FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease (FRAME-AMI)

Comparison of Clinical Outcomes Between Fractional Flow Reserve-guided Strategy and Angiography-guided Strategy in Treatment of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction

The aim of the study is to compare clinical outcomes following fractional flow reserve (FFR)-guided versus angiography only guided strategy in treatment of non-infarction related artery (non-IRA) stenosis in patients with acute myocardial infarction (AMI) with multivessel disease

Prospective, open-label, randomized, multicenter trial to test the clinical outcomes following FFR-guided or angiography-guided strategy in treatment of non-IRA stenosis in patients with acute AMI with multivessel disease.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Device: PCI using 2nd generation drug-eluting stent

Detailed Description

The presence of ischemia is a prerequisite for the improvement of clinical outcomes with percutaneous coronary intervention (PCI). It is well-known that the discrepancy exists between angiographic stenosis severity and the presence of myocardial ischemia. This discrepancy cannot completely overcome with even more precise invasive imaging modalities such as intravascular ultrasound or optical coherence tomography.

Currently, fractional flow reserve (FFR) is regarded as a gold-standard invasive method to define lesion-specific ischemia and FFR-guided PCI has been proven to reduce unnecessary revascularization and to enhance patient's clinical outcomes. Therefore, current guidelines recommend FFR measurement for intermediate coronary stenosis when there is no definite evidence of lesion-specific ischemia.

However, previous evidences which well demonstrated the benefit of FFR-guided strategy were mostly generated from non-acute myocardial infarction patients.1, 3-5 Recently FAMOUS-NAMI trial evaluated 176 patients with acute non-ST elevation myocardial infarction (NSTEMI) with multivessel disease, and demonstrated feasibility of FFR measurement in acute NSTEMI patients and also presented that FFR-guided decision making for non-infarct related artery (IRA) stenosis was significantly reduced unnecessary stent implantation without any difference in major adverse cardiovascular events at 1-year as well as medical cost, compared with angiography-only guided decision making process.

Nevertheless, there have been no evidence in clinical setting of acute myocardial infarction (AMI). Since about 30-50% of patients with AMI possess multivessel disease, the ability to accurately assess the functional significance of non-IRA stenoses at the time of initial primary PCI would potentially facilitate revascularization decisions with potential for health and economic benefit. Moreover, avoiding unnecessary stent implantation for non-IRA stenoses in patients with AMI with multivessel disease would reduce the possibility of stent- or procedure related complications, and enhance long-term prognosis of patients.

Therefore, the FRAME-AMI trial will compare clinical outcomes after index primary PCI between FFR-guided strategy versus angiography only-guided strategy for management of non-IRA stenoses in AMI with multivessel disease patients.

• Study Type: Interventional
• Enrollment (Actual): 1292
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

(1) Inclusion Criteria

1. Subject must be at least 19 years of age
2. Acute ST-segment elevation myocardial infarction (STEMI) A. ※ STEMI: "ST-segment elevation ≥0.1 mV in ≥2 contiguous leads B. or documented newly developed left bundle-branch block "

3. Acute non-ST-segment elevation myocardial infarction (NSTEMI)

   A. ※ NSTEMI: NSTEMI is defined as a combination of criteria with mandated elevation of a cardiac biomarker, preferably high-sensitive cardiac troponin with at least one value above 99th percentile of the upper reference limit and at least one of the following:

