A Multi-Center, Prospective, Observational Registry for the Evaluation of Coronary Artery Calcified Nodules Using Intravascular Ultrasound (IVUS) and/or Optical Coherence Tomography (OCT) in China (CN-IVI Registry)
Conditions: Coronary Artery Disease, Coronary Artery Atherosclerosis, Coronary Calcified Nodules, Coronary Calcification
Sponsor: Shanghai Zhongshan Hospital

 
1
 
  
A Multi-Center, Prospective, Observational Registry for the Evaluation of Coronary Artery 
Calcified Nodules Using Intravascular Ultrasound (IVUS) and/or Optical Coherence 
Tomography (OCT) in China (CN-IVI Registry) 
 
Brief title： Intravascular imaging evaluated Calcified nodule China Registry  
 
 
  
 
  
 
  
 
CN-IVI Registry  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Verson 2.0 ——Sep/20/2025  

 
2
 
  
 
  
Sponsor 
Zhongshan Hospital, Fudan University 
No. 180 Fenglin Road, Xuhui District 
Shanghai 200032 
China 
 
 

 
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II. Investigator Signature Page 
Study Title: 
Intravascular Imaging Evaluation of Calcified Nodules: A Chinese Registry Study 
Abbreviation: 
CN-IVI Registry 
Version: 
1.0, June 10, 2024 
 
We have read this protocol and/or amendments and appendices and agree to comply with the 
requirements. We will provide copies of this protocol and all relevant information to the 
personnel under our supervision. We will discuss these materials with them and ensure their full 
understanding. 
We undertake to conduct the study in accordance with this protocol, adhering to its requirements, 
relevant ethical and safety considerations, and guidelines. The study will be registered following 
ISO 14155:2020 and applicable regional regulatory requirements. 
 
Investigator Name and Title 
Name and Full Address of Site 
 
Investigator Signature 
Date (YYYY-MM-DD) 
  
 
  
 
 
  
 
 
 
 
 
 
 
 

 
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III. Protocol Summary 
Study Title 
Intravascular Imaging Evaluation of Calcified Nodules: A Chinese Registry Study 
Study Abbreviation 
CN-IVI Registry 
Study Type 
Prospective, observational, multicenter, single-arm registry study 
Trial Registry 
ClinicalTrials.gov 
Background 
Calcified nodules are a type of coronary calcified lesion. Based on morphological features, they 
can be classified into two types: those with a crater-like appearance (eruptive morphology) 
lacking a complete fibrous cap and sometimes accompanied by thrombus adhesion, which may 
be more closely associated with poor prognosis; and those with a non-eruptive morphology, 
typically covered by an intact fibrous cap. The natural course of calcified nodules and the 
selection of optimal treatment strategies require further clarification through large-scale clinical 
studies. 
Objectives 
1. To observe the natural course of calcified nodule lesions evaluated by intravascular 
imaging. 
2. For cases undergoing interventional treatment, to evaluate the impact of different 
treatment strategies on clinical outcomes. 
Study Design 
The IVI CN China Registry is a prospective, observational, multicenter, single-arm registry 
study. Patients scheduled for PCI in the catheterization laboratory will undergo intravascular 
imaging based on the operator’s clinical judgment, following standard medical practice. If 
calcified nodules are detected via intravascular imaging, patients will be further approached for 
informed consent to participate in the registry. The study plans to enroll 500 patients with 
coronary calcified nodules evaluated by intravascular imaging. Enrolled patients will be followed 
for up to 3 years. 
Study Centers 
Study Centers 
Approximately 20 research centers across China 
Study Plan 
Clinical observation of cases with calcified nodules evaluated by intravascular imaging 

 
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Reference Studies 
None 
Inclusion Criteria 
1. Patients must be ≥18 years of age. 
2. At least one calcified nodule lesion identified by coronary intravascular imaging. 
3. Patients are willing and able to comply with study procedures and follow-up until the 
study concludes. 
4. Subjects confirm understanding of the study risks, benefits, and alternative treatment 
options, and provide signed informed consent approved by the Ethics Committee before 
any protocol-related procedures are performed. 
Exclusion Criteria 
Contraindication to Procedure: Known contraindication to coronary angiography, PCI, or 
adjunctive pharmacologic therapy (e.g., aspirin, P2Y12 inhibitors, heparin, contrast media) that 
cannot be adequately managed with standard medical care. 
    Life Expectancy: Life expectancy of less than 1 year due to non-cardiac comorbid conditions 
(e.g., active malignancy, advanced organ failure). 
    Inability to Follow-Up: Inability or unwillingness to comply with the study protocol or 
scheduled follow-up visits. 
 
Screening and Informed Consent for Patients with Calcified Nodules 
• 
Patients with indications for angiography and potential PCI will be screened according to 
the inclusion/exclusion criteria. 
• 
After selective angiography, it will be determined whether intravascular imaging is 
required. Upon completion of intravascular imaging, if at least one calcified nodule is 
diagnosed, informed consent will be obtained from the patient. 
• 
The decision to treat the nodule and the treatment strategy will be at the operator’s 
discretion. 
• 
Planned angiographic follow-up is discouraged. If clinically indicated angiographic 
follow-up is performed, it must be documented in the eCRF. 
Non-Study Drug Therapy 
• 
Dual antiplatelet therapy, intraoperative anticoagulation regimens, and the use of GP 
IIb/IIIa inhibitors will be determined by the operator based on the clinical situation. 
IVI Core Lab Assessment and Angiographic Collection 

 
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• 
All intravascular imaging data will be collected via a secure electronic transmission 
system. 
• 
Post-PCI imaging for all subjects will be reviewed by an independent intravascular 
imaging core laboratory and evaluated according to optimization standards. Feedback 
will be provided to the clinical trial center when necessary. 
• 
Angiographic images at baseline and during the procedure (including staged procedures 
if required) for all revascularizations will be collected via a secure electronic transmission 
system. 
• 
Intravascular imaging and/or coronary physiology data will be assessed by the core 
laboratory for subsequent subgroup analyses. 
Study Endpoints 
Primary Endpoint: 
TVF (Target Vessel Failure) is defined as the composite of cardiac death, target vessel 
myocardial infarction*, or clinically indicated target vessel revascularization. 
*Periprocedural myocardial infarction will be defined according to ARC-2 but will not be 
included in the primary composite endpoint. Spontaneous myocardial infarctions (>48 hours 
post-procedure) will be classified according to the Fourth Universal Definition of Myocardial 
Infarction. 
Key Secondary Endpoints: 
1. Composite of target vessel myocardial infarction* and clinically indicated target vessel 
revascularization. 
2. Clinically indicated target vessel revascularization. 
3. Composite of cardiac death and target vessel myocardial infarction*. 
4. Target lesion failure, defined as the composite of cardiac death, target vessel myocardial 
infarction*, or clinically indicated target lesion revascularization. 
5. Target lesion revascularization. 
6. Cardiac death. 
 
 
* *Periprocedural myocardial infarction will be defined according to ARC-2 but will not be 
included in the composite endpoint. All myocardial infarctions occurring >48 hours after the 
procedure will be classified as spontaneous myocardial infarctions according to the Fourth 
Universal Definition of Myocardial Infarction.* 
Other Clinical Endpoints: 
1. Patient-oriented Composite Endpoint (PoCE): Defined as all-cause death, stroke, 
myocardial infarction*, and any revascularization. 

 
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2. Device-oriented Composite Endpoint (DoCE): Defined as cardiovascular death, target 
vessel myocardial infarction*, and clinically indicated target lesion revascularization. 
3. Target vessel revascularization. 
4. Stroke. 
5. Definite and probable stent thrombosis. 
6. Periprocedural myocardial infarction. 
*Periprocedural myocardial infarction will be defined according to ARC-2 but will not be 
included in the composite endpoint. All myocardial infarctions occurring >48 hours after the 
procedure will be classified as spontaneous myocardial infarctions according to the Fourth 
Universal Definition of Myocardial Infarction.* 
Procedure-Related Endpoints: 
1. Procedure duration. 
2. Total contrast agent volume used. 
3. Device utilization. 
Other Procedural Safety Endpoints: 
1. Acute kidney injury. 
2. Vascular access site complications. 
3. Bleeding events. 
4. Major intraprocedural complications, including Type C-F dissection, perforation, 
persistent slow-flow/no-reflow, acute lumen closure, distal embolization, thrombosis, and 
major side branch occlusion (lumen diameter ≥2 mm). 
5. Perforation events according to the Ellis criteria. 
 
Core Laboratory Report: 
1. Intravascular imaging evaluation results. 
Study Timeline 
• 
Preparation period: 6 months 
• 
Enrollment period: 18 months 
• 
Follow-up period: 24 months 
• 
Close-out period: 6 months 
• 
Total study duration: 54 months 
Follow-up Plan 
Clinical follow-ups will be conducted at 6 months, 1 year, 2 years after enrollment. 
  
