Impact of Optical Coherence Tomography-guided Versus Angiography-guided Stent Optimization on Post-Interventional Fractional Flow Reserve in Patients With Complex Coronary Artery Lesions
Phase: NA
Conditions: Coronary Artery Disease, Angina Pectoris
Sponsor: Chonnam National University Hospital

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Impact of Optical Coherence Tomography-guided versus 
Angiography-guided Stent Optimization on Post-Interventional 
Fractional Flow Reserve in Patients with Complex Coronary Artery 
Lesions 
 
PREcise Percutaneous Coronary Intervention for Stent OptimizatION 
in treatment of COMPLEX lesion 
(PRECISION-COMPLEX) 
 
 
 
 
 
 
 
 
 
 
Version No: 3.1 
 
Division of Cardiology, Department of Internal Medicine, 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Principal Investigator: Youngkeun Ahn 
 
 

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Table of Contents 
1. Title of Study ................................................................................................................. 11 
2. Clinical Research Center .............................................................................................. 11 
3. Principal Investigator, Staff, Co-researchers .............................................................. 11 
4. Funding Agencies ......................................................................................................... 12 
5. Background and Hypothesis ........................................................................................ 12 
5.1. Background ............................................................................................................................. 12 
5.2. Hypothesis .............................................................................................................................. 13 
6. Study Plans .................................................................................................................... 13 
6.1 Study Design ............................................................................................................................ 13 
6.2. Study Timeline ........................................................................................................................ 13 
6.3. Study Population ..................................................................................................................... 13 
6.4. Eligibility Criteria ..................................................................................................................... 13 
6.4.1. Inclusion Criteria ........................................................................................................... 13 
6.4.2. Exclusion Criteria .......................................................................................................... 14 
6.5. Sample Size Calculation ......................................................................................................... 15 
6.6. Patient Follow-up .................................................................................................................... 15 
6.7. Early Study Termination .......................................................................................................... 15 
6.8. Measures to Avoid/Minimize Bias ........................................................................................... 15 
7. Endpoints ...................................................................................................................... 16 
7.1. Primary Endpoint .................................................................................................................... 16 
7.2. Secondary Endpoints .............................................................................................................. 16 
7.3. Safety Endpoints ..................................................................................................................... 16 
7.4. Definitions of Clinical Endpoints ............................................................................................. 16 
8. Randomization .............................................................................................................. 19 
8.1. Randomization ........................................................................................................................ 19 
8.2. Stratification ............................................................................................................................ 20 
9. Patient Enrollment and Withdrawal ............................................................................. 20 
9.1. Patient Enrollment................................................................................................................... 20 
9.2. Patient Screening.................................................................................................................... 20 
9.3. Patient Discontinuation (Withdrawal Criteria) ......................................................................... 20 
9.4. Lost to Follow-up..................................................................................................................... 21 

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10. Study Protocols........................................................................................................... 21 
10.1. Flow Chart ............................................................................................................................. 22 
10.2. Study Procedure ................................................................................................................... 22 
10.3. Schedule of Measurements .................................................................................................. 24 
11. Measurement of Study Outcome Variables ............................................................... 26 
11.1. Visit 1 Screening & Baseline, Post-procedure ...................................................................... 26 
11.2. Follow-up ............................................................................................................................... 27 
12. Ethical Considerations and Confidentiality ............................................................... 28 
12.1. Institutional Review Board (IRB) / Ethical Committee Approval ........................................... 28 
12.2. Participant Safety .................................................................................................................. 28 
12.2.1. Elements of Informed Consent ................................................................................... 28 
12.2.2. Potential Risks ............................................................................................................ 29 
12.2.3. Adequacy of Protection against Risks ........................................................................ 29 
12.3. Confidentiality ....................................................................................................................... 30 
13. Study Organization ..................................................................................................... 30 
13.1. Steering Committee and Data Safety Monitoring Board (DSMB) ......................................... 30 
13.2. Clinical Event Adjudication Committee (CEAC) .................................................................... 30 
13.3. Data Coordination and Site Management ............................................................................ 30 
14. Statistical Analysis ...................................................................................................... 31 
14.1. Analysis Population ............................................................................................................... 31 
14.2. Primary Endpoint Analysis .................................................................................................... 31 
14.3. Secondary Endpoints Analyses ............................................................................................ 31 
14.4. Safety Endpoints Analyses ................................................................................................... 32 
14.5. Treatment of Missing Values ................................................................................................. 33 
14.6. Multivariable Analyses .......................................................................................................... 33 
14.7. Pre-specified subgroup analysis ........................................................................................... 33 
15. Publication Policy ....................................................................................................... 34 
15.1 Data Analysis and Release of Results ................................................................................... 34 
15.2 Review Process ..................................................................................................................... 34 
15.3 Authorship: Primary Outcome Paper ..................................................................................... 34 
15.4. Other Study Papers, Abstracts and Presentations ............................................................... 34 
16. Quality Assurances, Quality Control and Clinical Monitoring ................................. 35 

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16.1. Protocol Adherence .............................................................................................................. 35 
16.2. Data Collection: Electronic Case Report Forms (eCRF) ...................................................... 36 
16.3. Training/Certification and Retraining..................................................................................... 36 
16.4. Site Monitoring ...................................................................................................................... 37 
17. Adverse Events ........................................................................................................... 37 
17.1 Adverse Event ........................................................................................................................ 37 
17.2 Serious Adverse Event (SAE) ................................................................................................ 37 
18. Event Adjudication and Reporting ............................................................................. 38 
18.1 Investigator Responsibilities .................................................................................................. 38 
18.1.1. Adverse Events ........................................................................................................... 38 
18.1.2 Serious Adverse Events (SAE) .................................................................................... 39 
18.2 Endpoint and SAE Adjudication ............................................................................................. 40 
19. Regulatory Responsibilities ....................................................................................... 41 
19.1. Investigator Responsibilities ................................................................................................. 41 
19.2. Institutional Review Board (IRB) or Ethics Committee Approval .......................................... 41 
19.3. Informed Consent ................................................................................................................. 41 
19.4. Study Coordinator ................................................................................................................. 42 
20. Protocol Deviations and Amendments ...................................................................... 42 
20.1. Protocol Deviations ............................................................................................................... 42 
20.2. Protocol Amendments ........................................................................................................... 42 
21. Records Retention and Reports ................................................................................. 43 
21.1 Records .................................................................................................................................. 43 
21.2. Reports ................................................................................................................................. 43 
22. Investigational Agreement .......................................................................................... 45 
23. References ................................................................................................................... 54 
 
 
 

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Research Summary 
Study Title 
Impact of Optical Coherence Tomography-guided Stent Optimization  
on Post-Interventional Fractional Flow Reserve in Patients with Complex 
Coronary Artery Lesions 
Principal  
Investigator 
Youngkeun Ahn, MD, PhD 
Division of Cardiology, Department of Internal Medicine 
Chonnam National University Hospital, Chonnam National University Medical 
School, 42, Jebong-ro, Dong-gu, Gwangju 61469, Republic of Korea 
Telephone: 82-62-220-6246 
E-mail: cecilyk@hanmail.net 
Countries 
Involved 
Republic of Korea 
Purpose / Objectives: 
The aim of the study is to compare post-interventional fractional flow reserve (FFR) value 
between optical coherence tomography (OCT)-guided and angiography-guided strategy for 
treatment of complex coronary lesion.  
Backgrounds 
There has been ample evidence of the role of intracoronary imaging for optimizing the stent, 
especially among the patients with complex coronary lesions.1-3 Intracoronary imaging can be used 
during the entire process of percutaneous coronary intervention (PCI), from pre-PCI to post-PCI 
stages.1 Notably, approximately 15-20% of patients who underwent angiographically successful PCI 
showed significant stent underexpansion, malapposition, intra-stent thrombus formation, and edge 
dissection on intracoronary imaging studies, including OCT.1  
Meanwhile, the role of pre-interventional FFR measurement has been well established and 
recommended by recent guideline.4-7 However, although previous studies evaluated the efficacy and 
safety of FFR-guided decision-making followed by angiographic stent implantation, they did not 
evaluate functionally optimized revascularization. Actually, the vessels with low post-PCI FFR had 
substantial proportions of suboptimized stented (underexpansion and acute malapposition) and 
residual disease in non-stented segments.8,9 Furthermore, several large observational studies have 
suggested that suboptimal physiologic results after PCI is associated with an increased risk of clinical 
events.10-13 Previously, the DOCTORS trial found out that OCT-guided PCI was associated with 
higher post-PCI FFR than angiography-guided PCI (0.94±0.04 vs. 0.92±0.05, P=0.005).14  
Therefore, OCT can be a useful tool for acquiring functional optimal results after stent 
implantation. This synergic effect between OCT and post-PCI FFR can be maximized when we 
perform PCI for complex lesions. 
Protocol Summary 
1. 
Trial Design 
A prospective, multi-center, open-label, randomized controlled trial. The study will compare the 
outcomes of OCT-guided PCI with angiography-guided PCI in complex coronary lesions.  
 
2. 
Target Population 
Patients with complex coronary lesions undergoing PCI. 

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3. 
Enrollment Criteria 
(1) Inclusion criteria 
1) 
Patients >18 years old  
2) 
Patients with stable or unstable angina and complex coronary lesions* 
3) 
Patients who were indicated revascularization 
- 
Diameter stenosis >90% by angiography 
- 
Diameter stenosis with 50~90% with pre-interventional FFR ≤0.80 
4) 
Patients who underwent implantation of 2nd generation drug-eluting stent 
 
* Definitions of complex coronary lesions 
[1] True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) with side branch ≥2.5mm size 
[2] Chronic total occlusion (≥3 months) as target lesion  
[3] PCI for unprotected left main (LM) disease (LM os, body, distal LM bifurcation including non-true bifurcation) 
[4] Long coronary lesions (implanted stent ≥38 mm in length) 
[5] Multi-vessel PCI (≥2 major epicardial coronary arteries treated at one PCI session) 
[6] Multiple stents needed (≥3 more stent per patient) 
[7] In-stent restenosis lesion as target lesion  
[8] Severely calcified lesion (encircling calcium in angiography) 
[9] Left anterior descending (LAD), left circumflex artery (LCX), and right coronary artery (RCA) ostial lesion 
 
(2) Exclusion criteria 
1) 
Target lesions not amenable for PCI by operators’ decision 
2) 
Cardiogenic shock (Killip class IV) at presentation 
3) 
Less than TIMI 3 flow of target vessel after index procedure 
4) 
Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, Everolimus, 
Zotarolimus, Biolimus, or Sirolimus  
5) 
Known true anaphylaxis to contrast medium (not allergic reaction but anaphylactic shock) 
6) 
Renal insufficiency such that an additional contrast medium would be harmful for patient 
7) 
Recent ST-segment elevation myocardial infarction (STEMI) 
8) 
Inability to receive adenosine or nicorandil injection  
9) 
Pregnancy or breast feeding 
10) Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may 
result in protocol non-compliance (per site investigator’s medical judgment) 
11) Unwillingness or inability to comply with the procedures described in this protocol 
 
4. 
Study Endpoints 
(1) Primary endpoint 
Proportion of patients with a suboptimal final post-PCI FFR <0.85 
 
(2) Secondary endpoints 
1) 
Target vessel failure (TVF), a composite of cardiac death, target-vessel myocardial 
infarction (MI), and target-vessel revascularization (TVR) 
2) 
All-cause and cardiac death 
3) 
Target vessel MI without periprocedural MI  
4) 
Target vessel MI with periprocedural MI  
5) 
Target lesion revascularization (TLR) 

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6) 
Target vessel revascularization (TVR) 
7) 
Any MI  
8) 
Any revascularization (ischemia-driven or all) 
9) 
Stent thrombosis (definite/probable/possible) 
10) FFR gain between pre- and post-interventional stages 
11) Trans-stent FFR gradient  
12) Post-interventional non-hyperemic pressure ratios 
 
(3) Safety endpoints 
1) 
Incidence of contrast-induced nephropathy, defined as an increase in serum creatinine of 
≥0.5mg/dL or ≥25% from baseline within 48-72 hours after contrast agent exposure 
2) 
Total procedure time, min 
3) 
Total amount of contrast dose, mL 
4) 
Total fluoroscopy time, min 
5) 
Total amount of radiation dose, cGy/cm2 
 
5. 
Sample Size Calculation 
Hypothesis: OCT-guided strategy for treatment of complex coronary lesions would 
improve post-interventional FFR value, compared with angiography only-guided strategy. 
Null hypothesis: The post-PCI FFR will be not different between OCT-guided strategy 
and angiography only-guided strategy group for treatment of complex coronary lesions. 
 
 
Primary endpoint: Proportion of patients with a suboptimal final post-PCI FFR <0.85 
 
Assumed proportion of primary outcome:  
- 
OCT-guided PCI group (15%) vs. Angiography-guided PCI group (30%) 
 
Alpha = 0.05 (2-sided), β = 10%, Power (1- β) = 90% 
 
1:1 Randomization 
 
Primary statistical method: Two proportions using the Z-test 
 
Based on the above assumption, we would need a total of 320 patients (160 and 160 patients for 
OCT-guidance group and angiography only-guidance group, respectively) to detect a difference 
between the group proportions of 0.15.  
 
6. 
Randomization 
Patients will be randomized to either the OCT group or the angiography group with 1:1 ratio during 
the index procedure after diagnostic angiography. Stratified randomization according to participating 
center and clinical presentation (stable angina or unstable angina) will be performed. All processes 
will be done by a web-based randomization program, run by an independent organization. 
(1) Experimental group: OCT-guided PCI group 
(2) Control group: Angiography-guided PCI group 
 
7. 
Study Procedure 
(1) Flow chart 

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(2) OCT-guided Stent Optimization1 
Use of OCT will be strongly recommended at any step of PCI (pre-PCI, during PCI and post-
PCI), but OCT evaluation after stent implantation will be mandatory. In case of staged procedure 
during the same hospitalization, following the initially allocated strategy would be strongly 
recommended. In this group, the recommendations for selecting reference segment, selecting 
appropriated size of stent, and stent optimization are as follows. OPTIS imaging catheter (Abbott 
Vascular) will be used for the imaging arm. 
 
[MAX-MLD Algorithm] 
Pre-PCI OCT for “PCI Planning” 
Reference Site 
Most normal looking segment 
No Lipidic plaque 
Stent Sizing 
Operator can decide 1 of 2 methods 
[1] By measuring vessel diameter at the distal reference sites (in case 
of ≥180° of the external elastic membrane [EEL] can be identified). In 
this case, stent diameter will be determined using mean external elastic 
membrane diameter at the distal reference, rounded down to the 
nearest 0.25mm (Ex> mean external elastic membrane reference 
diameter 3.35mm, 3.25mm stent diameter will be chosen). 
 
[2] By measuring lumen diameter at the distal reference sites (in case 
of ≥180° of the external elastic membrane cannot be identified). In this 
case, stent diameter will be determined using mean lumen diameter at 
the distal reference, rounded up to the nearest 0.25mm (Ex> mean 
distal reference lumen diameter 2.55mm, 2.75mm stent diameter will be 
chosen). 
Stent Length 
By measuring distance from distal to proximal reference site 
Post-PCI OCT for “Stent Optimization” 
 Medial Dissection 
No major edge dissection extended to media layer with potential to 
provoke flow disturbances (defined as >60° of the circumference of the 
vessel at site of dissection and/or >2 mm in length of dissection flap) 

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 Apposition 
No major malapposition (defined as a distance from stent strut to 
adjacent intima ≥400 um and <1 mm length) of the stent over its entire 
length against the vessel wall 
 Expansion  
In-stent minimal lumen area (MSA) >80% of the average reference 
lumen area “OR” MSA >4.5 mm2 
Optimization Technique 
If 1 of above findings are notified, additional procedure including 
adjunctive post-dilatation or additional stent implantation for 
residual 
reference 
segment 
disease 
will 
be 
mandatorily 
recommended. 
 
In adjunctive post-dilatation procedure, the diameter of the non-
compliant post dilatation balloon chosen should not be larger than the 
post-PCI OCT determined mean reference external elastic membrane 
diameter of one or both segments (proximal or distal), or no more than 
0.5 mm larger than the mean reference segment lumen diameter of one 
or both segments (proximal or distal) nearest to the dilatation site (if the 
EEL cannot be measured). 
 
(3) Angiography-guided Stent Optimization 
The PCI procedure in this group will be performed as standard procedure. After deployment of 
stent, stent optimization will be done based on angiographic findings. The optimization guided 
by angiography should meet the criteria of angiographic residual diameter stenosis less than 
30% by visual estimation and the absence of flow limiting dissection (≥Type C dissection). 
When angiographic under-expansion of the stent is suspected, adjunctive balloon dilatation will 
be strongly recommended. In case of staged procedure during the same hospitalization, 
following the initially allocated strategy would be strongly recommended.  
 
(4) 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. Strategy for dual antiplatelet therapy 
(DAPT) maintenance and any adjunctive pharmacologic treatment will be left to operator’s 
discretion. For example, a loading dose of aspirin (300 mg) and clopidogrel (300-600mg) or 
aspirin (300 mg) and prasugrel (60 mg) or aspirin (300 mg) and ticagrelor (180mg), or use of 
glycoprotein IIbIIIa inhibitor, etc. In case of PCI is performed, dual antiplatelet therapy is 
recommended for at least 3~12 months in both groups. Thereafter, patients will receive single 
antiplatelet therapy (either aspirin or a P2Y12 inhibitor, at the discretion of the physician).  
 
8. 
Prespecified Subgroup Analysis 
Primary and Secondary outcome will be assessed in pre-specified subgroups below. 
(1) Age (dichotomized at the age of ≥65 years) 
(2) Sex 
(3) Clinical presentation 
(4) Diabetes mellitus vs. non-diabetes mellitus 
(5) Chronic kidney disease 
(6) Optimal vs. Suboptimal stent implantation 
(7) Duration of dual-antiplatelet therapy  
(8) Complex lesion type and number of complexity (≥3 or <3) 

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(9) LV dysfunction (EF <40% versus ≥40%)  
 
9. 
Study Duration and Dates 
IRB Approval dates ~ 31.DEC.2026 
 
10. Follow-up 
After the randomization, clinical follow-up will be done at 6, 12, and 24 months. 
The trial population will be continuously followed until 2 years after the last patient enrollment. 
Funding Agency 
Abbott Vascular 
 
 

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1. Title of Study 
Impact of Optical Coherence Tomography-guided Stent Optimization on Post-
Interventional Fractional Flow Reserve in Patients with Complex Coronary Artery 
Lesions  
PREcise Percutaneous Coronary Intervention for Stent OptimizatION in treatment of 
COMPLEX lesion (PRECISION-COMPLEX) 
 
2. Clinical Research Center 
Chonnam National University Hospital, Chonnam National University Medical School, 
Gwnagju, South Korea 
Samsung Medical Center, Seoul, South Korea 
Seoul National University Hospital, Seoul, South Korea 
Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, South Korea 
 
3. Principal Investigator, Staff, Co-researchers 
 
Name 
Center 
Position 
Principal 
investigator 
Youngkeun Ahn 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Professor 
Trial Manager 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Assistant 
Professor 
Co-
researchers 
Min Chul Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Associate 
Professor  
Myung Ho Jeong 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Professor 
Ju Han Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Professor 
Young Joon Hong 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Professor 
Doo Sun Sim 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Associate 
Professor 
Kyung Hoon Cho 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Assistant 
Professor 

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Dae Young Hyun 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Assistant 
Professor 
Joon Ho Ahn 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Assistant 
Professor 
Yonghwan Lim 
Chonnam National University Hospital, 
Chonnam National University Medical School, 
Gwnagju, South Korea 
Assistant 
Professor 
Joo Myung Lee 
Samsung Medical Center, Seoul, South Korea 
Associate 
Professor 
Joo-Yong Hahn 
Samsung Medical Center, Seoul, South Korea 
Professor 
Young Bin Song 
Samsung Medical Center, Seoul, South Korea 
Professor 
Ki Hong Choi 
Samsung Medical Center, Seoul, South Korea 
Assistant 
Professor 
Bon-Kwon Koo 
Seoul National University Hospital, Seoul, South 
Korea 
Professor 
Doyeon Hwang 
Seoul National University Hospital, Seoul, South 
Korea 
Assistant 
Professor 
Chang-Wook Nam 
Keimyung University Dongsan Hospital, Daegu, 
South Korea 
Professor 
Sang Yeob Lee 
Chung-Ang University Gwangmyeong Hospital, 
Gwangmyeong, South Korea 
Professor 
Administrator 
of study device 
Jeong Hun Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Radiograp
her 
 
4. Funding Agencies 
Abbott Vascular, USA 
 
5. Background and Hypothesis 
5.1. Background 
There has been ample evidence of the role of intracoronary imaging for optimizing the 
stent, especially among the patients with complex coronary lesions.1-3 Intracoronary imaging 
can be used during the entire process of percutaneous coronary intervention (PCI), from pre-
PCI to post-PCI stages.1 Notably, approximately 15-20% of patients who underwent 
angiographically successful PCI showed significant stent underexpansion, malapposition, 
intra-stent thrombus formation, and edge dissection on intracoronary imaging studies, 
including optical coherence tomography (OCT).1  
Meanwhile, the role of pre-interventional fractional flow reserve (FFR) measurement 
has been well established and recommended by recent guideline.4-7 However, although 
previous studies evaluated the efficacy and safety of FFR-guided decision-making followed 
by angiographic stent implantation, they did not evaluate functionally optimized 
revascularization. Actually, the vessels with low post-PCI FFR had substantial proportions of 

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suboptimized stented (underexpansion and acute malapposition) and residual disease in non-
stented segments.8,9 Furthermore, several large observational studies have suggested that 
suboptimal physiologic results after PCI is associated with an increased risk of clinical 
events.10-13 Previously, the DOCTORS trial found out that OCT-guided PCI was associated 
with higher post-PCI FFR than angiography-guided PCI (0.94±0.04 vs. 0.92±0.05, P=0.005).14  
Therefore, OCT can be a useful tool for acquiring functional optimal results after stent 
implantation. This synergic effect between OCT and post-PCI FFR can be maximized when 
we perform PCI for complex lesions. 
 
