
Xf 
Routine Laboratory (including serum 
creatinine, myocardial enzyme, CBC 
with Hemoglobin and Hematocrit, 
pregnancy tests)a 
X 
 
 
Xe 
Angiographic assessment 
 
Xb 
X 
 
FFR measurement C 
 
 
X 
 
Procedure Assessment (including 
stenting information) 
 
 
X 
 
Adverse Events and Device Deficiency 
Assessment 
 
 
X 
X 
 
X = required; 
a: pregnancy test is required within 72 hours prior to index procedure for potential child-bearing women. 
b:  According to Angiographic Inclusion criteria and exclusion criteria.  
c: both Comet and Certus pressure guidewire 
d: Antithrombotic, antiplatelet medications, and medications for FFR measurement (adenosine-5’-triphosphate (ATP), nitroglycerine). 
e: myocardial enzyme(12 to 24 hours post FFR procedure ) 
f : within 24 hours post FFR procedure  

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10.2 
Study Candidate Screening 
Patient with stable angina or any form of non-ST elevation acute coronary syndrome, who are 
scheduled for diagnostic angiography and pressure wire assessment, will be asked to sign the 
informed consent form (ICF) before participating in any screening procedure. After signing 
the ICF, the subject will receive a screening number and will be documented in a screening 
log.  Each clinical investigator must keep a log of all screened subjects, including both 
eligible and non-eligible subjects (screening failures). 
10.3 
Informed Consent 
Before any study specific tests or procedures are performed, subjects who meet the clinical 
inclusion criteria will be asked to sign the IRB/IEC-approved study ICF. Subjects must be given 
ample time to review ICF and have questions answered before signing ICF.  
Study personnel should explain to the subject that even if the subject agrees to participate in the 
trial and signs the ICF, coronary angiography may demonstrate that the subject is not a suitable 
candidate for the clinical trial. 
10.4 
Screening (Up to 14 days prior to index procedure) 
After a subject has signed the IRB/IEC-approved study ICF, the screening process may begin. 
The screening process will be used to determine the inclusion or exclusion of a subject in the 
study. This process includes the investigator’s assessment of subject’s medical records and 
diagnosis, and following pre-procedure data must be collected within 14 days prior to the index 
procedure (unless otherwise specified), for all subjects:  
• 
Confirmation of clinical eligibility criteria (inclusion and exclusion criteria)  
• 
Demographics including age, gender, and races others than Han (unless restricted by 
local laws)  
• 
Physical assessment, including weight, height and blood pressure 
• 
Medical history (including concomitant diseases, concomitant medication and medical 
treatments)  
• 
Routine laboratory tests  
✓ Serum creatinine  
✓ Complete blood count (CBC) , Hemoglobin and Hematocrit  
✓ Myocardial enzyme 
✓ Pregnancy test for females of child-bearing potential with analysis per local practice 
(serum and/or urine) is required within72 hours prior to the index procedure  
• 
Baseline 12-lead ECG 
10.5   Required Concomitant Medications 
Protocol-required concomitant medications must be reported in the electronic case report 
form (eCRF) from the time of the pre-procedure visit through the discharge from hospital. 
Other concomitant medications also should be reported according to pertinent China laws 
and regulations. Additional concomitant medications may be prescribed at the discretion of 
the investigator based on the standard clinical practice. 

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10.5.1   Prior and post to the index procedure 
Medications related to antithrombotic, antiplatelet medications prior and post to the index 
procedure will be prescribed based on standard clinical practice or at discretion of the 
treating physician. 
10.5.2   In the Catheterization Laboratory 
• 
At the time of the procedure, subjects should receive an intra-arterial bolus of heparin 
(usually 3000-5000 I.U.), or alternate anticoagulants as substitutes for heparin if justified 
by individual subject conditions. 
• 
Coronary injection of nitroglycerine (total: 50-100μg) prior to pressure measurement will 
be needed. The dosage can be adjusted according to the subject's blood pressure. 
• 
Maximal hyperemia will be induced by intravenous adenosine-5’-triphosphate (ATP) via 
the median cubital vein at ≥160 μg/kg/min, and <180 μg/kg/min. 
 10.6   Enrollment & Index Procedure 
Investigators will manage the cardiovascular risk factors and comorbidities for all subjects 
according to standard care. Coronary angiography must be performed using standard techniques 
to confirm angiographic eligibility of the target lesion. Visual angiographic assessment may be 
used to determine if inclusion/exclusion criteria are met. 
10.6.1FFR measurements 
Following key points of FFR measurement are required in this study:  
• 
The use of 6 French guiding catheters (GC) was mandated to optimize the quality of 
phasic pressure recording at the tip of the GC.  
• 
Simultaneous equalization of the aortic and pressure wire tracings was performed with 
both pressure wire sensors at the GC tip before wires were advanced, sequentially, down 
the coronary vessel. 
• 
Randomization by target vessel will be done to determine which wire to pass the target 
lesion first. 
• 
The two sensors of guidewires should be placed at the same location – 3 to 5cm distal to 
the target lesion. Confirmation of the two sensor locations must be obtained under two 
orthogonal radiographic projections. 
• 
Coronary injection of nitroglycerine (total: 50-100μg) prior to pressure measurement will 
be needed. The dosage can be adjusted according to the subject's blood pressure . 
• 
Baseline recordings of Pd/Pa need to be stable for ≥ 3 seconds  
• 
Maximal hyperemia will be induced by intravenous adenosine-5’-triphosphate (ATP) via 
the median cubital vein at ≥160 μg/kg/min, and <180 μg/kg/min. FFR values measured 
by both systems should be recorded during hyperemia for each target lesion at the 
“steady-state” at least 10 seconds of stable value during hyperemia.                
• 
After FFR measurement, withdraw the pressure wire and record ‘Pd/Pa’ when the sensor is at the 
tip of guiding catheter for calculating the drift. The Pd/Pa need to be stable for for ≥ 3 seconds 

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. (Drift is equal to the observed ‘Pd/Pa’ minus 1). 
 
The following information should be recorded during the index procedure: 
• Passthrough time of the target lesion of the two pressure wires (from guiding catheters tip 
to distal of the target lesion) 
• Baseline Pd/Pa, FFR, and drift. 
• Technical success (the pressure wire could be successfully passed to the desired location 
in the target vessel and FFR recording could be obtained) of every target lesion. 
• Medications given during the procedure, including antithrombotic and antiplatelet 
medications, nitroglycerine and ATP  
• Adverse events and device deficiency assessment during the index procedure 
 
Following the FFR measurement, revascularization decision-making will be based on FFR 
value achieved by Pressure Wire Certus®. 
10.6.2 End of the Index Procedure 
The end of index procedure is defined as the time the guiding catheter was removed (post 
final angiography).  The introducer(s) sheaths should be removed per standard local practice.  
• Record procedure information after FFR measurement 
• Collect adverse events 
10.7  Post-Procedure / Pre-Discharge 
The post-procedure/pre-discharge follow-up is an in-person visit and the following data will 
be collected: 
• 12-lead ECG（within 24 hours post FFR procedure） 
• Myocardial enzymes (12 to 24 hours post FFR procedure) 
• Adverse events 
• Medications, including antithrombotic and antiplatelet medications 
10.8 Study Completion 
Subject follow-up will end at hospital discharge post FFR measurement. 
10.9 Source Documents 
Where copies of the original source document as well as printouts of original electronic source 
documents are retained, these shall be signed and dated by a member of the investigation center 
team with a statement that it is a true reproduction of the original source document. 

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11 Statistical Considerations 
11.1  Endpoints 
11.1.1 Primary Endpoint 
Acceptable agreement between CometTM Pressure Guidewire and Pressure Wire Certus® in 
FFR measurements 
11.1.1.1 
Sample Size  
The sample size has been estimated based on the following assumptions13, 14: 
 
Pre-defined agreement limits = [-0.08, 0.08] 
 
Expected paired mean difference = 0.0013  
 
Expected paired standard deviation (SD) = 0.03 
 
Two-sided significance level=5% (alpha) 
 
Power > 80% 
 
Given the above assumptions, 100 paired measurements from up to 50 patients are needed 
for this study. 
11.1.1.2 
Statistical Methods 
Bland-Altman plot will be used to assess the agreement between CometTM Pressure 
Guidewire and Pressure Wire Certus® in FFR measurements 
11.1.2 Safety Endpoints 
 
Pressure wire-related death 
 
Pressure wire-related cardiac tamponade 
 
Pressure wire fracture 
 
Pressure wire-related unanticipated adverse event (UADE) 
11.2 General Statistical Methods 
11.2.1 Analysis Sets 
The primary endpoints will be analyzed on a per-protocol basis.  Only enrolled subjects who 
are measured paired FFR data with the Comet and Certus pressure wires  in the target lesion 
will be included in the primary endpoint analysis sample. Safety analysis will be based on the 
ITT basis. Subjects with unpaired data will be included as appropriate, if any. 
11.2.2 Control of Systematic Error/Bias 
Selection of subjects will be made from the investigators’ general or professional referral 
population. All subjects meeting the inclusion/exclusion criteria that have signed the 
protocol-specific ICF will be eligible for enrollment in the trial. Consecutively eligible 

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subjects should be enrolled into the study to minimize selection bias. In determining subject 
eligibility for the study, the investigator’s assessment of imaging will be used.  
11.2.3 Number of Subjects per Investigative Site 
A maximum of 35 patients (70% of total enrolled subjects) will be recruited from one site to 
avoid treatment center bias and ensure homogeneous study results. 
11.3  Data Analyses 
Subject demographics, clinical history, risk factors, and pre-procedure lesion characteristics 
will be summarized using descriptive statistics (e.g., mean, standard deviation, n, minimum, 
maximum) for continuous variables and frequency tables for discrete variables.   
11.3.1   Other Endpoints/Measurements  
Clinical event rates will be presented as proportions and continuous data will be summarized 
by presenting sample sizes, means, standard deviations, minimums, and maximums.  Point 
estimates and 95% confidence intervals will be provided.  No statistical testing will be 
performed for the additional endpoints. 
11.3.2  Interim Analyses  
No formal interim analyses are planned for the purpose of stopping this study early for 
declaring effectiveness or for futility. 
11.3.3  Subgroup Analyses 
No subgroup analyses are planned 
11.3.4 Multivariable Analyses 
No multivariable analyses are planned in this study. 
11.3.5  Other Analyses 
No other analyses are planned in this study. 
11.3.6  Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analysis will be 
documented in an amended Statistical Analysis Plan approved prior to performing the 
analysis. Changes from the planned statistical methods after performing the analysis will be 
documented in the clinical study report along with a reason for the deviation. 

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12 Data Management 
12.1  Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC system 
and will be issued to the site for appropriate response. Site staff will be responsible for 
resolving all queries in the database. 
12.2  Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain all 
essential study documents and source documentation that support the data collected on the 
study subjects in compliance with applicable regulatory requirements.   
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Sites are required to inform Boston Scientific in 
writing where paper or electronic files are maintained in case files are stored off site and are 
not readily available. 
12.3  Core Laboratories 
No Core laboratories are planned in this study. 
13  Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals from 
IRB/EC of the revised protocol must be obtained prior to implementation. 

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14 Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC/REB of any deviation from the investigational plan to 
protect the life or physical well-being of a subject in an emergency, and those deviations 
which affect the scientific integrity of the clinical investigation. Such notice shall be given as 
soon as possible, but no later than 5 working days after the emergency occurred, or per 
prevailing local requirements, if sooner than 5 working days.  
All protocol deviations (PDs) are classified to “major” and “minor” defined as below:  
➢ A major PD is a protocol deviation that directly or potentially disrupts the study 
progress (i.e., the study design, study data and results can be compromised), OR a 
protocol deviation that compromises the safety and welfare of study participants. 
➢ A minor PD is a protocol deviation that does not disrupt study progress (i.e., the study 
design, study data and results will not be compromised), AND does not compromise 
the safety and welfare of study participants. 
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor using EDC. Sites may also be 
required to report deviations to the IRB/EC/REB, per local guidelines and government 
regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
15 Device/Equipment Accountability for Products Labelled Investigational 
The investigational devices/equipment shall be securely maintained, controlled, and used 
only in this clinical study.  
Boston Scientific shall keep records to document the physical location of all investigational 
devices/ equipment from shipment of investigational devices from BSC or designated 
facility/equipment to the investigation sites until return or disposal. 
The principal investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the investigational devices/equipment, which shall include 
the following 
• Date of receipt 
• Identification of each investigational device/piece of equipment (batch number or unique 
code) 
• Expiry date, as applicable 
• Date or dates of use 

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• Subject identification 
• Date on which the investigational device/piece of equipment was returned/explanted from 
subject, if applicable 
• Date of return (and number) of unused, expired, or malfunctioning investigational 
devices/equipment, if applicable. 
16 Compliance 
16.1   Statement of Compliance 
This study will be conducted in accordance with ISO 14155:2011 (2nd Edition; 2011-02-01) 
Clinical Investigation of Medical Devices for Human Subjects- GCP, or the relevant parts of 
the ICH Guidelines for GCP, ethical principles that have their origins in the Declaration of 
Helsinki, and pertinent China’s laws and regulations. The study shall not begin until the 
required approval/favorable opinion from the IRB/EC/REB and/or regulatory authority has 
been obtained, if appropriate. Also, the study shall not begin prior to issuance of the site 
Authorization to Enroll, as provided by the sponsor. Any additional requirements imposed by 
the IRB/EC/REB or regulatory authority shall be followed, if appropriate.  
16.2   Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation 
plan, ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB/EC/REB, and prevailing local and/or 
country laws and/or regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Prior to beginning the study, sign the Investigator Brochure Signature Page and Protocol 
Signature page documenting his/her agreement to conduct the study in accordance with 
the protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 

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• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency, and provide 
analysis report, which includes the causality assessed by both investigator and BSC and 
decision on study continuance, to IRB/EC per local and/or country requirements. 
• Report to sponsor, per the protocol requirements, all AEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE. 
• Report to the IRB/EC/REB and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE and potential/USADE or UADE, if required by applicable 
laws or regulations or this protocol or by the IRB/EC/REB, and supply BSC with any 
additional requested information related to the safety reporting of a particular event. 
• Maintain the device accountability records and control of the device, ensuring that the 
investigational device is used only by authorized/designated users and in accordance with 
this protocol and instructions/directions for use. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the IRB/EC/REB when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC/REB requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the investigational device when it is used/operated by the subject. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 

