Clinical trial NCT02715518: FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myocardial Infarction
Keywords: Acute ST-segment elevation myocardial infarction
Acute myocardial infarction
Fractional flow reserve
Percutaneous coronary intervention
Multivessel disease
STEMI
NSTEMI
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Seoul National University Hospital
name: Inje University
name: Keimyung University Dongsan Medical Center
name: Sejong General Hospital
name: Wonju Severance Christian Hospital
name: Chungbuk National University Hospital
name: Chosun University Hospital
name: Inha University Hospital
name: Gyeongsang National University Hospital
name: KangWon National University Hospital
name: Incheon St.Mary's Hospital
name: Uijeongbu St. Mary Hospital
name: Ajou University School of Medicine
name: Chonnam National University Hospital
name: Kosin University Gospel Hospital
name: Samsung Changwon Hospital
name: Kangbuk Samsung Hospital
name: Yeungnam University Hospital
First posted: 2016-03-22
Enrollment: 1292
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: (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.

Primary outcomes:
measure: Patient-oriented composite outcome
timeFrame: 24 months
Secondary outcomes:
measure: All-cause mortality
timeFrame: 24 months
measure: Cardiac death
timeFrame: 24 months
measure: Any myocardial infarction without procedure-related myocardial infarction
timeFrame: 24 months
measure: Any myocardial infarction with periprocedural myocardial infarction
timeFrame: 24 months
measure: Any revascularization
timeFrame: 24 months
measure: Infarct-related artery (IRA) repeat revascularization
timeFrame: 24 months
measure: Non-IRA repeat revascularization
timeFrame: 24 months
measure: Stent thrombosis
timeFrame: 24 months
measure: Stroke
timeFrame: 24 months
measure: Total amount of contrast use
timeFrame: 1 week
measure: Incidence of contrast-induced nephropathy
timeFrame: 3 days
measure: Seattle Angina Questionnaires
timeFrame: 12-month
measure: Seattle Angina Questionnaires
timeFrame: 24-month
measure: All-cause death and myocardial infarction
timeFrame: 24-month
measure: Death, spontaneous myocardial infarction, or repeat revascularization
timeFrame: 24-month
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Joo-Yong Hahn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.