5.2. Hypothesis 
OCT-guided strategy for treatment of complex coronary lesions would improve post-
interventional FFR value, compared with angiography only-guided strategy. 
 
6. Study Plans 
6.1 Study Design 
A prospective, multi-center, open-label, randomized controlled trial. 
 
6.2. Study Timeline 
IRB approval date ~ 2027.12.31 
Subject enrollment: IRB approval date ~ 2024.12 (roughly 2.5 years of enrollment) 
End of follow-up period: 2026.12 (2 years after the last patient enrollment) 
Analysis and report: ~2027.12.31 
 
6.3. Study Population 
A total of 320 patients (160 per each group) will be enrolled at multiple centers in South Korea. 
Patients with stable or unstable angina undergoing complex lesion PCI will be eligible. All 
eligible patients will be on either OCT or angiography group as randomized. 
 
6.4. Eligibility Criteria 
6.4.1. Inclusion Criteria 
(1) Patients >18 years old 
(2) Patients with stable or unstable angina and complex coronary lesions* 
(3) Patients who were indicated revascularization 

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- Diameter stenosis >90% by angiography 
- Diameter stenosis with 50~90% with pre-interventional FFR ≤0.80 
(4) Patients who underwent implantation of 2nd generation drug-eluting stent 
* Definitions of complex coronary lesions 
[1] True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) with side branch ≥2.5mm size 
[2] Chronic total occlusion (≥3 months) as target lesion  
[3] PCI for unprotected left main (LM) disease (LM os, body, distal LM bifurcation including non-true 
bifurcation) 
[4] Long coronary lesions (implanted stent ≥38 mm in length) 
[5] Multi-vessel PCI (≥2 major epicardial coronary arteries treated at one PCI session) 
[6] Multiple stents needed (≥3 more stent per patient) 
[7] In-stent restenosis lesion as target lesion  
[8] Severely calcified lesion (encircling calcium in angiography) 
[9] Left anterior descending (LAD), left circumflex artery (LCX), and right coronary artery (RCA) ostial 
lesion 
 
6.4.2. Exclusion Criteria 
(1) Target lesions not amenable for PCI by operators’ decision 
(2) Cardiogenic shock (Killip class IV) at presentation 
(3) Less than TIMI 3 flow of target vessel after index procedure 
(4) Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, Everolimus, 
Zotarolimus, Biolimus, or Sirolimus  
(5) Known true anaphylaxis to contrast medium (not allergic reaction but anaphylactic 
shock) 
(6) Renal insufficiency such that an additional contrast medium would be harmful for 
patient 
(7) Recent ST-segment elevation myocardial infarction (STEMI) 
(8) Inability to receive adenosine or nicorandil injection  
(9) Pregnancy or breast feeding 
(10) Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may 
result in protocol non-compliance (per site investigator’s medical judgment) 
(11) Unwillingness or inability to comply with the procedures described in this protocol 

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6.5. Sample Size Calculation 
Hypothesis: OCT-guided strategy for treatment of complex coronary lesions would improve 
post-interventional FFR value, compared with angiography only-guided 
strategy. 
Null hypothesis: The post-PCI FFR will be not different between OCT-guided strategy and 
angiography only-guided strategy group for treatment of complex coronary 
lesions. 
 
 Primary endpoint: Proportion of patients with a suboptimal final post-PCI FFR <0.85 
 Assumed proportion of primary outcome:  
- 
OCT-guided PCI group (15%) vs. Angiography-guided PCI group (30%)10,14 
 Alpha = 0.05 (2-sided), β = 10%, Power (1- β) = 90% 
 1:1 Randomization 
 Primary statistical method: Two proportions using the Z-test 
 
Based on the above assumption, we would need a total of 320 patients (160 and 160 patients 
for OCT-guidance group and angiography only-guidance group, respectively) to detect a 
difference between the group proportions of 0.15.  
 
6.6. Patient Follow-up 
After the randomization, clinical follow-up will be done at 6, 12, 24 months. 
Trial population will be followed until 2 years after the 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 
In order 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 

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the trial period. 
 
7. Endpoints 
7.1. Primary Endpoint 
Proportion of patients with a suboptimal final post-PCI FFR <0.85 
 
7.2. Secondary Endpoints 
(1) Target vessel failure (TVF), a composite of cardiac death, target-vessel myocardial 
infarction (MI), and target-vessel revascularization (TVR). 
(2) All-cause and cardiac death 
(3) Target vessel MI without periprocedural MI  
(4) Target vessel MI with periprocedural MI  
(5) Target lesion revascularization (TLR) 
(6) Target vessel revascularization (TVR) 
(7) Any MI  
(8) Any revascularization (ischemia-driven or all) 
(9) Stent thrombosis (definite/probable/possible) 
(10) FFR gain between pre- and post-interventional stages 
(11) Trans-stent FFR gradient  
(12) Post-interventional non-hyperemic pressure ratios 
 
7.3. Safety Endpoints 
(1) Incidence of contrast-induced nephropathy, defined as an increase in serum 
creatinine of ≥0.5mg/dL or ≥25% from baseline within 48-72 hours after contrast 
agent exposure 
(2) Total procedure time, min 
(3) Total amount of contrast dose, mL 
(4) Total fluoroscopy time, min 
(5) Total amount of radiation dose, cGy/cm2 
 
7.4. Definitions of Clinical Endpoints 
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. 

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MI 
The definition of myocardial infarction used in this trial is adapted 
from the Fourth Universal Definition of Myocardial Infarction.15 
 
• 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: 
• 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 

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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 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 

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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 
 
Stent thrombosis 
Academic Research Consortium (ARC) definition of stent 
thrombosis is classified and defined as follows. 
• Definite/Confirmed stent thrombosis refers angiographic or 
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. 
 