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• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
16.2.1 Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, are competent to perform the tasks they have been delegated and 
adequate supervision of those to whom tasks are delegated. Where there is a sub investigator 
at a site, the sub investigator should not be delegated the primary supervisory responsibility 
for the site. The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  
16.3  Institutional Review Board/ Ethics Committee 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB/EC/REB for the clinical investigation before recruiting subjects and implementing all 
subsequent amendments, if required. 
A copy of the written IRB/EC/REB and/or competent authority (CA) approval of the 
protocol (or permission to conduct the study) and ICF, must be received by the sponsor 
before recruitment of subjects into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB/EC/REB before 
the changes are implemented to the study.  All changes to the ICF will be IRB/EC/REB 
approved; a determination will be made regarding whether a new ICF needs to be obtained 
from participants who provided consent, using a previously approved ICF. Annual 
IRB/EC/REB approval and renewals will be obtained throughout the duration of the study as 
required by applicable local/country laws or regulations or IRB/EC/REB requirements. 
Copies of the study reports and the IRB/EC/REB continuance of approval must be provided 
to the sponsor.  
16.4    Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 

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applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO), will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
16.4.1 Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during implant, testing required by the protocol, 
and follow-ups. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of BSC equipment/devices (including 
programmers, analyzers, and other support equipment). 
At the request of the investigator and while under investigator supervision, BSC personnel 
may operate equipment during implant or follow-up, assist with the conduct of testing 
specified in the protocol, and interact with the subject to accomplish requested activities.  
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 
• Discuss a subject’s condition or treatment with a subject  
• Independently collect critical study data (defined as primary or secondary endpoint data) 
• Enter data in electronic data capture systems or on paper case report forms 
16.5   Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 

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17 Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
18 Potential Risks and Benefits 
17.1   Anticipated Adverse Events Associated with the Study Device and Procedure 
The following anticipated adverse events (AE) have been identified for this study, including, 
but are not limited to, the following: 
• Abrupt closure 
• Allergic reaction  
• Angina or unstable angina 
• Arrhythmias 
• Cardiac tamponade/pericardial effusion 
• Contrast induced renal insufficiency or renal failure 
• Death 
• Embolism 
• Exposure to biohazardous material 
• Infection 
• Myocardial infarction or ischemia 
• Prolonged procedure 
• Restenosis (reocclusion) 
• Spasm 
• Stroke/cerebral vascular accident (CVA)/transient ischemic attack (TIA) 
• Vascular thrombus 
• Vessel trauma (dissection, perforation, rupture or injury) 

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17.2   Risks associated with Participation in the Clinical Study 
In addition to the aforementioned risks associated with the Comet pressure Guidewire, two 
pressure guidewires used in this study may prolong the procedure and increase the 
complexity of the procedure. There may be additional risks linked to the procedure, which 
are unforeseen at this time. 
17.3   Possible Interactions with Concomitant Medication 
For FFR measurement, coronary infusion of nitroglycerine and intravenous infusion of ATP 
are required. According to the guideline, the following anticipated adverse events (AE) have 
been identified, including, but are not limited to: atrioventricular block, bradycardia, sinus 
arrest, hypotension, chest tightness and palpitations. 
17.4  Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
17.5  Anticipated Benefits 
FFR measurement can assess the functional significance of coronary stenosis which have 
been proved to improve PCI decision-making and outcomes for patients with coronary artery 
disease[2-10]. 
17.6   Risk to Benefit Rationale 
The Comet pressure wire is expected to be suitable for its intended purpose. There are no 
unacceptable residual risks/intolerable risks and all applicable risks have been addressed 
though the provision of appropriate Directions for Use (DFU). Evaluation of the risks and 
benefits thar are expeted to be associated with use of the CometTM Pressure Guidewire 
demonstrate that when used under the conditions intended, the benefits associated with use of 
the CometTM Pressure Guidewire should outweigh the risks. 
18 Safety Reporting 
18.1 Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All AEs/SAEs 
• All Investigational Device Deficiencies  

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• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
• New findings/updates in relation to already reported events 
Any AE event required by the protocol, experienced by the study subject after informed 
consent and once considered enrolled in the study (as defined in study subject accountability 
section), whether during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity or 
frequency during the course of the investigation. Death should not be recorded as an AE, but 
should only be reflected as an outcome of one specific SAE. 
Refer to Section 17 for the known risks associated with the study device(s). 
In-patient hospitalization is defined as the subjects being admitted to the hospital, with the 
following exceptions. 
• A hospitalization that is uncomplicated and elective/planned (i.e., planned prior to 
enrollment) does not have to be reported as an SAE. 
• If complications or AEs occur during an elective/planned (i.e., planned prior to 
enrollment) hospitalization after enrollment, the complications and AEs must be 
reported as AEs or SAEs if they meet the protocol-specified definitions. However, the 
original elective/planned hospitalization(s) itself should not be reported as an SAE. 
18.2 Definitions and Classification 
Adverse event definitions are provided in Table 18.2-1. Administrative edits were made on 
the safety definitions from ISO 14155 and MEDDEV 2.7/3 for clarification purposes. 
Table 18.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the 
investigational medical device.  
NOTE 1: This includes events related to the investigational medical 
device or comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of an investigational medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies 
or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device. 

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Table 18.2-1: Safety Definitions 
Term 
Definition 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Note: This definition meets the reporting objectives and requirements of 
ISO 14155 and MEDDEV 2.7/3. 
Adverse event that: 
a) Led to death, 
b) Led to  serious deterioration in the health of the subject as defined by 
either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis 
report. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk analysis report. 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
An inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
 
 

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18.3  Relationship to Study Device(s) or Procedure or Required Medications during the 
Procedure 
The Investigator must assess the relationship of the reportable AE to the study device or 
procedure. See criteria in Table 18.3-1:  

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Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Ref: MEDDEV 2.7/3 
Relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
- the event has no temporal relationship with the use of the investigational device or 
the procedures; 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the 
device or procedure; 
- the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the investigational device 
used for diagnosis, when applicable; harms to the subject are not clearly due to use 
error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Unlikely Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the investigational device is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/ clinical condition or/and an effect of another device, drug or 
treatment). Cases were relatedness cannot be assessed or no information has been 
obtained should also be classified as possible. 
Probably Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the investigational device seems relevant and/or 
the event cannot be reasonably explained by another cause, but additional 
information may be obtained. 

