Strategic Comparison Of Ischemia-based Versus Plaque Burden and vulnErability-based Revascularization in High-Risk Coronary Artery Disease Patients

NCT ID: NCT07324720

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1944 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-19
• Study Completion Date: 2033-09-24

Brief Summary

1. Study Purpose This study aims to compare clinical outcomes between two revascularization strategies in patients with high-risk coronary artery disease and 50-90% angiographic stenosis: a plaque burden and vulnerability-based revascularization strategy guided by intravascular imaging versus an ischemia-based revascularization strategy guided by physiologic assessment.

2. Background Percutaneous coronary intervention (PCI), in conjunction with optimal medical therapy, is one of the main therapeutic strategies for improving outcomes in patients with CAD. To enhance the results of PCI, various diagnostic and adjunctive techniques have been developed-most notably, invasive physiologic assessment and intravascular imaging (IVI). Invasive physiologic indices such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are recognized as the most accurate methods to determine vessel-level myocardial ischemia, and current guidelines recommend PCI based on these physiological measurements. Recently, angiography-derived FFR has also been developed, allowing ischemia assessment without pressure wire measurement, and has been endorsed as a useful tool for guiding PCI decisions. Intravascular imaging, on the other hand, provides detailed anatomical insights into atherosclerotic plaque morphology and plays a critical role in achieving procedural optimization. Current guidelines recommend the use of IVI, particularly in the treatment of complex lesions. While most previous IVI studies have focused on procedural optimization, more recent investigations have begun to explore the use of IVI for PCI decision-making itself. Emerging data suggest that revascularization decisions based on quantitative and qualitative plaque assessment using IVI are non-inferior to those based on invasive physiologic testing. Moreover, IVI enables the identification of vulnerable plaques, and studies indicate that intervening on such lesions may improve outcomes.

At present, a physiology-guided decision-making strategy combined with IVI-guided optimization is considered the best evidence-based approach according to guidelines. However, recent data showing the potential advantages of IVI-guided decision-making and IVI-guided optimization-particularly in high-risk, complex patients and in those with vulnerable plaque morphology-suggest that IVI-based strategies may offer greater clinical benefit in such populations. Despite this, a comprehensive strategy that integrates both quantitative (plaque burden) and qualitative (vulnerability) aspects of plaque evaluation via IVI has yet to be clearly established. Therefore, this study seeks to propose IVI-based quantitative and qualitative criteria for high-risk CAD patients and to compare outcomes between a plaque burden and vulnerability-based revascularization strategy and the conventional ischemia-based revascularization strategy. For all patients undergoing PCI, IVI-guided optimization will be performed to ensure the highest possible procedural quality in both groups.

3. Study Procedures Patients undergoing coronary angiography for suspected or known CAD will be screened for eligibility. After providing a detailed explanation of the study, written informed consent will be obtained from those deemed appropriate for participation. Following coronary angiography, patients with significant coronary stenosis who meet all inclusion and no exclusion criteria will be enrolled in the study. Eligible participants will then be randomized in a 1:1 ratio to either the plaque burden and vulnerability-based revascularization group or the ischemia-based revascularization group. Stratified randomization will be performed according to participating center and presence or absence of acute coronary syndrome (ACS) to ensure balance between the groups.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Plaque burden and vulnerability-based revascularization

Percutaneous coronary intervention using drug-eluting stent(s) will be performed by IVUS or OCT-guided strategy.

Group Type: EXPERIMENTAL

Plaque burden and vulnerability-based revascularization

Intervention Type: PROCEDURE

For target lesions located in vessels with a reference diameter ≥2.5 mm, quantitative and qualitative plaque assessment will be performed using intravascular imaging. The criteria for revascularization are as follows:

1. When using IVUS:

Revascularization will be considered for lesions with a minimum lumen area (MLA) < 4 mm² if any of the following findings are present:

• Plaque burden > 70%

• Plaque rupture ③ Thrombosis ④ Posterior attenuation without high-intensity echo reflectors (involving > 180° of the vessel circumference) ⑤ maxLCBI₄mm > 315 on near-infrared spectroscopy (NIRS)

2. When using OCT:

Revascularization will be considered for lesions with a minimum lumen area (MLA) < 3.5 mm² if any of the following findings are present:

• Area stenosis ≥ 75%

• Plaque rupture

• Presence of a thin fibrous cap < 65 μm ④ Lipid arc > 180° ⑤ Macrophage infiltration

During revascularization, the operator should ensure optimal treatment of the target vessel and lesion, using intravascular

Ischemia-based revascularization

Percutaneous coronary intervention using drug-eluting stent(s) will be performed by FFR, iFR, or angiography-derived FFR-guided strategy.

Group Type: ACTIVE_COMPARATOR

Ischemia-based revascularization

Intervention Type: PROCEDURE

For target lesions located in vessels with a reference diameter ≥2.5 mm, the presence or absence of myocardial ischemia will be evaluated using FFR, iFR, or angiography-derived FFR. The criteria for revascularization are as follows:

1. Lesions with ≥50% diameter stenosis by visual estimation and FFR ≤ 0.80

2. Lesions with ≥50% diameter stenosis by visual estimation and iFR < 0.89

3. Lesions with ≥50% diameter stenosis by visual estimation and angiography-derived FFR ≤ 0.80

During revascularization, the operator should ensure optimal treatment of the target vessel and target lesion, utilizing intravascular imaging modalities such as IVUS or OCT. The criteria for optimal revascularization are as follows, and operators are strongly encouraged to achieve them:

1. For all treated vessels, achieve post-PCI FFR > 0.86, with a minimum threshold of post-PCI FFR > 0.80, to ensure functionally complete revascularization.

2. Achieve post-PCI ΔFFR ([FFR at the stent distal edge] - [FFR at the s

Interventions

Plaque burden and vulnerability-based revascularization

For target lesions located in vessels with a reference diameter ≥2.5 mm, quantitative and qualitative plaque assessment will be performed using intravascular imaging. The criteria for revascularization are as follows:

1. When using IVUS:

Revascularization will be considered for lesions with a minimum lumen area (MLA) < 4 mm² if any of the following findings are present:

• Plaque burden > 70%

• Plaque rupture ③ Thrombosis ④ Posterior attenuation without high-intensity echo reflectors (involving > 180° of the vessel circumference) ⑤ maxLCBI₄mm > 315 on near-infrared spectroscopy (NIRS)

2. When using OCT:

Revascularization will be considered for lesions with a minimum lumen area (MLA) < 3.5 mm² if any of the following findings are present:

• Area stenosis ≥ 75%

• Plaque rupture

• Presence of a thin fibrous cap < 65 μm ④ Lipid arc > 180° ⑤ Macrophage infiltration

During revascularization, the operator should ensure optimal treatment of the target vessel and lesion, using intravascular

Intervention Type: PROCEDURE

Ischemia-based revascularization

For target lesions located in vessels with a reference diameter ≥2.5 mm, the presence or absence of myocardial ischemia will be evaluated using FFR, iFR, or angiography-derived FFR. The criteria for revascularization are as follows:

1. Lesions with ≥50% diameter stenosis by visual estimation and FFR ≤ 0.80

2. Lesions with ≥50% diameter stenosis by visual estimation and iFR < 0.89

3. Lesions with ≥50% diameter stenosis by visual estimation and angiography-derived FFR ≤ 0.80

During revascularization, the operator should ensure optimal treatment of the target vessel and target lesion, utilizing intravascular imaging modalities such as IVUS or OCT. The criteria for optimal revascularization are as follows, and operators are strongly encouraged to achieve them:

1. For all treated vessels, achieve post-PCI FFR > 0.86, with a minimum threshold of post-PCI FFR > 0.80, to ensure functionally complete revascularization.

2. Achieve post-PCI ΔFFR ([FFR at the stent distal edge] - [FFR at the s

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

① Patients aged 19 years or older

② Patients with moderate to severe coronary artery stenosis identified on coronary angiography:

A. Diameter stenosis of 50%-90% by visual estimation B. De novo lesions (newly developed lesions) C. Reference vessel diameter ≥ 2.5 mm by visual estimation

③ Patients with either clinically high-risk features for recurrent ischemic events or complex high-risk lesions identified on angiography:

A. Clinically high-risk features i. Medically treated diabetes mellitus ii. Chronic kidney disease (≥ Stage 3B, eGFR < 45 mL/min/1.73 m²) iii. Acute coronary syndrome (ACS) iv. Previous myocardial infarction (MI)

B. Complex high-risk lesions i. True bifurcation lesions ii. Calcified lesions (moderate to severe calcification on angiography) iii. Diffuse long lesions (≥ 30 mm in length) iv. Multivessel disease v. Multiple lesions (≥ 3 lesions)

④ Patients who can verbally demonstrate an understanding of the risks, benefits, and alternative treatments of invasive physiologic or imaging assessment and PCI

⑤ Patients who agree to the study protocol and clinical follow-up plan, voluntarily decide to participate, and provide written informed consent to participate in this clinical trial

Exclusion Criteria

• Hypersensitivity or contraindication to any of the following medications: heparin, aspirin, clopidogrel, prasugrel, ticagrelor, adenosine, or nicorandil

• Hemodynamic instability requiring mechanical circulatory support (ECMO or IABP)

• Moderate or severe stenosis of the left main coronary artery (diameter stenosis > 50%)

• History of coronary artery bypass grafting (CABG)

• Severe asthma or severe chronic obstructive pulmonary disease (COPD) ⑥ Active bleeding

⑦ Major gastrointestinal or genitourinary bleeding within the previous 3 months

⑧ Bleeding diathesis or known coagulopathy, including a history of heparin-induced thrombocytopenia (HIT)

⑨ Life expectancy < 2 years due to non-cardiovascular comorbidities

⑩ Inability to provide signed informed consent

⑪ Any condition deemed by the investigator to make the patient unsuitable for this clinical trial or likely to increase study-related risks

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biotronik Korea Co., Ltd

INDUSTRY

Sponsor Role: collaborator

COBEMD

UNKNOWN

Sponsor Role: collaborator

Bon-Kwon Koo

OTHER

Sponsor Role: lead

Responsible Party

Bon-Kwon Koo

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Central Contacts

Bon-Kwon Koo, MD., PhD.

Role: CONTACT

bkkoo@snu.ac.kr

82-2-2072-7433

Doyeon Hwang, MD

Role: CONTACT

cardiol.intv@gmail.com

821074462779

Other Identifiers

2508-177-1673

Identifier Type: -

Identifier Source: org_study_id