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 

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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. 
Patients will be randomized to either OCT group or angiography group with 1:1 ratio. 
(1) Experimental group: OCT-guided PCI group  
(2) Control group: Angiography-guided PCI group 
 
8.2. Stratification 
To ensure balance among the strata, randomization will be stratified by participating center 
and clinical presentation (stable or unstable angina). All processes will be done by a web-
based randomization program, run by an independent organization. 
 
9. Patient Enrollment and Withdrawal 
9.1. Patient Enrollment 
A total of 320 patients derived from a population of Korean patients who undergoing complex 
lesion 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 with stable or unstable angina who undergoing complex lesion 
PCI 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) 

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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 r
eceive their assigned treatment. Every attempt should be made to collect follow-up inf
ormation, except for those patients who specifically withdraw consent for release of su
ch information. All procedures and laboratory specimens or tests requested for evaluati
on 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. 
 
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 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.  
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.  
 

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10.1. Flow Chart 
 
 
10.2. Study Procedure 
After randomization, patients will be treated with 2nd generation drug-eluting stents according to the 
allocated arm, OCT-guided versus angiography-guided strategy.  
(1) OCT-guided Stent Optimization1 
Use of OCT will be strongly recommended at any step of PCI (pre-PCI, during PCI 
and post-PCI), but OCT evaluation after stent implantation will be mandatory. In case 
of staged procedure during the same hospitalization, following the initially allocated 
strategy would be strongly recommended. In this group, the recommendations for 
selecting reference segment, selecting appropriated size of stent, and stent 
optimization are as follows. OPTIS imaging catheter (Abbott Vascular) will be used for 
the imaging arm. 
 
[MAX-MLD Algorithm] 
Pre-PCI OCT for “PCI Planning” 
Reference Site 
Most normal looking segment 
No Lipidic plaque 
Stent Sizing 
Operator can decide 1 of 2 methods 
[1] By measuring vessel diameter at the distal reference sites (in 
case of ≥180° of the external elastic membrane [EEL] can be 
identified). In this case, stent diameter will be determined using 
mean external elastic membrane diameter at the distal reference, 
rounded down to the nearest 0.25mm (Ex> mean external elastic 
membrane reference diameter 3.35mm, 3.25mm stent diameter will 
be chosen). 

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[2] By measuring lumen diameter at the distal reference sites (in 
case of ≥180° of the external elastic membrane cannot be 
identified). In this case, stent diameter will be determined using 
mean lumen diameter at the distal reference, rounded up to the 
nearest 0.25mm (Ex> mean distal reference lumen diameter 
2.55mm, 2.75mm stent diameter will be chosen). 
Stent Length 
By measuring distance from distal to proximal reference site 
Post-PCI OCT for “Stent Optimization” 
 Medial Dissection 
No major edge dissection extended to media layer with potential to 
provoke flow disturbances (defined as >60° of the circumference of 
the vessel at site of dissection and/or >2 mm in length of dissection 
flap) 
 Apposition 
No major malapposition (defined as a distance from stent strut to 
adjacent intima ≥400 um and <1 mm length) of the stent over its 
entire length against the vessel wall 
 Expansion  
In-stent minimal lumen area (MSA) >80% of the average reference 
lumen area “OR” MSA >4.5 mm2 
Optimization Technique 
If 1 of above findings are notified, additional procedure 
including adjunctive post-dilatation or additional stent 
implantation for residual reference segment disease will be 
mandatorily recommended. 
 
In adjunctive post-dilatation procedure, the diameter of the non-
compliant post dilatation balloon chosen should not be larger than 
the post-PCI OCT determined mean reference external elastic 
membrane diameter of one or both segments (proximal or distal), 
or no more than 0.5 mm larger than the mean reference segment 
lumen diameter of one or both segments (proximal or distal) nearest 
to the dilatation site (if the EEL cannot be measured). 
 
(2) Angiography-guided Stent Optimization 
The PCI procedure in this group will be performed as standard procedure. After 
deployment of stent, stent optimization will be done based on angiographic findings. 
The optimization guided by angiography should meet the criteria of angiographic 
residual diameter stenosis less than 30% by visual estimation and the absence 
of flow limiting dissection (≥Type C dissection). When angiographic under-
expansion of the stent is suspected, adjunctive balloon dilatation will be strongly 
recommended. In case of staged procedure during the same hospitalization, following 
the initially allocated strategy would be strongly recommended.  
 
(3) 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. Strategy for dual 
antiplatelet therapy (DAPT) maintenance and any adjunctive pharmacologic 
treatment will be left to the operator’s discretion. For example, a loading dose of 
aspirin (300 mg) and clopidogrel (300-600mg) or aspirin (300 mg) and prasugrel (60 
mg) or aspirin (300 mg) and ticagrelor (180mg), or use of glycoprotein IIbIIIa inhibitor, 

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etc. In case of PCI is performed, dual antiplatelet therapy is recommended for at least 
3~12 months in both groups. Thereafter, patients will receive single antiplatelet 
therapy (either aspirin or a P2Y12 inhibitor, at the discretion of the physician).  
 
