Randomized Controlled Trial of Optical Coherence Tomography Versus Angiography for Culprit Lesion Revascularization in Patients With Acute Myocardial Infarction
Phase: NA
Conditions: ST Elevation Myocardial Infarction, Myocardial Infarction
Sponsor: Chonnam National University Hospital

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Randomized Controlled Trial of Optical Coherence 
Tomography Versus Angiography for Culprit Lesion 
Revascularization in Patients with Acute Myocardial 
Infarction 
 
Optical Coherence Tomography Versus Angiography for Culprit Lesion 
Revascularization in Acute Myocardial Infarction PatiEnts  
(FRAME-AMI3 Trial) 
 
 
 
Version No: 1.3 
 
 
 
 
Division of Cardiology, Department of Internal Medicine,  
Heart Center, Chonnam National University Hospital, 
Chonnam National University Medical School 
 
Cardiovascular Center & Clinical Research Center,  
Heart Vascular Stroke Institute,  
Samsung Medical Center,  
Sungkyunkwan University School of Medicine 
 
 
 
 
 

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Table of Contents 
1. Title of Study .........................................................................................................................................................................5 
2. Clinical Research Center .................................................................................................................................................5 
3. Principal Investigator, Staff, Co-researchers ............................................................................................................5 
4. Background and Hypothesis ...........................................................................................................................................7 
5. Study Objectives .................................................................................................................................................................8 
6. Research Materials and Indication for Revascularization ....................................................................................9 
7. Study Population .............................................................................................................................................................. 10 
8. Study Period ...................................................................................................................................................................... 10 
9. Eligible criteria, Sample size calculation ................................................................................................................. 10 
10. Methods ............................................................................................................................................................................ 11 
11. Schedule of Assessments and Procedures ......................................................................................................... 13 
12. Measurement of study outcome variables ........................................................................................................... 14 
13. Potential risk and adequacy of protection against risks .................................................................................. 16 
14. Subject withdrawal ........................................................................................................................................................ 17 
15. Violence of study protocol .......................................................................................................................................... 17 
16. Event adjudication and reporting, Data safety and monitoring plan ........................................................... 17 
17. Statistical Consideration and Analysis ................................................................................................................... 19 
18. Care for the safety of the subjects .......................................................................................................................... 20 
19. References ....................................................................................................................................................................... 22 
 
 
 

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Research Summary 
Study title 
Randomized Controlled Trial of Optical Coherence Tomography 
Versus Angiography For Culprit Lesion Revascularization in 
Patients with Acute Myocardial Infarction: Optical 
Coherence 
Tomography Versus Angiography For Culprit Lesion Revascularization in Acute 
Myocardial Infarction Patients (FRAME-AMI3 Trial) 
Principle investigator 
Young Joon Hong, MD, PhD (Chonnam National University) 
Joo-Yong Hahn, MD, PhD (Samsung Medical Center) 
Trial Management 
Seung Hun Lee, MD, PhD (Chonnam National University) 
Joo Myung Lee, MD, MPH, PhD (Samsung Medical Center) 
Executive Committee 
Joo Myung Lee, MD, MPH, PhD (Samsung Medical Center) 
Young Bin Song, MD, PhD (Samsung Medical Center) 
Seung Hun Lee, MD, PhD (Chonnam National University) 
Min Chul Kim, MD, PhD (Chonnam National University) 
Funding agencies 
Abbott Vascular 
Purpose / Objectives 
The aim of the study is to compare clinical outcomes between optical 
coherence 
tomography-guided 
versus 
angiography-guided 
percutaneous coronary intervention (PCI) in patients with acute 
myocardial infarction (AMI). 
Study design 
Prospective, multicenter, open-label, randomized controlled trial to 
compare clinical outcomes between optical coherence tomography 
(OCT)-guided versus angiography-guided PCI in AMI patients 
undergoing PCI. 
Subject enrollment 
1500 Subjects with STEMI undergoing PCI. 
Study Duration  
IRB Approval dates ~ 31.DEC.2028 
Eligible criteria 
1) Inclusion criteria 
① Subject must be at least 19 years of age  
② Acute ST-segment elevation myocardial infarction (STEMI) 
*STEMI: ST-segment elevation ≥0.1 mV in ≥2 contiguous leads 
or documented newly developed left bundle-branch block1 
③ Primary percutaneous coronary intervention (PCI) in < 12 h after the 
onset of symptoms for STEMI patients  
④ Subject is able to verbally confirm understandings of risks, benefits 
and treatment alternatives of receiving invasive physiologic 
evaluation and PCI and he/she or his/her legally authorized 
representative provides written informed consent prior to any study 
related procedure. 
 
2) Exclusion criteria 
① Target lesions not amenable for PCI by operators’ decision 
② Ostial lesions located in left main vessel or right coronary artery (left 
main body or distal bifurcation lesions can be enrolled by operator’s 
discretion)  
③ Creatinine clearance ≤30 ml/min/1.73 m2 and not on dialysis 
(chronic dialysis dependent patients are eligible for enrolment 
regardless of creatinine clearance) 
④ Cardiogenic shock (Killip class IV) at presentation 
⑤ Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, or 
Everolimus 
⑥ Known true anaphylaxis to contrast medium (not allergic reaction but 
anaphylactic shock) 
⑦ Pregnancy or breast feeding 

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⑧ 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) 
⑨ Unwillingness or inability to comply with the procedures described in 
this protocol. 
Follow-up 
After the index procedure, clinical follow-up will occur at 1, 6, 12, 24 
months, and annually thereafter. 
Primary endpoint 
Target Vessel Failure (TVF, a composite of cardiac death, target-vessel 
myocardial 
infarction 
[MI], 
clinically-driven 
target-vessel 
repeat 
revascularization [TVR], definite or probable stent thrombosis) according 
to the Academic Research Consortium (ARC) II-consensus.2 
Secondary endpoint 
① All-cause death 
② Cardiac death 
③ Any MI, defined by Forth Universal definition of MI1 
④ Spontaneous MI, defined by Forth Universal definition of MI1 
⑤ Procedure-related MI, defined by ARC II definition2 
⑥ Any revascularization (clinically-driven or ischemia-driven) 
⑦ Target vessel revascularization 
⑧ Definite or probable stent thrombosis 
⑨ Total procedural time (primary PCI to end of the procedure including 
amount of staged procedure) 
⑩ Total fluoroscopy time (primary PCI to end of the procedure 
including amount of staged procedure) 
⑪ Total amount of contrast use (primary PCI to end of the procedure 
including amount of staged procedure) 
⑫ 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. 
 
 

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1. Title of Study 
Randomized Controlled Trial of Optical Coherence Tomography Versus Angiography For Culprit 
Lesion Revascularization in Patients with Acute Myocardial Infarction 
 
Abbreviation: Optical Coherence Tomography Versus Angiography For Culprit Lesion Revascularization in 
Acute Myocardial Infarction Patients (FRAME-AMI3 Trial) 
 
2. Clinical Research Center 
① Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, 
South Korea 
② Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea 
③ Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 
South Korea 
④ Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, South 
Korea 
⑤ Ewha Womans University Mokdong Hospital, Seoul, South Korea 
⑥ Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea 
⑦ Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea 
⑧ Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, South Korea 
⑨ Ewha Womans University Seoul Hospital, Seoul, South Korea 
⑩ Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea 
⑪ Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, South Korea 
⑫ Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, South Korea 
⑬ Jeju National University Hospital, Jeju National University School of Medicine, Jeju, South Korea 
⑭ Jeonbuk National University Hospital, Jeonju, South Korea 
⑮ Wonkwang University Hospital, Iksan, South Korea 
⑯  Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, 
Jinju, South Korea 
⑰  Daegu Catholic University Medical Center, Daegu, South Korea 
⑱  Dong-A University College of Medicine, Busan, South Korea 
⑲  St. Carollo Hospital, Suncheon, South Korea 
⑳  International St. Mary's Hospital, Catholic Kwandong University, Incheon, South Korea 
㉑  Kyungpook National University Hospital, Kyungpook National University School of Medicine, 
Daegu, South Korea 
 
 
3. Principal Investigator, Staff, Co-researchers 
 
Name 
Center 
Position 
Trial 
Principle 
investigator 
Young Joon Hong 
Chonnam National University Hospital, 
Chonnam National University 
Professor 
Joo-Yong Hahn 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Professor 
Trial 
Management 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
Joo Myung Lee 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Associate 
Professor 

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Co-researchers 
Joo Myung Lee 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Associate 
Professor 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
Young Bin Song 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Professor 
Youngkeun Ahn 
Chonnam National University Hospital, 
Chonnam National University 
Professor 
Min Chul Kim 
Chonnam National University Hospital, 
Chonnam National University 
Associate 
Professor 
Chan Joon Kim 
Uijeongbu St Mary's Hospital, College of 
Medicine, The Catholic University of Korea 
Assistant 
Professor 
Seonghyeon Bu 
Uijeongbu St Mary's Hospital, College of 
Medicine, The Catholic University of Korea 
Assistant 
Professor 
Ung Kim 
Yeungnam University Medical Center, 
Yeungnam University College of Medicine 
Professor 
Sodam Jung 
Ewha Womans University Mokdong Hospital 
Assistant 
Professor 
Eun Seok Shin 
Ulsan University Hospital, University of Ulsan 
College of Medicine 
Professor 
Mi Hee Jang 
Ulsan University Hospital, University of Ulsan 
College of Medicine 
Assistant 
Professor 
Dong Oh Kang 
Korea University Guro Hospital, Korea 
University College of Medicine 
Assistant 
Professor 
Jung Ho Heo 
Kosin University Gospel Hospital, Kosin 
University College of Medicine 
Professor 
Sanghoon Shin 
Ewha Womans University Seoul Hospital 
Associate 
Professor 
Jong-Young Lee 
Kangbuk Samsung Hospital, Sungkyunkwan 
University School of Medicine 
Associate 
Professor 
Weon Kim 
Kyung Hee University Hospital, Kyung Hee 
University School of Medicine 
Professor 
Jong Shin Woo 
Kyung Hee University Hospital, Kyung Hee 
University School of Medicine 
Associate 
Professor 
Wang Soo Lee 
Chung-Ang University College of Medicine, 
Chung-Ang University Hospital 
Professor 
Song-Yi Kim 
Jeju National University Hospital, Jeju 
National University School of Medicine 
Professor 
Joon-Hyouk Choi 
Jeju National University Hospital, Jeju 
National University School of Medicine 
Professor 
Sang-Rok Lee 
Jeonbuk National University Hospital 
Professor 

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Yi Sik Kim 
Jeonbuk National University Hospital 
Professor 
Kyeong Ho Yun 
Wonkwang University Hospital 
Professor 
Jae Young Cho 
Wonkwang University Hospital 
Professor 
Donghyeon Joo 
Wonkwang University Hospital 
Assistant 
Professor 
Jin-Sin Koh 
Gyeongsang National University Hospital, 
Gyeongsang National University School of 
Medicine 
Professor 
Min Gyu Kang 
Gyeongsang National University Hospital, 
Gyeongsang National University School of 
Medicine 
Professor 
Jin Bae Lee 
Daegu Catholic University Medical Center 
Professor 
Kyungil Park 
Dong-A University College of Medicine 
Professor 
Jang Hyun Cho 
St. Carollo Hospital, Suncheon, South Korea 
Professor 
Hyung-Bok Park 
International St. Mary's Hospital, Catholic 
Kwandong University 
Professor 
Nam Kyun Kim 
Kyungpook National University Hospital, 
Kyungpook National University School of 
Medicine 
Associate 
Professor 
Ju Han Kim 
Chonnam National University Hospital, 
Chonnam National University 
Professor 
Doo Sun Sim 
Chonnam National University Hospital, 
Chonnam National University 
Associate 
Professor 
Kyung Hoon Cho 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
Ki Hong Choi 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Assistant 
Professor 
Joon Ho Ahn 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
Dae Young Hyun 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
Yonghwan Lim 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
Seok Oh 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
 
4. Background and Hypothesis 
4.1. Background 
Percutaneous coronary intervention (PCI) is a standard treatment for significantly stenotic lesion of 
coronary arteries, especially in the setting of acute myocardial infarction (AMI) where timely reperfusion 