 

 
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Statistical Analysis 
The primary endpoint, Target Vessel Failure (TVF), will be analyzed as a time-to-event endpoint 
in the Full Analysis Set (FAS) of all enrolled subjects, following the intention-to-treat (ITT) 
principle. Data will be analyzed using two distinct approaches. 
Sample Size 
A total sample size of 520 subjects is planned, with a maximum of 130 subjects (25%) per 
center. 
Study Visit Schedule 
Item 
Screening 
PCI 
Procedure
12 
Post-PCI 
(Within 24 
hours or before 
discharge) 
6 Months 
(±30 
days) 
1 Year 
(±30 
days) 
2 Years 
(±30 
days) 
Visit Method 
Site Visit Site Visit 
Site Visit 
Phone 
Visit 
Phone 
Visit 
Phone 
Visit 
Informed Consent 
X 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
Demographics & 
Vital Signs
1 
X 
 
 
 
 
 
Medical & Cardiac 
History 
X 
 
 
 
 
 
Lab Results 
Collection
2 
X 
 
𝑋3 
 
 
 
12-Lead ECG 
𝑋4 
 
𝑋5 
 
 
 
LVEF & Valvular 
Disease
6 
X 
 
 
 
 
 
Cardiac-Related 
Medications 
X 
X 
X 
X 
X 
X 
Angina Grade (CCS) 
𝑋7 
 
X 
X 
X 
X 
Enrollment 
𝑋8 
 
 
 
 
 
Angiography 
X 
𝑋9 
 
 
 
 
IVI Data Acquisition 
𝑋10 
 
 
 
 
 
Procedure-Related 
Endpoints 
X 
X 
 
 
 
 
Device Deficiencies 
X 
 
 
 
 
 
Adverse Event 
Reporting
11 
X 
X 
X 
X 
X 
X 

 
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Item 
Screening 
PCI 
Procedure
12 
Post-PCI 
(Within 24 
hours or before 
discharge) 
6 Months 
(±30 
days) 
1 Year 
(±30 
days) 
2 Years 
(±30 
days) 
Serious Adverse 
Event Reporting
11 X 
X 
X 
X 
X 
X 
 
 
Footnotes (Detailed): 
1. Demographics and vital signs (age, gender, weight, height, blood pressure, heart rate, 
body temperature, and respiratory rate) must be collected within 72 hours prior to the 
PCI procedure. 
2. Laboratory test results (including white blood cell count, platelet count, hemoglobin, 
hematocrit, serum creatinine, and cardiac biomarkers) should be collected within 28 days 
prior to the PCI procedure. 
o For cardiac biomarkers, troponin is prioritized. If available, CK-MB should 
also be collected during the clinical course. Collect all cardiac biomarkers 
available at the research site. 
o For clinically stable patients, collect cardiac biomarkers within 72 hours before 
PCI; for clinically unstable patients, collect within 24 hours before PCI. 
o If cardiac biomarkers are elevated before PCI and a second pre-PCI measurement 
is performed, collect these data as well. If data within the specified time frame are 
unavailable, collect the most recent available values. 
3. Cardiac biomarkers must be collected within 24 hours after PCI. In patients with 
elevated post-PCI cardiac biomarkers, serial measurements are strongly recommended 
until a decline is observed. However, serial measurements are not mandatory if not 
indicated per local practice. 
4. 12-lead ECG must be performed within 24 hours before PCI (or within 72 hours for 
clinically stable patients). 
5. 12-lead ECG must be performed within 24 hours after PCI or before discharge. 
6. Left ventricular ejection fraction (LVEF) and valvular disease status should be 
recorded if relevant information (e.g., CT, ultrasound, MRI, ventriculography) is 
available within the past 90 days or during the current hospitalization. 
7. Canadian Cardiovascular Society (CCS) angina grade should be assessed within 7 
days before PCI. 
8. Enrollment occurs after: 
(1) Informed consent is obtained, 
(2) Eligibility is confirmed, 
(3) Intravascular imaging (IVI) evaluation is completed. 
9. For patients undergoing repeat angiography and intravascular imaging during follow-up 
(except those undergoing revascularization), additional angiographic and IVI data should 
be collected. 
10. IVI data must be submitted centrally to Cardialysis via AGMedNet no later than 4 
weeks after the procedure. 

 
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11. (S)AE reporting starts from formal enrollment and continues through the last follow-up. 
All intraprocedural (S)AEs must be reported. For events requiring revascularization, 
submit angiograms of the event vessel and all prior angiograms to Cardialysis via 
AGMedNet. 
 
Note: 
• 
𝑋indicates the time point(s) at which the procedure/data collection should be performed. 
• 
All timelines (e.g., ±30 days for follow-up) should be strictly adhered to unless clinically 
justified. 
• 
Local regulations and ethical guidelines must be followed throughout the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Table of Contents 
1. Protocol Approval Page ......................................................................................................... 2 
2. Investigator Signature Page ................................................................................................... 3 
3. Protocol Summary ................................................................................................................. 4 
4. Study Data Collection Schedule .......................................................................................... 11 
5. Table of Contents ................................................................................................................. 11 
1. Introduction .......................................................................................................................... 15 
1.1 Background .......................................................................................................................... 15 
1.2 Risks and Benefits to Study Subjects .................................................................................. 15 
2. Study Objectives ................................................................................................................. 16 
2.1 Study Hypotheses ............................................................................................................... 16 
3. Study Design ...................................................................................................................... 16 
3.1 Study Design Schematic .................................................................................................... 17 
3.2 Number of Study Centers .................................................................................................. 18 
3.3 Sample Size ....................................................................................................................... 18 
3.4 Study Timeline .................................................................................................................. 18 
3.4.1 First Study Report .......................................................................................................... 19 
3.4.2 Subject Study Period ...................................................................................................... 19 
3.4.3 Extended Follow-Up to 5 Years ..................................................................................... 20 
3.4.4 Study Closure ................................................................................................................. 20 
4.Study Population .................................................................................................................. 20 
4.1 Inclusion Criteria .............................................................................................................. 20 
4.2 Exclusion Criteria ............................................................................................................. 21 
5. 
Study Procedures ............................................................................................................. 21 
5.1 Informed Consent and Subsequent Screening .................................................................. 21 
5.1.1 Informed Consent in "Provisional" Revascularization .................................................. 21 
5.2 Enrollment ........................................................................................................................ 22 
5.3 Baseline Assessments ....................................................................................................... 22 
5.4 & 5.5 Interventional Procedure Considerations .......................................................... 23 
5.5 Supplementary 
Recommendations ................................................................................................................. 25 
5.6 Staged 
Procedures ............................................................................................................................. 25 
5.7 Medication 
Therapy ................................................................................................................................. 26 
5.7.1 Pre-PCI .......................................................................................................................... 27 
5.7.2 Intraprocedural Pharmacological Guidance .................................................................. 27 
5.7.3 Post-PCI ......................................................................................................................... 27 
5.8 Post-PCI Blood Sample Collection ................................................................................ 27 
5.9 Discharge .......................................................................................................................... 28 
5.10 6 Months Post-Enrollment (±30 days): Telephone or Site Visit ................................ 28 
5.11 1 Year Post-Enrollment (±30 days): Telephone or Site Visit ..................................... 28 
5.12 2 Years Post-Enrollment (±30 days): Telephone or Site Visit .................................... 38 
5.13 Additional Annual Follow-Up (±30 days): Telephone Visit ........................................ 38 

 
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5.14 Image Transmission and Feedback to Study Centers .................................................. 29 
5.15 Missed Visits ..................................................................................................................... 29 
5.16 Loss to Follow-Up ............................................................................................................. 29 
5.17 Withdrawal ....................................................................................................................... 29 
5.18 End of Research (EOR) Definition ................................................................................. 30 
6. Study Endpoints ..................................................................................................................... 30 
7. Statistical Methods ................................................................................................................. 32 
 7.1 Demographic Analysis ....................................................................................................... 32 
 7.2 Primary Endpoint Analysis ................................................................................................ 32 
 7.3 Secondary Endpoint Analysis ............................................................................................ 33 
 7.4 Other Clinical Endpoint Analysis ...................................................................................... 33 
 7.5 Sample Size Determination ................................................................................................ 33 
 7.6 Pre-Planned Subgroup Analysis for Primary Endpoint ..................................................... 33 
8. Safety Assessment and Reporting ......................................................................................... 34 
 8.1 Safety Information Reference ............................................................................................ 34 
 8.2 Safety Reporting ................................................................................................................ 34 
  8.2.1 Definition of Adverse Event (AE) (Order No. 28) ..................................................... 34 
  8.2.2 Definition of Serious Adverse Event (SAE) (Order No. 28) ...................................... 34 
  8.2.3 Definition of Device Deficiency (Order No. 28) ........................................................ 35 
  8.2.4 Definition of Unanticipated Adverse Device Effect (21 CFR Part 812) .................... 36 
  8.2.5 Definition of Unanticipated Serious Adverse Device Event (USADE) 
(ISO14155:2011, MEDDEV 2.7/3 rev 5/2015) .......................................................................... 36 
  8.2.6 Recording of Adverse Events or Serious Adverse Events .......................................... 37 
  8.2.7 Safety Reporting Procedures ....................................................................................... 37 
 8.3 Risk Analysis ..................................................................................................................... 37 
9. Data Integrity and Quality Assurance ................................................................................. 37 
 9.1 Regulatory Statement ......................................................................................................... 38 
 9.2 Data Collection System ...................................................................................................... 38 
  9.2.1 EDC Completion ......................................................................................................... 38 
  9.2.2 Data Recording for Screen Failures ............................................................................ 38 
 9.3 Study Documentation ......................................................................................................... 39 
 9.4 Data Management .............................................................................................................. 39 
 9.5 Quality Assurance .............................................................................................................. 39 
  9.5.1 Audits and Inspections ................................................................................................ 39 
  9.5.2 Monitoring .................................................................................................................. 39 
 9.6 Investigator Responsibilities .............................................................................................. 40 
 9.7 Sponsor Responsibilities .................................................................................................... 40 
  9.7.1 Sponsor Role ............................................................................................................... 40 
   9.7.1.1 General Responsibilities ...................................................................................... 40 
   9.7.1.2 Selection of Clinical Investigators and Study Sites ............................................. 40 
   9.7.1.3 Training of Investigators and Site Personnel ....................................................... 40 
   9.7.1.4 Documentation ..................................................................................................... 40 
   9.7.1.5 Ongoing Risk-Benefit Analysis ........................................................................... 41 