10.3. Schedule of Measurements 
Visit 
Screening 
& 
Baseline 
Post-
Procedure 
Follow-Up 
6-month 
±30days 
12-month 
±30days 
24-month 
±30days 
SCV 
Medical/Clinical/History 
(age, sex, risk factors, 
prior bleeding, clinical 
Dx, angina status) 
× 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
× 
 
 
 
 
 
Brief Physical 
Examination 
× 
 
 
 
 
 
Vital status 
× 
× 
× 
× 
× 
× 
Weight, height 
× 
 
 
 
 
 
12 lead ECG 
× 
× 
 
 
 
 
Informed Consent 
× 
 
 
 
 
 
Randomization1) 
× 
 
 
 
 
 
Quantitative Coronary 
angiography2) 
× 
× 
 
 
 
 
OCT3) 
× 
× 
 
 
 
 
Invasive physiologic 
assessment4) 
× 
× 
 
 
 
 
CBC 
× 
 
 
× 
 
× 
Electrolytes, LFT 
× 
 
 
× 
 
× 
Creatinine, BUN 
× 
× 
 
× 
 
× 
Fasting plasma TG, 
LDL, HDL, total 
cholesterol 
× 
 
 
× 
 
× 
Fasting glucose level, 
Hb A1c 
× 
 
 
× 
 
× 
CK-MB, Troponin I or 
Troponin T5) 
× 
× 
 
 
 
 

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Visit 
Screening 
& 
Baseline 
Post-
Procedure 
Follow-Up 
6-month 
±30days 
12-month 
±30days 
24-month 
±30days 
SCV 
proBNP or NT-proBNP 
× 
 
 
 
 
 
Echocardiography6) 
× 
 
 
 
 
 
Medications7) 
× 
× 
× 
× 
× 
× 
Clinical event8) 
 
× 
× 
× 
× 
× 
 
* Screening will be performed for patients who suspected coronary artery disease without exclusion 
criteria. And then, informed consent will be obtained after explanation of study protocol. Following 
angiography, patients with complex lesion that are eligible for coronary intervention will be randomized. 
* There will be no mandatory laboratory follow up. Because all follow-up 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. 
 
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 and clinical presentation (stable or unstable angina) will be performed. 
2) 
The raw data of pre- and post-coronary artery angiography will be collected and undergo 
quantitative coronary angiographic evaluation in the Core-Laboratory in Samsung Medical Center. 
3) 
The raw data of the OCT will be analyzed in the Core-Laboratory in Chonnam National University 
Hospital. In the OCT group, post-PCI OCT evaluation after stent implantation will be mandatory. 
4) 
Use of invasive physiologic method (for example, fractional flow reserve, non-hyperemic pressure 
ratios, coronary flow reserve, or index of microcirculatory resistance) will be left to the operator’s 
discretion. However, the measurement of post-PCI FFR will be mandated according to trial protocol. 
The raw data of the invasive physiologic method will be analyzed in the Core-Laboratory in 
Chonnam National University Hospital. 
5) 
The baseline and post-procedural cardiac enzyme (CK, CK-MB, Troponin I or T) measurement is 
mandatory to assess the peri-procedural myocardial infarction, defined according to ARC criteria. 
6) 
Echocardiography should be taken before or after the procedure. If not performed, it will be 
recorded with the closest result before the randomization. 
7) 
Medication data included medication at baseline (before admission) and post-discharge. 
8) 
Only endpoint-related clinical events (all-cause death, cardiovascular death, MI, repeat 
revascularization, stent thrombosis) will be collected. Follow-up visits will allow telephone contact 
if clinic visits are unavailable. The trial population will be continuously followed until 2 years after 
the last patient enrollment. 
 

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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-cerebral event) will be recorded at Screening& Baseline.  
Relevant medical history, including history of current disease, other pertinent cardiac 
history, bleeding 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 OCT or angiography group with 1:1 ratio. This 
process will be done by a web-based randomization program, 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) Quantitative Coronary angiography 

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Angiogram will be obtained at the time of index procedure. The raw data of pre- and 
post-coronary artery angiography will be collected and undergo quantitative coronary 
angiographic evaluation in the Core-Laboratory in Chonnam National University 
Hospital. 
(9) Invasive physiologic assessment data 
Use of invasive physiologic method (for example, fractional flow reserve, non-
hyperemic pressure, coronary flow reserve, or index of microcirculatory resistance) 
will be left to the operator’s discretion. However, the measurement of post-PCI FFR 
will be mandated according to trial protocol. The raw data of the invasive physiologic 
method will be analyzed in the Core-Laboratory in Chonnam National University 
Hospital. 
(10) OCT 
The raw data of the OCT will be analyzed in the Core-Laboratory in Chonnam National 
University Hospital. OCT is strongly recommended during pre- and post-PCI stages. 
However, when the OCT cannot be performed based on clinical decision, it will not be 
regarded as protocol violation. However, the post-PCI OCT evaluation after stent 
implantation will be mandatory. 
(11) Echocardiography 
Exam should be taken before or after PCI. 
(12) 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. 
(13) Adverse events/ Serious Adverse Event 
Information regarding occurrence of adverse events (any death, any MI or any 
revascularization etc.) will be captured throughout the study. Duration (start and stop 
dates and times), severity/grade, outcome, treatment and relation to procedure will be 
recorded on the case report form (e-CRF). 
 
11.2. Follow-up 
After the randomization, clinical follow-up will be done at 6, 12, and 24 months. The trial 
population will be continuously followed until 2 years after the 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 

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thrombosis, and Adverse Events/ Serious Adverse Events. Original source documents must 
be submitted for any clinical events (MI, repeat revascularization, stent thrombosis, 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 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 320 patients with a mean age in the 60s. Pregnant women 
and patients under the age of 18 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 

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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 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 th
e DSMB to review the data and establish limits of safety for the trial, as well as its ter
mination, 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. 
 

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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 Committ
ee 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 Division of 
Cardiology, Department of Internal Medicine, Chonnam National University Hospital. 
 