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Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Causal Relationship 
Ref: MEDDEV 2.7/3 
The serious event is associated with the investigational device or with procedures 
beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with investigational device use/application 
or procedures; 
- the event involves a body-site or organ that 
-the investigational device or procedures are applied to;-the investigational 
device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the investigational device used for 
diagnosis, when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious event. 
The Investigator must assess the relationship of the reportable AE to the protocol- required 
medication. See criteria in Table 18.3-1:  
Table 18.3-2: Criteria for Assessing Relationship of Protocol- required Medication to 
Adverse Event  
Classification  
Description  
Not Related  
Relationship to the protocol- required medication can be excluded when:  
- the event is not a known side effect of the medication category the protocol- required 
medication belongs to or of similar medication;  
- the event has no temporal relationship with the use of the protocol- required medication;  
- the serious event does not follow a known response pattern to the protocol- required 
medication (if the response pattern is previously known) and is biologically implausible;  
- the discontinuation of protocol- required medication use or the reduction of the dose of 
protocol- required medication - when clinically feasible – and reintroduction of its use (or 
increase of the dose of protocol- required medication), do not impact on the serious event;  
- the event involves a body-site or an organ not expected to be affected by the protocol- 
required medication; the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment or other 
risk factors);  
- the harms to the subject are not clearly due to use error;  
- In order to establish the non-relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of protocol- required medication and the serious 
event.  
Unlikely Related  
The relationship with the use of the protocol- required medication seems not relevant and/or 
the event can be reasonably explained by another cause, but additional information may be 

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obtained.  
Possibly Related  
The relationship with the use of the protocol- required medication is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). Cases were 
relatedness cannot be assessed or no information has been obtained should also be classified 
as possible.  
Probably Related  
The relationship with the use of the protocol- required medication seems relevant and/or the 
event cannot reasonably explained by another cause, but additional information may be 
obtained.  
Causal 
Relationship  
The serious event is associated with the protocol- required medication beyond reasonable 
doubt when:  
- the event is a known side effect of the medication category the protocol- required 
medication belongs to or of similar medication;  
- the event has a temporal relationship with protocol- required medication use;  
- the event involves a body-site or organ that  
o the protocol- required medication are applied to;  
o the protocol- required medication have an effect on;  
- the serious event follows a known response pattern to the protocol- required medication (if 
the response pattern is previously known);  
- the discontinuation of protocol- required medication use (or reduction of the dose of 
medication) and reintroduction of its use (or increase of the dose of medication), impact on 
the serious event (when clinically feasible);  
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment) have been adequately ruled out;  
- harm to the subject is due to error in use;  
- In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of protocol- requiredmedication and the serious event.  
 
18.4Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 18.4-1. 
Table 18.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline pre-market studies 
(MEDDEV 2.7/3:  
CLINICAL INVESTIGATIONS: SERIOUS 
ADVERSE EVENT REPORTING UNDER 
DIRECTIVES 90/385/EEC AND 93/42/EEC) 
Unanticipated Adverse Device 
Effect / Unanticipated Serious 
Adverse Device Effect  
 
Complete AE eCRF page 
with all available new and 
updated information.  
 
 Within 24 hours of first becoming aware 
of the event. 
 Terminating at the end of the study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event at request 
of medical advisor.  
 At request of sponsor.  
Serious Adverse Event  
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within 24 hours becoming aware of the 
event or as per local/regional regulations.  

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Table 18.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline pre-market studies 
(MEDDEV 2.7/3:  
CLINICAL INVESTIGATIONS: SERIOUS 
ADVERSE EVENT REPORTING UNDER 
DIRECTIVES 90/385/EEC AND 93/42/EEC) 
• 
Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event at request 
of medical advisor. 
• 
At request of sponsor 
Serious Adverse Device Effects 
 
Complete AE eCRF page 
with all available new and 
updated information. 
• 
Within 24 hours of first becoming aware of the 
event or as per local/regional regulations.  
• 
Reporting required through the end of the study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event at request 
of medical advisor.  
• 
When documentation is available 
• 
At sponsor request.  
Device Deficiencies (including 
but not limited to failures, 
malfunctions, and product 
nonconformities) 
Note:  Any Investigational 
Device Deficiency that might 
have led to a serious adverse 
event if a) suitable action had 
not been taken or b) 
intervention had not been made 
or c) if circumstances had been 
less fortunate is considered a 
reportable event. 
Complete Device Deficiency 
eCRF with all available new 
and updated information.  
• 
Within 24 hours of first becoming 
aware of the event.  
• 
Reporting required through the end of 
the study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event at request 
of medical advisor. 
• 
At request of sponsor  
Adverse Event including 
Adverse Device Effects 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• 
In a timely manner  (e.g. Recommend 
within 10 business days) after becoming 
aware of the information 
• 
Reporting required through the end of 
the study 
• 
At sponsor request 
Provide all relevant source 
documentation (de-
identified/pseudonymized) 
for reported event as 
applicable.  
Abbreviations: AE = adverse event; CRF = case report form; IDE = Investigational Device Exemption; UADE = 
unanticipated adverse device effect 

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18.5 Boston Scientific Device Deficiencies 
Device deficiencies (including but not limited to failures, malfunctions, use errors, product 
nonconformities, and inadequacy in the information supplied by the manufacturer) of study 
device will be documented and reported to BSC. If possible, the device(s) should be returned 
to BSC for analysis. Instructions for returning the investigational device(s) will be provided 
in Device Management Plan. If it is not possible to return the device, the investigator should 
document why the device was not returned and the final disposition of the device. Device 
deficiencies should also be documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency would be recorded as an adverse event on the appropriate eCRF. 
18.6 Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators 
BSC is responsible for reporting adverse event information and device deficiency to all 
participating Principal Investigators, IRBs/ECs/REBs, as applicable.  
The Principal Investigator is responsible for informing the IRB/EC/REB, and regulatory 
authorities of UADEs and SAEs as required by local/regional regulations. 
According to China local reporting requirements, Boston Scientific Corporation will report 
all SAEs and device deficiencies that could lead to SAEs to the local regulatory authorities 
within 5 business days of BSC first becoming aware of the event, and notify all participating 
investigators/sites and IRBs/ECs in a timely manner.  
BSC shall notify all participating study centers if SAEs/SADEs or Device Deficiencies occur 
which imply a possible increase in the anticipated risk of the procedure or use of the device 
or if the occurrence of certain SAEs/SADEs demands changes to the protocol or the conduct 
of the study in order to further minimize the unanticipated risks. 
 
19 Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC/REB, or central IRB, 
if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB/EC/REB.  Any modification requires acceptance from BSC prior to 
use of the form.  The ICF must be in a language understandable to the subject and if needed, 

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BSC will assist the site in obtaining a written consent translation. Translated consent forms 
must also have IRB/EC/REB approval prior to their use.  Privacy language shall be included 
in the body of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., FDA requirement is within 5 working days of 
learning of such an event). Any violations of the informed consent process must be reported 
as deviations to the sponsor and local regulatory authorities (e.g. IRB/EC/REB), as 
appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC/REB. The new version of the ICF must be approved 
by the IRB/EC/REB. Acceptance by Boston Scientific is required if changes to the revised 
ICF are requested by the site’s IRB/EC/REB. The IRB/EC/REB will determine the subject 
population to be re-consented. 
Study personnel should explain to the subject that even if the subject agrees to participate in 
the trial and signs the ICF, coronary angiography may demonstrate that the subject is not a 

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suitable candidate for the trial.  A Screening Log will be maintained to document select 
information about candidates who fail to meet the Comet China trial eligibility criteria, 
including, but not limited to, the reason for screen failure. 
20 Committees 
20.1  Safety Monitoring Process 
To promote early detection of safety issues, the BSC safety team and its delegated CRO 
safety team will provide evaluations of safety events. Success of this program requires 
dynamic collection of unmonitored data as soon as the event is reported. During regularly 
scheduled monitoring activities, clinical research monitors will support the dynamic 
reporting process through their review of source document and other data information. The 
BSC Medical Safety group includes physicians with expertise in cardiovascular intervention and 
with the necessary therapeutic and subject matter expertise to evaluate and classify the events 
into the categories outlined above. 
20.2  Executive Committee 
An Executive Committee composed of BSC Clinical Management, study Principal 
Investigator will be convened.  This committee will be responsible for the overall conduct of 
the study which will include protocol development, study progress, subject safety, overall 
data quality and integrity, and timely dissemination of study results through appropriate 
scientific sessions and publications.  As appropriate the Executive Committee may request 
participation of Comet China Investigators on the Committee. 
21 Suspension or Termination 
21.1 Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or business reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs/ECs/REBs, and regulatory authorities, as applicable, 
will be notified in writing in the event of study termination. 
21.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
• The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue development of the 
device. 

