Clinical trial NCT05812963: IVUS Versus FFR for Non-infarct Related Artery Lesions in Patients With Multivessel Disease and Acute MI
Official title: Randomized Controlled Trial of Intravascular Ultrasound Versus Fractional Flow Reserve for Non-infarct Related Artery Lesions in Patients With Multivessel Disease and Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ST Elevation Myocardial Infarction
Non-ST Elevation Myocardial Infarction
Keywords: ST-segment elevation MI
Fractional flow reserve
intravascular ultrasound
Multivessel disease
Complete revascularization
Non-ST Elevation Myocardial Infarction
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Chonnam National University
First posted: 2023-04-14
Enrollment: 1400
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, randomized controlled non-inferiority trial to compare clinical outcomes between IVUS-guided PCI versus FFR-guided PCI in patients with acute MI and multivessel disease.
Primary purpose: TREATMENT

Brief summary: 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 acute myocardial infarction (AMI) and multivessel disease.

Detailed description: The treatment of choice of acute myocardial infarction (AMI) including ST-segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) is reperfusion therapy, preferably with 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). As such, complete revascularization of a significant non-IRA stenosis is recommended after successful PCI for IRA in patients with AMI and multivessel disease 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 in patients with STEMI or NSTEMI and multivessel disease.

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 AMI 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 AMI 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.

Eligibility criteria: 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 block
* Acute non-ST-segment elevation myocardial infarction (NSTEMI)

  \*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:
  1. Symptoms of ischemia.
  2. New or presumed new significant ST-T wave changes
  3. Development of pathological Q waves on electrocardiography.
  4. Imaging evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality.
  5. Intracoronary thrombus detected on angiography.
* Successful 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-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.

Primary outcomes:
measure: Patient-Oriented Composite Outcome
timeFrame: 2 years after last patient enrollment
Secondary outcomes:
measure: All-cause death
timeFrame: 2 years after last patient enrollment
measure: Cardiac death
timeFrame: 2 years after last patient enrollment
measure: Spontaneous myocardial infarction
timeFrame: 2 years after last patient enrollment
measure: Procedure-related myocardial infarction
timeFrame: 2 years after last patient enrollment
measure: Any revascularization
timeFrame: 2 years after last patient enrollment
measure: Infarct-related artery revascularization
timeFrame: 2 years after last patient enrollment
measure: Non-Infarct-related artery revascularization
timeFrame: 2 years after last patient enrollment
measure: Definite or probable stent thrombosis
timeFrame: 2 years after last patient enrollment
measure: Stroke (ischemic or hemorrhagic)
timeFrame: 2 years after last patient enrollment
measure: Total procedural time
timeFrame: at least 1 week after index procedure
measure: Total fluoroscopy time
timeFrame: at least 1 week after index procedure
measure: Total amount of contrast use
timeFrame: at least 1 week after index procedure
measure: Incidence of contrast-induced nephropathy
timeFrame: at least 1 week after index procedure
measure: A composite of all-cause death or myocardial infarction
timeFrame: 2 years after last patient enrollment
measure: A composite of cardiac death or non-procedure-related myocardial infarction
timeFrame: 2 years after last patient enrollment
measure: Angina severity by Seattle Angina Questionnaire
timeFrame: At 2 years from index procedure
measure: Quality of life by EQ-5D-5L Questionnaire
timeFrame: At 2 years from index procedure
Other outcomes:
Locations:
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University
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
affiliation: Chonnam National University
name: Young Joon Hong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: