Revascularization Versus Medical Treatment in Patients With Ischemic Left Ventricular Dysfunction

Not Applicable

Recruiting

• Conditions: Heart Failure With Reduced Ejection Fraction; Ischemic Cardiomyopathy
• Interventions: Procedure: Percutaneous coronary intervention

• Registration Number: NCT05828719
• Lead Sponsor: Samsung Medical Center

Brief Summary

Randomized trial to compare clinical outcomes between revascularization versus medical treatment alone in patients with ischemic cardiomyopathy and left ventricular dysfunction.

Detailed Description

Ischemic cardiomyopathy, the term used to describe systolic dysfunction due to chronic myocardial ischemia from ischemic heart disease, is the most common form of heart failure. To adapt to this ischemic environment, myocardium is known to undergo downregulation that may revert after adequate perfusion is re-established, a phenomenon known as myocardium hibernation. This phenomenon has been a background for the main concept of management for ischemic cardiomyopathy via revascularization. Indeed, the recent 10-year follow-up reports from STICH trial demonstrated improved long-term clinical outcomes after coronary bypass graft surgery than optimal medical therapy (OMT) in patients with ischemic cardiomyopathy.

Percutaneous coronary intervention (PCI) is another intervention that is commonly used to revascularize significant coronary stenosis. Despite common belief that revascularization by PCI would improve perfusion to ischemic myocardium and improve clinical outcomes, several clinical trials have failed to show beneficial impact of PCI over OMT in stable ischemic heart disease other than symptomatic improvement. Recently published REVIVED trial compared effect of PCI and OMT in ischemic cardiomyopathy patients with left ventricular ejection fraction \< 35% and demonstrable viable myocardial segments, and found no significant difference in clinical outcomes of both groups.

However, whether PCI optimized by additional information can make a difference in this setting remains unanswered. It is known that intravascular imaging and coronary physiologic testing using intravascular ultrasound (IVUS), optical coherence tomography (OCT) or fractional flow reserve (FFR) result in better outcomes compared to conventional angiography alone. IVUS provides anatomical information regarding the lumen, plaque, and plaque characteristics, and can optimize stent placement minimizing stent-related problems and lead to better 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. Unfortunately, proportion of IVUS and FFR use is not disclosed in REVIVED trial, and it is possible there is a room for improvement if the PCI is further guided by these adjunctive diagnostic procedures in regard to the clinical outcomes.

In this regard, it is our hypothesis that PCI guided and optimized by intravascular imaging and FFR-guided strategy would bring additional benefit that may result in significant difference of prognosis for ischemic cardiomyopathy compared to OMT alone. Randomized controlled trial to test this hypothesis would provide valuable evidence to guide treatment strategy for ischemic cardiomyopathy. Therefore, RESTORE-PCI trial has been designed to compare clinical outcomes after state-of-the-art PCI or OMT for ischemic cardiomyopathy.

The aim of the study is to compare clinical outcomes between revascularization versus medical treatment alone in patients with ischemic cardiomyopathy and left ventricular dysfunction. Primary hypothesis is that revascularization guided by invasive physiologic indexes and optimized by intravascular imaging device plus optimal medical treatment (OMT) would reduce risk of primary composite end point (major adverse cardiac events \[MACE\], a composite of death, myocardial infarction (MI), admission for heart failure, or advanced heart failure requiring LVAD or transplantation) than OMT alone in patients with ischemic cardiomyopathy.

Study Timeline

• Study First Submitted: 2023-04-12
• Study First Submitted QC: 2023-04-12
• Study First Posted: 2023-04-25
• Study Start: 2023-06-16
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-28
• Primary Completion: 2028-07-01
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

• Subject must be at least 19 years of age
• Patients with stage C heart failure and left ventricular ejection fraction<40%
• Patients with significant coronary artery stenosis (diameter stenosis>50% with proven inducible myocardial ischemia by invasive physiologic assessment)
• Coronary artery disease is amenable for percutaneous coronary intervention (PCI)
• Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving invasive approach and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.

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Exclusion Criteria

• Myocardial infarction by universal definition within 4 weeks of randomization
• Non-viable myocardium in myocardial viability test (cardiac magnetic resonance, dobutamine-stress echocardiography, delayed single-photon emission computerized tomography, or aneurysmal change in echocardiography)
• Target lesions not amenable for PCI by operators' decision
• Patients who need left ventricular assisted device (LVAD) or heart transplantation at the time of randomization
• 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)
• Unwillingness or inability to comply with the procedures described in this protocol.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Revascularization group	Percutaneous coronary intervention	In the revascularization group, patients will undergo percutaneous coronary intervention (PCI) using standard techniques under current ACC/AHA/SCAI or ESC/EACTS guidelines. In the revascularization group, the procedure must be within 2 weeks of randomization. Revascularization criteria is presented as below. Revascularization indication 1. Diameter stenosis \>90% by visual assessment 2. Functionally significant stenosis (FFR≤0.80 or non-hyperemic pressure ratios≤0.89) 3. Chronic total occlusion with substantial ischemic territory. The below locations will be judged as having substantial ischemic territory. * Left main artery * Proximal to mid left anterior descending artery * Proximal left circumflex artery in left dominant coronary arterial system * Proximal to distal right coronary artery in right dominant coronary arterial system

Primary Outcome Measures

Name	Time	Method
major adverse cardiac events [MACE]	2 years after last patient enrollment	a composite of death, myocardial infarction (MI), admission for heart failure, or advanced heart failure requiring LVAD or transplantation

Secondary Outcome Measures

Name	Time	Method
Cardiac death	2 years after last patient enrollment	Cardiac death
Spontaneous myocardial infarction	2 years after last patient enrollment	Spontaneous myocardial infarction by Forth Universal definition of MI
Stroke	2 years after last patient enrollment	Stroke (ischemic or hemorrhagic)
Clinically-indicated unplanned revascularization	2 years after last patient enrollment	Clinically-indicated unplanned revascularization
NT-proBNP	at 6 month - 1 year follow-up after index procedure	NT-proBNP, pg/mL
All-cause death	2 years after last patient enrollment	All-cause death
Procedure-related myocardial infarction	After index procedure	Procedure-related myocardial infarction by ARC II definition
Admission for heart failure	2 years after last patient enrollment	Admission for acute decompensated heart failure
Any myocardial infarction	2 years after last patient enrollment	Any myocardial infarction by Forth Universal definition of MI
Implantable cardioverter-defibrillator (ICD) or Cardiac resynchronization therapy (CRT-D)	2 years after last patient enrollment	Incidence of Implantable cardioverter-defibrillator (ICD) or Cardiac resynchronization therapy (CRT-D) for documented ventricular tachycardia or ventricular fibrillation (secondary prevention).
Left ventricular ejection fraction	at 6 month - 1 year follow-up after index procedure	Left ventricular ejection fraction by echocardiography
EQ-5D-5L (quality of life)	at 6 month after index procedure	EQ-5D-5L (quality of life)
Advanced heart failure requiring LVAD or transplantation	2 years after last patient enrollment	Advanced heart failure requiring LVAD or transplantation
SAQ (angina severity)	at 6 month after index procedure	SAQ (angina severity)

Trial Locations

Locations (1)

Samsune Medical Center; 🇰🇷 Seoul, Korea, Republic of