IVUS Versus FFR for Non-infarct Related Artery Lesions in Patients With Multivessel Disease and Acute STEMI (FRAME-AMI2)

Randomized Controlled Trial of Intravascular Ultrasound Versus Fractional Flow Reserve for Non-infarct Related Artery Lesions in Patients With Multivessel Disease and Acute STEMI

The aim of the study is to compare clinical outcomes between intravascular ultrasound (IVUS)-guided treatment decision versus fractional flow reserve (FFR)-guided treatment decision for non-infarct related artery stenosis in patients with ST-segment elevation MI (STEMI) and multivessel disease.

Study Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Diagnostic test: FFR-guided PCI group; Diagnostic test: IVUS-guided PCI group

Detailed Description

The treatment of choice of ST-segment elevation myocardial infarction (STEMI) is acute reperfusion therapy, preferably with primary percutaneous coronary intervention (PCI). While need of treating the infarct related artery (IRA) is obvious, need for routine revascularization of non-infarct related artery (non-IRA) has been a topic of debate until recent years. Through a number of observational studies, randomized trials and meta-analyses, the benefits of non-IRA PCI have been continuously implied, and COMPLETE trial with 4041 patients of STEMI and multivessel coronary artery disease in 2019 demonstrated superiority of complete revascularization to culprit-only PCI in terms of cardiovascular death or MI (primary end point) and cardiovascular death, MI, or ischemia-driven revascularization (co-primary end point).8 As such, complete revascularization of a significant non-IRA stenosis is recommended after successful primary PCI in STEMI patients in current clinical guidelines.

Nevertheless, it has been unclear which criteria should be used to decide non-IRA PCI. Although potential significance of non-IRA lesions can be estimated by angiography, the limitation of angiographic visual assessment or quantitative coronary angiography has been well known. Various measurements are used for incremental information in addition to angiographic assessment in guiding PCI - namely, intravascular ultrasound (IVUS) and fractional flow reserve (FFR).

IVUS provides anatomical information regarding the lumen, plaque, and plaque characteristics, and can optimize stent placement minimizing stent-related problems and lead to better clinical outcomes. On the other hand, FFR provides information on amount of ischemia which the stenosis in question is causing, and also improves the quality of PCI which has been demonstrated by multiple previous trials, and current practice guidelines recommend the use of FFR to determine revascularization strategy as Class IA recommendation. Recent trials evaluated comparative prognosis between FFR-guided versus angiograph-guided PCI for non-IRA in patients with acute MI and multivessel disease. FLOWER-MI trial showed comparable clinical outcome between FFR-guided versus angiography-guided PCI for non-IRA in STEMI patients at 1-year follow-up. FRAME-AMI trial showed superiority of FFR-guided PCI over angiography-guided PCI in reducing death, MI, or repeat revascularization during median 3.5 years of follow-up.

Although IVUS and FFR differ in underlying basic concepts, previous studies demonstrated clinical outcomes following treatment decision by IVUS and FFR was similar between the 2 groups. However, these studies mainly evaluated low-risk stable ischemic heart disease patients with intermediate stenosis, and does not reflect population with acute myocardial infarction undergoing complete revascularization. Currently, the data directly comparing the benefit of IVUS and FFR for non-IRA PCI in STEMI is lacking. Considering that coronary atherosclerotic plaque in non-IRA of STEMI patients is associated with significantly higher risk of future clinical events, IVUS would have potential strength of detecting high risk plaque in non-IRA and treatment decision based on plaque characteristics. Conversely, FFR-guided treatment decision for non-IRA would detect functionally significant non-IRA stenosis and treatment decision based on functional significance would reduce unnecessary PCI, as demonstrated by previous trials.

In this regard, randomized controlled trial comparing clinical outcome following non-IRA PCI in STEMI patients with multivessel disease guided by IVUS or FFR would provide valuable evidence to enhance patient's prognosis after treatment of STEMI. Therefore, FRAME-AMI 2 trial is designed to compare clinical outcomes after non-IRA PCI using either IVUS-guided or FFR-guided strategy.

• Study Type: Interventional
• Enrollment (Estimated): 1400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joo Myung Lee, MD, MPH, PhD; Phone Number: 82-2-3410-2575; Email: drone80@hanmail.net
• Study Contact Backup: Name: Joo-Yong Hahn, MD, PhD; Phone Number: 82-2-3410-3419; Email: jooyong.hahn@gmail.com

Study Locations

• Korea, Republic of
  • Gwangju, Korea, Republic of
    • Not yet recruiting
    • Chonnam National University
    • Contact: Seung Hun Lee, MD, PhD; Email: lsh8602@naver.com
    • Sub-Investigator: Seung Hun Lee, MD, PhD
    • Contact: Young Joon Hong, MD, PhD; Email: hyj200@hanmail.net
    • Principal Investigator: Young Joon Hong, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Joo Myung Lee, MD, MPH, PhD; Phone Number: 82-2-3410-2575; Email: drone80@hanmal.net
    • Contact: Joo-Yong Hahn, MD, PhD; Phone Number: 82-2-3410-2575; Email: jooyong.hahn@gmail.com
    • Principal Investigator: Joo-Yong Hahn, MD, PhD
    • Sub-Investigator: Joo Myung Lee, MD, MPH, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject must be at least 19 years of age

• 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

• Successful primary percutaneous coronary intervention (PCI) for IRA in <12 h after the onset of symptoms
• Multivessel disease (at least one stenosis of >50% in a non-IRA ≥2.25 mm by visual estimation)
• 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.

Exclusion Criteria:

• Non-IRA stenosis not amenable for PCI treatment by operators' decision
• Cardiogenic shock (Killip class IV) already at presentation or the completion of IRA PCI
• Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, or Everolimus
• Known true anaphylaxis to contrast medium (not allergic reaction but anaphylactic shock)
• Pregnancy or breast feeding
• 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)
• Other primary valvular disease with severe degree: severe mitral regurgitation, mitral stenosis, severe aortic regurgitation, or aortic stenosis
• Unwillingness or inability to comply with the procedures described in this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fractional flow reserve-guided PCI; FFR measurement for non-IRA stenosis (>50% visual estimation) will be performed by continuous infusion of adenosine (140~180 ug/kg/min) or intracoronary nicorandil (2 mg bolus) injection. The FFR ≤0.80 will be targeted for PCI. In case of non-IRA stenosis >90%, we will judge FFR value of ≤0.80.	Diagnostic test: FFR-guided PCI group; In FFR-guided PCI group, FFR measurement for non-IRA stenosis (>50% visual estimation) will be performed by continuous infusion of adenosine (140~180 ug/kg/min) or intracoronary nicorandil (2 mg bolus) injection. The FFR ≤0.80 will be targeted for PCI. In case of non-IRA stenosis >90%, we will judge FFR value of ≤0.80.
Experimental: Intravascular Ultrasound-guided PCI; In IVUS-guided PCI group, the current trial evaluates clinical outcome following IVUS-guided treatment decision for revascularization of non-IRA stenosis. According to pre-defined criteria, the decision of revascularization will be made. Revascularization criteria in the IVUS-guided PCI group is 1) minimal lumen area (MLA) ≤ 3mm2 or 2) 3mm2 < MLA ≤4mm2 and plaque burden >70%.	Diagnostic test: IVUS-guided PCI group; In IVUS-guided PCI group, the current trial evaluates clinical outcome following IVUS-guided treatment decision for revascularization of non-IRA stenosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Oriented Composite Outcome	a composite of death, myocardial infarction, or repeat revascularization	2 years after last patient enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	All-cause death	2 years after last patient enrollment
Cardiac death	Cardiac death	2 years after last patient enrollment
Spontaneous myocardial infarction	Spontaneous myocardial infarction, defined by Forth Universal definition of myocardial infarction	2 years after last patient enrollment
Procedure-related myocardial infarction	Procedure-related myocardial infarction, defined by ARC II definition	2 years after last patient enrollment
Any revascularization	Any revascularization (clinically-driven or ischemia-driven)	2 years after last patient enrollment
Infarct-related artery revascularization	Infarct-related artery revascularization	2 years after last patient enrollment
Non-Infarct-related artery revascularization	Non-Infarct-related artery revascularization	2 years after last patient enrollment
Definite or probable stent thrombosis	Definite or probable stent thrombosis	2 years after last patient enrollment
Stroke (ischemic or hemorrhagic)	Stroke (ischemic or hemorrhagic)	2 years after last patient enrollment
Total procedural time	Total procedural time (from the end of primary PCI for IRA to the completion of non-IRA PCI including amount of staged procedure)	at least 1 week after index procedure
Total fluoroscopy time	Total fluoroscopy time (from the end of primary PCI for IRA to the completion of non-IRA PCI including amount of staged procedure)	at least 1 week after index procedure
Total amount of contrast use	Total amount of contrast use (from the end of primary PCI for IRA to the completion of non-IRA PCI including amount of staged procedure)	at least 1 week after index procedure
Incidence of contrast-induced nephropathy	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.	at least 1 week after index procedure
A composite of all-cause death or myocardial infarction	A composite of all-cause death or myocardial infarction	2 years after last patient enrollment
A composite of cardiac death or non-procedure-related myocardial infarction	A composite of cardiac death or non-procedure-related myocardial infarction	2 years after last patient enrollment
Angina severity by Seattle Angina Questionnaire	Angina severity by Seattle Angina Questionnaire	At 2 years from index procedure
Quality of life by EQ-5D-5L Questionnaire	Quality of life by EQ-5D-5L Questionnaire	At 2 years from index procedure

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Chonnam National University
• Investigators: Principal Investigator: Young Joon Hong, MD, PhD, Chonnam National University; Principal Investigator: Joo-Yong Hahn, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Fractional flow reserve; intravascular ultrasound; Complete revascularization; Multivessel disease; ST-segment elevation MI
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction
• Other Study ID Numbers: FRAMEAMI119023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of main paper, de-identified data will be shared upon reasonable requests after discussion by Executive Committee.
• IPD Sharing Time Frame: After publication of main paper.
• IPD Sharing Access Criteria: Executive Committee will discuss to share the de-identified data upon reasonable requests.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No