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21.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
/REB Approval 
Any investigator, or associated IRB/EC/REB or regulatory authority may discontinue 
participation in the study or withdraw approval of the study, respectively, with suitable 
written notice to Boston Scientific. Investigators, associated IRBs/ECs/REBs, and regulatory 
authorities, as applicable, will be notified in writing in the event of these occurrences. 
21.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB/EC/REB and regulatory authorities, as applicable, will be notified. Detailed information 
on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB/EC/REB terminates participation in the study, participating investigators, 
associated IRBs/ECs/REBs, and regulatory authorities, as applicable, will be notified in 
writing. Detailed information on how enrolled subjects will be managed thereafter will be 
provided by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
21.4 Criteria for Suspending/Terminating a Study Site 
Boston Scientific reserves the right to stop the inclusion of subjects at a study site at any time 
after the study initiation visit if no subjects have been enrolled  for a period beyond 6 months 
after site initiation, or if the site has multiple or severe protocol violations/noncompliance 
without justification and/or fails to follow remedial actions. 
In the event of termination of site participation, all study devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IRB/EC/REB and regulatory authorities, as applicable, will 
be notified. Study participants will be contacted, as applicable, and be informed of changes to 
study visit schedule. 
22 Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC will submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study. Boston Scientific adheres to the Contributorship Criteria set forth in the 
Uniform Requirements of the International Committee of Medical Journal Editors (ICMJE; 

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http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
assist authors and investigators in publication preparation provided the following guidelines 
are followed:  
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/).  
23 Bibliography 
1) Freddy Abnousi, Celina Yong, William Fearon. Cost–effectiveness of fractional flow 
reserve-guided percutaneous coronary intervention. Interv. Cardiol. (2015) 7(4), 387–
392. 
2) Tonino PA, Fearon WF, De Bruyne B, et al. Angiographic versus functional severity of 
coronary artery stenoses in the FAME study fractional flow reserve versus angiography 
in multivessel evaluation. J Am Coll Cardiol. 2010. 55(25):2816-21. 
3) Tonino PA, De Bruyne B, Pijls NH et al. FAME Study Investigators. Fractional flow 
reserve versus angiography for guiding percutaneous coronary intervention. N Engl J 
Med. (2009). 360, 213–224. 
4) De Bruyne B, Pijls NHJ, Kalesan B, Barbato E, Tonino PAL, Piroth Z, Jagic N, Mobius-
Winckler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engstrom T, Oldroyd KG, 
Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Juni P and 
Fearon WF. Fractional flow reserve-guided PCI versus medical therapy in stable 
coronary disease. N Engl J Med. 2012;367:991-1001. 
5) De Bruyne B, Fearon WF, Pijls NHJ, Barbato E, Tonino P, Piroth Z, Jagic N, Mobius-
Winckler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engström T, Oldroyd K, 
Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Limacher A, 
Nüesch E and Jüni P. Fractional flow reserve-guided PCI for stable coronary artery 
disease. N Engl J Med. 2014;371:1208-1217. 
6) Bech GJ, De Bruyne B, Pijls NHJ et al. Fractional flow reserve to determine the 
appropriateness of angioplasty in moderate coronary stenosis: a randomized trial. 
Circulation. (2001).103, 2928–2934. 
7) Pijls NHJ, De Bruyne B, Peels K et al. Measurement of fractional flow reserve to assess 
the functional severity of coronary artery stenoses. N. Engl. J. Med. (1996). 334, 1703–
1708 

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8) Hamilos M, Muller O, Cuisset T et al. Long-term clinical outcome after fractional flow 
reserve guided treatment in patients with angiographically equivocal left main coronary 
artery stenosis. Circulation 120, 1505–1512.(2009). 
9) Muller O, Mangiacapra F, Ntalianis A et al. Long-term follow-up after fractional flow 
reserve-guided treatment strategy in patients with an isolated proximal left anterior 
descending coronary artery stenosis. JACC Cardiovasc. Interv. 4, 1175–1182 (2011). 
10) Puymirat E, Peace A, Mangiacapra F et al. Long-term clinical outcome after fractional 
flow reserve-guided percutaneous coronary revascularization in patients with small-
vessel disease. Circ. Cardiovasc. Interv. 5, 62–68 (2012). 
11) Kushner FG, Hand M, Smith SC Jr et al. 2009 Focused updates: ACC/AHA guidelines 
for the management of patients with ST-elevation myocardial infarction (updating the 
2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on 
percutaneous coronary intervention (updating the 2005 guideline and 2007 focused 
update): a report of the American College of Cardiology Foundation/American Heart 
Association Task Force on Practice Guidelines. Circulation 120, 2271–2306 (2009). 
12) Wijns W, Kolh P, Danchin N et al. Guidelines on myocardial revascularization: the Task 
Force on Myocardial Revascu- larization of the European Society of Cardiology (ESC) 
and the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 31, 
2501–2555 (2010). 
13) Nick Curzen, Rod Stables. Randomised Comparison of Simultaneous Data from two 
Different Pressure Wires: the COMET trial(NCT02578381)   
14) Lu MJ, Zhong WH, Liu YX, Miao HZ, Li YC, Ji MH (2016) Sample size for assessing 
agreement between two methods of measurement by Bland-Altman method.  The 
International Journal of Biostatistics 12: issue 2 (8pp) 
15) Stables RH, Elguindy M, Kemp I,et al. Randomised Controlled Trial to Compare two 
Coronary Pressure Wires using Simultaneous Measurements in Human Coronary 
Arteries The COMET trial. EuroIntervention. 2018 Oct 30. pii: EIJ-D-18-00786. 
16) The Chinese expert consensus on the clinical application of coronary fractional flow 
reserve Chinese Journal of Cardiology. 2016,44(4):292-297. 
17) Lu MJ, Zhong WH, Liu YX, Miao HZ, Li YC, Ji MH (2016) Sample size for assessing 
agreement between two methods of measurement by Bland-Altman method.  The 
International Journal of Biostatistics 12: issue 2 (8pp) 
24  Abbreviations and Definitions  
24.1   Abbreviations 
Abbreviations are shown in Table 24-1. 
Table 24-1: Abbreviations 
Abbreviation/Acronym 
Term 
ACC 
American College of Cardiology 
ACT 
Activated clotting time  

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Abbreviation/Acronym 
Term 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AHA 
American Heart Association 
ARC 
Academic Research Consortium 
ATP 
Adenosine-5-triphosphate  
BSC 
Boston Scientific Corporation 
BMS 
Bare Metal Stent 
CABG 
Coronary Artery Bypass Graft 
CEC 
Clinical Events Committee 
CK 
Creatine Kinase 
CK-MB 
Creatine Kinase-Myoglobin Band 
CRO 
Contract Research Organization 
eCRF 
electronic Case Report Form 
CVA 
Cerebrovascular Accident 
DES 
Drug-Eluting Stent 
DFU 
Directions for Use 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
ESC 
European Society of Cardiology 
FDA 
Food and Drug Administration 
FFR 
Fractional Flow Reserve 
GCP 
Good Clinical Practices 
GC 
guiding catheters  
IC 
Intercontinental 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
IRB 
Institutional Review Board 
ISO 
International Standards Organization 
ITT 
Intention to Treat 
LAD 
Left Anterior Descending Coronary Artery 
LBBB 
Left Bundle Branch Block 
MACE 
Major Adverse Cardiac Event 
MI 
Myocardial Infarction 
MLD 
Minimum Lumen Diameter 

