Late-lumen Changes After Drug-Coated Balloon Angioplasty Versus Drug-Eluting Stents in De Novo Coronary Lesions
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Chonnam National University Hospital

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LAte-lumen ChanGEs AfteR Drug-Coated Balloon 
Angioplasty Versus Drug-Eluting Stents in De novo 
Coronary Lesions 
(LARGER-DCB) 
 
 
 
 
 
 
 
 
 
 
Version No: 1.0 
 
 
 
 
Department of Cardiology,  
Chonnam National University Hospital, 
Chonnam National University Medical School 
 
Principal Investigator: Young Joon Hong 
 
 

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Table of Contents 
1. Title of Study ................................................................................................................. 10 
2. Clinical Research Center .............................................................................................. 10 
3. Principal Investigator, Staff, Co-researchers .............................................................. 10 
4. Funding Agencies ......................................................................................................... 11 
5. Background and Hypothesis ........................................................................................ 11 
5.1. Background ............................................................................................................................. 11 
5.2. Hypothesis .............................................................................................................................. 11 
6. Study Plans ................................................................................................................... 11 
6.1 Study Design ............................................................................................................................ 11 
6.2. Study Timeline ........................................................................................................................ 11 
6.3. Study Population ..................................................................................................................... 12 
6.4. Eligibility Criteria ..................................................................................................................... 12 
6.4.1. Inclusion Criteria ........................................................................................................... 12 
6.4.2. Exclusion Criteria .......................................................................................................... 12 
6.5. Sample Size Calculation ......................................................................................................... 12 
6.6. Patient Follow-up .................................................................................................................... 13 
6.7. Early Study Termination .......................................................................................................... 13 
6.8. Measures to Avoid/Minimize Bias ........................................................................................... 13 
7. End points ..................................................................................................................... 13 
7.1. Primary Efficacy End Point ..................................................................................................... 13 
7.2. Secondary Efficacy End points ............................................................................................... 13 
7.3. Secondary Clinical End Points ................................................................................................ 13 
7.4. Definitions of End Points ......................................................................................................... 14 
8. Randomization .............................................................................................................. 17 
8.1. Randomization ........................................................................................................................ 17 
8.2. Stratification ............................................................................................................................ 18 
9. Patient Enrollment and Withdrawal ............................................................................. 18 
9.1. Patient Enrollment................................................................................................................... 18 
9.2. Patient Screening.................................................................................................................... 18 
9.3. Patient Discontinuation (Withdrawal Criteria) ......................................................................... 18 
9.4. Lost to Follow-up..................................................................................................................... 18 

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10. Study Protocols........................................................................................................... 19 
10.1. Flow Chart ............................................................................................................................. 19 
10.2. Study Procedure ................................................................................................................... 19 
10.3. Schedule of Measurements .................................................................................................. 20 
11. Measurement of Study Outcome Variables ............................................................... 21 
11.1. Visit 1 Screening & Baseline, Post-procedure ...................................................................... 21 
11.2. Follow-up ............................................................................................................................... 22 
12. Ethical Considerations and Confidentiality ............................................................... 22 
12.1. Institutional Review Board (IRB) / Ethical Committee Approval ........................................... 22 
12.2. Participant Safety .................................................................................................................. 23 
12.2.1. Elements of Informed Consent ................................................................................... 23 
12.2.2. Potential Risks ............................................................................................................ 23 
12.2.3. Adequacy of Protection against Risks ........................................................................ 23 
12.3. Confidentiality ....................................................................................................................... 24 
13. Study Organization ..................................................................................................... 24 
13.1. Steering Committee and Data Safety Monitoring Board (DSMB) ......................................... 24 
13.2. Clinical Event Adjudication Committee (CEAC) .................................................................... 24 
13.3. Data Coordination and Site Management ............................................................................ 24 
14. Statistical Analysis ...................................................................................................... 24 
14.1. Analysis Population ............................................................................................................... 24 
14.2. Sample Size Calculation ....................................................................................................... 25 
14.3. Primary Efficacy End Point Analysis ..................................................................................... 25 
14.4. Secondary Efficacy End Points Analyses ............................................................................. 26 
14.5. Secondary Clinical End points Analyses .............................................................................. 26 
14.6. Treatment of Missing Values ................................................................................................. 27 
14.7. Multivariable Analyses .......................................................................................................... 27 
14.8. Pre-specified subgroup analysis ........................................................................................... 27 
15. Publication Policy ....................................................................................................... 28 
15.1 Data Analysis and Release of Results ................................................................................... 28 
15.2 Review Process ..................................................................................................................... 28 
15.3 Authorship: Primary Outcome Paper ..................................................................................... 28 
15.4. Other Study Papers, Abstracts and Presentations ............................................................... 28 

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16. Quality Assurances, Quality Control and Clinical Monitoring ................................. 29 
16.1. Protocol Adherence .............................................................................................................. 29 
16.2. Data Collection: Electronic Case Report Forms (eCRF) ...................................................... 30 
16.3. Training/Certification and Retraining..................................................................................... 30 
16.4. Site Monitoring ...................................................................................................................... 30 
17. Adverse Events ........................................................................................................... 30 
17.1 Adverse Event ........................................................................................................................ 30 
17.2 Serious Adverse Event (SAE) ................................................................................................ 31 
18. Event Adjudication and Reporting ............................................................................. 31 
18.1 Investigator Responsibilities .................................................................................................. 31 
18.1.1. Adverse Events ........................................................................................................... 31 
18.1.2 Serious Adverse Events (SAE) .................................................................................... 32 
18.2 Endpoint and SAE Adjudication ............................................................................................. 32 
19. Regulatory Responsibilities ....................................................................................... 33 
19.1. Investigator Responsibilities ................................................................................................. 33 
19.2. Institutional Review Board (IRB) or Ethics Committee Approval .......................................... 33 
19.3. Informed Consent ................................................................................................................. 33 
19.4. Study Coordinator ................................................................................................................. 33 
20. Protocol Deviations and Amendments ...................................................................... 34 
20.1. Protocol Deviations ............................................................................................................... 34 
20.2. Protocol Amendments ........................................................................................................... 34 
21. Records Retention and Reports ................................................................................. 34 
21.1 Records .................................................................................................................................. 34 
21.2. Reports ................................................................................................................................. 35 
22. Investigational Agreement .......................................................................................... 36 
23. References ................................................................................................................... 43 
 
 
 

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Research Summary 
Study Title 
Late-lumen Changes After Drug-Coated Balloon Angioplasty Versus Drug-
Eluting Stents in De novo Coronary Lesions (LARGER-DCB) 
Principal  
Investigator 
Young Joon Hong MD, PhD 
Department of Cardiology,  
Chonnam National University Hospital, 
Chonnam National University Medical School, Gwangju, Korea 
hyj200@hanmail.net 
Trial 
Management 
Seung Hun Lee, MD, PhD (Chonnam National University Hospital) 
Joo Myung Lee, MD, MPH, PhD (Samsung Medical Center) 
Countries 
Involved 
Republic of Korea 
Purpose / Objectives: 
The aim of the study is to compare the late-lumen loss of drug-coated balloon angioplasty 
with drug-eluting stent implantation in large de novo coronary lesions. 
Backgrounds 
Drug-eluting stent (DES) is the standard of care for patients with coronary artery disease who 
are eligible for percutaneous coronary intervention (PCI).1 During long-term follow-up, remained 
metallic stent strut continuously related with stent-related cardiovascular events.2 As an alternative 
option to DES, drug-coated balloon (DCB) which has benefit of having shorter DAPT maintenance 
duration due to the absence of metallic scaffolds and polymers, has been introduced. Based on meta-
analysis based on many randomized clinical trials (RCT),3,4 its use has been established in in-stent 
restenosis of bare-metal stents and DES.5  
Furthermore, recent RCTs demonstrated efficacy and safety of DCB in de novo coronary lesions 
in small vessels with reference vessel size <3.0mm.6,7 For the patients with de novo, non-complex 
coronary artery lesions, REC-CAGEFREE I tested the non-inferiority of DCB angioplasty with DES 
implantation, irrespective of vessel diameter.8 Overall, 2272 patients were randomly assigned to the 
DCB or the DES group. At 2 years, adverse events occurred in 6.4% of DCB group and 3.4% of DES 
group and failed to prove the non-inferiority of DCB angioplasty (P for non-inferiority=0.65). 
Regarding the heterogenous results, it is questionable that DCB angioplasty for large de novo lesions 
is safe and effective compared with DES implantation. 
On this background, the current study aims to compare late-lumen loss (LLL) between DCB and 
DES to treat de novo coronary artery stenosis by intravascular ultrasound (IVUS). 
Protocol Summary 
1. 
Trial Design 
A prospective, multi-center, off-label, randomized controlled, non-inferiority trial. The current trial will 
evaluate non-inferiority of DCB angioplasty, compared with DES implantation to treat de novo 
coronary artery stenosis, in terms of late-lumen loss by IVUS. 
 
2. 
Target Population 
Patients with de novo coronary artery stenosis undergoing PCI. 
 
3. 
Enrollment Criteria 
(1) Inclusion criteria 
1) 
Subject must be at least 19 years of age 
2) 
Subject who is able to understand risks, benefits and treatment alternatives and sign 
informed consent voluntarily 
3) 
Patients with at least one lesion with greater than 50% diameter stenosis or fractional flow 
reserve ≤0.80 requiring revascularization in de novo coronary artery of reference vessel 
size ≥3.0 mm 
 
(2) Exclusion criteria 
1) 
Patients unable to provide consent 

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2) 
Patients with known intolerance to aspirin, P2Y12 inhibitors, or components of drug-eluting 
stents 
3) 
Patients with angiographic findings of  
1) 
Left main coronary artery disease 
2) 
In-stent restenosis is the cause of target lesion 
3) 
Target lesion in bypass graft 
4) 
True bifurcation lesion that requires upfront 2-stenting 
4) 
Patients who have non-cardiac co-morbid conditions with life expectancy <1 year  
5) 
Patients who may result in protocol non-compliance (site investigator’s medical judgment) 
6) 
Patients with cardiogenic shock or cardiac arrest 
7) 
Patients with severe left ventricular systolic dysfunction (ejection fraction <30%) 
8) 
Patients with severe valvular heart disease requiring open heart surgery 
9) 
Pregnant or lactating women 
 
4. 
Study End Points 
(1) Primary efficacy end point 
Mean difference of late-lumen loss between DCB and DES in IVUS 
 
(2) Secondary efficacy end points 
1) 
Mean difference of minimal lumen diameter (MLD) in quantitative coronary angiography 
(QCA) 
2) 
Mean difference of %diameter stenosis in QCA 
3) 
Mean difference of MLD in IVUS 
 
(3) Secondary clinical end points 
1) 
Cardiovascular death  
2) 
All-cause death 
3) 
Target-vessel myocardial infarction (MI) 
4) 
Non-fatal MI 
5) 
Clinically indicated target-lesion revascularization (TLR) 
6) 
Clinically indicated target-vessel revascularization (TVR) 
7) 
Any revascularization 
8) 
Vessel or stent thrombosis (definite or probable by Academic Research Consortium [ARC] 
definition)  
9) 
Cardiovascular death or target-vessel MI  
10) All-cause death or non-fatal MI 
11) Target vessel failure (TVF, a composite of cardiovascular death, target-vessel MI, and 
clinically indicated TVR) 
12) Target lesion failure (TLF, a composite of cardiovascular death, target-vessel MI, and 
clinically indicated TLR)  
13) Cardiovascular death, target-vessel MI, or vessel or stent thrombosis  
14) All-cause death, non-fatal MI, or TVR  
15) BARC type 2, 3, or 5 bleeding 
16) Cerebrovascular accident (CVA) 
∙ Ischemic stroke  
∙ Hemorrhagic stroke  
∙ Transient ischemic attack (TIA) 
 
5. 
Sample Size Calculation 
Primary hypothesis: DCB angioplasty would be noninferior to DES late-lumen loss (LLL) in large 
de novo coronary stenosis. 
Secondary Hypothesis (Superiority): If non-inferiority is established, test for superiority of DCB 
over DES in LLL. 
 

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Based on the previous trial that compared late-lumen loss of DCB or DES by QCA or IVUS,9-14 the 
expected LLL of DCB is -0.41 mm2 and DES is 0.18 mm2 (mean difference of LLL 0.59 mm2) on IVUS 
(standard deviation of both group would be 1.28 mm2). 
 
 
LLL of DCB group: -0.41 mm2 
 
LLL of DES group: 0.18 mm2 
 
Mean Difference of LLL: 0.59 mm2 
 
Standard deviation of both group: 1.28 (DCB group 1.29 and DES group 1.27) 
 
Non-inferiority margin: 0.47 mm2  
 
Type I Error (Alpha):  
- 
Non-inferiority test: 1-sided alpha of 0.025 
- 
Superiority Test (if non-inferiority is met): 2-sided alpha of 0.05 
 
Power: 80% 
 
Drop-out rate 10% 
 
Based on the above assumption, a total of 256 patients (128 patients for DCB group and 128 
patients for DES group) will be needed to show non-inferiority of DCB compared to DES with 80% of 
statistical power at a 1-sided alpha of 2.5%. If non-inferiority is confirmed, the sequential testing of 
superiority of DCB will be tested at a significance level of 2-sided alpha of 5.0%. The planned sample 
size will provide statistical power of 99% to test the potential superiority of DCB than DES in terms 
of LLL.  
 
6. 
Randomization 
Patients will be randomized to either the DCB group or the DES group with 1:1 ratio during the index 
procedure after diagnostic angiography. Stratified randomization according to participating center, 
clinical presentation (acute coronary syndrome [ACS] or chronic coronary syndrome [CCS]), and 
severely calcified lesions (encircling calcium in angiography) will be performed. All processes will be 
done by a web-based randomization program with a permutated block size of 4, run by an 
independent organization. 
(1) Experimental (Standard therapy): DCB group 
(2) Control group (Standard therapy): DES group 
 
7. 
Study Procedure 
(1) Flow chart 

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(2) Optimal lesion preparation and treatment according to allocated group 
IVUS (OPTICROSS, Boston Scientific, USA) will be essential to select proper size of 
predilatation balloon (semi- or non-compliant balloon), DCB, or DES. Optimal lesion preparation 
is defined as satisfying all of the followings: 1) a fully inflated balloon of the correct size for the 
vessel (balloon with vessel ratio >0.90); 2) ≤35% residual stenosis; 3) TIMI (Thrombolysis In 
Myocardial Infarction) flow grade 3; and 4) the absence of a flow-limiting coronary artery 
dissection.15 After successful lesion preparation, patients will receive either DCB or DES 
according to randomly allocated groups. 
 
(3) Drug-coated balloon angioplasty 
In DCB group, commercially available DCB (Agent, Boston Scientific, USA) will be used. DCB 
angioplasty will be recommended as follows to fully optimized procedural results. First, DCB size 
should be 1:1 ratio with reference vessel size. Second, delivery time of DCB should be within 30 
seconds. Third, total inflation time of DCB will be recommended from 30 to 60 seconds.15,16 
 
(4) Drug-eluting stent  
In DES group, latest second-generation DES will be used in accordance with standard practice 
guideline.5,17 
 
(5) Bail-out stenting in DCB group 
In case of 1) flow disturbance after lesion preparation (TIMI glow grade <3), 2) significant re-coil 
or residual stenosis after lesion preparation (residual stenosis ≥50%), 3) major dissection with 
significant ischemic changes (dissection type D, E, or F), bail-out implantation of DES will be 
permitted.15 Patients treated by bail-out stenting will be analyzed as originally assigned DCB 
group in the intention-to-treat analysis and will be analyzed as DES group in the per-protocol 
analysis of the as-treated population. However, primary hypothesis will be tested according to 
the intention-to-treat analysis. 
 
(6) Intravascular Imaging devices 
IVUS will be mandatory during pre-interventional lesion assessment and planning and post-
interventional optimization. In DCB arm, optimal size of pre-dilatation balloon and DCB will be 
decided based on the information from intravascular imaging devices. In DES arm, optimal size 
of pre-dilatation balloon, stent size, and post-stent implantation optimization will be decided 

LARGER-DCB_V1.0_April_2025                                           CONFIDENTIAL 
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based on the information from IVUS.18 
 
(7) Adjunctive medical treatment for both arms 
Regardless of allocated arms, best available medical treatment will be the performed according 
to the current ACC/AHA/SCAI or ESC/EACTS guidelines.5,17 Patients will be recommended to 
receive 1-3 months dual antiplatelet therapy of aspirin plus a P2Y12 inhibitor. Thereafter, patients 
will receive single antiplatelet therapy (a P2Y12 inhibitor alone will be preferred).19,20 In patients 
who need oral anticoagulant therapy, aspirin can be discontinued at hospital discharge. In ACS 
patients, a potent P2Y12 inhibitor (Ticagrelor or Prasugrel) or conventional P2Y12 inhibitor 
(Clopidogrel) can be used at the discretion of the operator according to appropriate assessment 
of bleeding risk which is recommended by the current guidelines. Any adjunctive pharmacologic 
treatment will be left to the operator’s discretion. 
 
8. 
Prespecified Subgroup Analysis 
(1) Primary and Secondary efficacy end point will be assessed in pre-specified subgroups below. 
1)  Age (age ≥65 vs. <65) 
2)  Sex 
3)  Diabetes mellitus vs. non-diabetes mellitus 
4) 
Acute coronary syndrome vs. chronic coronary syndrome 
5) 
Optimal vs. Suboptimal lesion-preparation in DCB procedure 
6) 
Complex vs. non-complex lesion 
 
(2) Secondary clinical end point will be assessed in pre-specified subgroups below.  
1) 
Age (age ≥65 vs. <65) 
2) 
Sex 
3) 
Diabetes mellitus vs. non-diabetes mellitus 
4) 
Acute coronary syndrome vs. chronic coronary syndrome 
5) 
Ischemic territory (proximal lesion in major epicardial coronary artery vs. others) 
6) 
Complex vs. non-complex lesion 
7) 
1-month vs. 3-month dual antiplatelet therapy 
 
9. 
Study Duration and Dates 
IRB approval date ~ 2028.12.31 
Subject enrollment: IRB approval date ~ 2026.12 (accrual period: 1.5 years) 
End of follow-up period: 2027.12 (1 year after last patient enrollment) 
Analysis and report: ~2028.12.31 
 
10. Follow-up 
After the randomization, angiographic and IVUS follow-up will be done at 9 months. Clinical follow-
up will be done at 6 and 12 months, and annually thereafter until 1 year from last patient enrollment. 
Funding Agency 
Boston Scientific (USA) 
 
 

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1. Title of Study 
Late-lumen Changes After Drug-Coated Balloon Angioplasty Versus Drug-Eluting Stents in De novo 
Coronary Lesions (LARGER-DCB) 
 
2. Clinical Research Center 
① Chonnam National University Hospital, Chonnam National University Medical School, South Korea 
② Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea 
③ Jeonbuk National University Hospital, Jeonju, South Korea 
④ Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea\ 
⑤ Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, South Korea 
⑥ Ewha Womans University Mokdong Hospital, Seoul, South Korea 
⑦ Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea 
⑧ Keimyung University Dongsan Hospital, Daegu, South Korea 
⑨ Yeosu Jeil Hospital, Yeosu, South Korea 
 
3. Principal Investigator, Staff, Co-researchers 
 
Name 
Center 
Position 
Trial 
Principle 
investigator 
Young Joon Hong 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Trial 
Management 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Associate 
Professor 
Joo Myung Lee 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Associate 
Professor 
Co-researchers 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Associate 
Professor 
Joon Ho Ahn 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Associate 
Professor 
Joo Myung Lee 
Samsung Medical Center, Seoul, South 
Korea 
Associate 
Professor 
Yi Sik Kim 
Jeonbuk National University Hospital 
Professor 
Eun Seok Shin 
Ulsan University Hospital, University of Ulsan 
College of Medicine 
Professor 
Jung Ho Heo 
Kosin University Gospel Hospital, Kosin 
University College of Medicine 
Professor 
Sodam Jung 
Ewha Womans University Mokdong Hospital 
Assistant 
Professor 
Dong Oh Kang 
Korea University Guro Hospital, Korea 
University College of Medicine 
Assistant 
Professor 
Hyuck-Jun Yoon 
Keimyung University Dongsan Hospital 
Professor 

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Sang-Cheol Cho 
Yeosu Jeil Hospital 
Director 
Yonghwan Lim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Seok Oh 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
 
4. Funding Agencies 
Boston Scientific (USA) 
 
5. Background and Hypothesis 
5.1. Background 
Drug-eluting stent (DES) is the standard of care for patients with coronary artery disease who are 
eligible for percutaneous coronary intervention (PCI).1 During long-term follow-up, remained metallic 
stent strut continuously related with stent-related cardiovascular events.2 As an alternative option to 
DES, drug-coated balloon (DCB) which has benefit of having shorter DAPT maintenance duration due 
to the absence of metallic scaffolds and polymers, has been introduced. Based on meta-analysis based 
on many randomized clinical trials (RCT),3,4 its use has been established in in-stent restenosis of bare-
metal stents and DES.5  
Furthermore, recent RCTs demonstrated efficacy and safety of DCB in de novo coronary lesions 
in small vessels with reference vessel size <3.0mm.6,7 For the patients with de novo, non-complex 
coronary artery lesions, REC-CAGEFREE I tested the non-inferiority of DCB angioplasty with DES 
implantation, irrespective of vessel diameter.8 Overall, 2272 patients were randomly assigned to the 
DCB or the DES group. At 2 years, adverse events occurred in 6.4% of DCB group and 3.4% of DES 
group and failed to prove the non-inferiority of DCB angioplasty (P for non-inferiority=0.65). Regarding 
the heterogenous results, it is questionable that DCB angioplasty for large de novo lesions is safe and 
effective compared with DES implantation. 
On this background, the current study aims to compare late-lumen loss (LLL) between DCB and DES 
to treat de novo coronary artery stenosis by intravascular ultrasound (IVUS). 
 
5.2. Hypothesis 
DCB angioplasty would be noninferior to DES late-lumen loss in large de novo coronary stenosis. 
 
6. Study Plans 
6.1 Study Design 
A prospective, multi-center, off-label, randomized controlled, non-inferiority trial. 
 
6.2. Study Timeline 
IRB approval date ~ 2028.12.31 
Subject enrollment: IRB approval date ~ 2026.12 (accrual period: 1.5 years) 
End of follow-up period: 2027. 12 (1 year after last patient enrollment) 
Total follow-up duration: 1~2.5 years (Median 1.5 years) 
Analysis and report: ~2028.12.31 
 

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6.3. Study Population 
A total of 256 patients (128 per each group) will be enrolled at multiple centers in South Korea. Patients 
with large de novo coronary stenosis (≥3.0 mm) undergoing PCI will be eligible. All eligible patients will 
be on either DCB or DES group as randomized. 
 
6.4. Eligibility Criteria 
6.4.1. Inclusion Criteria 
(1) Subject must be at least 19 years of age 
(2) Subject who is able to understand risks, benefits and treatment alternatives and sign informed 
consent voluntarily 
(3) Patients with at least one lesion with greater than 50% diameter stenosis or fractional flow 
reserve ≤0.80 requiring revascularization in de-novo coronary artery of reference vessel size 
≥3.0 mm 
6.4.2. Exclusion Criteria 
(1) Patients unable to provide consent 
(2) Patients with known intolerance to aspirin, P2Y12 inhibitors, or components of drug-eluting 
stents 
(3) Patients with angiographic findings of  
1) 
Left main coronary artery disease 
2) 
In-stent restenosis is the cause of target lesion 
3) 
Target lesion in bypass graft 
4) 
True bifurcation lesion that requires upfront 2-stenting 
(4) Patients who have non-cardiac co-morbid conditions with life expectancy <1 year  
(5) Patients who may result in protocol non-compliance (site investigator’s medical judgment) 
(6) Patients with cardiogenic shock or cardiac arrest 
(7) Patients with severe left ventricular systolic dysfunction (ejection fraction <30%) 
(8) Patients with severe valvular heart disease requiring open heart surgery 
(9) Pregnant or lactating women 
 
6.5. Sample Size Calculation 
Primary hypothesis: DCB angioplasty would be noninferior to DES late-lumen loss (LLL) in large de 
novo coronary stenosis. 
Secondary Hypothesis (Superiority): If non-inferiority is established, test for superiority of DCB over 
DES in LLL. 
 
Based on the previous trial that compared late-lumen loss of DCB or DES by QCA or IVUS,9-14 the 
expected LLL of DCB is -0.41 mm2 and DES is 0.18 mm2 (mean difference of LLL 0.59 mm2) on IVUS 
(standard deviation of both group would be 1.28 mm2). 
 
 
LLL of DCB group: -0.41 mm2 
 
LLL of DES group: 0.18 mm2 
 
Mean Difference of LLL: 0.59 mm2 
 
Standard deviation of both group: 1.28 (DCB group 1.29 and DES group 1.27) 
 
Non-inferiority margin: 0.47 mm2  
 
Type I Error (Alpha):  
- 
Non-inferiority test: 1-sided alpha of 0.025 
- 
Superiority Test (if non-inferiority is met): 2-sided alpha of 0.05 

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 
Power: 80% 
 
Drop-out rate 10% 
 
Based on the above assumption, a total of 256 patients (128 patients for DCB group and 128 patients 
for DES group) will be needed to show non-inferiority of DCB compared to DES with 80% of statistical 
power at a 1-sided alpha of 2.5%. If non-inferiority is confirmed, the sequential testing of superiority of 
DCB will be tested at a significance level of 2-sided alpha of 5.0%. The planned sample size will provide 
statistical power of 99% to test the potential superiority of DCB than DES in terms of LLL.  
 
6.6. Patient Follow-up 
After the randomization, angiographic and IVUS follow-up will be done at 9 months. Clinical follow-up 
will be done at 6 and 12 months, and annually thereafter until 1 year from last patient enrollment. 
 
6.7. Early Study Termination 
No statistical rule for early trial termination is defined. An independent Data Safety Monitoring Board 
(DSMB) will review the safety data including death, myocardial infarction (MI), stroke or other serious 
adverse events. The DSMB will be powered to recommend suspension of enrollment or termination of 
the study based on safety concerns (refer to section 13.1 Steering Committee and DSMB). The Steering 
Committee will make the final decision for early study termination based on DSMB recommendations. 
 
6.8. Measures to Avoid/Minimize Bias 
To minimize bias in assessing clinical events, an independent Clinical Event Adjudication Committee 
(CEAC) (refer to section 13.2 Clinical Event Adjudication Committee) and DSMB (refer to section 13.1 
Steering Committee and DSMB) will be established. Data management will be performed by an 
independent data management core center, and a web-based electronic case report form (eCRF) and 
a web-based online randomization program will be utilized. Restricted access to the data management 
system will be maintained throughout the trial period. 
 
7. End points 
7.1. Primary Efficacy End Point 
Mean difference of late-lumen loss between DCB and DES in IVUS  
 
7.2. Secondary Efficacy End points 
① 
Mean difference of minimal lumen diameter (MLD) in quantitative coronary angiography 
(QCA) 
② 
Mean difference of %diameter stenosis in QCA 
③ 
Mean difference of MLD in IVUS 
 
7.3. Secondary Clinical End Points 
① Cardiovascular death  
② All-cause death 
③ Target-vessel myocardial infarction (MI) 
④ Non-fatal MI 
⑤ Clinically indicated target-lesion revascularization (TLR) 

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⑥ Clinically indicated target-vessel revascularization (TVR) 
⑦ Any revascularization 
⑧ Vessel or stent thrombosis (definite or probable by Academic Research Consortium [ARC] 
definition)  
⑨ Cardiovascular death or target-vessel MI  
⑩ All-cause death or non-fatal MI 
⑪ Target vessel failure (TVF, a composite of cardiovascular death, target-vessel MI, and clinically 
indicated TVR) 
⑫ Target lesion failure (TLF, a composite of cardiovascular death, target-vessel MI, and clinically 
indicated TLR)  
⑬ Cardiovascular death, target-vessel MI, or vessel or stent thrombosis  
⑭ All-cause death, non-fatal MI, or TVR  
⑮ BARC type 2, 3, or 5 bleeding 
⑯  Cerebrovascular accident (CVA) 
 
Ischemic stroke  
 
Hemorrhagic stroke  
 
Transient ischemic attack (TIA) 
 
7.4. Definitions of End Points 
Cardiovascular 
death 
Cardiovascular death includes sudden cardiac death, death due to 
acute MI, heart failure or cardiogenic shock, other 
cardiovascular causes, or any unknown death without undisputed non-
cardiac cause. 
MI 
The definition of myocardial infarction used in this trial is adapted from the 
Fourth Universal Definition of Myocardial Infarction.21 
 
• Clinical criteria for MI: 
The clinical definition of MI denotes the presence of acute 
myocardial injury detected by abnormal cardiac biomarkers in the 
setting of evidence of acute myocardial ischemia. 
• Criteria for Myocardial Injury: 
Detection of an elevated cardiac troponin (cTn) value above the 99th 
percentile upper reference limit (URL) is defined as myocardial injury. The 
injury is considered acute if there is a rise and/or fall of cTn values. 
Type 1 MI 
(Spontaneous MI) 
Detection of a rise and/or fall of cTn values with at least 1 value above the 
99th percentile URL and with at least 1 of the following: 
• Symptoms of acute myocardial ischemia; 
• New ischemic ECG changes; 
• Development of pathological Q waves; 
• Imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality in a pattern consistent with an ischemic 
etiology; 
• Identification of a coronary thrombus by angiography including 
intracoronary imaging or by autopsy. 
Type 2 MI 
(MI secondary to an 
ischemic 
imbalance) 
Detection of a rise and/or fall of cTn values with at least 1 value above the 
99th percentile URL, and evidence of an imbalance between myocardial 
oxygen supply and demand unrelated to acute coronary atherothrombosis, 
requiring at least 1 of the following: 

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• Symptoms of acute myocardial ischemia; 
• New ischemic ECG changes; 
• Development of pathological Q waves; 
• Imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality in a pattern consistent with an ischemic 
etiology 
Type 3 MI 
(MI resulting in 
death) 
Patients who suffer cardiac death, with symptoms suggestive of myocardial 
ischemia accompanied by presumed new ischemic ECG changes or 
ventricular fibrillation, but die before blood samples for biomarkers can be 
obtained, or before increases in cardiac biomarkers can be identified, or MI is 
detected by autopsy examination. 
Type 4 and 5 MI 
Cardiac procedural myocardial injury is arbitrarily defined by increases of cTn 
values (>99th percentile URL) in patients with normal baseline values (≤99th 
percentile URL) or a rise of cTn values >20% of the baseline value when it is 
above the 99th percentile URL but it is stable or falling. 
Type 4a MI 
(PCI-Related MI ≤48 
Hours After the 
Index Procedure) 
Coronary intervention–related MI is arbitrarily defined by an elevation of cTn 
values >5 times the 99th percentile URL in patients with normal baseline 
values. In patients with elevated preprocedure cTn in whom the cTn level are 
stable (≤20% variation) or falling, the postprocedure cTn must rise by >20%. 
However, the absolute postprocedural value must still be at least 5 times the 
99th percentile URL. In addition, 1 of the following elements is required: 
• New ischemic ECG changes; 
• Development of new pathological Q waves*; 
• Imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality in a pattern consistent with an ischemic 
etiology; 
• Angiographic findings consistent with a procedural flow-limiting 
complication such as coronary dissection, occlusion of a major 
epicardial artery or a side branch occlusion/thrombus, disruption of 
collateral flow, or distal embolization. 
Type 4b MI 
(MI related to 
stent/scaffold 
thrombosis) 
A subcategory of PCI-related MI is stent/scaffold thrombosis, type 4b MI, as 
documented by angiography or autopsy using the same criteria utilized for 
type 1 MI. 
Type 4c MI 
(Restenosis 
Associated with 
PCI) 
This PCI-related MI type is designated as type 4c MI, defined as focal or 
diffuse restenosis, or a complex lesion associated with a rise and/or fall of 
cTn values above the 99th percentile URL applying, the same criteria utilized 
for type 1 MI. 
Type 5 MI 
(CABG-Related MI 
≤48 Hours After the 
Index Procedure) 
CABG-related MI is arbitrarily defined as elevation of cTn values >10 times 
the 99th percentile URL in patients with normal baseline cTn values. In 
patients with elevated preprocedure cTn in whom cTn levels are stable (≤20% 
variation) or falling, the postprocedure cTn must rise by >20%. However, the 
absolute postprocedural value still must be >10 times the 99th percentile 
URL. In addition, 1 of the following elements is required: 
• Development of new pathological Q waves; 
• Angiographic documented new graft occlusion or new native coronary 
artery occlusion; 
• Imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality in a pattern consistent with an ischemic 
etiology. 
TLR, TVR, and 
Repeat 
revascularization 
The coronary segments revascularized will be sub-classified as: 
 
• Target Lesion: A lesion revascularized in the index procedure (or 

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during a planned or provisional staged procedure). The LM target 
lesion extends from the left main stem ostium to the end of the 5 mm 
proximal segments of the left anterior descending and left circumflex 
arteries as well as the ramus intermedius if the latter vessel has a 
vessel diameter of ≥2 mm. 
• Target Vessel: The target vessel is defined as the entire major 
coronary vessel proximal and distal to the target lesion including 
upstream and downstream branches and the target lesion itself. The 
left main and any vessel originating from the left main coronary 
artery or its major branches is, by definition, considered a target 
vessel for the purposes of this trial. 
• Target Vessel Non-Target Lesion: The target vessel non-target 
lesion consists of a lesion in the epicardial vessel/branch/graft that 
contains the target lesion; however, this lesion is outside of the 
target lesion by at least 5 mm distal or proximal to the target lesion 
determined by quantitative coronary angiography (QCA). 
• Non-Target Vessel: Any vessels which was not attempted to be 
revascularized at index procedure 
 
All revascularization events will be adjudicated as either clinically-driven or 
non-clinically-driven. Revascularization will be considered clinically-driven if 
the diameter stenosis of the revascularized coronary segment is ≥50% by 
QCA and any of the following criteria for ischemia are met: 
① A positive functional study corresponding to the area served by the 
target lesion; or 
② Ischemic ECG changes at rest in a distribution consistent with the 
target vessel; or 
③ Typical ischemic symptoms referable to the target lesion; or 
④ positive invasive physiologic test (fractional flow reserve ≤0.80 or 
instantaneous wave-free ratio ≤0.89); or 
⑤ presence of stenosis with ≥70% diameter stenosis, even in the 
absence of other criteria 
 
BARC (Bleeding 
Academic Research 
Consortium) 
bleeding 
Type 2: Any clinically overt sign of hemorrhage that “is actionable” and 
requires diagnostic studies, hospitalization, or treatment by a health care 
professional 
 
Type 3:  
 
• a. Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided 
hemoglobin drop is related to bleed); transfusion with overt bleeding 
• b. Overt bleeding plus hemoglobin drop of 5 g/dL (provided 
hemoglobin drop is related to bleed); cardiac tamponade; bleeding 
requiring surgical intervention for control; bleeding requiring IV 
vasoactive agents 
• c. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar 
puncture; intraocular bleed compromising vision 
 
Type 5: 
• a. Probable fatal bleeding 
• b. Definite fatal bleeding (overt or autopsy or imaging confirmation) 
Stent thrombosis 
Academic Research Consortium (ARC) definition of stent thrombosis is 
classified and defined as follows. 
• Definite/Confirmed stent thrombosis refers angiographic or 

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pathologic confirmation of partial or total thrombotic occlusion within 
the per-stent region with either i) acute ischemic symptoms, ii) 
ischemic EKG changes, iii) elevated cardiac biomarkers.  
• Probable stent thrombosis is defined as any unexplained death 
within 30 days of stent implantation or any myocardial infarction, 
which is related to documented acute ischemia in the territory of the 
implanted stent without angiographic confirmation of stent 
thrombosis and in the absence of any other obvious cause. 
• Possible stent thrombosis is defined as any unexplained death 
beyond 30 days of stent implantation. 
Cerebrovascular 
accident (CVA) 
Sudden onset of vertigo, numbness, aphasia, dysarthria or central neurologic 
deficit secondary to vascular lesions of the brain such as hemorrhage, 
embolism, thrombosis, or rupturing aneurysm, that persists for > 72 hours. 
Hemorrhagic 
A stroke with documentation on imaging (e.g., CT 
scan or MRI of hemorrhage in the cerebral 
parenchyma, or a subdural or subarachnoid 
hemorrhage). Evidence of hemorrhagic stroke 
obtained from lumbar puncture, neurosurgery, or 
autopsy can also confirm the diagnosis. 
Nonhemorrhagic 
A focal neurological deficit that results from a 
thrombus or embolus (and not due to hemorrhage) 
that appears and is still partially evident for more 
than 24 hours. 
Transient 
Ischemic 
Neurological Attack 
(TIA)  
A sudden onset of reversible focal neurological 
deficits due to vascular lesions of the brain that lasts 
≤ 24 hours. 
 
8. Randomization 
8.1. Randomization 
Patients will be screened for eligibility and, if qualified, a written informed consent will be obtained from 
all patients. After obtaining informed consent, patients will be randomly assigned to a treatment group 
via the internet by the independent online randomization system. Randomization will be done 
immediately after the initial coronary angiogram, but before PCI. Stratified randomization according to 
participating center, clinical presentation (acute coronary syndrome [ACS] or chronic coronary 
syndrome [CCS]), and severely calcified lesions (encircling calcium in angiography) will be performed. 
All processes will be done by a web-based randomization program with a permutated block size of 4, 
run by an independent organization. 
 
Patients will be randomized to either DCB group or DES group with 1:1 ratio. 
(1) Experimental group (Standard therapy): DCB  
(2) Control group (Standard therapy): DES 

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8.2. Stratification 
To ensure balance among the strata, randomization will be stratified by participating center, clinical 
presentation (acute coronary syndrome [ACS] or chronic coronary syndrome [CCS]), and severely 
calcified lesions (encircling calcium in angiography). All processes will be done by a web-based 
randomization program with a permutated block size of 4, run by an independent organization. 
 
9. Patient Enrollment and Withdrawal 
9.1. Patient Enrollment 
A total of 256 patients derived from a population of Korean patients with large de novo coronary stenosis 
undergoing PCI will be enrolled in the study. It is recommended that each enrolling investigator review 
the most recent instructions for use (IFU) and assess the contraindications, warnings, and precaution 
sections for treating potential patients. 
 
9.2. Patient Screening 
Consecutive patients presenting at participating centers will be evaluated for entry into the study. All 
consecutive patients should be invited to participate in the study. 
Screening will be performed for patients without exclusion criteria. If patients meet enrollment criteria, 
informed consent will be obtained after explanation of study protocol. 
A member of each research team should review the patients’ medical history for eligibility. If all eligibility 
criteria are met and written informed consent is provided, the patient may be enrolled in the study. 
Patients will be entered into the eCRF only after informed consent has been obtained. 
 
9.3. Patient Discontinuation (Withdrawal Criteria) 
Once enrolled, each patient should remain in the study until the required follow-up period is complete. 
However, all patients have the right to withdraw at any point during the study without penalty or loss of 
benefit. The investigator may discontinue any patient at any time if medically necessary. Data obtained 
to the last follow-up will be used for the analysis. It will be documented whether or not each patient 
completed the clinical study. If the study treatment(s) or observations are discontinued in any patient, 
the reason will be recorded, and the data coordinating center must be notified promptly.  
 
The following events will result in terminating the patient’s follow-up:  
• Patient voluntary withdrawal  
• Patient withdrawn by investigator as clinically indicated  
 
It is imperative to obtain complete follow-up data for all patients, whether or not they receive their 
assigned treatment. Every attempt should be made to collect follow-up information, except for those 
patients who specifically withdraw consent for release of such information. All procedures and 
laboratory specimens or tests requested for evaluation after enrollment in the study should be carried 
out when possible, whether or not a patient continues to receive treatment according to the protocol. 
Patients will not be replaced in this trial. 
Even patients with lost to follow-up according to the above criteria, cross-validation of vital status will 
be performed using the National Health Insurance Data and Korean Statistics od Death Record.  
 
9.4. Lost to Follow-up 
Patients that do not complete the scheduled follow-up visits and have not officially withdrawn from the 
study are considered lost to follow-up; this term does not apply to missed visits. Site personnel should 
make considerable effort to locate and communicate with the patient using all available methods (ex, 
telephone, emails, and postcards). The following contact procedure is recommended at each time point:  
• A minimum of 2 telephone calls on different days over the specified follow-up windows should be 

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recorded in the source documentation including date, time, and site personnel initials for staff 
attempting to contact the patient.  
• If these attempts are unsuccessful, a certified letter should be sent to the patient.  
• cross-checking of National Health Insurance Data will be performed for all patients to confirm vital 
status of enrolled patients. 
If the patient misses 2 consecutive scheduled contact time points and the above-mentioned attempts 
at communicating with the patient are unsuccessful, the patient will be considered lost to follow-up. 
 
10. Study Protocols 
After the patient has been enrolled in the present study, the following procedures will take place. The 
schedule of events for this trial is located in section 11.1 Schedule of Events. It is recommended that 
each enrolling investigator review the most recently updated IFU and assess the contraindications, 
warnings, and precaution sections for treating potential patients.  
 
10.1. Flow Chart 
 
 
10.2. Study Procedure 
(1) Optimal lesion preparation and treatment according to allocated group 
IVUS (OPTICROSS, Boston Scientific, USA) will be recommended to select proper size of 
predilatation balloon (semi- or non-compliant balloon), DCB, or DES. Optimal lesion 
preparation is defined as satisfying all of the followings: 1) a fully inflated balloon of the correct 
size for the vessel (balloon with vessel ratio >0.90); 2) ≤35% residual stenosis; 3) TIMI 
(Thrombolysis In Myocardial Infarction) flow grade 3; and 4) the absence of a flow-limiting 
coronary artery dissection.15 After successful lesion preparation, patients will receive either 
DCB or DES according to randomly allocated groups. 

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(2) Drug-coated balloon angioplasty 
In DCB group, commercially available DCB (Agent, Boston Scientific, USA) will be used. DCB 
angioplasty will be recommended as follows to fully optimized procedural results. First, DCB 
size should be 1:1 ratio with reference vessel size. Second, delivery time of DCB should be 
within 30 seconds. Third, total inflation time of DCB will be recommended from 30 to 60 
seconds.15,16 
(3) Drug-eluting stent  
In DES group, latest second-generation DES will be used in accordance with standard practice 
guideline.5,17 
(4) Bail-out stenting in DCB group 
In case of 1) flow disturbance after lesion preparation (TIMI glow grade <3), 2) significant re-
coil or residual stenosis after lesion preparation (residual stenosis ≥50%), 3) major dissection 
with significant ischemic changes (dissection type D, E, or F), bail-out implantation of DES will 
be permitted.15 Patients treated by bail-out stenting will be analyzed as originally assigned 
DCB group in the intention-to-treat analysis and will be analyzed as DES group in the per-
protocol analysis of the as-treated population. However, primary hypothesis will be tested 
according to the intention-to-treat analysis. 
(5) Intravascular Imaging devices 
IVUS will be mandatory during pre-interventional lesion assessment and planning and post-
interventional optimization. In DCB arm, optimal size of pre-dilatation balloon and DCB will be 
decided based on the information from intravascular imaging devices. In DES arm, optimal 
size of pre-dilatation balloon, stent size, and post-stent implantation optimization will be 
decided based on the information from IVUS.18 
(6) Adjunctive medical treatment 
Regardless of allocated arms, best available medical treatment will be the performed 
according to the current ACC/AHA/SCAI or ESC/EACTS guidelines.5,17 Patients will be 
recommended to receive 1-3 months dual antiplatelet therapy of aspirin plus a P2Y12 inhibitor. 
Thereafter, patients will receive single antiplatelet therapy (a P2Y12 inhibitor alone will be 
preferred).19,20 In patients who need oral anticoagulant therapy, aspirin can be discontinued at 
hospital discharge. In ACS patients, a potent P2Y12 inhibitor (Ticagrelor or Prasugrel) or 
conventional P2Y12 inhibitor (Clopidogrel) can be used at the discretion of the operator 
according to appropriate assessment of bleeding risk which is recommended by the current 
guidelines. Any adjunctive pharmacologic treatment will be left to the operator’s discretion. 
 
10.3. Schedule of Measurements 
Visit 
Screening 
& 
Baseline 
Post-
Procedure 
Follow-Up 
6-month 
±30days 
9-month 
±30days 
12-
month 
±30days 
24-
month 
±30days 
SCV 
Medical/Clinical/History 
(age, sex, risk factors, 
clinical Dx, angina 
status) 
× 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
× 
 
 
 
 
 
 
Brief Physical 
Examination 
× 
 
 
 
 
 
 
Vital status 
× 
 
× 
× 
× 
× 
× 
Weight, height 
× 
 
 
 
 
 
 

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Visit 
Screening 
& 
Baseline 
Post-
Procedure 
Follow-Up 
6-month 
±30days 
9-month 
±30days 
12-
month 
±30days 
24-
month 
±30days 
SCV 
12 lead ECG 
× 
 
 
 
 
 
 
Informed Consent 
× 
 
 
 
 
 
 
Randomization1) 
× 
 
 
 
 
 
 
Coronary angiogram 
× 
 
 
× 
 
 
 
IVUS 
× 
 
 
× 
 
 
 
CBC, Electrolytes, LFT, 
Creatinine, BUN 
× 
 
 
× 
 
 
 
CK-MB, Troponin I or T, 
NT-proBNP 
× 
 
 
× 
 
 
 
Fasting plasma TG, 
LDL, HDL, total 
cholesterol 
× 
 
 
× 
 
 
 
Fasting glucose level, 
HbA1C 
× 
 
 
× 
 
 
 
Echocardiography2) 
× 
 
 
 
 
 
 
Medications3) 
× 
× 
× 
× 
× 
× 
× 
Clinical event4) 
 
 
× 
× 
× 
× 
× 
1) 
Randomization will be done immediately after the initial coronary angiogram, but before PCI. 
The subject identification code will be assigned consecutively from XX (institution number)-0001 
by the interactive web response system of e-CRF. Stratified randomization according to 
participating center, clinical presentation (acute coronary syndrome [ACS] or chronic coronary 
syndrome [CCS]), and severely calcified lesions (encircling calcium in angiography) will be 
performed. All processes will be done by a web-based randomization program with a permutated 
block size of 4, run by an independent organization 
2) 
Echocardiography should be taken before or after the procedure. If not performed, it will be 
recorded with the closest result before the randomization. 
3) 
Medication data included medication at baseline (before admission) and post-discharge. 
4) 
Only endpoint-related clinical events (all-cause death, cardiovascular death, MI, repeat 
revascularization, stent thrombosis, bleeding) will be collected. Follow-up visits will allow telephone 
contact if clinic visits are unavailable. 
* 
Because all test results are collected only when performed with clinical requirements, it will not be 
recorded as a protocol violence whether or not the tests are done. 
 
11. Measurement of Study Outcome Variables 
11.1. Visit 1 Screening & Baseline, Post-procedure 
(1) Medical/Clinical/ History 
Demographic information (age, sex, risk factors, angina status, cardiac history, and cardio-

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cerebral event) will be recorded at Screening& Baseline.  
Relevant medical history, including history of current disease, other pertinent cardiac history, 
and information regarding underlying diseases will be recorded at Screening & Baseline. 
(2) Brief Physical Examination, Height and Weight, Vital signs 
Height, weight, blood pressure and pulse will be measured 
(3) 12 lead ECG 
ECG will be obtained at Screening & baseline visits.  
(4) Inclusion/Exclusion Criteria 
Review of subject eligibility 
(5) Informed consent 
Patients will be informed about the study aims, procedures, and possible risks and the 
investigator will ensure that the patient or the patient’s legally acceptable representative has 
provided written informed consent. Written consent should include signature and date of legally 
authorized representatives and investigator. 
A copy of the signed consent form will be given to the subject or legal representative of the 
subject and the original will be maintained with the subject’s records. 
(6) Randomization 
Patients will undergo randomization processes depending on the number of studies enrolled. 
Randomization will be done immediately after the initial coronary angiogram, but before PCI. 
Patients will be randomized to either DCB or DES group with 1:1 ratio. All processes will be 
done by a web-based randomization program with a permutated block size of 4, run by an 
independent organization. 
(7) Blood tests 
Blood tests including CBC (complete blood count), chemistry, and cardiac-related blood tests 
will be collected at Screening & Baseline. 
(8) Coronary angiography 
Angiogram will be obtained at the time of index procedure. 
(9) IVUS 
IVUS will be obtained during at the time of index procedure. 
(10) Echocardiography 
Exam should be taken before or after PCI. 
(11) Concomitant Medication 
Concomitant medication will be documented at Baseline/Screening and at follow-up. Dose, 
route, unit frequency of administration, and indication for administration and dates of 
medication will be captured. 
 
11.2. Follow-up 
After the randomization, angiographic and IVUS follow-up will be done at 9 months. Clinical follow-up 
will be done at 6 and 12 months, and annually thereafter until 1 year from last patient enrollment. 
 
Follow-ups should be office visits, but telephone contact will be allowed. Data collected during all follow-
up visits will include vital signs, blood tests, concomitant medications, angina class and major adverse 
ischemic events including death, MI, repeat revascularization, stent thrombosis, stroke, bleeding, and 
Adverse Events/ Serious Adverse Events. Original source documents must be submitted for any clinical 
events (MI, repeat revascularization, stent thrombosis, stroke, bleeding or any other SAE within 1 year). 
If the patient is readmitted to a non-study hospital, all possible efforts should be made to obtain original 
source documents from that hospital. For all reinfarctions, ECGs and cardiac enzymes (CK-MB, 
troponins) must be obtained and recorded. 
 
12. Ethical Considerations and Confidentiality 
12.1. Institutional Review Board (IRB) / Ethical Committee Approval 
Institutional Review Board / Ethical Committee approval for the protocol and informed consent form will 
be obtained by the investigator prior to study participation. The approval letter must be signed by the 

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IRB Chairperson or authorized representative prior to beginning the present study. No changes will be 
made to the protocol or informed consent form without appropriate approval from the IRB. According to 
IRB requirements, the investigator will report study progress until it is completed. Further, any protocol 
amendments as well as associated informed consent changes will be submitted to the IRB and written 
approval must be obtained prior to implementation. 
 
12.2. Participant Safety 
12.2.1. Elements of Informed Consent 
We anticipate enrolling a total of 256 patients with a mean age in the 60-70s. Pregnant women and 
patients under the age of 19 will be excluded from the trial for ethical and safety concerns. Women of 
child-bearing potential must have a negative serum/urine pregnancy test prior to enrollment and 
sexually active females must use contraception for up to 1-year following the index procedure. 
Prior to collecting study data, the details of the study will be explained to the participant including: (1) 
that the study represents a phase IV clinical trial, (2) that participation is voluntary, and there is no 
penalty for withdrawal, (3) anticipated costs to the patient for participation, (4) potential risks and 
benefits for participation, and (5) contact information for additional concerns. Patients are informed of 
the purpose of the study, the treatment alternative, the random manner of assignment to treatment, the 
need to be available for telephone follow-up and return clinic visits at regular intervals for questionnaires 
and/or medical tests, and of their options to accept or refuse entry into the study without affecting their 
clinical care. 
All patients or legally authorized patient representatives must sign the current IRB-approved informed 
consent form prior to any study-related activities and the index procedure. Failure to obtain signed 
informed consent will render the patient ineligible for the study. The signed informed consent will be 
kept in the patient’s medical records and a copy is given to the patient or legally authorized patient 
representative.  
All sources of research materials will be in the form of medical records, coronary angiograms, 
electrocardiograms and routine blood work. This material will be obtained both for routine medical care 
as well as for research purposes. 
 
12.2.2. Potential Risks 
Risks of PCI 
Complications that may be associated with PCI include but are not limited to thrombosis with reinfarction 
and even death, intramural hematoma, side branch occlusion, stroke, stent migration, arterial 
rupture/perforation, dissection, embolization, and stent deformability. However, performing 
interventional procedures on these lesions is a standard treatment currently used in clinical practice, 
and participation in this study does not have an additional direct risk associated with the 
procedure. 
 
Pharmacological Risks 
Patients treated with PCI will be given aspirin, clopidogrel, ticagrelor and prasugrel to minimize the 
likelihood of thrombus formation at the stent site. Nonetheless, aspirin may increase the likelihood of 
gastrointestinal adverse effects and bleeding. Clopidogrel is uncommonly associated with rash, 
headache, dizziness, stomach pain, nausea, diarrhea, indigestion, increase in cholesterol levels, 
leucopenia, or thrombocytopenia. Ticagrelor may cause bleeding, dyspnea, nausea, dizziness, gout, 
and transient increased of serum creatinine. Reported side effects of prasugrel includes bleeding, 
hypertension, headache, hyperlipidemia, nausea, back pain. However, these drugs are standard 
medications currently used in clinical practice after coronary interventions, and taking these 
medications cannot be viewed as an additional risk from participation of the study. 
 
12.2.3. Adequacy of Protection against Risks 
The Data Coordinating Center (DCC), CEAC, and the DSMB play key roles in detecting any hazards 
the study may pose for its participants. Data are routinely collected and regularly monitored to document 
morbidity or mortality associated with study-related procedures in each clinic. Serious adverse events 

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must be reported to the DCC within 48 hours. Timely reports will be made to the DSMB. In addition, the 
DCC is responsible for calling the Board’s attention to significant interim safety concerns. Results for 
the different clinics are compared to identify the sources and causes of any trends deviating from the 
average performance.  
The DSMB is responsible for advising early termination of the trial in the event if there are non-rectifiable, 
serious safety concerns in any group. It will be the responsibility of the DSMB to review the data and 
establish limits of safety for the trial, as well as its termination, however, the final decision on the early 
termination of the study will be made by the Steering committee upon the recommendations of the 
DSMB. This study will not be stopped early based on efficacy results. 
 
12.3. Confidentiality 
The confidentiality of protected health information shall be maintained by all parties involved at all times 
throughout the clinical trial. All data should be secured against unauthorized access. Study patients will 
be assigned a unique coded identifier on eCRFs. Patient data will be protected by the use of locked 
cabinets at the Clinical Center and use of passwords, data encryption and secure, limited access 
storage of electronic data. The DCC has programs, policies and procedures in use at all times to ensure 
the security and confidentiality of the data. The explicit issue of privacy and confidentiality is outlined in 
the Informed Consent Form.  
 
13. Study Organization 
13.1. Steering Committee and Data Safety Monitoring Board (DSMB) 
The Steering committee comprised of the chairperson and the primary investigators of the main 
participating center, approved the study design, protocol, and amendments issued to the DSMB and 
the participating center. An independent DSMB will review the safety data from the study and construct 
recommendations for adverse events/serious adverse events, protocol deviation, and follow-up case 
reports. Scheduled DSMB meetings will discuss safety or compliance issues and will provide advice on 
modifying or stopping the study as needed. However, the final decisions regarding changes in the study 
protocol remain in the hands of the Steering committee. In addition, the DSMB will help to conduct the 
trial appropriately by reviewing and reporting the cumulative investigational data for accuracy and 
completeness, ensuring protocol compliance. The DSMB will develop a consensus understanding of all 
trial endpoints and definitions used in the event adjudication process. 
 
13.2. Clinical Event Adjudication Committee (CEAC) 
CEAC is comprised of interventional and non-interventional cardiologists who are not participants in the 
study. The CEAC is charged with the development of specific criteria used for the categorization of 
clinical events and clinical endpoints in the study which are based on protocol. At the onset of the trial, 
the CEAC will establish explicit rules outlining the minimum amount of date required, and the algorithm 
followed in order to classify a clinical event. All members of the CEAC will be blinded to the primary 
results of the trial. 
The CEAC will meet regularly to review and adjudicate all clinical events. The Committee will also 
review and rule on all deaths that occur throughout the trial. 
 
13.3. Data Coordination and Site Management 
Data coordination and site management services will be performed at the Heart Vascular Stroke 
Institute, Samsung Medical Center. 
 
14. Statistical Analysis 
14.1. Analysis Population 
Subjects are to be randomized in a 1:1 fashion to either DCB or DES groups. All primary and secondary 

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endpoints will be analyzed both on an intention-to-treat basis (all subjects analyzed as part of their 
assigned treatment group), on a per-protocol basis (patients analyzed as part of their assigned 
treatment group only if they actually received their assigned treatment group and without major protocol 
violation), and as-treated basis (patients are categorized according to the actual treatment during the 
procedure). For intention-to-treat analysis, all subjects who signed the written informed consent form 
and are randomized in the study will be included in the analysis sample, regardless of whether or not 
the correct treatment was administered, or whether crossover occurred, or they withdraw the informed 
consent.  
Per-protocol population will be defined as population who did not violate the study protocol. The 
definition of protocol violation is as follows; 
 
(1) Using neither DCB nor DES for PCI 
(2) Using different devices contrary to the assigned devices 
 
Analysis with per-protocol population or as-treated population will be performed as exploratory and 
sensitivity analysis for that of intention-to-treat population. The baseline coronary angiographic 
characteristics will be analyzed on per-lesion. 
 
14.2. Sample Size Calculation 
Primary hypothesis: DCB angioplasty would be noninferior to DES late-lumen loss (LLL) in large de 
novo coronary stenosis. 
Secondary Hypothesis (Superiority): If non-inferiority is established, test for superiority of DCB over 
DES in LLL. 
 
Based on the previous trial that compared late-lumen loss of DCB or DES by QCA or IVUS,9-14 the 
expected LLL of DCB is -0.41 mm2 and DES is 0.18 mm2 (mean difference of LLL 0.59 mm2) on IVUS 
(standard deviation of both group would be 1.28 mm2). 
 
 
LLL of DCB group: -0.41 mm2 
 
LLL of DES group: 0.18 mm2 
 
Mean Difference of LLL: 0.59 mm2 
 
Standard deviation of both group: 1.28 (DCB group 1.29 and DES group 1.27) 
 
Non-inferiority margin: 0.47 mm2  
 
Type I Error (Alpha):  
- 
Non-inferiority test: 1-sided alpha of 0.025 
- 
Superiority Test (if non-inferiority is met): 2-sided alpha of 0.05 
 
Power: 80% 
 
Drop-out rate 10% 
 
Based on the above assumption, a total of 256 patients (128 patients for DCB group and 128 patients 
for DES group) will be needed to show non-inferiority of DCB compared to DES with 80% of statistical 
power at a 1-sided alpha of 2.5%. If non-inferiority is confirmed, the same sample size will be used to 
assess superiority with adequate power. 
 
14.3. Primary Efficacy End Point Analysis 
Primary efficacy end point will be analyzed on an intention-to-treat basis, and then, per-protocol basis. 
Primary efficacy end point will be analyzed on per-patient basis. Analyses will be performed 9 months 
after last patient enrollment. A 1-sided t-test or analysis of covariance (ANCOVA) to compare mean late-
lumen loss between DCB and DES in IVUS, adjusting for any significant baseline covariates that might 
impact the outcome. If non-inferiority is met, conduct a 2-sided t-test for superiority, with appropriate 

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confidence intervals and p-values.  
 
Primary End point 
Statistical methods 
Time point of analysis 
Mean difference in LLL 
between the DCB and 
DES groups 
Non-inferiority test: 1-sided t-test 
or ANCOVA 
Sequential superiority test: 2-
sided t-test 
9 months after last patient 
enrollment 
 
14.4. Secondary Efficacy End Points Analyses 
Secondary efficacy end points will be analyzed on an intention-to-treat basis, and then, per-protocol 
basis. Secondary efficacy end points will be analyzed on per-patient basis. Analyses will be performed 
9 months after last patient enrollment. A 1-sided t-test or ANCOVA to compare differences of parameters 
between DCB and DES in QCA or IVUS, adjusting for any significant baseline covariates that might 
impact the outcome. If non-inferiority is met, conduct a 2-sided t-test for superiority, with appropriate 
confidence intervals and p-values. 
 
Major Secondary End point 
Statistical methods 
Time point of analysis 
Mean difference of minimal 
lumen diameter (MLD) in QCA 
Non-inferiority test: 1-
sided t-test or ANCOVA 
Sequential superiority 
test: 2-sided t-test 
9 months after last patient 
enrollment 
Mean difference of %diameter 
stenosis in QCA 
Non-inferiority test: 1-
sided t-test or ANCOVA 
Sequential superiority 
test: 2-sided t-test 
9 months after last patient 
enrollment 
Mean difference of MLD in IVUS 
Non-inferiority test: 1-
sided t-test or ANCOVA 
Sequential superiority 
test: 2-sided t-test 
9 months after last patient 
enrollment 
 
14.5. Secondary Clinical End points Analyses 
Secondary clinical end points will be analyzed on an intention-to-treat basis and per-protocol basis. 
Secondary clinical end points will be analyzed on per-patient basis. Analyses will be performed 1 year 
after last patient enrollment. Cox proportional hazard regression and Kaplan-Meier analysis will be used 
to determine the cumulative incidences of the secondary clinical end points. For the secondary 
outcomes, HRs and 95% CIs will be generated using Cox proportional hazards models. All statistical 
analysis will be stratified according to participating centers, clinical presentations, and severe calcified 
lesion (randomization stratification factors). 
 
Secondary End point 
Statistical methods 
Time point of analysis 
Cardiovascular death 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
All-cause death 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
Target vessel-MI 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
Non-fatal MI 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
Clinically indicated TLR 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
Clinically indicated TVR 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
Any revascularization 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 

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Secondary End point 
Statistical methods 
Time point of analysis 
Vessel or stent thrombosis 
(definite or probable) 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
Cardiovascular 
death 
or 
target vessel-related MI 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
All-cause death or non-fatal 
MI 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
TVF 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
TLF 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
Cardiovascular death, target-
vessel MI, or vessel or stent 
thrombosis 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
All-cause death, non-fatal MI, 
or TVR 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
BARC type 2, 3, or 5 bleeding 
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
CVA  
Cox’s proportional hazard method 
1 year after last patient 
enrollment 
 
14.6. Treatment of Missing Values 
The primary analysis of the study end points will not be covariate-adjusted. No imputation methods will 
be used to infer missing values of baseline variables. For the study endpoints, patients lost to follow-up 
and subsequently lost to assessment of study endpoints will be considered to be censored in the 
estimation of all analyses. 
 
14.7. Multivariable Analyses 
Multivariable predictors of primary and secondary efficacy end points will be univariate analysis, which 
tests each variable for association with LLL. Variables with p-values < 0.10 will be considered for 
multivariable analysis. 
Multivariable predictors of secondary clinical end points will be determined using Cox’s proportional 
hazard models. Forward or backward stepwise selection algorithms will be used to select predictors as 
needed. Baseline demographic and clinical variables that are predictive at the 0.1 level of p value will 
be included in the models. The purpose of this is twofold: to do a covariate-adjusted analysis of 
treatment for all primary and secondary endpoints and to identify the risk factors which are associated 
with the study endpoints.  
The included covariates in univariate analysis will be as with Table 1. 
 
Table 1.  
Demographics 
Cardiac Risk Factors 
Procedural Factors 
Medications  
Age, years 
Current smoker 
Lesion location 
Aspirin 
Gender 
Previous MI  
Total lesion length 
Clopidogrel 
Height, Weight 
Previous PCI  
Reference vessel size 
Prasugrel 
Diabetes mellitus 
Previous CABG 
Balloon or stent diameter 
Ticagrelor 
Hypertension  
Previous CHF 
 
Statin 
Dyslipidemia 
Family history of CAD  
 
Ezetimibe 
Peripheral artery disease  
Previous CVA 
 
 ACE inhibitor or ARB 
Chronic kidney disease 
LV ejection fraction 
 
Beta-blocker 
 Clinical presentation 
LV dysfunction (LVEF<50%) 
 
Warfarin or NOAC 
 
 
 
Calcium-channel blocker 
 
14.8. Pre-specified subgroup analysis 
(1) Primary and Secondary efficacy end points will be assessed in pre-specified subgroups below. 

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1)  Age (age ≥65 vs. <65) 
2)  Sex 
3)  Diabetes mellitus vs. non-diabetes mellitus 
4)  Acute coronary syndrome vs. chronic coronary syndrome 
5)  Optimal vs. Suboptimal lesion-preparation in DCB procedure 
6)  Complex vs. non-complex lesion 
 
(2) Secondary clinical end point will be assessed in pre-specified subgroups below.  
1) 
Age (age ≥65 vs. <65) 
2) 
Sex 
3) 
Diabetes mellitus vs. non-diabetes mellitus 
4) 
Acute coronary syndrome vs. chronic coronary syndrome 
5) 
Ischemic territory (proximal lesion in major epicardial coronary artery vs. others) 
6) 
Complex vs. non-complex lesion 
7) 
1-month vs. 3-month dual antiplatelet therapy 
 
15. Publication Policy 
Study-derived data are the property of the participating investigators. However, individual investigators 
will not use study-related data for any purpose other than study completion or for generating publication 
material as stated in the study site agreement without prior consent from the Steering committee.  
 
15.1 Data Analysis and Release of Results 
No results will be released publicly before the completion of the final analysis regarding the primary 
endpoint of this study. The statistical analysis will be performed according to the pre-specified analysis 
plan as described in this protocol. Any decisions on release of results will be undertaken by the Steering 
Committee after the approval of the DSMB. 
 
15.2 Review Process 
The Steering Committee will review the primary outcome data according to the pre-specified statistical 
analysis plan, and then will (i) decide on the early dissemination of the information at national and 
international scientific meetings (ii) provide the data to the publications committee which will in turn (a) 
first prepare a formal presentation to the Steering Committee members and (b) after taking under 
account the input and comments of the Steering Committee will proceed with submitting the manuscript 
to the Steering Committee. No study results will be released to the scientific or lay community without 
the approval of the Steering Committee. 
 
15.3 Authorship: Primary Outcome Paper 
Authorship of the primary outcome paper will be credited collectively to the “Investigators”. 
 
15.4. Other Study Papers, Abstracts and Presentations 
Manuscripts on Ancillary Studies or Subset Analyses should be approved by the Steering Committee. 
The investigators significantly contributing to the study, considering both the number of patients enrolled 
by the specific investigators and their contribution to the study design will have the priority in the 
authorships of the ancillary studies or subset analysis. The first priority of authorship on subset studies 
will be given to the primary investigator or an investigator designated by the primary investigator. Each 
presentation of results on behalf of the investigators should have the approval of the Steering 
Committee. 
 

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16. Quality Assurances, Quality Control and Clinical Monitoring 
The purposes are: 
• 
To ensure accuracy of study data; 
• 
To ensure that data collection at multiple sites meets pre-specified criteria to ensure standard 
implementation; 
• 
To provide constructive feedback to site and core laboratory staff to improve and/or maintain 
high performance; 
• 
To document data quality for the study record. 
This section addresses of issues with respect to protocol adherence, data collection at the clinical 
centers, and interpreter variability at the core laboratories. 
 
16.1. Protocol Adherence 
There are three key components, each of which is pre-specified. The DATABASE will be programmed 
to monitor: eligibility criteria, correct treatment administration, and completion in a timely manner of all 
required data collection (no missed visits, missed studies or specimens). Eligibility criteria are also 
checked for all or a random sample of patients at every clinic site visit by auditing the patient’s 
record/worksheet. 
It is the Investigator's responsibility to ensure that there are no deviations from the protocol except in 
cases of medical emergencies when the deviation is necessary to protect the life or physical well-being 
of the patient. The DCC will monitor these aspects of protocol adherence continually. In addition, clinic 
site personnel will have clearly specified timeframes for entry of all data and for resolution of any edit 
queries. All of these aspects of protocol can be monitored at the DCC via real-time reporting, in 
aggregate and by clinic site. 
Any of the protocol violations listed below will be reviewed immediately by the DCC and communicated 
to the principal investigator. All remedial actions will be jointly decided and, in general, implemented by 
the DCC. Any clinical site being considered for temporary or permanent termination of patient 
recruitment may be visited administratively by the monitoring group. The major protocol violations for 
this study consist of, but are not limited to, the following:  
 
Protocol Violations: 
• Eligibility not confirmed, or subject found to be ineligible; 
• Informed consent not obtained (or not obtained in a timely manner); 
• Randomized therapy not implemented per protocol (crossover to other treatment, excessive delay 
following randomization, non-certified operator performing procedure); 
• Failure to conduct protocol required clinical follow-ups and within time windows; 
• Failure to report serious adverse events according to protocol requirements.  
 
In the event of any deviation from the protocol, the Investigator will be notified of the site’s non-
compliance. Corrective actions will be required if necessary. After any one violation, the DCC will work 
closely with the site primary investigator to ensure further violations are avoided. Any clinic investigator, 
certified for the trial, who commits any two of the above violations will be immediately considered for 
suspension from participation in the trial and the clinic site primary investigator will also be given notice 
that further violations by investigators at that site may result in site suspension (after an administrative 
site visit). If a site is suspended early in the trial, all patient recruitment and follow-up (except for vital 
status and safety) may be terminated. A site suspended later in the trial may still be required to complete 
follow-up on those subjects already randomized, assuming that the site’s adherence to the follow-up 
protocol is satisfactory or can be remediated. Poor performance at a site with respect to data entry and 
edit resolution will, in general, be remediated via conference calls and site visits initiated by the DCC.  
 

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16.2. Data Collection: Electronic Case Report Forms (eCRF) 
DCC personnel will determine form content, considering (1) Identify the minimal set of measurements 
for the specified variables; (2) Choose those measurements (if more than one candidate) which are 
valid and reliable and, other considerations being equal, are least burdensome to the subject; and (3) 
Develop, test and assess reliability of new measures as required. Experienced DCC staff will then order 
and format items to ensure clarity, smooth flow and to minimize missing information, using clear skip 
patterns, consistent coding for all close-ended items, and standard "footers" to identify form name, 
version date, and page number. Standard, modular data forms will be identified and developed to be 
used in both the Trial and Registry as needed.  
Case report forms will be developed by the Clinical Research Center as an online electronic form where 
investigators from individual site can access and input the data via the internet. 
 
16.3. Training/Certification and Retraining 
The DCC will be responsible for providing training to the investigator and appropriate clinical site 
personnel. It is recommended that investigators review the IFU. Designated monitors will be trained 
appropriately to monitor study progress including but not limited to the protocol and eCRFs. The DCC 
will support trainings over a 1-month period, to ensure standard protocol implementation, data collection 
and management across sites. These training sessions will be carried out on-site or at the conference 
meeting. Clinical staff training components include (1) The Trial and Registry Protocols; (2) DATABASE 
SYSTEMS and eCRF for local web-based data entry; 3) medical record abstraction; 4) specimen/media 
collection and handling; 5) data handling; 6) interview techniques and 7) quality control expectations. 
 
16.4. Site Monitoring 
The DCC will monitor the trial over its duration. A designated trial monitor, at appropriate intervals, will 
review investigational data for accuracy and completeness and to ensure compliance with the protocol. 
This trial monitor may inspect all documents and required records that are maintained by the 
Investigator/site, including medical records (office, clinic, or hospital) for the subjects in this trial. The 
Investigator/site will permit access to such records. 
 
17. Adverse Events 
The Principal Investigator is responsible for ensuring that all staff involved in the study is familiar with 
the content of this section. 
Definitions 
17.1 Adverse Event 
For the purpose of this trial, an adverse event (AE) is defined as any untoward medical occurrence in a 
patient or clinical investigation subject administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment. An adverse event can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom 
or disease temporally associated with the use of a medicinal product, whether or not considered related 
to the medicinal product. 
An AE includes but is not limited to any clinically significant worsening of a subject’s pre-existing 
condition. An abnormal laboratory finding (including ECG finding) that requires an action or intervention 
by the investigator, or a finding judged by the investigator to represent a change beyond the range of 
normal physiologic fluctuation, should be reported as an AE. 
AE may be treatment emergent (i.e., occurring after initial receipt of investigational product) or non-
treatment emergent. A non-treatment-emergent AE is any new sign or symptom, disease, or other 
untoward medical event that begins after written informed consent has been obtained but before the 
subject has received investigational product.  
Elective treatment or surgery or preplanned treatment or surgery (that was scheduled prior to the 
subject being enrolled into the study) for a documented pre-existing condition, that did not worsen from 
baseline, is not considered an AE (serious or non-serious). An untoward medical event occurring during 

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the prescheduled elective procedure or routinely scheduled treatment should be recorded as an AE or 
SAE. 
The term AE is used to include both serious and non-serious AEs. 
 
17.2 Serious Adverse Event (SAE) 
An adverse event is considered serious for this trial if it meets one or more of the following criteria: 
 
• Results in death 
• Is life-threatening, i.e., the patient was, in the opinion of the Investigator, at immediate risk of death 
from the event as it occurred (It does not include an event that, had it occurred in a more severe 
form, might have caused death.) 
• Results in persistent or significant disability or incapacity (significant, persistent or permanent 
change or disruption in patient’s body function/structure, physical activity or quality of life) 
• Requires in-patient hospitalization or prolongs hospitalization 
• Results in a congenital anomaly/birth defect or, 
• An important medical event that may not result in death, be life-threatening, or require 
hospitalization but may be considered serious when, based upon appropriate medical judgment, 
may jeopardize the patient and/or may require intervention to prevent one of the outcomes listed in 
this definition and/or necessitates immediate medical or surgical intervention to prevent permanent 
impairment of a body function/structure or to relieve unanticipated temporary impairment or 
damage. Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyspraxias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
A distinction is to be drawn between serious and severe adverse events. A severe adverse event may 
not be serious and a serious adverse event need not be considered severe. The term “severe” is used 
to describe the intensity of a specific event (as in mild, moderate, severe). However, the event itself 
may be of minor medical significance (e.g., severe headache). This is not the same as “serious”, which 
is based on patient/event outcome or action criteria usually associated with events that pose a threat 
to a patient’s life or functioning. 
Note: All events included in the endpoint events are considered SAEs (the cause for an unscheduled 
revascularization will represent the SAE). 
 
18. Event Adjudication and Reporting 
18.1 Investigator Responsibilities 
18.1.1. Adverse Events 
AEs will be assessed by the investigator for severity, relationship to the investigational product, possible 
etiologies, and whether the event meets criteria of a SAE 
The following variables will be collected for each AE: 
• 
AE (verbatim) 
• 
The date when the AE started and stopped 
• 
Whether the AE is serious or not 
• 
Investigator causality rating against investigational product (yes or no)  
• 
Action taken with regard to investigational product / comparator / combination agent 
• 
Outcome 
The following variables will be collected for SAEs as applicable: 
• 
Center number (if applicable) 
• 
Patient identification 
• 
Age 
• 
Sex 

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• 
Investigational product(s) dose, start & stop date 
• 
Event term as reported by the investigator  
• 
SAE onset & stop date 
• 
Investigator’s assessment of seriousness, according to ICH definitions 
• 
Date of death (if applicable) 
• 
Causality assessment in relation to investigational product 
• 
Causality assessment in relation to study procedure(s) 
• 
Causality assessment in relation to additional study drug (if applicable) 
• 
SAE outcome 
AEs will be notified to Steering Committee according to the clinical relevance with the study. SAEs will 
be recorded from time of signature of informed consent, throughout the treatment period and including 
the follow-up period. 
During the course of the study, all SAEs should be proactively followed up for each subject. Every effort 
should be made to obtain a resolution for all events, even if the events continue after 
discontinuation/study completion. 
The investigator is responsible for following all SAEs until resolution, until the subject returns to baseline 
status, or until the condition has stabilized with the expectation that it will remain chronic, even if this 
extends beyond study participation. 
 
18.1.2 Serious Adverse Events (SAE) 
All events meeting the SAE criteria must be reported to the DCC within 48 hours of becoming aware of 
the events, which will be notified promptly to the DSMB and CEAC. To be noted that all endpoint events 
fall into this category and must be reported within the above timeframe.   
The Investigator must complete the CRF for each serious adverse event, whether related or not to study 
product or procedure. The information provided must be sufficient to allow for independent medical 
assessment of the event. The Safety Officer will contact the Investigator should it be necessary to clarify 
any information. The Investigator should provide any additional follow-up information regarding the 
event to DCC as soon as it becomes available. All AEs should be followed until resolution or stabilization 
The site IRB must be notified by the Investigators within the timeframe specified by their local standard 
operating procedures (SOPs) and the applicable regulations. Complications associated with PCI, such 
as abrupt closure, dissection, no reflow, thrombosis, dissection, embolism, stroke, perforation and/or 
extravascular staining, will be recorded on the CRF as such, and will be recorded specifically as an 
AE/SAE.  
Planned hospital admissions and/or planned surgical operations for an illness or disease which existed 
before the patient was randomized in a clinical study are not to be considered AEs.  However, baseline 
conditions which deteriorate during a clinical study may be considered AEs. 
It should be noted here that all clinical endpoints, including MI/CVA, unscheduled revascularization and 
death will require central adjudication and are included here, even though they contribute to trial 
outcomes. The study investigators will be responsible to provide all applicable and available source 
documentation to the DCC in order to allow an independent assessment of these events by the CEAC 
members. 
All SAEs will be reported, whether or not considered causally related to the investigational product, or 
to the study procedure(s). The reporting period for SAEs is the period immediately following the time 
that written informed consent is obtained through study period. The investigator and/or Sponsor are 
responsible for informing the IRB/Ethics Committee and the Regulatory Authority of the SAE as per 
local requirements. 
SAEs will be notified to IRB, if judged necessary by Steering Committee. 
 
18.2 Endpoint and SAE Adjudication 
With the exception of all-cause mortality, most endpoints will require clear, prespecified criteria, and 
centralized review. These endpoints will be captured during patient interview, supplemented by death 
certificates; hospital record abstracts and related reports (autopsy, biopsy, diagnostic output). These 
endpoints will be adjudicated using the same procedure as SAEs. 

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From extensive experience, the following approach is proposed. First, all required documents, reports, 
hospital records will be identified, made anonymous, and copied to the DCC by clinical staff. Second, 
the DCC will check to ensure confidentiality and, if required, have the records centrally abstracted onto 
standard forms by trained DCC staff. Central abstraction in large (>30) batches is recommended to 
reduce variability and secular drift and maintain adequate accuracy and completeness. Third, centrally 
prepared forms and documents will be circulated to CEAC members for assessment. 
 
19. Regulatory Responsibilities 
19.1. Investigator Responsibilities 
The investigator is responsible for ensuring that the trial is conducted according to all signed 
agreements, the study protocol and good clinical practice (GCP) requirements. Also, each investigator 
must complete and sign the Investigator's Agreement. In signing, the investigator agrees to: 
• Sign and adhere to the Investigator Agreement 
• Participate in Investigator meetings and training sessions as scheduled by Sponsor 
• Maintain up-to-date angiographic and intravascular ultrasound equipment (if applicable) 
• Be willing to provide original cine films/CD ROMs/intravascular ultrasound videotape for analysis 
• Have access to cardiac surgery 
• Be willing to perform and be capable of performing treatment procedures as outlined in this protocol 
• Comply with all required elements of this protocol (e.g., perform testing and follow-up as specified, 
especially during personnel transitions) and supply angiographic material suitable for quantitative 
analysis 
• Obtain written Informed Consent from each study participant before any study specific procedures 
are performed in accordance with GCP 
• Complete all electronic case report forms for completed patients visits and/or applicable events (i.e., 
SAE, TVR) prior to scheduled monitoring visits 
• Be willing to change hospital routine if required by protocol (as long as patient safety and well-being 
is not compromised) 
• Adhere to all relevant Core Laboratory requirements and, 
 
19.2. Institutional Review Board (IRB) or Ethics Committee Approval 
The investigator must submit the study protocol to his IRB or Ethics Committee and obtain their written 
approval before being allowed to conduct and participate in the study. The investigator is also 
responsible for fulfilling any conditions of approval imposed by the IRB, such as regular reporting, study 
timing, etc. The investigator will provide the Sponsor with copies of such approvals and reports. 
 
19.3. Informed Consent 
Part of the IRB/Ethics Committee approval must include approval of an Informed Consent text specific 
to the study. The investigator must administer this approved Informed Consent text to each prospective 
study patient and obtain the patient's signature on the text prior to enrollment in the study. This may be 
modified to suit the requirements of the individual site. The investigator will provide the Sponsor with a 
copy of the approved Informed Consent for his/her site. 
 
19.4. Study Coordinator 
To assure proper execution of the study protocol, each investigator must identify at least one study 
coordinator for the site. Working with and under the authority of the investigator, the study coordinator 
assures that all study requirements are fulfilled and is the contact person at the site for all aspects of 
study administration. 
 

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20. Protocol Deviations and Amendments 
20.1. Protocol Deviations 
This study will be conducted as described in this protocol, except for an emergency situation in which 
the protection, safety, and well-being of the patient require immediate intervention, based on the 
judgment of the investigator (or a responsible, appropriately trained professional designated by the 
investigator). In the event of a significant deviation from the protocol due to an emergency, accident, or 
mistake, the investigator or designee must contact the Steering committee at the earliest possible time 
by telephone. This will allow an early joint decision regarding the patient’s continuation in the study. The 
investigator will document this decision. The IRB or Ethics Committee will be informed of all protocol 
changes by the investigator in accordance with the IRB or Ethics Committee established procedure. No 
deviations from the protocol of any type will be made without complying with all the IRB or Ethics 
Committee established procedures. 
It is intended that all statistical analyses specified in this protocol will be performed. However, it is 
conceivable that due to the study observations, some scheduled analyses may not be performed. In 
addition, study observations or analysis results may suggest the need for additional statistical analyses 
of the collected study data. In either case, deviations (subtractions or additions) from the planned 
statistical analysis will be fully described in the final clinical study report. Furthermore, any additional 
analyses performed beyond those specified in this protocol will be descriptive in nature and will not 
include hypothesis testing for the purposes of inferential conclusions.  
 
20.2. Protocol Amendments 
In case any revisions to the protocol are required, protocol amendments will be provided to 
investigators by the Steering committee prior to implementation. The Primary Investigator(s) will be 
responsible for notifying the IRB of the protocol amendment with administrative changes or obtaining 
IRB approval of the protocol amendment with changes in patient care or safety. Institutional Review 
Board acknowledgements/approvals must be documented in writing prior to implementing protocol 
amendments.  
 
21. Records Retention and Reports 
To comply with ICH guidelines, the Primary Investigator will maintain all records relevant to this study 
for 2 years following study completion, unless the records are archived by an external vendor. The 
investigator shall take responsibility for maintaining adequate and accurate hard copy source 
documents of all observations and data generated as required during this study. Such documentation 
may be subject to inspection by appropriate regulatory agencies.  
 
21.1 Records 
Each investigator must maintain the following accurate, complete, and current records relating to the 
conduct of the investigation. (The data for some of these records may be available in computerized 
form from the Data Coordinating Center; however, the final responsibility for maintaining remains with 
the investigator.)   
• All correspondence with another investigator, an IRB, a Core Laboratory, the Sponsor, a monitor, 
Data Coordinating Center, including required reports. 
 
• Records of each subject's case history, including study-required Case Report Forms, evidence of 
informed consent, all relevant observations of adverse drug effects, the condition of each subject 
upon entering and during the course of the investigation, relevant medical history, the results of all 
diagnostic testing, and the date of each study treatment. 
 

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21.2. Reports 
Below is a list of the reports which are the investigator's responsibility to generate. The table also 
shows to whom the report is to be sent and with what frequency or within what time constraints. While 
some of these reports will be developed by or with the assistance of the Data Coordinating Center, 
the final responsibility for them rests with the investigator.  
 
Reports Required from Clinical Investigators: 
Type of Report 
Prepared by Investigator For: 
Time Constraints of 
Notification 
Serious adverse event  
IRB 
Per local regulations 
DCC/SC/Principal 
investigator/DSMB 
Within 48 hours   
Patient withdrawal 
DCC 
Notify within 7 days 
Annual progress report 
SC/Principal investigator 
Submitted per 1 year 
Deviations from investigational plan 
IRB 
Per local standard. 
SC/Principal investigator 
Notify within 7 days. 
Informed consent not obtained 
DCC/IRB 
Notify within 7 days. 
Final summary report 
SC/Principal investigator 
Within 1 month. 
* DCC: Data Coordinating Center; DSMB; Data Safety Monitoring Board; SC: Steering Committee (Co-
researchers) 
 

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22. Investigational Agreement 
I have read and understand the protocol (including the Investigator’s Brochure) and agree that it 
contains all the ethical, legal and scientific information necessary to conduct this trial. I will personally 
conduct the study as described and agree to adhere strictly to the attached protocol.  
I will provide copies of the protocol to all physicians, nurses and other professional personnel, who 
under my responsibility will participate in this study. I will discuss the protocol with them to assure that 
they are sufficiently informed regarding the drugs used in the study, the concurrent medications, the 
efficacy and safety parameters, and the overall execution of the study in general. I am aware that this 
protocol must be approved by the Institutional Review Board (IRB) or Ethics Committee (EC) 
responsible for such matters in the clinical study facility where the drug will be tested, prior to 
commencement of this study.  I agree that clinical data entered on case report forms by the staff and 
I, can be utilized in various ways including, but not limited to, publication in peer journals, submission 
as abstracts, submission to governmental regulatory authorities and/or in combination with clinical data 
gathered from other research sites, whenever applicable.  I agree to allow monitors and auditors as 
well as inspectors from regulatory authorities, full access to all medical records at the research facility 
for patients screened or randomized in the study. 
I agree to provide all patients with informed consent forms, as required by government and ICH 
regulations. I further agree to report to the DCC any adverse experiences in accordance with the terms 
of this protocol, KFDA regulation, and ICH guideline. 
 
 
 
 
 
 
Principal Investigator 
(print) 
 
 
Principal Investigator (signature) 
 
Date 
Institution Name/Location 
 
 
 

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Appendix A. Definitions 
 
Anticipated Adverse Event  
Any undesirable experience (sign, symptom, illness, abnormal laboratory value, or other medical event) 
occurring to a patient, whether or not considered related to the investigational product(s) or drug 
regimen prescribed as part of the protocol, predefined in the protocol and/or IFU, that is identified or 
worsens or occurs in frequency that is not considered normal during a clinical trial. See also: Adverse 
Event (AE), Serious Adverse Event (SAE).  
 
Adverse Event (AE)  
An AE is any untoward medical occurrence in a patient or clinical investigation when the patient was 
administered a study product and which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product whether or not related to the study product. See also: Anticipated Adverse 
Event, Serious Adverse Event (SAE).  
 
Angina  
Canadian Cardiovascular Society Classification of Stable Angina 
I. Ordinary physical activity does not cause angina, such as walking or climbing stairs. Angina occurs 
with strenuous, rapid or prolonged exertion at work or recreation.  
II. Slight. Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly, walking 
uphill, walking or stair climbing after meals, or in cold, in wind, under emotional stress or only during the 
few hours after awakening. Angina occurs on walking more than two blocks on the level and climbing 
more than one flight of ordinary stairs at a normal pace and in normal condition.  
III. Marked. Marked limitation of ordinary physical activity. Angina occurs on walking one to two blocks 
on the level and climbing one flight of stairs in normal conditions and at a normal pace.  
IV. Inability. Inability to carry on any physical activity without discomfort. angina symptoms may be 
present at rest.  
 
Braunwald Classification of Unstable Angina 
I. New onset of severe or accelerated angina: Patients with new onset (< 2 months in duration) 
exertional angina pectoris that is severe or frequent (> 3 episodes/day) or patients with chronic stable 
angina who develop accelerated angina (that is, angina distinctly more frequent, severe, longer in 
duration, or precipitated by distinctly less exertion than previously) but who have not experienced pain 
at rest during the preceding 2 months.  
II. Angina at rest, subacute: Patients with 1 or more episodes of angina at rest during the preceding 
month but not within the preceding 48 hours.  
III. Angina at rest, acute: Patients with 1 or more episodes of angina at rest within the preceding 48 
hours.   
 
Bleeding/Hemorrhagic Complications  
An episode of bleeding is defined by the BARC criteria as: 
Type 0 
No bleeding 
Type 1 
Bleeding that is not actionable and does not cause the patient to seek treatment 
Type 2 
Any clinically overt sign of hemorrhage that “is actionable” and requires diagnostic studies, 
hospitalization, or treatment by a health care professional 
Type 3 
a. Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is 
related to bleed); transfusion with overt bleeding 
b. Overt bleeding plus hemoglobin drop < 5 g/dL (provided hemoglobin drop is related to 
bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding 
requiring IV vasoactive agents 
c. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular 
bleed compromising vision 
Type 4 
Coronary artery bypass graft surgery-related bleeding within 48 hours 
Type 5 
a. Probable fatal bleeding 
b. Definite fatal bleeding (overt or autopsy or imaging confirmation) 

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Cerebrovascular accident (CVA) 
Sudden onset of vertigo, numbness, aphasia, dysarthria or central neurologic deficit secondary to 
vascular lesions of the brain such as hemorrhage, embolism, thrombosis, or rupturing aneurysm, that 
persists for > 72 hours 
 
* CVA type 
1. 
Hemorrhagic: A stroke with documentation on imaging (e.g., CT scan or MRI of hemorrhage 
in the cerebral parenchyma, or a subdural or subarachnoid hemorrhage). Evidence of 
hemorrhagic stroke obtained from lumbar puncture, neurosurgery, or autopsy can also 
confirm the diagnosis. 
2. 
Nonhemorrhagic: A focal neurological deficit that results from a thrombus or embolus (and 
not due to hemorrhage) that appears and is still partially evident for more than 24 hours 
Unknown/no imaging performed: if the type of stroke could not be determined by imaging or other 
means (from lumbar puncture, neurosurgery, or autopsy) 
 
Death  
Death defined by the Academic Research Consortium is as follows:  
All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. 
Specifically, any unexpected death even in patients with coexisting potentially fatal noncardiac disease 
(eg, cancer, infection) should be classified as cardiac. The cause of death (cardiac vs. non-cardiac) will 
be adjudicated by an independent clinical event adjudication committee 
Cardiac death: Any death due to proximate cardiac cause (eg, myocardial infarction, low-output 
failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure-related 
deaths, including those related to concomitant treatment, will be classified as cardiac death.  
Vascular death: Death caused by noncoronary vascular causes, such as cerebrovascular disease, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular diseases.  
Non-cardiovascular death: Any death not covered by the above definitions, such as death caused by 
infection, malignancy, sepsis, pulmonary causes, accident, suicide, or trauma.  
 
Myocardial Infarction (MI)  
The definition of myocardial infarction used in this trial is adapted from the Fourth Universal Definition 
of Myocardial Infarction. 
 
1. Clinical criteria for MI 
The clinical definition of MI denotes the presence of acute myocardial injury detected by abnormal 
cardiac biomarkers in the setting of evidence of acute myocardial ischemia. 
 
2. Criteria for Myocardial Injury 
Detection of an elevated cardiac troponin (cTn) value above the 99th percentile upper reference limit 
(URL) is defined as myocardial injury. The injury is considered acute if there is a rise and/or fall of cTn 
values. 
 
3. Criteria for Type 1 MI 
Detection of a rise and/or fall of cTn values with at least 1 value above the 99th percentile URL and with 
at least 1 of the following: 
• Symptoms of acute myocardial ischemia; 
• New ischemic ECG changes; 
• Development of pathological Q waves; 
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a 
pattern consistent with an ischemic etiology; 
• Identification of a coronary thrombus by angiography including intracoronary imaging or by autopsy. 
 
4. Criteria for Type 2 MI 
Detection of a rise and/or fall of cTn values with at least 1 value above the 99th percentile URL, and 
evidence of an imbalance between myocardial oxygen supply and demand unrelated to acute coronary 
atherothrombosis, requiring at least 1 of the following: 

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• Symptoms of acute myocardial ischemia; 
• New ischemic ECG changes; 
• Development of pathological Q waves; 
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a 
pattern consistent with an ischemic etiology 
 
5. Criteria for Type 3 MI 
Patients who suffer cardiac death, with symptoms suggestive of myocardial ischemia accompanied by 
presumed new ischemic ECG changes or ventricular fibrillation, but die before blood samples for 
biomarkers can be obtained, or before increases in cardiac biomarkers can be identified, or MI is 
detected by autopsy examination. 
 
6. Criteria for Cardiac Procedural Myocardial Injury 
Cardiac procedural myocardial injury is arbitrarily defined by increases of cTn values (>99th percentile 
URL) in patients with normal baseline values (≤99th percentile URL) or a rise of cTn values >20% of 
the baseline value when it is above the 99th percentile URL but it is stable or falling. 
 
 
6-1. Criteria for PCI-Related MI ≤48 Hours After the Index Procedure (Type 4a MI) 
Coronary intervention–related MI is arbitrarily defined by an elevation of cTn values >5 times 
the 99th percentile URL in patients with normal baseline values. In patients with elevated 
preprocedure cTn in whom the cTn level are stable (≤20% variation) or falling, the 
postprocedure cTn must rise by >20%. However, the absolute postprocedural value must still 
be at least 5 times the 99th percentile URL. In addition, 1 of the following elements is required: 
• New ischemic ECG changes; 
• Development of new pathological Q waves*; 
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality 
in a pattern consistent with an ischemic etiology; 
• Angiographic findings consistent with a procedural flow-limiting complication such as 
coronary dissection, occlusion of a major epicardial artery or a side branch occlusion/thrombus, 
disruption of collateral flow, or distal embolization. 
 
 
6-2. Criteria for MI Related to Stent/Scaffold Thrombosis (Type 4b MI) 
A subcategory of PCI-related MI is stent/scaffold thrombosis, type 4b MI, as documented by 
angiography or autopsy using the same criteria utilized for type 1 MI.  
 
 
6-3. Restenosis Associated with PCI (Type 4c MI) 
This PCI-related MI type is designated as type 4c MI, defined as focal or diffuse restenosis, or 
a complex lesion associated with a rise and/or fall of cTn values above the 99th percentile 
URL applying, the same criteria utilized for type 1 MI. 
 
6-4. Criteria for CABG-Related MI ≤48 Hours After the Index Procedure (Type 5 MI) 
CABG-related MI is arbitrarily defined as elevation of cTn values >10 times the 99th percentile 
URL in patients with normal baseline cTn values. In patients with elevated preprocedure cTn 
in whom cTn levels are stable (≤20% variation) or falling, the postprocedure cTn must rise by 
>20%. However, the absolute postprocedural value still must be >10 times the 99th percentile 
URL. In addition, 1 of the following elements is required: 
• Development of new pathological Q waves; 
• Angiographic documented new graft occlusion or new native coronary artery occlusion; 
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality 
in a pattern consistent with an ischemic etiology. 
 
7. Criteria for Prior or Silent/Unrecognized MI 
Any 1 of the following criteria meets the diagnosis for prior or silent/unrecognized MI: 
• Pathological Q waves as described in below Table, with or without symptoms, in the absence of 
nonischemic causes; 
• Imaging evidence of loss of viable myocardium in a pattern consistent with ischemic etiology; 
• Pathological findings of a prior MI. 

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Table. Electrocardiographic Changes Associated with Prior Myocardial Infarction (In the 
Absence of Left Ventricular Hypertrophy and Left Bundle Branch Block) 
Any Q wave in leads V2 –V3 >0.02 s or QS complex in leads V2 –V3. 
Q wave ≥0.03 s and ≥1 mm deep or QS complex in leads I, II, aVL, aVF or V4 – V6 in any 2 leads of 
a contiguous lead grouping (I, aVL; V1 – V6; II, III, aVF) 
R wave >0.04 s in V1 – V2 and R/S >1 with a concordant positive T wave in absence of conduction 
defect. 
 
Principal Investigator  
A physician-specialist responsible for overseeing trial conduct at all sites, protocol compliance, and 
relevant KFDA regulations  
 
Repeat coronary revascularization 
See revascularization 
 
Restenosis  
Re-narrowing of the artery following the removal or reduction of a previous narrowing. 
 
Binary restenosis: Percent diameter stenosis > 50% at angiographic follow-up 
 
Revascularization  
Revascularization is defined by the Academic Research Consortium as follows:  
 
Target lesion revascularization: TLR is defined as any repeat percutaneous intervention of the target 
lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target 
lesion. All TLRs should be classified prospectively as clinically indicated* or not clinically indicated by 
the investigator prior to repeat angiography. An independent angiographic core laboratory should verify 
that the severity of percent diameter stenosis meets requirements for clinical indication and will overrule 
in cases where investigator reports are not in agreement. The target lesion is defined as the treated 
segment from 5 mm proximal to the stent and to 5 mm distal to the stent. 
Target vessel Revascularization: TVR is defined as any repeat percutaneous intervention or surgical 
bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary 
vessel proximal and distal to the target lesion, which includes upstream and downstream branches and 
the target lesion itself. 
Non-Target Lesion Revascularization (non-TLR): Any revascularization in a lesion other than the target 
lesion is considered a non-target lesion revascularization.  
Non-Target Vessel Revascularization (non-TVR): Any revascularization in a vessel other than the target 
vessel is considered a non-target vessel revascularization.  
 
*Clinically indicated revascularization: A revascularization is considered clinically indicated if 
angiography at follow-up shows a percent diameter stenosis ≥ 50% (core laboratory quantitative 
coronary angiography assessment) and if one of the following occurs:  
(1) A positive history of recurrent angina pectoris, presumably related to the target vessel;  
(2) Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), 
presumably related to the target vessel;  
(3) Abnormal results of any invasive functional diagnostic test (eg, Doppler flow velocity reserve, 
fractional flow reserve);  
(4) A TLR or TVR with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic 
signs or symptoms.  
 
Stent Thrombosis  
Stent thrombosis is defined and discussed by the Academic Research Consortium as follows: 
 
Stent thrombosis should be reported as a cumulative value at the different time points and with the 
different separate time points. Time 0 is defined as the time point after the guiding catheter has been 
removed and the subject left the catheterization laboratory.  

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Timing 
Acute stent thrombosis* 
0-24 hours post stent implantation  
Subacute stent thrombosis*: 
> 24 hours-30 days post stent implantation  
Late stent thrombosis†: 
> 30 days-1-year post stent implantation  
Very late stent thrombosis†: 
> 1-year post stent implantation  
* Acute/subacute can also be replaced by early stent thrombosis. Early stent thrombosis (0-30 days) is 
currently used in the community. 
† Including “primary” as well as “secondary” late stent thrombosis; “secondary” late stent thrombosis is 
a stent thrombosis after a target segment revascularization.  
 
Stent Thrombosis Categories: a) Definite b) Probable, and c) Possible  
 
a) Definite stent thrombosis: Definite stent thrombosis is considered to have occurred by either 
angiographic or pathologic confirmation.  
Angiographic confirmation of stent thrombosis [*The incidental angiographic documentation of stent 
occlusion in the absence of clinical signs or symptoms is not considered a confirmed stent thrombosis 
(silent occlusion).]: The presence of a thrombus [†Intracoronary thrombus] that originates in the stent 
or in the segment 5 mm proximal or distal to the stent and presence of at least 1 of the following 
criteria within a 48-hour time window: 
. Acute onset of ischemic symptoms at rest  
. New ischemic ECG changes that suggest acute ischemia  
. Typical rise and fall in cardiac biomarkers (refer to definition of spontaneous MI)  
. Nonocclusive thrombus: Intracoronary thrombus is defined as a (spheric, ovoid, or irregular) 
noncalcified filling defect or lucency surrounded by contrast material (on 3 sides or within a 
coronary stenosis) seen in multiple projections, or persistence of contrast material within the lumen, 
or a visible embolization of intraluminal material downstream.  
. Occlusive thrombus: TIMI 0 or TIMI 1 intrastent or proximal to a stent up to the most adjacent 
proximal side branch or main branch (if originates from the side branch).  
Pathological confirmation of stent thrombosis: Evidence of recent thrombus within the stent 
determined at autopsy or via examination of tissue retrieved following thrombectomy.  
b) Probable stent thrombosis: Clinical definition of probable stent thrombosis is considered to have 
occurred after intracoronary stenting in the following cases:  
. Any unexplained death within the first 30 days [‡ For studies with ST-elevation MI population, one 
may consider the exclusion of unexplained death within 30 days as evidence of probable stent 
thrombosis.] 
. Irrespective of the time after the index procedure, any MI that is related to documented acute 
ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis 
and in the absence of any other obvious cause  
c) Possible stent thrombosis: Clinical definition of possible stent thrombosis is considered to have 
occurred with any unexplained death from 30 days after intracoronary stenting until end of trial follow-
up.  
 
Successful Stent Implantation 
10% or less residual stenosis by visual assessment over the entire stent length, with TIMI – 3 flow and 
no more than an NHLBI type A peri-stent dissection. 
 
Target Lesion  
A lesion to be treated during the index procedure  
 
Target Vessel  
The entire epicardial vessel containing the treated lesion  
 
Thrombosis in Myocardial Infarction (TIMI) Flow Grades 
Definitions of perfusion in the TIMI Trial 
Grade 0 (no perfusion): There is no antegrade flow beyond the point of occlusion. 
Grade 1 (penetration with minimal perfusion): The contrast material passes beyond the area of 

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obstruction, but "hangs up" and fails to opacify the entire coronary bed distal to the obstruction for 
duration of the cine run. 
Grade 2 (partial perfusion): The contrast material passes across the obstruction and opacifies the 
coronary bed distal to the obstruction. However, the rate of entry of contrast material into the vessel 
distal to the obstruction or its rate of clearance from the distal bed (or both) are perceptibly slower than 
its entry into or clearance from comparable areas not perfused by the previously occluded vessel, e.g., 
the opposite coronary artery or the coronary bed proximal to the obstruction. 
Grade 3 (complete perfusion): Antegrade flow into the bed distal to the obstruction occurs as promptly 
as antegrade flow into the bed proximal to the obstruction, and clearance of contrast material from the 
involved bed is as rapid as clearance from an uninvolved bed in the same vessel or the opposite artery. 
 
Transient Ischemic Neurological Attack (TIA)  
A sudden onset of reversible focal neurological deficits due to vascular lesions of the brain that lasts ≤ 
24 hours 
 
 

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