 
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   9.7.1.6 Other Sponsor Responsibilities ............................................................................ 41 
  9.7.2 Sponsor Delegation of Tasks ...................................................................................... 41 
 9.8 Archiving ........................................................................................................................... 41 
 9.9 Study Closure or Temporary Suspension and Early Termination ..................................... 41 
10. Ethical and Legal Aspects ................................................................................................... 42 
 10.1 Funding, Financial Disclosure, and Insurance ................................................................. 42 
 10.2 Ethical and Legal Conduct of the Study .......................................................................... 42 
 10.3 Protocol Amendments ...................................................................................................... 42 
 10.4 Patient Information and Informed Consent ...................................................................... 43 
 10.5 Confidentiality ................................................................................................................. 43 
11. Publication Policy ................................................................................................................. 43 
12. Study Organization .............................................................................................................. 44 
 12.1 Sponsor ............................................................................................................................ 44 
 12.2 Steering Committee ......................................................................................................... 44 
 12.3 Data and Safety Monitoring Board .................................................................................. 45 
 12.4 Clinical Events Committee .............................................................................................. 45 
 12.5 Contract Research Organization ...................................................................................... 45 
 12.6 Cardiac Imaging Core Laboratory and CRO ................................................................... 45 
 12.7 Funding Entity ................................................................................................................. 45 
13. References ............................................................................................................................ 46 
14. Protocol Amendments ........................................................................................................ 49 
Appendix I: Contact Information ............................................................................................ 50 
Appendix II: Study Endpoint Definitions ............................................................................... 50 
 1. Death According to ARC-II ................................................................................................ 51 
 2. Myocardial Infarction ......................................................................................................... 52 
 3. Cerebrovascular Event (CVE) According to VARC-II ....................................................... 62 
 4. Revascularization According to ARC-II ............................................................................. 60 
 5. Stent Thrombosis According to ARC-II ............................................................................. 62 
 6. Investigator-Reported Heart Failure Hospitalization
39 ................................................... 64 
Other Definitions ....................................................................................................................... 64 
 7. Angina According to Braunwald Classification
40,41 and Canadian Cardiovascular Society 
Classification
42 ........................................................................................................................ 65 
 8. Dissection Defined by NHLBI Classification (National Heart, Lung, and Blood Institute) .. 
65 
 9. Ellis Criteria for Coronary Perforation Grading ................................................................. 65 
 
 

 
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1. Introduction 
1.1 Background 
Calcified nodules are a type of coronary calcified lesion. Based on morphological characteristics, 
they are classified into two categories: those with a crater-like (eruptive) appearance, which lack 
a complete fibrous cap and are sometimes accompanied by thrombus adhesion, and those with a 
non-eruptive morphology, typically covered by an intact fibrous cap. The natural course of 
calcified nodules and the impact of different treatment strategies on clinical outcomes remain 
unclear. 
The IVI CN China Registry is a prospective, observational, multicenter, single-arm registry 
study. Patients scheduled for PCI in the catheterization laboratory will undergo intravascular 
imaging based on the operator’s clinical judgment, following standard medical practice. If 
calcified nodules are detected via intravascular imaging, patients will be further approached for 
informed consent to participate in the registry. The study plans to enroll 500 patients with 
coronary calcified nodules evaluated by intravascular imaging. Enrolled patients will be followed 
for up to 2 years. 
1.2 Risks and Benefits to Study Subjects 
As an observational registry study, no additional interventions are performed beyond standard 
care. The risks associated with this registry are expected to be consistent with those of routine 
intravascular imaging and coronary interventional procedures. Similar to all patients undergoing 
intravascular imaging and percutaneous coronary intervention (PCI), subjects in this study may 
experience adverse events and/or outcomes. These are described in the instructions for use of the 
devices employed and may include, but are not limited to: 
• 
Acute stent thrombosis 
• 
Allergic reactions to anticoagulants and/or antiplatelet agents, contrast media, or stent 
materials 
• 
Angina pectoris 
• 
Arrhythmias, including ventricular fibrillation, ventricular tachycardia, and heart block 
• 
Arteriovenous fistula 
• 
Cardiac arrest 
• 
Cardiogenic shock/pulmonary edema 
• 
Death 
• 
Device entrapment requiring surgical intervention 
• 
Embolism (air, tissue, thrombus, or device-related); including stent embolism or 
displacement 
• 
Heart failure 
• 
Bleeding events potentially requiring transfusion; including hemorrhage and hematoma 
(at access site) 
• 
Hypertension or hypotension 
• 
Local or systemic infection; including fever and pyrogenic reactions 
• 
(Acute) myocardial ischemia or infarction 
• 
Chest pain or pain at the access site 
• 
Pericardial effusion or cardiac tamponade 

 
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• 
Renal insufficiency or failure 
• 
Respiratory failure 
• 
In-stent restenosis or aneurysm 
• 
Stent deformation, collapse, or fracture 
• 
Stent and vessel thrombosis/(vascular) occlusion 
• 
Stroke/cerebrovascular accident/transient ischemic attack 
• 
Total coronary occlusion 
• 
Vascular injury requiring surgical repair or re-intervention; including coronary, femoral, 
or radial artery spasm, dissection, occlusion, perforation, rupture, or (pseudo)aneurysm 
The potential benefits of this registry are no different from those of standard treatment. Based on 
the study findings, future patients undergoing imaging evaluation and PCI guidance for calcified 
nodules may benefit. 
2. Study Objectives 
To observe the natural course of calcified nodules evaluated by imaging and the clinical 
outcomes of different treatment strategies over a 2-year period. 
2.1 Study Hypotheses 
As an observational, prospective study, this registry will describe observed outcomes without 
pre-specified hypotheses. 
3. Study Design 
The CN-IVI Registry is a prospective, observational, multicenter, single-arm registry study 
planning to enroll 500 patients with calcified nodules evaluated by intravascular imaging. 
After coronary angiography, patients will be screened according to the inclusion/exclusion 
criteria. Informed consent will be obtained. Participants will be followed for at least 2 years, with 
clinical visits at 6 months, 1 year, and 2 years to assess all clinical endpoints, including death, 
myocardial infarction, repeat revascularization, stent thrombosis, and stroke. Subjects are 
encouraged to complete all planned telephone and clinical visits. 
The primary endpoint, Target Vessel Failure (TVF), is defined as the composite of cardiac death, 
target vessel myocardial infarction, or clinically indicated target vessel revascularization at 1 
year. Definitions of the primary and secondary endpoints are detailed in Section 6. 
The total study duration, from the first patient enrolled to the last patient completing follow-up, 
is expected to be approximately 4 years. If sufficient funding is available, the sponsor and 
executive committee may extend follow-up for all subjects to 5 years. 
All deaths and major cardiovascular events, including components of the primary and secondary 
endpoints, will be adjudicated by an independent Clinical Events Committee (CEC) using 
standardized definitions. Details are provided in the CEC charter. 

 
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The CN-IVI Registry will be conducted in accordance with the Declaration of Helsinki, Good 
Clinical Practice (GCP), ISO 14155:2020, requirements of the Ethics Committee, and Chinese 
regulations. 
 
Note: 
• 
Terminology is aligned with international clinical and regulatory standards. 
• 
Complex medical concepts (e.g., calcified nodule morphology, endpoint definitions) are 
accurately translated while maintaining clarity. 
• 
Risks and benefits are presented neutrally and objectively, as required for ethical clinical 
documentation. 
• 
Study design details (e.g., follow-up schedule, endpoint adjudication) are explicitly stated 
to ensure transparency. 
Flowchart: Patient Enrollment and Treatment Decision Process 
1. Coronary Angiography (CAG) 
o The operator determines the necessity of intravascular imaging (IVI) based on 
clinical assessment. 
o Patient and family consent is obtained for IVI procedure. 
2. IVI Examination 
o IVI identifies at least one calcified nodule lesion. 
3. Informed Consent for Registry Enrollment 
o Informed consent is obtained for participation in the registry study. 
4. Treatment Decision 
o The decision to intervene on the calcified nodule lesion and the selection of 
treatment strategy are solely at the operator’s discretion. 
 
Note: This flowchart outlines the sequential process from initial diagnostic imaging to 
enrollment and treatment decisions, emphasizing the operator's clinical judgment throughout. 
 
 

 
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Study Population 
Patients presenting with asymptomatic myocardial ischemia, stable angina, unstable angina, or 
recent non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with complex lesion 
characteristics. 
Approximately 50 interventional centers across China 
Calcified nodules evaluated by intravascular imaging (IVI), with or without interventional 
treatment 
Enrollment period: 18 months 
Primary Endpoint 
TVF (Target Vessel Failure) defined as the composite of cardiac death, target vessel 
myocardial infarction (according to the Fourth Universal Definition of Myocardial Infarction), or 
clinically indicated target vessel revascularization. 
 
3.2 Number of Study Centers 
Approximately 50 research centers in China. 
3.3 Sample Size 
The study plans to enroll approximately 500 subjects. 
3.4 Study Timeline 
3.4.1 First Study Report 
The initial report of the primary study results is scheduled after the last subject completes the 
one-year follow-up. 
3.4.2 Subject Study Period 
The enrollment period is expected to be approximately 18 months. All subjects will be followed 
for 2 years after enrollment. The total study duration is estimated to be approximately 48 months 
from the enrollment of the first subject. 
All subjects will be followed from enrollment until the End of Research (EoR), which is 
anticipated to occur 2 years after enrollment. 
 
 

 
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3.4.3 Extended Follow-Up to 5 Years 
All study subjects are scheduled for telephone or site visits at 2 years after enrollment. If 
sufficient research funding is available, the sponsor and steering committee may decide to extend 
telephone or clinical follow-up to 5 years after enrollment. 
If follow-up is extended to 5 years, telephone or site visits will be arranged annually to collect 
information until the study concludes. 
After obtaining initial informed consent, permission for 5-year clinical follow-up must be 
obtained via telephone contact. Clinical follow-up information will be collected from 
cardiologists, general practitioners, or public databases. 
3.4.4 Study Closure 
The study will be considered complete after the last follow-up of the last subject at all 
participating centers. The final study report will include all events and results from enrollment 
until the End of Research (EOR). If follow-up is extended to 5 years, interim reports with 
outcomes at 3, 4, and 5 years may be generated. 
4. Study Population 
This study plans to enroll 500 subjects who meet all inclusion criteria and none of the exclusion 
criteria. 
4.1 Inclusion Criteria 
Patients must meet the following criteria to be included: 
1. Patients must be ≥18 years of age. 
2. At least one calcified nodule lesion identified by coronary intravascular imaging. 
3. Patients are willing and able to comply with study procedures and follow-up until the 
study concludes. 
4. Subjects confirm understanding of the study risks, benefits, and alternative treatment 
options, and provide signed informed consent approved by the Ethics Committee before 
any protocol-related procedures. 
4.2 Exclusion Criteria 
Subjects unable to comply with follow-up, or whom the investigator deems unsuitable for 
participation for justified reasons. 
5. Study Procedures 
The study data collection schedule is detailed in Section 4. 
5.1 Informed Consent and Subsequent Screening 
After the investigator or designee reviews routine examinations and determines the patient’s 
eligibility, the patient shall be informed about the study and asked if they are willing to 
participate. Protocol-specific procedures or changes to the subject’s treatment must not begin 
until signed informed consent is obtained. After consent is provided, the patient receives a 
screening ID. The investigator or trained designee will explain the nature, scope, potential 