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Abbreviation/Acronym 
Term 
NHLBI 
NMPA 
National Heart, Lung, and Blood Institute 
National Medical Products Administration 
PCI 
Percutaneous Coronary Intervention 
QCA 
Quantitative Coronary Angiography 
RCA 
Right Coronary Artery 
RVD 
Reference Vessel Diameter 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SCAI 
Society for Cardiovascular Angiography and Interventions 
STEMI 
ST Elevation Myocardial Infarction 
TIA 
Transient Ischemic Attack 
TIMI 
Thrombolysis in Myocardial Infarction 
TLF 
Target Lesion Failure 
TLR 
Target Lesion Revascularization 
TVF 
Target Vessel Failure 
TVR 
Target Vessel Revascularization 
ULN 
 Upper Limit of Normal 
24.2  Definitions 
ABRUPT VESSEL CLOSURE 
Abrupt vessel closure is the occurrence of new severely reduced flow (TIMI grade 0 or 1) 
within the target vessel that persists and requires bailout, including emergency surgery, or 
results in MI or death. Abrupt stent closure requires proven association with a mechanical 
dissection of the treatment site or instrumented vessel, coronary thrombus, or severe spasm. 
Abrupt stent closure does not connote “no reflow” due to microvascular flow limitation in 
which the epicardial artery is patent but has reduced flow. Abrupt stent closure also does not 
connote transient closure with reduced flow in which the assigned treatment reversed the 
closure. 
Sub-abrupt closure is an abrupt closure that occurs after the target procedure is completed 
and the subject has left the catheterization laboratory and before hospital discharge. 
Threatened abrupt closure is a grade B dissection and 50% diameter stenosis or any 
dissection of grade C or higher. 
ARRHYTHMIA 
An arrhythmia is any variation from the normal rhythm of the heart, including sinus 
arrhythmia, premature beats, heart block, atrial or ventricular fibrillation, atrial or ventricular 
flutter, and atrial or ventricular tachycardia. 

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BIFURCATION LESION 
A bifurcation lesion is a lesion associated with the area where a branch vessel >2.0 mm in 
diameter by visual estimate originates. 
BINARY RESTENOSIS 
Binary restenosis is a diameter stenosis >50% at the previously treated lesion site, including 
the original treated area and the adjacent proximal and distal QCA analysis segment. 
BLEEDING CLASSIFICATIONS (Ref: GUSTO) 
• Severe or life-threatening: Either intracranial hemorrhage or bleeding that causes 
hemodynamic compromise and requires intervention 
• Moderate: Bleeding that requires blood transfusion but does not result in hemodynamic 
compromise 
• Mild: Bleeding that does not meet criteria for either severe or moderate bleeding 
 
BRAUNWALD CLASSIFICATION OF UNSTABLE ANGINA 
Severity 
• Class I: New onset, severe or accelerated angina. Subjects with angina of less than 
2 months duration, severe or occurring 3 or more times per day, or angina that is 
distinctly more frequent and precipitated by distinctly less exertion; no pain at rest in the 
last 2 months. 
• Class II: Angina at rest, subacute.  Subjects with 1 or more episodes of angina at rest 
during the preceding month, but not within the preceding 48 hours. 
• Class III: Angina at rest, acute. Subjects with 1 or more episodes of angina at rest within 
the preceding 48 hours. 
Clinical Circumstances 
• Class A: Secondary unstable angina. A clearly identified condition extrinsic to the 
coronary vascular bed that has intensified myocardial ischemia (e.g., anemia, fever, 
infection, hypotension, tachyarrhythmia, thyrotoxicosis, and hypoxemia secondary to 
respiratory failure). 
• Class B: Primary unstable angina. 
• Class C: Postinfarction unstable angina (within 2 weeks of documented MI). 
 
CARDIAC TAMPONADE 
Cardiac tamponade is an acute compression of the heart due to effusion of the fluid into the 
pericardium, or the collection of blood in the pericardium, from rupture of the heart or 
penetrating trauma. 
CARDIOGENIC SHOCK 
Cardiogenic shock is a clinical state of hypoperfusion characterized by a systolic blood 
pressure <80 mmHg and/or a central filling pressure >20 mmHg, or a cardiac index 
<1.8 liters/min/m2 where there is evidence of insufficient end organ profusion. Shock is also 
considered present if intravenous inotropes and/or intra-aortic balloon pump (IABP) are 

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needed to maintain a systolic blood pressure >80 mmHg and a cardiac index 
>1.8 liters/minute/m2. 
CREATINE KINASE-MYOGLOBIN BAND 
Creatine kinase-myoglobin band (CK-MB) is an isoenzyme of creatine kinase (CK) with a 
distinct molecular structure specific as an indicator of myocardial cell injury. It is used to 
evaluate possible causes of chest pain, to detect and diagnose acute MI and re-infarction, and 
to monitor the severity of myocardial ischemia. 
CLINICAL EVENTS COMMITTEE 
A CEC is an independent group of individuals with pertinent expertise that review and 
adjudicate important endpoints and relevant AEs reported by study investigators. 
CLINICAL EVENTS COMMITTEE EVENT 
The CEC will adjudicate all reported cases of stent thrombosis, TVR, MI (Q-wave and non–
Q-wave), and death (to ensure appropriate classification of death as cardiac or non-cardiac). 
A case adjudicated by the CEC is considered to be a CEC event. 
CLINICAL PROCEDURAL SUCCESS (VISUAL ESTIMATE) 
Clinical procedural success is post-procedure diameter stenosis <30% in 2 near-orthogonal 
projections with TIMI 3 flow in all target lesions, as visually assessed by the physician, 
without the occurrence of in-hospital MI, TVR, or cardiac death. 
COMPLICATION (ANGIOGRAPHIC OR CLINICAL) 
A complication (angiographic or clinical) is an undesirable clinical event that results in death, 
injury, or invasive intervention. Complications may include, but are not limited to, 
perforation, occlusion, intimal flap, dissection, loss of side branch, distal embolization, non-
fatal MI, elevated CK Total, prolonged angina, hypotension, hematoma, arrhythmias, etc. 
Complications may or may not be related to the investigational device. 
CONGESTIVE HEART FAILURE 
Congestive heart failure is an inadequacy of the heart such that it fails to maintain adequate 
circulation of blood, so that congestion and edema develop in the tissues. Clinical syndrome 
is characterized by shortness of breath, non-pitting edema, enlargement of the liver, engorged 
neck veins, and pulmonary rales. 
CORONARY ANEURYSM 
A coronary aneurysm is a pathologic dilatation of a segment of a blood vessel involving all 
three layers of the vessel wall 1.5× the RVD. 
CORONARY ARTERY SPASM 
Coronary artery spasm, or coronary vasospasm, is a spasm of a coronary artery, resulting in a 
decrease in lumen diameter. It may occur distal to the treatment site and is generally reversed 
with intracoronary administration of NTG or with adjunct balloon dilatation. 
DEATH 
Death is categorized as cardiac or non-cardiac. 