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is important.3 Traditionally, visual assessment by coronary angiography has been the main tool to 
identify coronary artery disease and guide revascularization.4 However, it is known that angiography 
alone is unable to adequately evaluate significance of stenotic lesion or optimization status of the stent, 
and that angiography suffers from high intra- and interobserver variability.5 Thus, methods for 
intracoronary imaging and/or physiology have been developed to aid these limitations.6 
During the PCI procedure, intravascular imaging devices such as intravascular ultrasound (IVUS) and 
optical coherence tomography (OCT) are useful tools for providing information on lesion characteristics 
and optimal stent implantation with regard to appropriate reference segment, stent expansion, stent 
apposition, and possible acute complications.7 Therefore, intravascular imaging guidance may improve 
clinical outcomes after complex PCI. However, although previous randomized controlled trial and 
registries showed significantly lower rates of major adverse clinical events following IVUS-guided PCI 
compared with angiography-guided PCI,8-13 the randomized controlled trials were limited with small 
sample size and dealt with very selected lesion subsets such as chronic total occlusion (CTO) or long 
lesions. Moreover, although some studies observed similar clinical outcomes between IVUS-guided PCI 
and OCT-guided PCI,14-16 it is uncertain whether OCT-guided PCI improves clinical outcomes compared 
with angiography-guided PCI.  
Currently, randomized controlled trial to support beneficial impact of OCT-guided PCI, especially in 
patients with acute myocardial infarction (AMI) is lacking. One randomized clinical trial in 2016 with 240 
non-ST-elevation myocardial infarction patients have reported higher postprocedural fractional flow 
reserve and similar incidence of major adverse cardiac events with the use of OCT compared to 
angiography alone,17 but this study mostly focused on immediate physiologic findings of OCT-guided 
PCI and only demonstrated clinical outcomes on short-term follow-up. Although the ILUMIEN IV trial 
evaluated efficacy of OCT-guided PCI among high risk patients including lesions were considered to be 
responsible for a recent myocardial infarction, there was no apparent difference in the target-vessel 
failure at 2 years.18 There is no randomized controlled trial that can provide information on its long-term 
clinical impact, and current clinical guidelines puts OCT on Class 2a recommendation as an alternative 
for IVUS, with the exception of ostial left main disease.19,20 
In this regard, randomized controlled trial comparing clinical outcome following PCI in patients with AMI 
where procedural optimization is performed under OCT-guidance or angiography alone would provide 
valuable evidence to enhance prognosis after treatment of AMI. Therefore, FRAME-AMI3 trial has been 
designed to compare clinical outcomes after PCI for infarct-related artery using either OCT-guided or 
angiography-guided strategy. 
 
4.2. Primary Hypothesis 
Optical coherence tomography (OCT)-guided PCI would reduce risk of a target vessel failure (TVF, a 
composite of cardiac death, target-vessel myocardial infarction [MI], clinically-driven target-vessel 
repeat revascularization [TVR], definite or probable stent thrombosis), compared with angiography-
guided PCI in AMI patients undergoing PCI. 
 
5. Study Objectives 
5.1. Primary endpoint 
Target Vessel Failure (TVF, a composite of cardiac death, target-vessel myocardial infarction [MI], 
clinically-driven target-vessel repeat revascularization [TVR], definite or probable stent thrombosis) 
according to the Academic Research Consortium (ARC) II-consensus.2 
 
Definitions of clinical events is attached as Appendix #1. 
 
5.2. Secondary endpoint 
① All-cause death 
② Cardiac death 
③ Any MI, defined by Forth Universal definition of MI1 
④ Spontaneous MI, defined by Forth Universal definition of MI1 
⑤ Procedure-related MI, defined by ARC II definition2 

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⑥ Any revascularization (clinically-driven or ischemia-driven) 
⑦ Target vessel revascularization 
⑧ Definite or probable stent thrombosis 
⑨ Total procedural time (primary PCI to end of the procedure including amount of staged 
procedure) 
⑩ Total fluoroscopy time (primary PCI to end of the procedure including amount of staged 
procedure) 
⑪ Total amount of contrast use (primary PCI to end of the procedure including amount of 
staged procedure) 
⑫ 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. 
 
6. Research Materials and Indication for Revascularization 
1) General principle of procedure for coronary artery lesions 
Complete revascularization during index hospitalization will be recommended. In case of staged 
procedure during the same hospitalization is planned for non-infarct related artery stenosis, following 
the initially allocated strategy would be strongly recommended. Treatment decision regarding non-
infarct related artery will be guided by angiographic stenosis (>70% diameter stenosis by visual 
estimation) or fractional flow reserve (≤0.80), according to operator’s discretion. Use of XienceTM stents 
(everolimus-eluting stent) are recommended.  
 
2) Optical coherence tomography-guided PCI group 
Use of OCT will be allowed at any step of PCI (pre-PCI, during PCI and post-PCI), but OCT after stent 
implantation will be mandatory. In this group, the recommendations for selecting reference segment, 
selecting appropriate size of stent, and stent optimization are as follows. OPTIS imaging catheter 
(Abbott Vascular) will be used for the imaging arm according to MLD MAX algorithm. 
 
 
OCT 
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 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 0.25 mm 
(Ex> mean external elastic membrane reference diameter 3.15 mm  3.0 
mm 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 0.25 mm (Ex> mean distal reference 
lumen diameter 2.55 mm, 2.75 mm stent diameter will be chosen). 
Stent Length 
By measuring distance from distal to proximal reference site 
Stent Optimization 
 Stent Expansion 
Visually assess residual angiographic diameter stenosis <10% “AND”  
① In non-LM lesions: In-stent minimal lumen area (MSA) > 80% of 
the average reference lumen area “OR” >4.5 mm2  
② In LM lesion: MSA>7 mm2 for distal LM and >8 mm2 for proximal 
LM 
 Stent 
Apposition 
No major malapposition (defined as a distance from stent strut to adjacent 
intima ≥400 um and < 1mm length) of the stent over its entire length against 
the vessel wall 
 Edge 
No major edge dissection in the proximal or distal reference segments, 

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Dissection 
defined as 5 mm from the edge of the stent, 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) 
Optimization 
technique of the 
stent 
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 PCI group 
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 10% 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. 
 
4) Adjunctive treatment/procedure 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.19-22 Any adjunctive pharmacologic treatment will be 
left to the operator’s discretion. For example, a loading dose of aspirin (300 mg) and P2Y12 inhibitor – 
clopidogrel (600 mg) or prasugrel (60 mg) or ticagrelor (180 mg) – or use of glycoprotein IIbIIIa inhibitor, 
etc. In case of PCI is performed, dual antiplatelet therapy is recommended according to current 
ACC/AHA/SCAI or ESC/EACTS guidelines and operator’s discretion. In addition, in both groups, the 
use of invasive physiologic assessment at pre- and post-PCI will be left to operator’s discretion. If the 
patient misses scheduled follow-up visits, other effort using telephone, e-mail to communicate with the 
patient will be available. 
 
 
7. Study Population 
1500 Subjects with STEMI undergoing primary PCI with balloon dilatation or stent implantation for 
revascularization will be enrolled in the present trial.  
 
8. Study Period 
IRB Approval dates ~ 31.DEC.2028 
Subject enrollment: IRB approval date ~ DEC. 2026 (roughly 36 months of enrollment) 
Analysis and report: ~31.DEC.2028 
 
9. Eligible criteria, Sample size calculation 
9.1. Eligible Criteria 
1) Inclusion criteria 
① Subject must be at least 19 years of age  
② Acute ST-segment elevation myocardial infarction (STEMI) 
*STEMI: ST-segment elevation ≥0.1 mV in ≥2 contiguous leads or documented newly developed 
left bundle-branch block1 
③ Primary percutaneous coronary intervention (PCI) in < 12 h after the onset of symptoms for STEMI 
patients 
④ Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of 

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receiving invasive physiologic evaluation and PCI and he/she or his/her legally authorized 
representative provides written informed consent prior to any study related procedure. 
 
2) Exclusion criteria 
① Target lesions not amenable for PCI by operators’ decision 
② Ostial lesions located in left main vessel or right coronary artery (left main body or distal bifurcation 
lesions can be enrolled by operator’s discretion)  
③ Creatinine clearance ≤30 ml/min/1.73 m2 and not on dialysis (chronic dialysis dependent patients 
are eligible for enrolment regardless of creatinine clearance) 
④ Cardiogenic shock (Killip class IV) at presentation 
⑤ Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, or Everolimus 
⑥ Known true anaphylaxis to contrast medium (not allergic reaction but anaphylactic shock) 
⑦ Pregnancy or breast feeding 
⑧ 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) 
⑨ Unwillingness or inability to comply with the procedures described in this protocol. 
 
 
9.2. Sample Size Calculation 
Hypothesis: Optical coherence tomography-guided PCI would reduce risk of a target vessel failure 
(TVF, a composite of cardiac death, target-vessel myocardial infarction [MI], clinically-driven target-
vessel repeat revascularization [TVR], definite or probable stent thrombosis), compared with 
angiography-guided PCI in AMI patients undergoing PCI. 
 
Null hypothesis: Optical coherence tomography-guided PCI would not reduce risk of a target vessel 
failure, compared with angiography-guided PCI in AMI patients undergoing PCI. 
 
Based on the previous studies23-26 which compared Intravascular OCT-guided PCI versus 
angiography-guided PCI in AMI patients, the following assumptions were made. 
 
Primary end point: Time to occurrence of TVF 
 
Expected annual rate of TVF  
Angiography-guidance group (6.0%) vs. OCT-guidance group (4.2%) 
 
Accrual time: 3 years 
 
Total follow-up time: 2~5 years (median 3.5 years, until 2 years after the last patient enrollment) 
 
1:1 Randomization 
 
Drop-out rates: total 4.0% up to 2-year 
 
Based on the above assumption, a total of 1500 patients (750 patients for OCT guidance group and 
750 patients for angiography guidance group) will provide 80% power at a 2-sided alpha of 5%. 
 
9.3. Recruitment 
All consecutive patients with AMI will be screened for enrollment in this study. 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. 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) potential risks and benefits for participation, and (4) contact information for additional 
concerns. Vulnerable subjects are excluded according to the eligible criteria. 
 
10. Methods 
10.1. Study designs 

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Before primary PCI for STEMI, the patients who are eligible for enrollment without any exclusion criteria 
will be randomized 1:1 at the time of enrollment to undergo either OCT-guided strategy or angiography-
guided strategy for PCI.  
After identification of infarct-related artery and lesion, intervention will be done per operator’s decision. 
As recommended, OCT will be allowed to be used at any step of PCI but OCT at post-stent implantation 
will be mandatory in OCT-guided PCI group. According to the pre-defined criteria for stent optimization, 
determination of stent site and length, assessment of stent expansion and apposition state as well as 
identification of acute complication will be done. On the other hand, stent optimization will be done 
based on angiographic findings in angiography-guided PCI group. Optimization criteria should include 
residual diameter stenosis less than 10% by visual estimation and absence of acute complication 
including flow limiting dissection. 
If malapposition, underexpansion or edge dissection of stent is identified in any of the group, adjunctive 
therapy such as post-dilation by balloon or additional stent implantation is mandatorily recommended. 
If any violation of the recommendation of protocols (for example, OCT is not used in the OCT-guided 
PCI group, or OCT is used in the angiography-guided PCI group) occurs according to operator’s 
discretion, the specific reasons will be mandatorily described in electronic case report form. 
Regarding the extent of revascularization, complete revascularization during index hospitalization will 
be recommended based on the current ACC/AHA/SCAI or ESC/EACTS guidelines.19-22. 
Regardless of allocated arms, best available medical treatment will be the performed according to the 
current ACC/AHA/SCAI or ESC/EACTS guidelines. Any adjunctive pharmacologic treatment will be left 
to the operator’s discretion. For example, a loading dose of aspirin (300 mg) and P2Y12 inhibitor – 
clopidogrel (600mg), prasugrel (60 mg bolus) or ticagrelor (180mg) – or use of GPIIbIIIa inhibitor, etc. 
Duration and dosing of dual antiplatelet therapy after initial PCI is recommended as with the current 
guideline. If the patient misses scheduled follow-up visits, other effort using telephone or e-mail to 
communicate with the patient will be available. 
 
10.2. Flow chart 
  

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10.3. Randomization 
Patients will be randomized to either the OCT guidance group or angiography guidance group at the 
time of enrollment with 1:1 ratio. Stratified randomization according to participating center and presence 
of multi-vessel disease will be performed. This process will be done by a web-based randomization 
program, run by an independent organization (S-software, Seoul, Korea). 
 
 
11. Schedule of Assessments and Procedures 
Visit 
Screening 
& 
Baseline 
-30day 
Post-
Procedure 
Follow Up 
1 month 
±14days 
6 month 
±30days 
1 year 
±30days 
2 years 
±30days 
3, 4 ~  
years 
±90days 
SCV 
Medical/Clinical History (age, 
sex, risk factors, clinical dx, 
angina status, cardiac hx) 
× 
 
 
 
 
 
 
 
Informed Consent 
× 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
× 
 
 
 
 
 
 
 
Brief Physical Examination 
× 
 
 
 
 
 
 
 
Vital status 
× 
 
× 
× 
× 
× 
 
 
Weight, height 
× 
 
 
 
 
 
 
 
12 lead ECG1) 
× 
× 
× 
 
 
× 
 
 
Angiogram2) 
× 
× 
 
 
 
 
 
 
Randomization 
× 
 
 
 
 
 
 
 
Quantitative coronary 
angiography2) 
× 
× 
 
 
 
 
 
 
Intravascular imaging3) 
× 
× 
 
 
 
 
 
 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
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Visit 
Screening 
& 
Baseline 
-30day 
Post-
Procedure 
Follow Up 
1 month 
±14days 
6 month 
±30days 
1 year 
±30days 
2 years 
±30days 
3, 4 ~  
years 
±90days 
SCV 
CBC 
× 
 
 
 
 
× 
 
 
Electrolytes, LFT 
× 
 
 
 
 
× 
 
 
Creatinine, BUN 
× 
× 
 
 
 
× 
 
 
Fasting plasma TG, HDL, 
LDL, total cholesterol 
× 
 
× 
× 
× 
× 
 
 
Fasting glucose level 
× 
 
 
 
 
× 
 
 
HbA1C 
× 
 
 
 
 
× 
 
 
Medications4) 
× 
× 
× 
× 
× 
× 
 
 
CK, CK-MB,  
Troponin I or Troponin T5) 
× 
× 
 
 
 
 
 
 
BNP/NT-proBNP 
× 
 
 
 
 
× 
 
 
Clinical event6) 
 