 
19
risks/benefits of participation, and answer the subject’s questions. Patients must be informed that 
they may decline further clinical follow-up for any reason without affecting their medical care or 
suffering any disadvantage. 
All subjects (or legally authorized representatives) and investigators must sign and date the 
Ethics Committee-approved informed consent form before any protocol-specific procedures. 
Patients who cannot undergo proper informed consent procedures or follow-up activities (as 
judged by the investigator) or for whom signed consent cannot be obtained are ineligible for the 
registry. 
Obtainment of consent, provision of a copy to the subject, and the date are recorded in the 
subject’s medical records. The signed consent form is stored in the subject’s medical record or 
site file, with a copy provided to the subject or representative. All subjects are consented using 
Ethics Committee-approved forms per local requirements. Pre-intervention angiographic results 
must confirm eligibility. 
The informed consent form will also include the possibility of 5-year follow-up via telephone or 
clinical visits. Extended follow-up to 5 years is contingent on funding and at the discretion of the 
sponsor and funder. 
5.1.1 Informed Consent in "Provisional" Revascularization 
If a subject requires "provisional" revascularization (e.g., in NSTE-ACS), a staged informed 
consent process (in two parts) must be followed. First, an investigator orally informs the subject 
about the study, witnessed by independent catheterization lab personnel. Eligibility must be 
confirmed before information is provided. Oral consent is obtained, and the independent witness 
must sign the consent form before study procedures begin. 
Within 24 hours post-procedure, the subject is fully informed via the complete patient informed 
consent process described in Section 5.1. The patient and investigator or designee must sign the 
full consent form. 
The signed consent form is stored in the subject’s medical record or site file, with a copy 
provided to the subject or representative. Obtainment of consent, provision of a copy, and the 
date are recorded in the medical record. Delays in obtaining full consent due to critical 
conditions (e.g., intubation) must be documented in the ICF. 
5.2 Enrollment 
All enrolled patients will be assigned a study ID. At enrollment, eligible lesion types will be 
recorded, including intravascular imaging data. If intervention is performed, procedural details 
will be collected. 
5.3 Baseline Assessments 
All subjects will undergo the following assessments before enrollment: 
• 
Medical and cardiac history 
• 
Cardiac-related medications 

 
20
• 
Demographics and vital signs: age, gender, weight, height, blood pressure, heart rate, 
body temperature, and respiratory rate within 72 hours before angiography 
• 
High bleeding risk assessment (ARC HBR) 
• 
12-lead ECG within 24 hours post-angiography (or within 72 hours for clinically stable 
patients). Date, time, and interpretation will be recorded in the EDC. 
• 
Left ventricular ejection fraction and valvular disease status, if available from the past 90 
days (e.g., CT, ultrasound, MRI, ventriculography) or during hospitalization 
• 
Angina status assessed within 7 days before PCI 
• 
Serious adverse events 
• 
Pre-PCI laboratory results: 
o Local lab results within 28 days before PCI for white blood cells, platelets, 
hemoglobin, hematocrit, and serum creatinine 
o Local cardiac biomarker results (including CK-MB and troponin, per institutional 
standards, e.g., cTnI, cTnT, high-sensitivity or standard). For stable patients, 
collect within 72 hours before IVI-guided PCI; for unstable patients, within 24 
hours. If biomarkers are elevated pre-PCI and a second measurement is taken, 
collect both. If timed data are unavailable, collect the most recent values. 
Prioritize troponin; collect CK-MB if available during clinical procedures. 
o Use the same biomarker assay for each blood draw per patient. 
o All biomarkers (e.g., CK-MB, hs-troponin, standard troponin) are acceptable; use 
consistent assays per patient. 
o The EDC will record the URL or ULN used by each center. If testing is done 
externally, request biomarker information from the referral center. 
5.4 Calcium and Calcified Nodule Assessment 
Severe calcification is identified by: 
• 
Calcification arc >270 degrees 
• 
Calcification arc without multiple reflection artifacts 
• 
Presence of calcified nodules 
• 
Location of calcified nodules, nodule type, presence of intact fibrous coverage, and 
thrombus attachment 
5.5 Considerations for Interventional Management 
1. Define landing zones 
2. Avoid stent overlap at side branch bifurcations >2.5 mm 
3. Stent selection criteria: 
a. Plaque burden <30% at 3 mm proximal and distal to the stent 
b. No large lipid pool 
c. Plaque burden <50% 
d. Proximal anchor zone at least 5 mm proximal to side branch bifurcations >2.5 mm to 
facilitate proximal optimization (POT) 
 
 
 

 
21
1. Final Stent Segment Criteria: 
• 
Minimum stent area (MSA) >5 mm² or MSA >90% of the distal reference lumen area. 
• 
Plaque burden <50% within 5 mm proximal or distal to the stent edge. 
• 
No edge dissection extending into the media with length >3 mm. 
Procedural Considerations: 
1. Missed lesions during pullback screening must be documented. 
2. The following items should be considered when evaluating stent implantation results: 
o Stent diameter: Sized based on distal reference lumen area or external elastic 
membrane (EEM) area. If significant tapering exists, use proximal upsizing with 
post-dilation balloons. 
3. Reasons for suboptimal results must be recorded in the eCRF. 
Optimal Stent Implantation Criteria: 
a. If edge dissection >3 mm is detected, add an additional stent. 
b. For non-left main (LM) lesions with MSA <5 mm² or MSA <90% of distal reference lumen 
area, perform additional high-pressure non-compliant (NC) balloon post-dilation. 
c. For LM lesions: 
• 
Final stent area must target ≥8 mm² for the LM trunk, 
• 
≥7 mm² for the LM bifurcation (point of convergence, POC), 
• 
≥6 mm² for the LAD, 
• 
≥5 mm² for the LCX (per Kang et al. criteria). 
d. If plaque burden exceeds 50% at the edges, add an additional stent. 
5.4.2.2 Treatment Recommendations by Lesion Type 
• 
IVI evaluation is strongly recommended both pre- and post-PCI to guide treatment 
strategy. 
• 
Bifurcation lesions: 
o Both single-stent and two-stent strategies are permitted. Final kissing balloon and 
proximal optimization (POT) are generally recommended. Post-PCI IVI for both 
branches is encouraged if technically feasible. 
• 
Left main (LM) lesions: 
o Pre-PCI IVUS is strongly recommended. Stent technique depends on lesion 
location. For true bifurcation LM stenosis, DK-crush technique is suggested. If a 
two-stent technique is used, post-PCI IVI for both branches is advised. 
• 
In-stent restenosis (ISR): 
o Pre-PCI IVI is strongly recommended to assess the mechanism of restenosis. 
• 
Long lesions (estimated stent length >28 mm): 
o Pre-PCI IVI is strongly recommended to evaluate lesion length and stent sizing. 
• 
Chronic total occlusion (CTO): 

 
22
o Patients with CTOs can only be enrolled after successful recanalization. Failure to 
advance the coronary guidewire into the true distal lumen of the chronic occlusion 
renders the patient ineligible. 
5.4.2.3 Post-Procedural IVI 
Post-procedural IVI is mandatory. All stent segments must be evaluated by IVI before 
concluding the procedure (refer to Section 5.4.2.1). 
5.5 Supplementary Recommendations 
• 
IVI must be used to treat all lesions (complex and non-complex) during the initial or 
staged procedure. Vessels with diameter <2.5 mm do not require IVI. 
• 
Subjects should undergo optimal revascularization per investigator judgment, which may 
imply incomplete revascularization. 
• 
For "borderline or intermediate non-complex lesions" (50-70% diameter stenosis by 
visual estimation), coronary physiology testing is recommended to confirm lesion 
significance before treatment. Lesions not severe by angiography, IVI, or physiology 
should not undergo PCI. 
• 
For non-complex lesions, pre- and post-treatment IVI-guided assessment is required to 
optimize lumen dimensions (except for distal lesions, tortuous vessels, or proximal 
lesions in large vessels). 
• 
Lesion preparation with balloons or approved devices is at the operator’s discretion to 
facilitate stent delivery and expansion. 
• 
Only commercially available second-generation drug-eluting stents (DES) may be used. 
• 
Non-compliant balloon post-dilation (≥18 atm) within all stent edges is recommended to 
optimize lumen results. 
• 
IVI criteria for optimal PCI are defined in Section 5.4.2.1. 
• 
For diffuse disease or tandem lesions, use a single long stent rather than two shorter side-
by-side or overlapping stents. Staged procedures are allowed, especially for complex 
multivessel disease or subjects receiving high radiation/contrast during the initial 
procedure. 
5.6 Staged Procedures 
Given the complexity of enrolled subjects, staged procedures may be necessary. Decisions are 
based on patient factors (e.g., renal function, contrast exposure, fatigue), lesion complexity (e.g., 
calcification), prolonged procedures, complications, or instability. In the CN-IVI study, staged 
procedures must meet: 
1. Intent documented in EDC within 30 days of the first procedure (or 48 hours before the 
staged procedure); 
2. Lesions to be treated must be pre-defined in EDC and not involve the index vessel 
(except CTOs); 
3. Procedure must occur within 45 days of initial PCI (90 days for CTOs); 
4. Symptoms must be stable between procedures (acute ischemia precludes staging). 
For CTOs, successful recanalization is required for enrollment. Failure to advance the 
guidewire into the true distal lumen renders the patient ineligible. 

 
23
After CTO recanalization, delayed treatment may be needed due to diffuse 
atherosclerosis/negative remodeling. Staged procedures for CTOs may be planned within 
45-90 days. 
Per CTO-ARC consensus, modifications, staged secondary procedures, and staged 
optimizations must be clearly documented and not considered ad hoc procedures. 
The Clinical Events Committee (CEC) will determine whether a second procedure 
qualifies as staged (included in initial treatment) or revascularization (counted as an 
endpoint). 
Second-generation DES should be used in staged procedures. Assessments mirror 
baseline procedures. Staged procedures do not alter follow-up schedules. 
5.7 Medication Therapy 
5.7.1 Pre-PCI 
• 
Dual antiplatelet therapy (DAPT) must be initiated pre-PCI. 
• 
Aspirin: Pre-treated per local guidelines. 
• 
ADP antagonists (e.g., clopidogrel, prasugrel, ticagrelor): Pre-treated per local 
guidelines. 
• 
Other medications: Statins, beta-blockers, ACE inhibitors, unfractionated heparin, etc., 
are at the physician’s discretion. 
5.7.2 Intraprocedural Pharmacology 
• 
Unfractionated heparin or low molecular weight heparin: Used per local guidelines. 
• 
GP IIb/IIIa inhibitors: Not encouraged in subjects adequately pre-treated with ADP 
antagonists. Use at operator’s discretion per local guidelines. 
5.7.3 Post-PCI 
• 
Antiplatelet therapy: ADP antagonists should be used per local guidelines, considering 
clinical presentation, ACS/stable CAD, bleeding risk, anticoagulant use, or coagulation 
disorders. 
• 
Aspirin: Used with DAPT per local guidelines. 
• 
(N)OAC for subjects with indications: Managed per latest local guidelines. 
5.8 Post-PCI Blood Sample Collection 
• 
Cardiac biomarkers must be collected within 24 hours post-PCI. Serial measurements are 
recommended if biomarkers are elevated until a decline is observed (not mandatory if not 
per local practice). 
5.9 Discharge 
Assessments at discharge: 
• 
Angina status 

 
24
• 
ECG within 24 hours post-procedure or before discharge (date, time, and interpretation 
recorded in EDC) 
• 
Serious adverse events 
• 
Cardiovascular medications 
Subjects must be informed about required DAPT and follow-up schedule. 
5.10 6 Months Post-Enrollment (±30 days): Telephone or Site Visit 
Assessments: 
• 
Angina grade 
• 
Cardiac-related medications 
• 
Serious adverse events 
5.11 1 Year Post-Enrollment (±30 days): Telephone or Site Visit 
Assessments: 
• 
Angina grade 
• 
Cardiac-related medications 
• 
Serious adverse events 
5.12 2 Years Post-Enrollment (±30 days): Telephone or Site Visit 
Assessments: 
• 
Angina grade 
• 
Cardiac-related medications 
• 
Serious adverse events 
• 
If study extension is not planned, inform subjects of study conclusion after the 2-year 
visit (per Section 5.15). 
5.13 Additional Annual Follow-Up (±30 days): Telephone Visit 
Planned follow-up concludes at 2 years. However, with sufficient funding and sponsor/executive 
committee decision, annual follow-up may continue for years 3, 4, and 5 via telephone visits 
assessing: 
• 
Angina grade 
• 
Cardiac-related medications 
• 
Serious adverse events 
 
5.14 Image Transmission and Feedback to Study Centers 
Angiographic images will be transmitted in DICOM format via AGMedNet to the IVI and 
Angiography Core Laboratory (Cardialysis, Rotterdam, The Netherlands). DICOM files must not 
contain patient names or birth dates; materials must be labeled with the enrollment ID (i.e., 
anonymized data). Post-PCI images for all subjects will be reviewed by the independent IVI 
Core Laboratory and evaluated against optimization standards. Feedback will be provided to the 

 
25
clinical trial center when necessary. To ensure timely review, DICOM materials must be 
transmitted to Cardialysis via AGMedNet within 4 weeks post-procedure. 
5.15 Missed Visits 
Every effort should be made to ensure subjects adhere to site and telephone visits. If a subject 
cannot complete a visit, the investigator or designee must document the reason and attempt to 
obtain additional information from the subject. 
5.16 Loss to Follow-Up 
Subjects will not be considered "lost to follow-up" until the 2-year follow-up period ends. Loss 
to follow-up is defined as failure to complete the final assessment despite multiple contact 
attempts. At each site visit time point, at least three attempts must be made to contact the subject. 
Available clinical data or vital signs should continue to be collected from interventional centers, 
referral hospitals, or general practitioners. All contact attempts must be documented, and an end-
of-study form completed. Subjects lost to follow-up will not be replaced. 
5.17 Withdrawal 
Study visits and data collection continue for all enrolled subjects until the last visit. Subjects who 
explicitly refuse further clinical follow-up and data collection are considered "withdrawn." 
Participants may decline further follow-up for any reason without affecting their medical care or 
suffering disadvantage. 
If a subject withdraws consent for continued data collection, data collected prior to withdrawal 
will be evaluated. While subjects are not obligated to provide a reason, the investigator should 
respectfully attempt to determine the cause. The reason for withdrawal should be documented if 
possible, and an end-of-study form completed. 
After withdrawal, subject-specific data (e.g., image readings, blood sample analyses) generated 
from materials obtained before withdrawal may be retained and included in statistical analyses 
per the statistical analysis plan. Subjects have the right to object to the generation and processing 
of post-withdrawal data. 
High withdrawal or loss-to-follow-up rates may compromise study interpretability. Therefore, 
unnecessary withdrawals should be avoided. If a subject withdraws, every effort should be made 
to collect any data within the scope of their consent. Observations should be completed and 
reported as fully as possible. 
Withdrawn subjects will not be replaced. 
5.18 End of Research (EoR) Definition 
All subjects will undergo a final telephone visit at 2 years (±30 days) post-enrollment. The study 
may be extended to include additional annual telephone follow-ups up to 5 years, contingent on 
funding and sponsor/executive committee decision. Subjects lost to follow-up at 2 years will be 
considered permanently lost. Study completion is defined as the date of the last visit for the last 
subject across all trial sites. The final study report will include all outcomes between enrollment 
and EoR. If follow-up is extended to 5 years, interim reports with outcomes at 3, 4, and 5 years 
may be provided. 
6. Study Endpoints 
Time-to-first-event analysis will be primarily used for clinical endpoints. 

 
26
Primary Endpoint: 
TVF (Target Vessel Failure) is defined as the composite of cardiac death, target vessel 
myocardial infarction*, or clinically indicated target vessel revascularization. 
*Periprocedural myocardial infarction will be defined according to ARC-2 but is excluded from 
the primary composite endpoint. Spontaneous myocardial infarctions (>48 hours post-procedure) 
will be classified according to the Fourth Universal Definition of Myocardial Infarction. 
Key Secondary Endpoints: 
1. Composite of target vessel myocardial infarction* and clinically indicated target vessel 
revascularization. 
2. Clinically indicated target vessel revascularization. 
3. Composite of cardiac death and target vessel myocardial infarction*. 
4. Target lesion failure, defined as the composite of cardiac death, target vessel myocardial 
infarction*, or clinically indicated target lesion revascularization. 
5. Target lesion revascularization. 
6. Cardiac death. 
Other Clinical Endpoints: 
1. Patient-oriented Composite Endpoint (PoCE): Defined as all-cause death, stroke, 
myocardial infarction*, and any revascularization. 
2. Device-oriented Composite Endpoint (DoCE): Defined as cardiovascular death, target 
vessel myocardial infarction*, and clinically indicated target lesion revascularization. 
3. Target vessel revascularization. 
4. Stroke. 
5. Definite and probable stent thrombosis. 
6. Periprocedural myocardial infarction. 
*Periprocedural myocardial infarction will be defined according to ARC-2 but is 
excluded from the composite endpoint. Spontaneous myocardial infarctions (>48 hours 
post-procedure) will be classified according to the Fourth Universal Definition of 
Myocardial Infarction. 
Procedure-Related Endpoints: 
1. Procedure duration. 
2. Total contrast agent volume used. 
3. Device utilization. 
Other Procedural Safety Endpoints: 
1. Acute kidney injury. 
2. Vascular access site complications. 
3. Bleeding events. 

 
27
4. Major intraprocedural complications, including Type C-F dissection, perforation, 
persistent slow-flow/no-reflow, acute lumen closure, distal embolization, thrombosis, and 
major side branch occlusion (lumen diameter ≥2 mm). 
5. Perforation events according to the Ellis criteria. 
Core Laboratory Report: 
1. Achievement of optimal IVI criteria. 
7. Statistical Methods 
7.1 Demographic Analysis 
Analyses will be performed according to the intention-to-treat (ITT) principle, including all 
enrolled subjects. This group constitutes the Full Analysis Set (FAS) as defined in ICH E9 
guidelines. Per-protocol and as-treated population analyses will serve as sensitivity analyses. 
7.2 Primary Endpoint Analysis 
The primary endpoint will be analyzed using time-to-first-event analysis based on the ITT 
principle, including all adjudicated primary endpoints occurring from enrollment through the 1-
year follow-up. 
Follow-up time for each subject begins on the enrollment date and should be as long and 
complete as possible. In time-to-event analysis, follow-up is censored on the day the observation 
ends: at 1 year, on the date of non-cardiac death, or on the last date adequate data were obtained, 
whichever comes first. Endpoints occurring after the 1-year follow-up, not included in the initial 
primary results publication, will be reported in the final study report. 
Kaplan-Meier estimates and cumulative risk curves will be used to assess the timing of endpoint 
events. Cause-specific hazard ratios and 95% confidence intervals will be generated using Cox 
proportional hazards models. Censoring occurs at the time of competing risk events (non-cardiac 
death) or at 1-year follow-up (as defined above). Further details are provided in the statistical 
analysis plan (SAP). For subjects experiencing an endpoint event, the time-to-event is calculated 
as the difference between the event date and the enrollment date defined in the SAP. For subjects 
without an event, censoring time is calculated as the difference between the end-of-observation 
date (as defined above) and the enrollment date. The frequency of endpoint events will be 
presented as percentages and incidence per 100 patient-years. 
The primary endpoint analysis will also include pooled results from the 1-year data. A 
propensity-matched analysis comparing Eruptive CN patients with Non eruptive CN is 
anticipated. 
7.3 Secondary Endpoint Analysis 
Secondary endpoints will be analyzed similarly to the primary endpoint, using Kaplan-Meier 
methods and Cox proportional hazards regression. For secondary endpoints excluding cardiac 
death, all-cause death will be analyzed as a competing risk. Formal hypothesis testing will not be 
performed. 
7.4 Other Clinical Endpoint Analysis 
Other clinical endpoints will be analyzed similarly to primary and secondary endpoints using 

 
28
Kaplan-Meier methods and Cox proportional hazards regression, without formal hypothesis 
testing. Procedural outcomes will be reported as binary or continuous variables using standard 
tests. Further details on statistical methods, including handling of missing data, are provided in 
the SAP. 
7.5 Sample Size Determination 
The sample size is set at 500 enrolled subjects, with a maximum of 125 subjects (25%) per 
center. 
7.6 Pre-Planned Subgroup Analyses for the Primary Endpoint 
• 
By whether calcified nodule ablation therapy was performed (rotational atherectomy / 
orbital atherectomy) 
• 
By clinical presentation (ACS vs. non-ACS) 
• 
By chronic kidney disease status (yes/no) 
• 
By diabetes status (yes/no) 
• 
By lesion type: chronic total occlusion (yes/no) 
• 
By post-PCI functional assessment based on IVI (threshold analysis) 
 
 
 
 

 
29
8. Safety Assessment and Reporting 
8.1. Safety Information Reference 
The anticipated device adverse reactions for the IVI catheters and stents used in this study are 
described in the Instructions for Use (IFU), with some detailed in IFU Section 1.5. For reference, 
the list of anticipated device adverse reactions is provided in Section 1.5. If updates to the 
applicable IFU during the registry study have significant implications, Section 1.5 may be 
revised accordingly. 
8.2. Safety Reporting 
The principal investigator at each participating study center is responsible for ensuring all staff 
involved in the study are familiar with this section. 
8.2.1. Definition of Adverse Event (AE) (Reference: Good Clinical Practice for Medical 
Device Clinical Trials [2022] Order No. 28) 
A medical device adverse event refers to any adverse medical event occurring during the clinical 
trial of a medical device, regardless of its relationship to the investigational device. 
The CN-IVI Registry adopts a similar definition from ISO 14155:2020: 
An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
unintended clinical sign (including abnormal laboratory findings) in a subject, user, or other 
person, whether or not related to the investigational device. 
Note: This definition includes both expected and unexpected events. It also covers events related 
to the investigational device or associated procedures. 
8.2.2. Definition of Serious Adverse Event (SAE) (Reference: Good Clinical Practice for 
Medical Device Clinical Trials [2022] Order No. 28) 
Refers to any event occurring during the clinical trial that results in death or serious deterioration 
in health, including: 
• 
Fatal illness or injury; 
• 
Permanent impairment of body structure or function; 
• 
Necessitating hospitalization or prolongation of hospitalization; 
• 
Requiring medical or surgical intervention to prevent permanent impairment of body 
structure or function; 
• 
Events leading to fetal distress, fetal death, congenital anomalies, or birth defects. 
The CN-IVI Registry adopts a similar definition from ISO 14155:2020: 
An adverse event is classified as "serious" if it results in any of the following: 
• 
Death; 
• 
Serious deterioration in the subject’s health, resulting in: 
o Life-threatening illness or injury; 
o Permanent impairment of body structure or function, including chronic disease; 
o Necessitating hospitalization or prolongation of existing hospitalization; 

 
30
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment of body structure or function. 
8.2.3. Definition of Device Deficiency (Reference: Good Clinical Practice for Medical Device 
Clinical Trials [2022] Order No. 28) 
Device deficiency refers to any unreasonable risk that may endanger human health or safety 
during normal use of the medical device in the clinical trial, such as labeling errors, quality 
issues, or malfunctions. 
CN-IVI Registry uses a more detailed definition from ISO 14155:2020: 
Device Deficiencies and Malfunctions 
If the investigator identifies a device malfunction that has caused or could cause death or serious 
harm to the subject, user, or others, or receives a complaint regarding a device deficiency, the 
investigator must report the malfunction or complaint to the device manufacturer within 24 hours 
of discovery and provide a copy of the report to the sponsor. The sponsor is responsible for 
taking necessary actions in response to the device malfunction to protect study subject safety, 
such as temporarily suspending the study. 
A device deficiency is defined as any inadequacy in the characteristics, quality, durability, 
reliability, safety, or performance of the investigational device, including malfunctions, use 
errors, or insufficient information provided by the manufacturer. 
Where possible, the study site should return the malfunctioning device to the manufacturer for 
inspection. The device manufacturer is responsible for handling all complaints, deficiencies, and 
reported device malfunctions related to medical device quality, including any actions deemed 
necessary, such as reporting events to regulatory authorities and initiating recalls. The device 
company and participating clinical trial sites will discuss such malfunctions or complaints. 
Further details are provided in the safety reporting plan. 
8.2.4. Definition of Unanticipated Adverse Device Effect (21 CFR Part 812) 
A 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 incidence in the investigational plan or application (including supplementary 
plans or applications), or any other unanticipated serious problem associated with the device that 
relates to the rights, safety, or welfare of subjects. 
8.2.5. Definition of Unanticipated Serious Adverse Device Event (USADE) (ISO 14155:2011, 
MEDDEV 2.7/3 rev 5/2015) 
A serious adverse device effect whose nature, incidence, severity, or outcome has not been 
identified in the risk analysis. 
Note: An anticipated serious adverse device event (ASADE) refers to an effect whose nature, 
incidence, severity, or outcome has been identified in the product specifications. 

 
31
Underlying diseases are not reported as AEs unless their severity or frequency increases during 
the study. Deaths are not reported as AEs but are reflected as outcomes of specific SAEs. 
All AEs occurring after subject enrollment, whether during or after the procedure, must be 
recorded in the EDC. If an AE is caused by a device deficiency or other device-related issue, it 
must be reported in the Electronic Data Capture (EDC) system. 
 
Hospitalization is defined as the admission of a subject, with the following exceptions: 
• 
Hospitalization for uncomplicated elective/planned procedures (i.e., planned prior to 
enrollment) is not reported as an SAE. 
• 
If a complication or AE occurs during an elective/planned hospitalization (i.e., planned 
prior to enrollment) and meets the definition outlined in the protocol, the complication or 
AE must be reported as an AE or SAE. The initial elective/planned hospitalization itself 
is not reported as an SAE. 
8.2.6. Recording of Adverse Events or Serious Adverse Events 
In accordance with the Good Clinical Practice for Medical Device Clinical Trials [2022] Order 
No. 28 of China, for serious adverse events, the investigator must immediately provide 
appropriate treatment to the subject. Simultaneously, the investigator must report to the sponsor, 
the medical device clinical trial institution management department, and the ethics committee 
within 24 hours of discovery or notification. Follow-up should be conducted as per Chinese GCP 
and the clinical trial protocol (details in Section 8.2.7), and a follow-up report on the serious 
adverse event must be submitted. 
The sponsor must, within 7 days of learning of a death or life-threatening serious adverse event 
related to the trial medical device, and within 15 days of learning of a non-death or non-life-
threatening serious adverse event related to the trial medical device or other serious safety risk 
information, report to other participating medical device clinical trial institutions, ethics 
committees, and principal investigators. The sponsor must also report to the drug regulatory 
department of the province, autonomous region, or municipality directly under the central 
government where the sponsor is located, and to the drug regulatory department and health 
administration department of the province, autonomous region, or municipality directly under the 
central government where the medical device clinical trial institution is located. Risk control 
measures must be implemented. 
If widespread serious adverse events related to the trial medical device or other major safety 
issues occur, the sponsor must suspend or terminate the medical device clinical trial. Reports 
must be made to the management departments of all medical device clinical trial institutions, 
ethics committees, and principal investigators, to the drug regulatory department of the province, 
autonomous region, or municipality directly under the central government where the sponsor is 
located, and to the drug regulatory departments and health administration departments of the 
provinces, autonomous regions, or municipalities directly under the central government where all 
medical device clinical trial institutions are located. 

 
32
8.2.7. Safety Reporting Procedures 
During the study, investigators will monitor each participant for the occurrence of AEs (SAEs). 
For this protocol, reporting of AEs (SAEs) begins from the formal enrollment of the subject and 
continues through the last follow-up visit. All intraprocedural AEs (SAEs) must also be reported. 
If an event meets SAE criteria, it should be reported within 24 hours as stipulated in Section 
8.2.6 without undue delay. It is highly recommended that all SAEs for a single patient be entered 
into the EDC system within a 30-calendar-day window. Only EDC data will be used for outcome 
reporting and endpoint adjudication and will be cross-checked with investigator-reported SAEs. 
When reporting events in the EDC system, it is not necessary to send supporting source 
documents for the events. For clinical event adjudication and safety verification, Cardialysis will 
request supporting source documents for events. All SAEs will be followed until the event is 
resolved (with or without sequelae). 
The sponsor is responsible for classifying SAEs according to local standard practices and for the 
ongoing safety assessment of the clinical study. The sponsor should review the investigator's 
assessment of all SAEs and device deficiencies, determine and document in writing the sponsor's 
judgment on severity and relationship to the investigational device. If there is a discrepancy 
between the sponsor's and the principal investigator's opinions, both opinions should be 
reflected. 
All devices used in this study protocol have been approved by the regulatory authorities in the 
region where the study is conducted and are used within the approved indications. 
Details on SAE handling, distribution, and reporting are provided in the Safety Reporting Plan. 
8.3. Risk Analysis 
Risk-benefit assessment is detailed in Section 1.5, and ongoing risk-benefit assessment is 
covered in Section 9.7.1.5. 
9. Data Integrity and Quality Assurance 
9.1. Regulatory Statement 
The protocol, ICF, and other study-related documents will be submitted to the EC and any other 
regulatory authorities as required by local regulations. The study will be conducted in accordance 
with the ethical principles of ISO 14155:2020 "Clinical investigation of medical devices for 
human subjects—Good Clinical Practice," the relevant sections of the ICH GCP guidelines, the 
"Medical Device Clinical Trial Quality Management (No. 28 [2022])," and the Declaration of 
Helsinki. This study may only commence after obtaining the necessary approval/favorable 
opinion from the EC and/or regulatory authorities. The study must comply with all additional 
requirements from the EC or regulatory authorities. 
9.2. Data Collection System 
The data recording tool for this study is a validated EDC system. 

 
33
To protect the data within the EDC system, all access is password-protected. All relevant study 
personnel (Sponsor, Investigational Site, Contract Research Organization (CRO), or others) 
seeking access to the EDC system will receive training before access is granted. The Investigator 
must maintain a signature and delegation log signed by qualified and trained site staff. All site 
personnel authorized to enter and/or correct data in the EDC system are listed in the signature 
and delegation log. 
All personnel with access to the EDC system are supported by a help desk. The EDC system 
includes a system-generated audit trail that records any changes made to data fields, including 
who made the change, the reason for the change, and the date and time of the change. 
9.2.1 EDC Entry 
It is highly recommended that all data entry into the EDC system be completed within 30 
calendar days after subject enrollment/visit/contact, including all reported SAEs, to allow 
monitors to review subject status throughout the enrollment period (see Section 9.5). Subject 
data in the EDC system is entered by the Investigator or a qualified designee and is reviewed and 
signed (electronically) by the Investigator. Data entered into the EDC system is supported by 
source documents maintained by the investigational site for all subjects enrolled in the study (see 
Section 9.3). 
Before the first subject is enrolled at a site, the site staff will be provided with EDC system data 
entry guidelines. 
9.2.2 Recording Data for Screen Failures 
A subject may have signed the ICF but is later considered a screen failure after subsequent 
screening procedures. This is referred to as a screen failure. Data from screen failures will not be 
recorded in the EDC system. Only formally enrolled patients will be recorded in the eCRF. 
9.3. Study Documentation 
Source documents are original records containing source data. Examples include original records 
or certified copies of hospital records, clinical and office charts, laboratory records, subject 
diaries, and records kept by laboratories involved in the clinical study. Source data can be either 
paper-based or electronic. All data intended for entry into the EDC system must have source 
documents available at the investigational site. All data intended for entry into the EDC system 
must have source documents accessible at the investigational site. 
In accordance with the regulations described in Section 9.1, the Investigator and study staff are 
responsible for maintaining a comprehensive and centralized file of all essential study-related 
documents (the Investigator Site File) for inspection at any time by representatives of the 
Sponsor and/or applicable regulatory authorities. The Investigator and study staff must ensure 
that only authorized personnel, auditors, and monitors have access to the study data. 
9.4. Data Management 

 
34
Clinical data management will be performed according to applicable CRO standards and data 
cleaning procedures. This applies to data recorded in the EDC system as well as data from other 
(external) sources (e.g., review committees). 
 
9.5. Quality Assurance 
Each clinical investigational site will conduct internal quality management for the conduct of the 
study, data and biospecimen collection, documentation, and completion. Quality control 
procedures will be implemented, starting with EDC and data QC checks run on the database. 
Any missing data or data anomalies will be communicated to the investigational site for 
clarification/resolution. Furthermore, monitoring visits, and potentially audits and inspections, 
ensure oversight of the entire quality control process. 
9.5.1 Audits and Inspections 
To ensure compliance with the guidelines and regulations described in Section 9.1, members of 
the CRO's Quality Assurance department may schedule a site audit to assess the site's study 
performance and the performance of study documents originating from the site. The Investigator 
will be informed of the audit findings. 
Additionally, inspections may be conducted by representatives of health regulatory authorities 
and the EC. The Investigator must notify the Sponsor immediately of any such inspection. Audits 
and inspections may occur at any time during or after the completion of the study. 
9.5.2 Monitoring 
According to the guidelines and regulations described in Section 9.1, the Monitor will contact the 
site before the study begins to review the protocol, study requirements, and the site staff's 
responsibilities for meeting regulatory, ethical, and Sponsor requirements. 
Per the monitoring plan, on-site and/or remote monitoring visits will be conducted throughout 
the study to verify compliance with the protocol/amendments; validate the authenticity, 
completeness, accuracy, and consistency of the data; verify that the rights and well-being of 
human participants are protected; and confirm adherence to the guidelines and regulations 
described in Section 9.1. The CN-IVI Registry does not constitute an investigation of a marketed 
device but aims to describe the outcomes of this clinical strategy; The Monitor must have access 
to subjects' medical records and other study-related documents. If electronic patient records 
(ePD) are used, controlled read-only access must be arranged for the Monitor. If the ePD is not 
validated, or if the Monitor cannot access it, there must be a procedure for generating certified 
copies of source documents. 
The Monitor will inform the Investigator of and document significant deviations from the 
protocol, SOPs, guidelines, and regulations as described in Section 9.1, and will verify that 

 
35
appropriate measures are taken to prevent the recurrence of identified deviations. Further details 
are available in the monitoring plan. 
9.6. Investigator Responsibilities 
Before subject enrollment begins, the Site Principal Investigator must read and understand this 
study protocol and sign and date the protocol signature page. The Site Investigator Agreement 
documents all conditions agreeing to the study protocol and the agreement to conduct the study 
accordingly. The Site Principal Investigator is responsible for ensuring the study is conducted in 
accordance with the provisions in Section 9.1. 
The Site Principal Investigator, site staff, and the site agree to permit the Monitor, Auditor, or 
Inspector direct access to all relevant source data/documents and will cooperate with the 
Monitor/Auditor/Inspector in discussing any findings. 
9.7. Sponsor Responsibilities 
 
9.7.1 Sponsor Role 
The Sponsor is fully responsible for the conduct of the study, including ensuring the study 
complies with the international standards and regulatory requirements of the relevant 
(competent) authorities described in Section 9.1. 
9.7.1.1. Overall Responsibilities 
Before allowing subject enrollment to begin at a site, the Sponsor is responsible for selecting the 
Investigator, ensuring EC approval is obtained (if applicable), and executing a clinical trial 
agreement with the Investigator and/or the hospital. Furthermore, the Sponsor is responsible for 
ensuring adequate supervision of the clinical investigational site. 
9.7.1.2. Selection of Clinical Investigators and Sites 
The Sponsor will select qualified Investigators and sites with an adequate patient population to 
meet the study requirements. 
9.7.1.3. Training of Investigators and Site Staff 
Training of the Investigator and appropriate clinical site staff will be the responsibility of the 
Sponsor and may be conducted during investigator meetings, site initiation visits, and/or other 
appropriate training sessions. Training on IVI acquisition/use will be provided before the first 
subject is enrolled. The Investigator is responsible for training site staff who were not present 
during the initiation visit. 
9.7.1.4. Documentation 

 
36
The Sponsor will collect, store, safeguard, and ensure the completion of the following documents 
by the relevant parties: 
  All study-related documents (e.g., protocol, EC approvals and opinions, notifications or 
approvals and opinions, patient information and informed consent forms, relevant 
correspondence, etc.) 
  Signed and dated EDC pages 
  Records of any SAEs reported to the Sponsor during the clinical study 
  Any statistical analyses and underlying supporting data 
  The final report and/or publications of the clinical study 
9.7.1.5. Ongoing Risk-Benefit Analysis 
The Sponsor is responsible for the continuous evaluation of the risk-benefit analysis throughout 
the study. An independent Data and Safety Monitoring Board has not been contracted for this 
study. 
9.7.1.6. Other Sponsor Responsibilities 
Other legal responsibilities of the Sponsor, including patient insurance, are described in Section 
9.1. 
9.7.2 Sponsor Delegation of Tasks 
For this study, the Sponsor has delegated specific tasks to a Clinical Research Organization 
(CRO), as described in Section 12. Whenever "Sponsor" is mentioned in this protocol, it includes 
its delegate(s), where applicable. 
9.8. Archiving 
Upon study completion, essential documents will be archived in a manner that ensures they are 
readily available upon request by regulatory authorities. Subjects' medical records shall be 
retained for the maximum period permitted by applicable law and the investigational site. 
Essential clinical registry documents (including EDC), aside from subject medical records, must 
be retained for at least 10 years after registry completion or termination according to Chinese 
requirements, and for at least 15 years according to Dutch requirements. Study documents must 
not be destroyed without prior written consent from the Sponsor and the Investigator. If the 
Investigator wishes to transfer the study records to another party or move them to another 
location, he/she must notify the Sponsor in writing of the new custodian and/or the new location. 
9.9. Study Termination or Temporary Halt and Premature Study Conclusion 
The Sponsor will notify the relevant regulatory authorities of the study conclusion within 90 
days. If the study is temporarily halted, the Sponsor will immediately notify the relevant 
regulatory authorities, including the reason for the halt. If the study is concluded prematurely, the 
Sponsor shall notify the relevant regulatory authorities within 15 days, including the reason for 
the premature termination. Within one year after the study conclusion, the Investigator/Sponsor 

 
37
shall submit a final study report to the relevant regulatory authorities, which includes the study 
results or any publications/abstracts of the study. 
This study may be temporarily suspended or terminated prematurely if fully justified and 
reasonable grounds exist. The party suspending or terminating will provide written notice to the 
Investigator, the funding party, and the regulatory authorities, documenting the reason for the 
suspension or termination. If the study is terminated prematurely or suspended, the Investigator 
shall immediately notify the EC and provide the reason for the termination or suspension. Study 
subjects will be contacted as appropriate and informed of changes to the site visit schedule. 
The study may potentially resume once the issues are resolved and the suspending party is 
satisfied.  
 
10. Ethical and Legal Aspects 
10.1 Funding, Financial Disclosure, and Insurance 
This study is sponsored by Zhongshan Hospital, Fudan University, as an investigator-initiated 
registry study. Boston Scientific International Medical Trading (Shanghai) Co., Ltd. has 
provided a grant to fund this study. 
A clinical registry agreement will be executed between the Investigator and/or the institution and 
the Sponsor before subject recruitment. 
As this is a post-market clinical registry study, the Sponsor is not required by local regulations to 
purchase insurance for the patients. 
10.2 Ethical and Legal Conduct of the Study 
The procedures set forth in this protocol related to the implementation, evaluation, and 
documentation of this study are designed to ensure that the Sponsor and Investigator adhere to 
the guidelines stipulated in Section 9.1. All aspects of the study's conduct require strict 
compliance with all quality standards set out in this protocol; the Investigator must not modify or 
change the procedures described herein. 
No amendments to the study protocol may be made by the Sponsor or the Investigator without 
mutual agreement. However, the Investigator or Sponsor may deviate from or change the 
protocol to eliminate apparent immediate hazards to the study subjects without prior EC/Sponsor 
approval/favorable opinion. The implemented deviation or change, the reason for it, and, where 
appropriate, a proposed protocol amendment should be submitted to the EC/institution 
head/Sponsor as soon as possible. 
10.3 Protocol Amendments 

 
38
As the study progresses, any appropriate study protocol amendments will be communicated to 
the Investigator by the Sponsor. All substantial protocol amendments will undergo the same 
review and approval process as the original protocol. All substantial and non-substantial 
amendments are handled according to local regulations and may be submitted to the local 
competent authorities for notification or approval. Unless changes must be implemented 
immediately for subject safety reasons, they shall be implemented after the protocol amendment 
has received EC approval. 
10.4 Patient Information and Informed Consent 
The ICF and all other written information provided to subjects will be revised when important 
new information becomes available that might be relevant to the subject's consent, or when 
changes are required due to a protocol amendment affecting the subject information sheet and/or 
the content of the written ICF. The Investigator will promptly inform subjects about the changes 
and ask subjects to sign the revised ICF to confirm their participation in the study. Any revised 
written ICF and written information must receive EC approval/favorable opinion before use. 
10.5 Confidentiality 
All records that could identify subjects will be kept confidential to the extent permitted by 
applicable laws and/or regulations. Subject names will not be provided to the Sponsor. If a 
subject's name appears on any other document (e.g., angiograms, IVUS, ECG), it must be 
removed before a copy of the document is provided to the Sponsor. Images sent to the 
angiographic core laboratory are anonymized. Study results stored on computers will be stored in 
accordance with local data protection laws. If the study results are published, the identity of the 
participants will remain confidential. The Investigator will retain a list to allow identification of 
the subjects. A subject identification code list will be used to link data to the subjects, only 
insofar as it is necessary to be able to trace the data back to an individual subject (for 10 years in 
China). The code must not be based on patient initials and date of birth. The key to the code shall 
be kept by the Investigator. The processing of personal data will comply with the Chinese 
privacy regulations and the EU General Data Protection Regulation (GDPR), as well as national 
legislation. 
  
 
11. Publication Policy 
The Steering Committee is committed to publishing and widely disseminating the study results. 
The data from this study will not be withheld, regardless of the outcome. The CN-IVI Registry 
was initiated by Professor Junbo Ge and is scientifically driven by the Steering Committee, with 
ECRI acting as a co-organizer. All public presentations and the writing and submission of 
manuscripts are conducted under the leadership of the Steering Committee. This study represents 
the collaborative effort of the Steering Committee, Investigators, Professor Junbo Ge (Sponsor), 
and ECRI representatives. Therefore, the parties have agreed that suggestions from all parties 

 
39
regarding manuscripts should be considered when preparing the final scientific documents for 
publication or presentation, according to the agreed publication policy. 
The final locked database will be stored at the data management centers of the local CRO and 
Cardialysis. The CRO may not publicly release data or study-related materials, presentations, or 
manuscripts without the explicit written permission of the Sponsor. The final locked database 
will also be transferred in its entirety to Cardialysis. Cardialysis will be responsible for analyzing 
the combined dataset, including the results of the registry, and performing aggregated data 
analysis. Prior to the publication of the primary results, the Principal Investigator (PI) will have 
full access to the data (i.e., all requested results will be provided). After the publication of the 
primary results for the primary endpoint event, the PI, high-enrolling personnel, and the 
manufacturer may request secondary analyses under the auspices of the Steering Committee. 
Proposals must be submitted to the Sponsor, who will liaise with the Steering Committee and the 
Publications Committee to determine priority, relevance, scientific merit, and novelty. Approved 
subgroup analyses will be handled by the Cardialysis statistics department. The publication 
and/or presentation of results from individual centers is not permitted prior to the publication 
and/or presentation of the multi-center results. All data from individual centers intended for 
public dissemination must be generated from the central database—local database projects are 
not permitted. All proposed publications and reports originating from or related to the study 
(whether from multi-center or single-center analyses) must be submitted to Professor Junbo Ge. 
Mr. Ge is responsible for liaising with the Publications Committee for review and approval prior 
to submission for publication or presentation. 
12. Study Organization 
12.1 Sponsor 
Zhongshan Hospital, Fudan University 
Shanghai, China 
12.2 Steering Committee 
The Steering Committee is responsible for the overall design, implementation, and supervision of 
the study, including the development of any protocol amendments. The Steering Committee also 
periodically reviews the study's progress to ensure subject safety and study integrity. The 
composition of the Steering Committee and other details are outlined in the Steering Committee 
charter. 
12.3 Data and Safety Monitoring Board (DSMB) 
As the CN-IVI Registry is an observational study of commercial devices and treatment strategies 
in accordance with guideline recommendations, a DSMB has not been installed for this study. 
12.4 Clinical Events Committee 
Clinical events will be reviewed and adjudicated by an independent Clinical Events Committee 
(CEC) organized by Cardialysis. For detailed information regarding the definitions of clinical 
events, please refer to the Appendix. Further details on endpoint subcategories and other CEC 
processes are outlined in the CEC charter. 

 
40
12.5 Contract Research Organization (CRO) 
The local CRO will be responsible for project management, EDC development, data 
management, site management and monitoring, safety reporting, generating lists for Cardialysis 
(e.g., for the CEC) based on EDC SAE reports and any other identified SAEs or triggers, 
performing statistical analysis of the study data, and transferring data to Cardialysis. 
Address: 
Fengsheng Chuangjian Building 
763 Mengzi Road, Huangpu District 
Shanghai, China 200023 
 
  
 
  
 
 
 

 
41
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45
INFORMED CONSENT FORM 
Study Title: A Chinese Registry Study on Coronary Calcified Nodules Evaluated by 
Intravascular Imaging (CN-IVI Registry) 
Version: 1.0 
Date: pending 
Principal Investigator at this site: Junbo Ge 
Institution: Zhongshan Hospital, Fudan University 
Contact Phone Number: 86 13816767665 
 
1. Invitation and Study Purpose 
You are invited to take part in a research study because you have a specific type of coronary 
artery plaque called a “calcified nodule,” which was found during your recent heart 
catheterization procedure using advanced imaging inside your blood vessels (IVUS or OCT). 
Calcified nodules are a form of hardened plaque that can sometimes be challenging to treat. 
However, doctors do not yet fully understand their long-term behavior or the best way to manage 
them. The purpose of this registry study is to collect information about patients like you who 
have these nodules. By observing your health status and treatment results over time, we hope to 
learn more about the natural course of these nodules and which treatments lead to the best 
outcomes for future patients. 
Approximately 500 patients across about 20 hospitals in China will be enrolled in this study. 
2. What Will Happen in This Study? 
If you agree to participate, your involvement will be as follows: 
• 
Your Standard Care: The treatment you receive for your heart condition will be 
decided solely by you and your doctor. This study does not change your treatment 
plan. Whether your nodule is treated with angioplasty, a stent, or not at all, it is a 
decision based on your medical needs, not this study. 
• 
Data Collection: We will ask for your permission to collect the images and data from 
your coronary angiography and intravascular imaging procedure that have already been 
done. 
• 
Medical Record Review: Researchers will review your hospital medical records to 
collect information about your health, the procedures you underwent, and the results. 
• 
Follow-Up Visits: You will be asked to participate in follow-up visits or phone calls with 
the study team at 1 year, 2 years, and 3 years after your initial procedure. During these 
contacts, we will ask about your health, any hospital visits, medications, and how you are 
feeling. These can often be done over the phone to make it easier for you. 

 
46
Your total participation in this study will last for 3 years. 
3. Risks and Discomforts 
Since this is an observational study that does not involve any experimental procedures or 
changes to your standard medical care, the risks to you are minimal. 
• 
The main risk is the potential loss of privacy and confidentiality of your personal health 
information. We have strict measures in place to protect your data (see Confidentiality 
section). 
• 
The follow-up phone calls may take some of your time. 
4. Benefits 
You may not receive any direct benefit from participating in this study. However, the 
information learned from this research may help doctors better understand how to treat patients 
with calcified nodules in the future, which could benefit others with your condition. 
5. Alternatives 
Your alternative is to not participate in this registry. This decision will not affect the medical 
care you receive now or in the future in any way. 
6. Confidentiality 
Your privacy is very important to us. All information collected about you for this study will be 
kept strictly confidential. Your name and personal identifying information will be replaced with 
a unique code number. Any documents or databases used for the research will use this code 
number instead of your name. The list connecting your name to this code will be kept secure and 
separate from the research data. 
Your records may be reviewed by authorized representatives of the sponsor (Zhongshan 
Hospital) or regulatory authorities to ensure the study is conducted properly, but they will also be 
required to keep your information confidential. 
7. Costs and Compensation 
There are no costs to you for participating in this study. You will not be paid for your 
participation. 
8. Voluntary Participation 
Taking part in this study is entirely your choice. Your decision to participate or not will not 
affect your relationship with your doctors or the quality of your medical care now or in the 
future. You have the right to withdraw from the study at any time, for any reason, without any 
penalty or loss of benefits to which you are otherwise entitled. 

 
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9. Questions and Contact Information 
If you have any questions about this study now or in the future, you can contact: 
• 
Your Study Doctor:                      , Phone:  
• 
Institutional Review Board (IRB)/Ethics Committee:                 , Phone:    Email:  
• 
 
You will receive a copy of this signed and dated informed consent form to keep. 
 
Statement of Consent 
I have read this consent form, or it has been read to me. I have had the opportunity to ask 
questions, and all my questions have been answered to my satisfaction. I voluntarily agree to 
participate in this study. 
Subject Signature: _________________________ 
Printed Name: _________________________ 
Date (YYYY-MM-DD): _________________________ 
Witness Signature (if required): _________________________ 
Printed Name: _________________________ 
Date (YYYY-MM-DD): _________________________ 
Investigator/Designee Signature: _________________________ 
Printed Name: _________________________ 
Date (YYYY-MM-DD): _________________________