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Cardiac death is defined as death due to any of the following. 
• Acute MI 
• Cardiac perforation/pericardial tamponade 
• Arrhythmia or conduction abnormality 
• CVA through hospital discharge or CVA suspected of being related to the procedure 
• Death due to complication of the procedure, including bleeding, vascular repair, 
transfusion reaction, or bypass surgery 
• Any death in which a cardiac cause cannot be excluded 
Non-cardiac death is defined as a death not due to cardiac causes as defined above. 
DISSECTION, NHLBI CLASSIFICATION 
• Type A: Small radiolucent area within the lumen of the vessel disappearing with the 
passage of the contrast material 
• Type B: Appearance of contrast medium parallel to the lumen of the vessel disappearing 
within a few cardiac cycles 
• Type C: Dissection protruding outside the lumen of the vessel persisting after passage of 
the contrast material 
• Type D: Spiral shaped filling defect with or without delayed run-off of the contrast 
material in the antegrade flow 
• Type E: Persistent luminal filling defect with delayed run-off of the contrast material in 
the distal lumen 
• Type F: Filling defect accompanied by total coronary occlusion 
DIABETES MELLITUS 
Subjects will be categorized as having diabetes mellitus if medical treatment (oral or 
injection) is required for control of blood glucose levels. 
DISTAL EMBOLIZATION 
Distal embolization is migration of a filling defect or thrombus to distally occlude the target 
vessel or one of its branches. 
EPICARDIAL VESSEL 
Epicardial vessels include the LAD and its branches, the LCX and its branches, and the RCA 
and its branches. 
HYPERTENSION 
Hypertension is persistently high arterial blood pressure. Various criteria for its threshold 
have been suggested, ranging from 140 mmHg systolic and 90 mmHg diastolic to as high as 
220 mmHg systolic and 110 mmHg diastolic. Hypertension may have no known cause or be 
associated with other primary diseases. 

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HYPOTENSION 
Sustained hypotension is a systolic blood pressure less than 80 mmHg lasting more than 
30 minutes or requiring intervention (e.g., pacing, IABP, intravenous vasopressors, to sustain 
systolic blood pressure). This excludes transient hypotension or vagal reactions, which are 
self-limited or readily reversible. 
INDEX PROCEDURE START TIME 
Index procedure start time is defined as the time of guide catheter insertion into sheath for the 
interventional procedure. 
INDEX PROCEDURE END TIME 
Index procedure end time is defined as the time the guide catheter is removed after the final 
angiography. 
LEFT MAIN DISEASE 
Left main disease is a significant lesion in the left main coronary artery of at least 50% 
diameter stenosis. A protected left main artery means left main with a functioning graft, 
either venous or arterial, placed to any of the branches of the left main. This is usually the 
LAD or CX, but could also include one of the branches of those vessels. Having a stent in the 
left main coronary artery does not in itself constitute a protected left main. 
LESION CHARACTERISTICS (ACC/AHA CLASSIFICATION) 
• Type A lesions: Minimally complex, length <10 mm, concentric, readily accessible, 
non-angulated segment (<45), smooth contour, little or no calcification, less than totally 
occlusive, not ostial in location, no major side branch involvement, and an absence of 
thrombus. 
• Type B lesions: Moderately complex, tubular (length 10 to 20 mm), eccentric, moderate 
tortuosity of proximal segment, moderately angulated segment (>45, <90), irregular 
contour, moderate or heavy calcification, total occlusions <3 months old, ostial in 
location, bifurcation lesions requiring double guidewire, and some thrombus present. 
• Type C lesions: Severely complex, diffuse (length 20 mm), excessive tortuosity of 
proximal segment, extremely angulated segments >90, total occlusions >3 months old 
and/or bridging collaterals, inability to protect major side branches, and degenerated vein 
grafts with friable lesions. 
LESION LENGTH 
Lesion length is measured as distance from the proximal to the distal shoulder in the view 
that demonstrates the stenosis in its most elongated projection. Lesion length is classified as 
discrete (<10 mm), tubular (10-20 mm), or diffuse (>20 mm). 
LESION LOCATION 
Lesion location is the location of the lesion according to the specific coronary artery (i.e., left 
main, LAD, LCX, or RCA) or bypass graft, and is specified as proximal, mid, or distal. A 
standard map will be provided to be used for location descriptions. 

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Note: In this trial, the ramus will be considered to be a branch of the LCX for purposes of 
determining eligibility and for determining TVR. 
LEUKOPENIA 
Leukopenia is a leukocyte count of <3.0 × 109/liter for more than 3 days. 
MALFUNCTION 
A malfunction is a failure of the device to meet performance specifications or otherwise 
perform as intended. 
MULTI-VESSEL DISEASE 
Multi-vessel disease refers to the presence of >50% diameter stenosis as measured by caliper 
method or QCA on-line in 2 or 3 major epicardial coronary vessels or bypassed branches. 
MYOCARDIAL INFARCTION 
In this trial, MI will be defined according to the definition provided below.  
 

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PERFORATION 
Perforations are classified as follows: 
• Angiographic perforation: Perforation detected by clinical site or Angiographic Core 
Laboratory at any point during the procedure. 
• Clinical perforation: Perforation requiring additional treatment, including efforts to seal 
the perforation or pericardial drainage, or resulting in significant pericardial effusion, 
abrupt closure, MI, or death. 
• Pericardial hemorrhage/tamponade: Perforation causing tamponade. 
PSEUDOANEURYSM 
A pseudoaneurysm is an encapsulated hematoma in communication with an artery. It is often 
difficult to distinguish from an expanding hematoma at the site of arterial puncture. It usually 
requires surgical repair. 
REFERENCE DIAMETER OF NORMAL ARTERY SEGMENT 
Reference diameter of the normal artery segment is an angiographic measurement of the 
artery proximal and/or distal to the lesion intended for angioplasty. This is also referred to as 
“reference vessel diameter” (RVD). 
REPEAT INTERVENTION 
Repeat intervention is a PCI or CABG performed after the end of the index procedure. The 
repeat intervention should be performed to improve blood flow. 
RESTENOSIS 
See Binary Restenosis. 
STENT THROMBOSIS (Ref: Academic Research Consortium Definition) 31 
Stent thrombosis should be reported as a cumulative value at the different time points and 
with the different separate time points. Time 0 is defined as the time point after the guide 
catheter has been removed and the patient left the catheterization lab. 
Timing: 
• Acute stent thrombosis*: 0-24 hours after stent implantation 
• Subacute stent thrombosis*: >24 hours to 30 days after stent implantation 
• Late stent thrombosis: >30 days to 1 year after stent implantation 