4. Symptoms of ischaemia.
5. New or presumed new significant ST-T wave changes
6. Development of pathological Q waves on electrocardiography (ECG).
7. Imaging evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality.
8. Intracoronary thrombus detected on angiography.
9. Primary percutaneous coronary intervention (PCI) in < 12 h after the onset of symptoms for STEMI patients (In case of NSTEMI, PCI should be performed within 72 hours of symptom onset)
10. Multivessel disease (at least one stenosis of >50% in a non-culprit vessel ≥ 2.0 mm by visual estimation)
11. 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. Severe stenosis with TIMI flow ≤ II of the non-IRA artery
2. Unprotected left main coronary artery disease (stenosis > 50% by visual estimation)
3. Non-IRA stenosis not amenable for PCI treatment by operators' decision)
4. Chronic total occlusion in non-IRA
5. Cardiogenic shock (Killip class IV) already at presentation or the completion of IRA PCI
6. Intolerance to Aspirin, Clopidogrel, Plasugrel, Ticagrelor, Heparin, Bivaluridin, or Everolimus, Zotarolimus
7. Known true anaphylaxis to contrast medium (not allergic reaction but anaphylactic shock)
8. Pregnancy or breast feeding
9. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
10. Other primary valvular disease with severe degree: severe mitral regurgitation, mitral stenosis, severe aortic regurgitation, or aortic stenosis
11. Patients with a history of Coronary Artery Bypass Graft (CABG) or treated with fibrinolytic Therapy
12. 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: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FFR-guided strategy arm; FFR measurement for non-IRA stenosis (>50% visual estimation) will be performed by continuous infusion of adenosine (140~180ug/kg/min) or intracoronary nicorandil (2mg bolus) injection. The FFR ≤ 0.80 will be targeted for PCI using 2nd generation drug-eluting stent. In case of non-IRA stenosis > 90%, we will judge FFR value of ≤ 0.80. The evaluation of non-IRA stenosis by FFR will be recommended to perform during same intervention with primary PCI for IRA. However, exceptions can be made for complex lesions including ACC/AHA classification B2/C lesion where the operator estimates that the revascularization procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a staged procedure during the same hospitalization.	Device: PCI using 2nd generation drug-eluting stent; Percutaneous coronary intervention (PCI) using 2nd generation drug-eluting stent for non-IRA stenosis will be decided according to the allocated arms.; FFR-guided strategy arm; Angiography-guided strategy arm
Active Comparator: Angiography-guided strategy arm; Non-IRA stenosis with > 50% stenosis will be the target of PCI using 2nd generation drug-eluting stent. As for the angiography-guided strategy arm, PCI for non-IRA stenosis will be recommended during same procedure. However, exceptions can be made for complex lesions including ACC/AHA classification B2/C lesion where the operator estimates that the revascularization procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a staged procedure during the same hospitalization.	Device: PCI using 2nd generation drug-eluting stent; Percutaneous coronary intervention (PCI) using 2nd generation drug-eluting stent for non-IRA stenosis will be decided according to the allocated arms.; FFR-guided strategy arm; Angiography-guided strategy arm

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	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	All-cause mortality	24 months
Cardiac death	Cardiac death	24 months
Any myocardial infarction without procedure-related myocardial infarction	Any myocardial infarction without procedure-related myocardial infarction	24 months
Any myocardial infarction with periprocedural myocardial infarction	Any myocardial infarction with periprocedural myocardial infarction	24 months
Any revascularization	ischemia-driven or all	24 months
Infarct-related artery (IRA) repeat revascularization	ischemia-driven or all	24 months
Non-IRA repeat revascularization	ischemia-driven or all	24 months
Stent thrombosis	ARC-defined definite stent thrombosis	24 months
Stroke	ischemic and hemorrhagic	24 months
Total amount of contrast use	From primary PCI to end of the procedure including amount of staged procedure	1 week
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	3 days
Seattle Angina Questionnaires	Angina severity	12-month
Seattle Angina Questionnaires	Angina severity	24-month
All-cause death and myocardial infarction	A composite of all-cause death and any myocardial infarction (MI) according to the ARC consensus	24-month
Death, spontaneous myocardial infarction, or repeat revascularization	A composite of Death, spontaneous myocardial infarction, or repeat revascularization	24-month

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Chonnam National University Hospital; Seoul National University Hospital; Ajou University School of Medicine; Inje University; Gyeongsang National University Hospital; Yeungnam University Hospital; Kangbuk Samsung Hospital; Keimyung University Dongsan Medical Center; Sejong General Hospital; Wonju Severance Christian Hospital; Chungbuk National University Hospital; Incheon St.Mary's Hospital; Inha University Hospital; KangWon National University Hospital; Kosin University Gospel Hospital; Chosun University Hospital; Uijeongbu St. Mary Hospital; Samsung Changwon Hospital
• Investigators: Principal Investigator: Joo-Yong Hahn, MD, PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Shin D, Rhee TM, Lee SH, Lee JM. Revascularization Strategies in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease: Is FFR-Guided Strategy Still Valuable? Korean Circ J. 2022 Apr;52(4):280-287. doi: 10.4070/kcj.2021.0416.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2016
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimated): March 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: STEMI; Fractional flow reserve; Percutaneous coronary intervention; NSTEMI; Acute myocardial infarction; Acute ST-segment elevation myocardial infarction; Multivessel disease
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: FRAME16453143

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked
• IPD Sharing Time Frame: After reporting of the main results.
• IPD Sharing Access Criteria: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP