Revascularization Versus Medical Treatment in Patients With Ischemic Left Ventricular Dysfunction

Heart Failure With Reduced Ejection Fraction Clinical Trial

— RESTORE-PCI  

Official title:

Randomized Controlled Trial of Revascularization Versus Medical Treatment on Clinical Outcomes in Patients With Reduced Left Ventricular Function

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05828719
• Other study ID #: RESTORE119023
• Status: Recruiting
• Phase: N/A
• Start date: June 16, 2023
• Est. completion date: December 31, 2030

Study information

• Verified date: July 2023
• Source: Samsung Medical Center
• Contact: Young Bin Song, MD, PhD
• Phone: 82-2-3410-6653
• Email: youngbien.song[@]samsung.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: December 31, 2030
• Est. primary completion date: July 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Heart Failure With Reduced Ejection Fraction
• Ischemia
• Ischemic Cardiomyopathy

Intervention

Procedure:
• Percutaneous coronary intervention
Revascularization indication Diameter stenosis >90% by visual assessment Functionally significant stenosis (FFR=0.80 or non-hyperemic pressure ratios=0.89) 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

Locations

Country	Name	City	State
Korea, Republic of	Samsune Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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