× 
× 
× 
× 
× 
× 
× 
1) Except pre- and post-PCI cardiac biomarkers, lack of blood laboratory tests will not be regarded as 
protocol violation.  
2) Coronary angiograms (with or without coronary physiologic test) will be systematically collected and 
analyzed by quantitative coronary angiography in independent core laboratory in Chonnam National 
University Hospital.  
3) Images will be systematically collected and analyzed in independent core laboratory in Chonnam 
National University Hospital. 
4) Medication profiles include baseline and discharge medications.  
5) Baseline (pre-PCI) and post-PCI cardiac biomarkers (CK, CK-MB, and high sensitive troponin) will 
be mandatorily collected to adjudicate periprocedural MI.  
6) Clinical events including primary and secondary endpoints will be systematically collected. Clinical 
follow-up will occur at 1, 6, 12, 24 months after the procedure, and annually thereafter. Angiographic 
follow-up is not routinely recommended to all participants. Investigator or designee may conduct follow-
up as telephone contacts or office visits. Last follow-up will be finished 24 months after last patient 
enrollment. 
 
12. Measurement of study outcome variables 
12.1. Visit 1 Screening & Baseline(-30day)  
① Informed consent 
Informed consent will be acquired before diagnostic coronary angiography and randomization will be 
performed before or during PCI in patients without exclusion criteria. However, as this study includes 
patients in critical medical conditions who need primary PCI for AMI, in patients presenting with 
conditions that preclude their understanding of the trial process, informed consent will be obtained after 
stabilization by revascularization of target lesion.  
Before any examination, they 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. If possible, verbal consent of patient will be obtained. When 
written consent is obtained from the patient after the procedure, the patient will voluntarily choose to or 
not to participate in this study. After coronary interventions are performed, written consent of patients 
should be obtained at the earliest possible time.  
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.  
 
② Inclusion/Exclusion Criteria 
Refer to ‘Eligible Criteria’ 
 
③ Medical/Clinical History  
Demographic information (age, sex, risk factors, clinical diagnosis, angina status, cardiac history, 
cardiovascular, and cerebral event) will be recorded at Screening & Baseline. 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
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Relevant medical history, including history of current disease, other pertinent cardiac history, and 
information regarding underlying diseases will be recorded at Screening & Baseline 
 
④ Brief Physical Examination, Height and Weight, Vital signs 
Height, weight, blood pressure and pulse will be measured 
 
⑤ 12 lead ECG, Angiogram 
Angiogram will be obtained at Screening & baseline visits. [At the time of the index PCI] ECG at 
follow up visits will only be obtained when clinically indicated such as recurrent chest pain, ischemia, 
or significant arrhythmias, heart failure or other signs or symptoms of clinical instability 
 
⑥ Randomization 
Patients will be randomized to either the OCT-guided strategy or angiography-guided strategy at the 
time of enrollment with 1:1 ratio. Stratified randomization by participating center and presence of ST 
elevation in ECG will be performed. This process will be done by a web-based randomization program, 
run by an independent organization. 
 
⑦ Intravascular imaging/ Quantitative coronary angiography 
The raw data of intravascular imaging measurement data will be analyzed in the Core-Laboratory in 
Chonnam National University Hospital. The post-procedural data will be collected in case PCI is 
performed. Baseline and post-primary PCI for coronary angiography will be collected and undergo 
quantitative coronary angiographic evaluation in the Core-Laboratory in Chonnam National University 
Hospital. 
 
⑧ Clinical Laboratory Measurements 
CBC 
WBC, RBC, Hb, Hct, Platelet count, WBC differential count 
Electrolytes, LFT 
AST, ALT, ALP, T. Bilirubin Na, Ca, P, K, Cl 
Chemistry profile 
Creatinine, BUN, Fasting glucose level, HbA1c, Fasting plasma TG, HDL, 
LDL, Total cholesterol 
Cardiac enzymes 
CK, CK-MB, Troponin I or Troponin T, BNP/NT-proBNP 
 
⑨ 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. 
 
12.2. Visit 2 (Post-Procedure) 
① 12 lead ECG 
ECG at follow up visits will only be obtained when clinically indicated such as recurrent chest pain, 
ischemia, or significant arrhythmias, heart failure or other signs or symptoms of clinical instability 
② Intravascular imaging/ Quantitative coronary angiography 
The raw data of intravascular imaging measurement data will be analyzed in the Core-Laboratory in 
Chonnam National University Hospital. The post-procedural data will be collected in case PCI is 
performed. 
Baseline and post-primary PCI for coronary angiography will be collected and undergo quantitative 
coronary angiographic evaluation in the Core-Laboratory in Chonnam National University Hospital. 
③ Clinical Laboratory Measurements 
Chemistry profile 
Creatinine, BUN 
Cardiac enzymes 
CK, CK-MB, Troponin I or Troponin T 
④ Adverse events/ Serious Adverse Event 
Information regarding occurrence of adverse events (death, MI or repeat 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 (eCRF). 
⑤ Concomitant medication 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
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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. 
 
12.3. Follow-up 
Follow-up will occur at 1, 6, 12 and 24months. Investigator or designee may conduct follow-up as 
office visits. 
① Vital signs 
Blood pressure and pulse will be measured. 
② 12 lead ECG 
ECG at follow up visits will only be obtained when clinically indicated such as recurrent chest pain, 
ischemia, or significant arrhythmias, heart failure or other signs or symptoms of clinical instability. 
③ Clinical Laboratory Measurements 
- Clinical Laboratory Measurements will be done at 24months 
CBC 
WBC, RBC, Hb, Hct, Platelet count, WBC Differential count 
Electrolytes, LFT 
AST, ALT, ALP, Total Bilirubin, Na, Ca, P, K, Cl 
Chemistry profile 
Creatinine, BUN, Fasting glucose level, HbA1C,  
Cardiac enzyme 
NT-proBNP 
- Clinical Laboratory Measurements will be test at 1, 6, 12 and 24months 
Chemistry profile 
Fasting plasma TG, HDL, LDL, Total cholesterol 
④ Concomitant Medication 
⑤ Adverse events/ Serious Adverse Event 
Information regarding occurrence of adverse events (death, MI or repeat 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 (eCRF). 
 
