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

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ClinicalTrials.gov Identifier: NCT02715518

Recruitment Status : Active, not recruiting

First Posted : March 22, 2016

Last Update Posted : September 8, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

Seoul National University Hospital

Inje University

Keimyung University Dongsan Medical Center

Sejong General Hospital

Wonju Severance Christian Hospital

Chungbuk National University Hospital

Chosun University Hospital

Inha University Hospital

Gyeongsang National University Hospital

KangWon National University Hospital

Incheon St.Mary's Hospital

Uijeongbu St. Mary Hospital

Ajou University School of Medicine

Chonnam National University Hospital

Kosin University Gospel Hospital

Samsung Changwon Hospital

Kangbuk Samsung Hospital

Yeungnam University Hospital

Information provided by (Responsible Party):

Joo-Yong Hahn, Samsung Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acute Myocardial Infarction	Device: PCI using 2nd generation drug-eluting stent	Not Applicable

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1292 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Investigator, Outcomes Assessor)
Masking Description:	Clinical event adjudication and statistical analysis will be blindly performed by independent investigators.
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	August 19, 2016
Actual Primary Completion Date :	June 30, 2022
Estimated Study Completion Date :	December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Genetic and Rare Diseases Information Center resources: Acute Graft Versus Host Disease

U.S. FDA Resources

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures :

Patient-oriented composite outcome [ Time Frame: 24 months ]
a composite of death, myocardial infarction, or repeat revascularization

Secondary Outcome Measures :

All-cause mortality [ Time Frame: 24 months ]
All-cause mortality
Cardiac death [ Time Frame: 24 months ]
Cardiac death
Any myocardial infarction without procedure-related myocardial infarction [ Time Frame: 24 months ]
Any myocardial infarction without procedure-related myocardial infarction
Any myocardial infarction with periprocedural myocardial infarction [ Time Frame: 24 months ]
Any myocardial infarction with periprocedural myocardial infarction
Any revascularization [ Time Frame: 24 months ]
ischemia-driven or all
Infarct-related artery (IRA) repeat revascularization [ Time Frame: 24 months ]
ischemia-driven or all
Non-IRA repeat revascularization [ Time Frame: 24 months ]
ischemia-driven or all
Stent thrombosis [ Time Frame: 24 months ]
ARC-defined definite stent thrombosis
Stroke [ Time Frame: 24 months ]
ischemic and hemorrhagic
Total amount of contrast use [ Time Frame: 1 week ]
From primary PCI to end of the procedure including amount of staged procedure
Incidence of contrast-induced nephropathy [ Time Frame: 3 days ]
defined as an increase in serum creatinine of ≥0.5mg/dL or ≥25% from baseline within 48-72 hours after contrast agent exposure
Seattle Angina Questionnaires [ Time Frame: 12-month ]
Angina severity
Seattle Angina Questionnaires [ Time Frame: 24-month ]
Angina severity
All-cause death and myocardial infarction [ Time Frame: 24-month ]
A composite of all-cause death and any myocardial infarction (MI) according to the ARC consensus
Death, spontaneous myocardial infarction, or repeat revascularization [ Time Frame: 24-month ]
A composite of Death, spontaneous myocardial infarction, or repeat revascularization

Eligibility Criteria

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Ages Eligible for Study:	19 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

(1) Inclusion Criteria

Subject must be at least 19 years of age
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 "
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:
Symptoms of ischaemia.
New or presumed new significant ST-T wave changes
Development of pathological Q waves on electrocardiography (ECG).
Imaging evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality.
Intracoronary thrombus detected on angiography.
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)
Multivessel disease (at least one stenosis of >50% in a non-culprit vessel ≥ 2.0 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.

(2) Exclusion criteria

Severe stenosis with TIMI flow ≤ II of the non-IRA artery
Unprotected left main coronary artery disease (stenosis > 50% by visual estimation)
Non-IRA stenosis not amenable for PCI treatment by operators' decision)
Chronic total occlusion in non-IRA
Cardiogenic shock (Killip class IV) already at presentation or the completion of IRA PCI
Intolerance to Aspirin, Clopidogrel, Plasugrel, Ticagrelor, Heparin, Bivaluridin, or Everolimus, Zotarolimus
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 <1 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
Patients with a history of Coronary Artery Bypass Graft (CABG) or treated with fibrinolytic Therapy
Unwillingness or inability to comply with the procedures described in this protocol.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02715518

Locations

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

Sponsors and Collaborators

Samsung Medical Center