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14. Statistical Analysis 
14.1. Analysis Population 
Subjects are to be randomized in a 1:1 fashion to either OCT or angiography groups. All 
primary and secondary endpoints will be analyzed both on an intention-to-treat basis (all 
subjects analyzed as part of their assigned treatment group) and on a per-protocol basis 
(patients analyzed as part of their assigned treatment group only if they actually received their 
assigned treatment group). 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.  
Per-protocol population will be defined as population who did not violate the study protocol. 
The definition of protocol violation is as follows; 
 
① OCT was used in angiography-guided strategy arm  
② OCT was not used in OCT-guided strategy arm  
 
Analysis with Per-protocol population will be performed as exploratory and sensitivity analysis 
for that of intention-to-treat population. 
 
14.2. Primary Endpoint Analysis 
Primary endpoint will be analyzed on an intention-to-treat basis, and then, per-protocol basis. 
Primary endpoint will be analyzed on per-patient basis. Chi-square test will be used to 
determine the incidences of the primary and endpoint. For the primary endpoint, odds ratio 
and 95% confidence interval will be generated using logistic regression models. 
 
Primary Endpoint 
Statistical methods 
Time point of analysis 
Proportion of patients with 
a suboptimal final post-
PCI FFR <0.85 
Chi-square test 
Logistic regression method 
After the last patient 
enrollment 
 
14.3. Secondary Endpoints Analyses 
Secondary endpoints will be analyzed on an intention-to-treat basis and per-protocol basis. 
Secondary endpoints will be analyzed on per-patient basis. Analyses will be performed at the 
end of the follow-up of trial population, which will be 2 years after the last patient enrollment. 
Kaplan-Meier estimates were used to determine the cumulative incidences of the secondary 
endpoints. For the secondary endpoints, hazard ratios and 95% confidence intervals were 
generated using Cox proportional hazards models. 
 

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Secondary Endpoint 
Statistical methods 
Time point of analysis 
Target vessel failure (TVF), a 
composite of cardiac death, 
target-vessel myocardial 
infarction (MI), and target-
vessel revascularization (TVR) 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
All-cause death 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
Cardiac death 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
Target vessel MI without 
periprocedural MI 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
Target vessel MI with 
periprocedural MI 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
Any MI 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
Target lesion revascularization 
(TLR) 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
TVR 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
Any revascularization 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
Vessel or stent thrombosis 
(definite or probable) 
Cox’s proportional hazard 
method 
2 years after the last 
patient enrollment 
FFR gain between pre- and 
post-interventional stages 
Independent T-test 
Chi-square test 
After the last patient 
enrollment 
Trans-stent FFR gradient 
Independent T-test 
Chi-square test 
After the last patient 
enrollment 
Post-interventional non-
hyperemic pressure ratios 
Independent T-test 
Chi-square test 
After the last patient 
enrollment 
 
14.4. Safety Endpoints Analyses 
Safety endpoints will be analyzed on an intention-to-treat basis and per-protocol basis. Safety 
endpoints will be analyzed on per-patient basis. Chi-square test and independent T-test will 
be used to determine the statistical significance according to the allocated arms. 
 
Safety Endpoint 
Statistical methods 
Time point of analysis 
Incidence of contrast-induced 
nephropathy 
Chi-square test 
After the last patient 
enrollment 
Total procedure time, min 
Independent T-test 
After the last patient 
enrollment 
Total amount of contrast dose, 
mL 
Independent T-test 
After the last patient 
enrollment 
Total fluoroscopy time, min 
Independent T-test 
After the last patient 
enrollment 
Total amount of radiation dose, 
Independent T-test 
After the last patient 

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Safety Endpoint 
Statistical methods 
Time point of analysis 
cGy/cm2 
enrollment 
 
14.5. Treatment of Missing Values 
The primary analysis of the study endpoints 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. 
 
14.6. Multivariable Analyses 
Multivariable predictors of all primary and secondary endpoints 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 
Medications  
Age, years 
Current smoker 
Aspirin 
Gender 
Previous MI (Not index PCI) 
Clopidogrel 
Height, Weight 
Previous PCI (Not index PCI) 
Prasugrel 
Diabetes mellitus 
Previous CABG 
Ticagrelor 
Hypertension  
Previous CHF 
Statin 
Dyslipidemia 
Family history of CAD  
ACE inhibitor or ARB 
Peripheral artery disease  
Previous CVA 
Beta-blocker 
Chronic kidney disease 
LV ejection fraction 
Warfarin or NOAC 
 
LV dysfunction (EF <40%) 
Calcium-channel blocker 
 
14.7. Pre-specified subgroup analysis 
Primary outcome will be assessed in pre-specified subgroups below. 
(1) Age (dichotomized at the age of ≥65 years) 
(2) Sex 
(3) Clinical presentation 
(4) Diabetes mellitus vs. non-diabetes mellitus 
(5) Chronic kidney disease 
(6) Optimal vs. Suboptimal stent implantation 
(7) Duration of dual-antiplatelet therapy  

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(8) Complex lesion type and number of complexity (≥3 or <3) 
(9) LV dysfunction (EF <40% versus ≥40%)  
 
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 t
he 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.  

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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.  
 
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. 
 

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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 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: 
 

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• 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)  

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• 
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 
• 
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 

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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 Daiichi Sankyo, 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. 
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. 
 

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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. 

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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. 
 
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.  
 

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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. 
 
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 
IRB 
Per local standard. 

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plan 
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.  

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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.  
 
 
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)  

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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: 
• 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 

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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 

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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. 
 
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 

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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 implantat
ion  
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 

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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.  
 
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 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. 
 
 

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