13. Potential risk and adequacy of protection against risks 
Complications of OCT imaging includes coronary dissection, thrombus formation, transient ST-elevation, 
bradycardia, ventricular arrhythmia, coronary spasm, etc. Previous studies reported little to no serious 
adverse events related to OCT, and almost all complications were self-limiting which resolved after 
catheter retrieval.27-29 Therefore, OCT is deemed safe procedure which poses no additional hazard in 
conducting this study.28,29  
Complications caused by angiography itself are commonly shown in complications from insertion of 
guidewire, balloon dilatation or stent insertion, which does not cause additional risks related to 
procedures or devices used in the study.  
Patients are randomized at a 1:1 ratio to two arms, OCT-guided strategy arm and Angiography-
guided strategy arm. The possibility to be assigned to each arm is 50% each.  
Expected adverse events in each arm are as follows: 
1) OCT-guided strategy arm – adverse events related to OCT 
OCT catheter itself is 2.7F thick which can cause damage to a coronary artery when forcefully inserted, 
resulting in complications such as coronary spasm, coronary dissection or perforation. Also the entry of 
OCT catheter could disrupt thrombose or cause blockage of narrow lesion. However, previous studies 
demonstrated rare incidence of adverse events, most of which were self-limiting, and reported no 
significant difference in safety profile compared to intravascular ultrasound (IVUS) or angiography-
guided PCI.27-29  
Of note is the fact that OCT uses contrast injection to acquire imaging, and that OCT-guided PCI uses 
significantly higher volume of contrast compared to IVUS-guided or angiography-guided PCI.15,16 While 
this could pose higher risk of contrast-induced nephropathy, studies report no significant difference in 
the incidence of nephropathy.17,29 
3) Both arms – adverse events related to angiography and PCI 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
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- Complications during procedures 
If coronary angiography is only performed, its death rate is very low, but it will increase with old age, 
significant decrease in heart function, severe heart failure, severe heart valve diseases, serious lesion 
of coronary artery origin, and other critical medical conditions. Other than those, there might be 
complications related to arteries such as myocardial infarction, stroke, and severe bradycardia or 
tachycardia.  
- Complications after procedures 
The most common complications are hematoma in insertion area, bleeding, complications involving 
arteries and veins, and other local complications such as infection. Complications related contrast 
agents are skin rash, urticaria, nausea or vomiting, headache, hypotension, fever, and stiffness. 
Severe complications like anaphylactic shock caused by contrast agent are very rarely shown. 
Conditions like kidney dysfunction, arrhythmia, chest pain and others due to uses of contrast agents 
may occur, which is very unlikely to be observed. 
Methods of safety monitoring will be given at the bottom of this page. 
 
14. Subject withdrawal 
Once enrolled, each Subject should remain in the study until the required follow-up period is completed. 
However, all Subjects have the right to withdraw at any point during the study without penalty or loss of 
benefit. The investigator may discontinue any Subject at any time if medically necessary. 
The following events will result in terminating the patient’s follow-up: 
① Patient voluntary withdrawal 
② Patient withdrawn by investigator as clinically indicated 
If the study treatment(s) or observations are discontinued in any Subject, the reason will be recorded, 
and the data coordinating center must be notified promptly. 
 
15. Violence of study protocol 
Although the strategy of stent selection and optimization during PCI for AMI subjects will be decided by 
randomization process to either OCT-guided strategy or angiography-guided strategy, specific response 
to information acquired through OCT or angiography will be left to operator’s discretion according to the 
clinical situation. However, the followings will be recorded as protocol violation and the reason will be 
recorded and the data coordinating center must be notified promptly. 
① OCT was not used after stent implantation (OCT-guided strategy arm). 
② OCT was used in the angiography-guided PCI group. 
 
16. Event adjudication and reporting, Data safety and monitoring plan 
16.1. Data safety and monitoring plan 
Type of Report 
Prepared by Staffs for: 
Time limit of notification 
Serious adverse event 
IRB 
According to IRB regulation of Site 
DCC/EC/Principle investigator 
DSMB 
Within 48 hours 
Annual progress report 
EC/Principle investigator 
Submitted per 1 year 
Deviations from 
investigational plan 
IRB 
According to IRB regulation of Site 
EC/Principle investigator 
Notify within 7 days. 
Final summary report 
EC/Principle investigator 
Within 1 month 
*DCC: Data Coordinating Center, EC: Executive Committee (Co-researchers) 
 
16.2. Executive Committee 
 
Name 
Center 
Position 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
Page 18 / 29 
 
Chairman 
Young Joon Hong 
Chonnam National University Hospital, 
Chonnam National University 
Professor 
Joo-Yong Hahn 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Professor 
Committee 
members 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
Joo Myung Lee 
Samsung Medical Center, Sungkyunkwan 
University School of Medicine 
Assistant 
Professor 
Young Bin Song 
Chonnam National University Hospital, 
Chonnam National University 
Professor 
Min Chul Kim  
Chonnam National University Hospital, 
Chonnam National University 
Assistant 
Professor 
 
16.3. Serious Adverse Events 
The definition of serious adverse events is in the following paragraph. It must be reported to the 
principal investigator within 48hours after recognition of the event and to the IRB according to 
IRB regulation of site.  
① Results in persistent or significant disability or incapacity (significant, persistent or permanent 
change or disruption in subject’s body function/structure, physical activity or quality of life 
② Requires in-patient hospitalization or prolongs hospitalization 
③ Results in a congenital anomaly/birth defect or, 
④ Life-threatening events or death 
Clinical events include not only TVF, all death, stent thrombosis, stroke, but also other endpoint events. 
Clinical events and safety data will be reported to principal investigator regularly, and examined by staffs 
for subject’s safety throughout the study. 
The coordinating center needs to report progress to Executive committee and principal investigator 
annually. This study will not be stopped early based on efficacy results. 
 
16.4. Event adjudication Committee 
All primary and secondary events will be independently adjudicated by Event Adjudication Committee. 
 
Name 
Center 
Position 
Chairman 
Hyun Kuk Kim 
Chosun University Hospital, Gwangju, 
Korea 
Professor 
Committee 
members 
Sung-Woo Cho  
Inje University Paik Hospital, Ilsan, Korea 
Assistant 
Professor 
Doyeon Hwang 
Seoul National University Hospital, Seoul, 
Korea 
Assistant 
Professor 
 
16.5. Data Safety and Monitoring Board 
All serious adverse events will be reviewed by independent DSMB. 
 
Name 
Center 
Position 
Chairman 
Joon-Hyung Doh 
Inje University Paik Hospital, Ilsan, Korea 
Professor 
Committee 
members 
Seon Woo Kim 
Academic Research Service Headquarter, 
LSK Global PS, Seoul, Korea 
Executive 
ARS Director 
Sang Yeob Lim 
Korea University Ansan Hospital, Ansan, 
Korea 
Professor 
 
16.6. Data safety monitoring plan 
The principal investigator will make the monitoring manager to visit and examine coordinating centers 
regularly. A designated trial monitor will review data not only for completeness, but also for accordance 
of the hospital data and eCRF data. Compliance with the protocol and adverse events will be also 
examined. This trial monitor may inspect all documents and required records that are maintained by the 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
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Investigator/site, including medical records (office, clinic, or hospital) for the subjects in this trial. The 
coordinating centers will permit access to such records. 
 
17. Statistical Consideration and Analysis 
17.1. Analysis Population 
All subjects are to be randomized in a 1:1 fashion to either OCT-guided strategy or Angiography-guided 
strategy group. 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).  
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 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 not used after stent implantation (OCT-guided strategy arm). 
② OCT was used in the angiography-guided PCI group. 
 
Analysis with Per-protocol population will be performed as exploratory and sensitivity analysis for that 
of intention-to-treat population. 
 
17.2. Primary Endpoint Analysis 
Primary endpoints (target vessel failure) will be analyzed firstly on an intention-to-treat basis (all 
subjects analyzed as part of their assigned treatment group), and then, per-protocol basis. The null 
hypothesis will be evaluated with Kaplan-Meier survival with log rank test. All primary and secondary 
endpoints will be analyzed on per-patient basis.  
 
17.3. Secondary Endpoint Analysis 
The individual components of primary composite outcome will be analyzed on an intention-to-treat basis 
and per-protocol basis.  
Other secondary endpoints including all-cause and cardiac death, any myocardial infarction with or 
without periprocedural myocardial infarction and any revascularization, will be analyzed using χ2-test 
and Kaplan-Meier survival with log rank test. Acute success of procedure (device, lesion, and 
procedure), incidence of contrast-induced nephropathy will be analyzed using χ2-test.  
Total amount of contrast use, total procedural time, and total fluoroscopy time will be compared between 
the two groups with independent sample t-test. 
 
17.4. Treatment of Missing Values 
The primary analysis of the study endpoints will not be covariate adjusted. No imputation meth
ods 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 primary endpoint, will be considered to be 
censored in the estimation of Kaplan-Meier event rates. As a secondary analysis, we will also e
xamine the patients who have been lost to follow-up. We will perform a comparison of baseline 
characteristics in patients with vs. without follow up. In addition, a sensitivity analysis will be pe
rformed to assess the impact of these patients on the study outcomes. For patients lost to foll
ow-up, multiple imputation techniques will be used to calculate pooled estimates of the treatme
nt effect and confidence intervals which will then be compared to the primary statistical analysi
s. 
 
17.5. Multivariate Analyses 
Multivariate predictors of all primary and secondary endpoints will be determined using multivariate 
regression models, using either binary or Cox’s proportional hazard method. 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 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 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
Page 20 / 29 
 
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 
Severity of AMI 
Age, years 
Current smoker 
Killip Class 
Gender 
Previous PCI 
 
Diabetes mellitus 
Previous CABG 
 
Hypertension  
Previous MI 
 
Dyslipidemia 
Previous CHF 
 
Peripheral artery disease  
Previous CVA 
 
Chronic kidney disease 
Family history of CAD 
 
 
LV ejection fraction  
 
 
LV dysfunction (LVEF<30%) 
 
Complexity of CAD 
Medication at discharge 
 
Angiographic disease extent 
Aspirin 
 
1VD 
Prasugrel 
 
2VD 
Clopidogrel 
 
3VD 
Statin 
 
No. of treated lesion/patients 
Type B2 or C lesions†  
ACE inhibitor/ Angiotensin-II 
receptor blocker  
 
At least 1 ISR 
At least 1 Bifurcation 
At least 1 Small vessel* 
At least 1 Long lesion** 
Severe calcification 
Beta-blocker 
Calcium-channel blocker 
 
† Type B2 or C lesions according to ACC/AHA classification. 
*small vessel denotes lesion with reference diameter ≤2.75mm 
**long lesion denotes lesion with length ≥20mm 
 
 
17.6. Survival Analyses 
All time-to-event outcomes will be summarized using Kaplan-Meier survival estimates and compared 
between treatment groups using log-rank tests. 
 
17.7. Pre-specified subgroup analysis 
① Pre-specified sub-analysis regarding imaging-related parameters 
 
Comparison of TVF according to optimized versus un-optimized procedure defined by 
prespecified imaging protocols 
 
Prognostic impact of 3 major imaging parameters (stent expansion, stent malapposition, and 
edge dissection) 
② Pre-specified subgroup analysis will be performed in various subgroups  
 
Intended timing of non-infarct related artery (non-IRA) PCI (during primary PCI, staged PCI 
during same hospitalization) 
 
Complete revascularization defined by residual SYNAX of 0 
 
IRA involving LM or LAD vs. non-LM or non-LAD 
 
Sex 
 
Age 
 
Left ventricular ejection fraction  
 
Diabetes mellitus 
 
Type of P2Y12 inhibitor (Clopidogrel, Ticagrelor, Prasugrel) 
 
18. Care for the safety of the subjects 
18.1. 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 

FRAME-AMI3 Trial V1.3_August_2025                                         CONFIDENTIAL 
Page 21 / 29 
 
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. 
 
18.2. Elements of Informed Consent 
This trial will involve patients with AMI who need primary PCI with balloon dilatation or stent implantation 
for revascularization. We anticipate enrolling 1500 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.  
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) potential risks and benefits for participation, and (4) 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. However, as this study includes patients 
in critical medical conditions who need primary percutaneous coronary intervention (PCI) within 12 
hours for STEMI after the onset of symptoms, written consent from legally authorized representatives 
or verbal consent from patients should be obtained in advance. After coronary interventions are 
performed, written consent of patients should be obtained at the earliest possible time.  
The signed informed consent will be kept in the patient’s medical records and a copy given to the patient 
or legally authorized patient representative. All sources of research materials will be in the form of 
medical records, coronary angiograms, electrocardiograms and routine blood work. This material will 
be obtained both for routine medical care as well as for research purposes.  
 
18.3. 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 electronic case report form (eCRF). Patient data will be 
protected by the use of locked cabinets at the Clinical Centers and use of passwords, data encryption 
and secure, limited access storage of electronic data. The explicit issue of privacy and confidentiality is 
outlined in the Informed Consent Form. 
 

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2018;72:2231-2264. doi: 10.1016/j.jacc.2018.08.1038 
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Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel 
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Boersma E, Primary Coronary Angioplasty vs. Thrombolysis G. Does time matter? A pooled 
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Shin DH, Hong SJ, Mintz GS, Kim JS, Kim BK, Ko YG, Choi D, Jang Y, Hong MK. Effects of 
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Haase J, Ozaki Y, Di Mario C, Escaned J, De Feyter P, Roelandt J, Serruys P. Can intracoronary 
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Appendix #1. Definitions of Clinical Events 
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).  
 
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 
Hemorrhagic: A stroke with documentation on imaging (e.g., CT scan or MRI of hemorrhage in the 
cerebral parenchyma, or a subdural or subarachnoid hemorrhage). Evidence of hemorrhagic stroke 
obtained from lumbar puncture, neurosurgery, or autopsy can also confirm the diagnosis. 
Nonhemorrhagic: A focal neurological deficit that results from a thrombus or embolus (and not due to 
hemorrhage) that appears and is still partially evident for more than 24 hours 
Unknown/no imaging performed: if the type of stroke could not be determined by imaging or other 
means (from lumbar puncture, neurosurgery, or autopsy) 
 
Contrast-induced Nephropathy 
contrast-induced nephropathy is defined as an increase in serum creatinine of ≥0.5mg/dL or ≥25% from 
baseline within 48-72 hours after contrast agent exposure. 
 
Death  
Death defined by the Academic Research Consortium II2 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, 

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including those related to concomitant treatment, will be classified as cardiac death.  
Vascular death: Death caused by noncoronary vascular causes, such as cerebrovascular disease, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular diseases.  
Non-cardiovascular death: Any death not covered by the above definitions, such as death caused by 
infection, malignancy, sepsis, pulmonary causes, accident, suicide, or trauma. 
 
Myocardial Infarction (MI)  
The definition of myocardial infarction used in this trial is based on the Academic Research Consortium 
II and Fourth Universal Definition of Myocardial Infarction with modification.1,2  
 
The term acute myocardial infarction (MI) should be used when there is evidence of myocardial necrosis 
in a clinical setting consistent with acute myocardial ischemia. Under these conditions any one of the 
following criteria meets the diagnosis for MI: 
1. 1) Detection of a rise and/or fall of cardiac troponin (cTn) with at least one value above the 99th 
percentile upper reference limit (URL) and with at least one of the following: 
▪ Symptoms of ischemia. 
▪ New or presumed new significant ST-segment–T wave (ST–T) changes or new left bundle branch 
block (LBBB). 
 ▪ Development of pathological Q waves in the ECG. 
 ▪ Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. 
▪ Identification of an intracoronary thrombus by angiography or autopsy. 
 2) For recurrent MI including MI originated from non-culprit lesions in patients with elevated and are 
stable or falling cTn values during the index hospitalization, cTn must rise by >20% and be at least 5 
times the 99th percentile URL. Additionally, new ischemic symptoms of at least 20 minutes and new 
significant ST–T changes or new LBBB are required. These ECG changes must be distinct from the 
original myocardial infarction and not due to the usual ECG evolution of this event.  
2. Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG 
changes or new LBBB, but death occurred before cardiac biomarkers were obtained, or before cardiac 
biomarker values would be increased. 
3. 1) Percutaneous coronary intervention (PCI) related MI is defined by absolute rise in cardiac troponin 
(from baseline) ≥35 times URL plus 1 (or more) of the following criteria: (i) new significant* Q waves or 
equivalent; (ii) flow-limiting angiographic complications; or (iii) new “substantial” loss of myocardium on 
imaging (e.g., echocardiography). 
* Q-wave criteria requires the development of new Q waves ≥40 ms in duration and ≥1 mm deep in voltage in ≥
2 contiguous leads 
2) For procedure-related MI from PCI for non-culprit lesions, 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 need to be 
confirmed. 
 
4. Stent thrombosis associated with MI when detected by coronary angiography or autopsy in the setting 
of myocardial ischemia and with a rise and/or fall of cardiac biomarker values with at least one value 
above the 99th percentile URL. 

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5. Coronary artery bypass grafting (CABG) related MI is arbitrarily defined by elevation of cardiac 
biomarker values (>10 × 99th percentile URL) in patients with normal baseline cTn values (≤99th 
percentile URL). In addition, either (i) new pathological Q waves or new LBBB, or (ii) angiographic 
documented new graft or new native coronary artery occlusion, or (iii) imaging evidence of new loss of 
viable myocardium or new regional wall motion abnormality. 
 
Revascularization  
Revascularization is defined by the Academic Research Consortium II2 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.  
 
[1] 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.  
 
[2] Ischemia driven revascularization is defined as a revascularization procedure with one of the 
followings, 
A positive history of recurrent angina pectoris, presumably related to the target vessel 
Objective signs of ischemia at rest (EKG changes) or during exercise test (or equivalent), presumably 
related to the target vessel 
Abnormal results of any invasive functional diagnostic test (eg, fractional flow reserve) 

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Stent Thrombosis  
Stent thrombosis is defined and discussed by the Academic Research Consortium II2 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.  
 
Timing 
Acute stent thrombosis* 
0-24 hours post stent implantation  
Subacute stent thrombosis*: 
> 24 hours-30 days post stent implantation  
Late stent thrombosis†: 
> 30 days-1-year post stent implantation  
Very late stent thrombosis†: 
> 1-year post stent implantation  
* Acute/subacute can also be replaced by early stent thrombosis. Early stent thrombosis (0-30 days) is 
currently used in the community. 
† Including “primary” as well as “secondary” late stent thrombosis; “secondary” late stent thrombosis is 
a stent thrombosis after a target segment revascularization.  
 
Stent Thrombosis Categories: a) Definite b) Probable, and c) Possible  
 
a) Definite stent thrombosis: Definite stent thrombosis is considered to have occurred by either 
angiographic or pathologic confirmation.  
Angiographic confirmation of stent thrombosis [*The incidental angiographic documentation of stent 
occlusion in the absence of clinical signs or symptoms is not considered a confirmed stent thrombosis 
(silent occlusion).]: The presence of a thrombus [†Intracoronary thrombus] that originates in the stent 
or in the segment 5 mm proximal or distal to the stent and presence of at least 1 of the following 
criteria within a 48-hour time window: 
. Acute onset of ischemic symptoms at rest  
. New ischemic ECG changes that suggest acute ischemia  
. Typical rise and fall in cardiac biomarkers (refer to definition of spontaneous MI)  
. Nonocclusive thrombus: Intracoronary thrombus is defined as a (spheric, ovoid, or irregular) 
noncalcified filling defect or lucency surrounded by contrast material (on 3 sides or within a 
coronary stenosis) seen in multiple projections, or persistence of contrast material within the lumen, 
or a visible embolization of intraluminal material downstream.  
. Occlusive thrombus: TIMI 0 or TIMI 1 intrastent or proximal to a stent up to the most adjacent 
proximal side branch or main branch (if originates from the side branch).  
Pathological confirmation of stent thrombosis: Evidence of recent thrombus within the stent 
determined at autopsy or via examination of tissue retrieved following thrombectomy.  

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b) Probable stent thrombosis: Clinical definition of probable stent thrombosis is considered to have 
occurred after intracoronary stenting in the following cases:  
. Any unexplained death within the first 30 days [‡ For studies with ST-elevation MI population, one 
may consider the exclusion of unexplained death within 30 days as evidence of probable stent 
thrombosis.] 
. Irrespective of the time after the index procedure, any MI that is related to documented acute 
ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis 
and in the absence of any other obvious cause  
c) Possible stent thrombosis: Clinical definition of possible stent thrombosis is considered to have 
occurred with any unexplained death from 30 days after intracoronary stenting until end of trial follow-
up.