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• Very late stent thrombosis: >1 year after stent implantation 
* Acute/subacute can also be replaced by early stent thrombosis. Early stent thrombosis is 0-30 days. 
Stent thrombosis may be defined as: 
• Confirmed/definite 
• Probable 
• Possible 
Confirmed/Definite (is considered either angiographic confirmed or pathologic confirmed) 
Angiographic confirmed stent thrombosis is considered to have occurred if: 
• TIMI flow is: 
o TIMI flow grade 0 with occlusion originating in the stent or in the segment 5mm 
proximal or distal to the stent region in the presence of thrombus* 
o TIMI flow grade 1, 2 or 3 originating in the stent or in the segment 5mm proximal or 
distal to the stent region in the presence of a thrombus* 
AND at least one of the following criteria, up to 48 hours, has been fulfilled: 
• New onset of ischemic symptoms at rest (typical chest pain with duration >20 minutes) 
• New ischemic ECG changes suggestive of acute ischemia 
• Typical rise and fall in cardiac biomarkers (>2× ULN of CK) 
The incidental angiographic documentation of stent occlusion in the absence of clinical 
syndromes is not considered a confirmed stent thrombosis (silent thrombosis). 
* Intracoronary thrombus 
Non-occlusive thrombus: Spheric, ovoid or irregular non-calcified filling defect or lucency surrounded by 
contrast material (on 3 sides of within a coronary stenosis) seen in multiple projections, or persistence of 
contrast material within the lumen, or a visible embolization of intraluminal material downstream. 
Occlusive thrombus: A TIMI 0 or TIMI 1 intra-stent or proximal to a stent up to the most adjacent proximal 
side branch or main branch (if originating from the side branch). 
Probable 
Clinical definition of probable stent thrombosis is considered to have occurred in the 
following cases: 
• Any unexplained death within the first 30 days 
• Irrespective of the time after the index procedure and MI in the absence of any obvious 
cause which is related to documented acute ischemia in the territory of the implanted 
stent without angiographic confirmation of stent thrombosis 
Possible 
Clinical definition of possible stent thrombosis is considered to have occurred with any 
unexplained death beyond 30 days. 

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STROKE/CEREBROVASCULAR ACCIDENT 
An acute symptomatic episode of neurological dysfunction attributed to a vascular cause 
lasting more than 24 hours or lasting 24 hours or less with a brain imaging study or autopsy 
showing infarction. 
Classification: 
• Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal 
dysfunction caused by an infarction of central nervous system tissue. 
• Hemorrhagic Stroke: An acute symptomatic episode of focal or global cerebral or spinal 
dysfunction caused by a nontraumatic intraparenchymal, intraventricular, or subarachnoid 
hemorrhage. 
• Undetermined Stroke: A stroke with insufficient information to allow categorization as 
ischemic or hemorrhagic. 
An event that lasts < 24 hours may be adjudicated as a stroke if the following treatments 
were used: 
• Pharmacologic, i.e., thrombolytic drug administration, or 
• Non-pharmacologic, i.e., neurointerventional procedure (e.g., intracranial angioplasty) 
TARGET LESION 
The target lesion is the lesion selected by the Investigator for FFR measurement.  
TARGET LESION FAILURE 
Target lesion failure is any ischemia-driven revascularization of the target lesion, MI (Q-
wave and Non-Q-wave MI) related to the target vessel, or (cardiac) death related to the target 
vessel. For the purposes of this protocol, if it cannot be determined with certainty whether the 
MI was related to the target vessel, it will be considered a TLF. if it cannot be determined 
with certainty whether the Cardiac death was related to the target vessel, it will be considered 
a TLF. 
TARGET LESION REVASCULARIZATION 
Target lesion revascularization is any ischemia-driven repeat percutaneous intervention, to 
improve blood flow, of the successfully treated target lesion or bypass surgery of the target 
vessel with a graft distally to the successfully treated target lesion. A TLR will be considered 
as ischemia-driven if the target lesion diameter stenosis is 50% by QCA and there is 
presence of clinical or functional ischemia which cannot be explained by other coronary or 
graft lesions. Clinical or functional ischemia is any of the following: 
• The subject has a positive functional study corresponding to the area served by the target 
lesion. 
• The subject has ischemic ECG changes at rest in a distribution consistent with the target 
vessel. 
• The subject has ischemic symptoms referable to the target lesion. 
A TLR will be considered as ischemia-driven if the lesion diameter stenosis is 70% by 
QCA even in the absence of clinical or functional ischemia. 

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TARGET VESSEL 
The target vessel is any coronary vessel (e.g., left main coronary artery, LAD, LCX, or RCA) 
containing a target lesion. Side branches of a target vessel such as the LAD are also 
considered part of the target vessel. 
TARGET VESSEL FAILURE 
Target vessel failure is any ischemia-driven revascularization of the target vessel, MI (Q-
wave and non–Q-wave) related to the target vessel or death related to the target vessel. For 
the purposes of this protocol, if it cannot be determined with certainty whether the MI or 
death was related to the target vessel, it will be considered a TVF. 
TARGET VESSEL REVASCULARIZATION 
Target vessel revascularization is defined as a TLR (see definition above) or a TVR remote 
(see definition below). 
TARGET VESSEL REVASCULARIZATION REMOTE 
Target vessel revascularization remote is any ischemia-driven repeat percutaneous 
intervention, to improve blood flow, or bypass surgery of not previously existing lesions 
diameter stenosis ≥50% by QCA in the target vessel, excluding the target lesion. A TVR will 
be considered ischemia-driven if the target vessel diameter stenosis is 50% by QCA and any 
of the following are present: 
• The subject has a positive functional study corresponding to the area served by the target 
vessel. 
• The subject has ischemic ECG changes at rest in a distribution consistent with the target 
vessel. 
• The subject has ischemic symptoms referable to the target vessel. 
A TVR will also be considered as ischemia-driven if the lesion diameter stenosis is 70% 
even in the absence of clinical or functional ischemia. 
TECHNICIAN WORKSHEET 
A Technician Worksheet is a record for listing the filming sequence and angulations of x-ray 
equipment, details of inflations, and description of lesion(s). 
THROMBUS (ANGIOGRAPHIC) 
Thrombus (angiographic) is discrete, mobile intraluminal filling with defined borders 
with/without associated contrast straining, classified as either absent or present. 
THROMBOLYSIS IN MYOCARDIAL INFARCTION CLASSIFICATION 
• TIMI 0: No perfusion. 
• TIMI 1: Penetration with minimal perfusion. Contrast fails to opacify the entire bed distal 
to the stenosis of the duration of the cine run. 
• TIMI 2: Partial perfusion. Contrast opacifies the entire coronary bed distal to the stenosis. 
However, the rate of entry and/or clearance is slower in the coronary bed distal to the 
obstruction than in comparable areas not perfused by the dilated vessel. 

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• TIMI 3: Complete perfusion. Filling and clearance of contrast equally rapid in the 
coronary bed distal to stenosis as in other coronary beds. 
TOTAL OCCLUSION 
A total occlusion is a lesion with no flow (i.e., TIMI flow 0). 
 
 
 
 
 
 
 

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Investigator’s Declaration 
 
1. I agree to conduct the trial in accordance with the Declaration of Helsinki, applicable 
laws and regulations in China, as well as the study protocol. 
2. I agree to record all data accurately in the Case Report Form (CRF) and to complete the 
clinical research report within the study timeline. 
3. I agree to give the sponsor and its designated monitor/auditor and regulatory 
authorities’ representatives consent to monitor, audit and inspect this trial. 
4. I agree to abide by the clinical research contract /agreement signed by all parties.  
My signature below indicates that I have read and understood the study protocol and the 
contents above. 
 
Sponsor    
                                                                      
Signature(stamp) 
                        Date 
 
 
Principal/Coordinating Investigator  
                    
Signature 
                     Date 
 
 
Institution of clinical trial on medical device 
 
                                 
                       Signature 
                          Date