PCI With Guideline-Directed Medical Therapy for HFpEF Patients With Ischemic Cardiomyopathy (PCI-GULF)

Nanjing Medical University

Status: Not yet enrolling

Conditions: Coronary Artery Disease; Heart Failure With Reduced Ejection Fraction

Treatments: Drug: Guideline-directed medical therapy; Procedure: Percutaneous coronary intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT07349979

BE2019615 (Other Grant/Funding Number)

KY20251223-09

Details and patient eligibility

About

To evaluate whether percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) combined with guideline-directed medical therapy (GDMT), compared to GDMT alone, reduces the time to first occurrence of major adverse cardiovascular events (MACE) through 12 months in patients with ischemic cardiomyopathy and a left-ventricular ejection fraction (LVEF) ≤40%. MACE is a composite of cardiovascular [CV] death, spontaneous myocardial infarction (MI), any unplanned revascularization, heart failure (HF)-related rehospitalization, heart transplantation, requirement of device implantation (e.g., valvular treatment, pacemaker, or left ventricular assist device [LVAD]), or requirement of intravenous medications due to worsening heart failure in outpatients.

Full description

A prospective, randomized, controlled, open-label, multicenter trial with blinded endpoint adjudication (PROBE design).

A total of 654 patients with LVEF ≤40%, angiographically proven coronary artery disease (CAD) amenable to PCI, and symptomatic heart failure (NYHA Class II-IV) on stable GDMT will be assigned at a 1:1 ratio to:

Experimental Group: PCI with contemporary DES plus GDMT

Control Group: GDMT only

Angiographically proven CAD is defined as a visually estimated diameter stenosis (DS) <90% with a quantitative flow ratio (QFR) ≤0.80 in a major epicardial vessel (reference vessel diameter [RVD] ≥2.5 mm), which is deemed amenable to successful PCI with DES by an interventional cardiologist.

Complete revascularization of all angiographically significant lesions (visually estimated stenosis ≥70% in vessels with RVD ≥2.5 mm) is encouraged, to be performed either during the index procedure or within a staged procedure within 30 days.

Both arms receive optimized GDMT according to current guidelines. Given the nature of the intervention (PCI vs. no PCI), treating physicians and patients cannot be blinded. To minimize bias, a PROBE design is employed with a blinded independent Clinical Events Committee (CEC), blinded core laboratories, and blinded statisticians. The catheterization laboratory team is unblinded but not involved in follow-up decisions or endpoint assessments.

Clinic/telephone follow-up is conducted at 30 days and 3, 6, 9, and 12 months, with annual passive follow-up to 24 months.

Enrollment: 654 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Both male and female subjects aged ≥18 years at screening.
• Documented LVEF ≤40% assessed by echocardiography, or cardiac magnetic resonance imaging (CMR), or ventriculography within 90 days prior to randomization.
• Symptomatic heart failure (NYHA Functional Class II, III, or ambulatory class IV)
• Angiographically proven CAD with at least one lesion (50~89% stenosis by visual estimate in a major epicardial vessel ≥2.5mm in diameter, or ≥50% left main stenosis, both requiring a QFR≤0.8) considered amenable to PCI with DES by an interventional cardiologist.
• On stable, optimally titrated GDMT for at least 2 weeks prior to randomization, as tolerated. This includes, at a minimum, a beta-blocker and a renin-angiotensin-aldosterone system inhibitor (ACEi/ARB/ARNI) at maximal tolerated doses.
• The subject, or their legal guardian, has a clear understanding of the trial's design and procedures, provides written informed consent, and able to comply with follow-up.

Exclusion criteria

• Acute coronary syndrome (ACS) within 30 days requiring urgent/emergent revascularization.
• Non-cardiac life expectancy <1 year at screening (e.g., malignancy, advanced liver disease).
• Coronary anatomy unsuitable for PCI or requiring urgent surgical revascularization (e.g., diameter stenosis ≥90%, diameter stenosis <90% but QFR>0.8, complex multi-vessel disease deemed better suited for coronary artery bypass grafting [CABG] by Heart Team).
• Prior CABG.
• HF due to specific cardiomyopathies, including restrictive/infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, severe valvular stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).
• Contraindication to GDMT medications, dual antiplatelet therapy, or iodinated contrast.
• Pregnancy, lactation, or women of childbearing potential not using effective contraception. A negative urine pregnancy test is required at each visit for women of childbearing potential.
• Participation in another investigational trial that may interfere with the PCI and GDMT as specified in this protocol.
• Any other circumstances that the investigator deems inappropriate for participation, including but not limited to conditions that may jeopardize patient safety, confound data interpretation, or patients unlikely to comply with study procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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654 participants in 2 patient groups

PCI with contemporary DES + GDMT

Experimental group

Description:

PCI will be performed according to standard techniques. Use of a contemporary, FDA/CE-approved drug-eluting stent is mandatory. Complete revascularization of all angiographically significant lesions (visually estimated stenosis \<90% in vessels with RVD ≥2.5 mm and QFR ≤0.80) is encouraged, to be performed either during the index procedure or within a staged procedure within 30 days. Post-PCI, dual antiplatelet therapy (DAPT) with aspirin (75-100 mg daily) and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel per operator choice) will be prescribed for a minimum of 6-12 months, after which single antiplatelet therapy continues indefinitely. All subjects receive evidence-based GDMT per guidelines throughout the study.

Treatment:

Procedure: Percutaneous coronary intervention

Drug: Guideline-directed medical therapy

GDMT only

Active Comparator group

Description:

The control group will receive GDMT; this is approved treatments for preventing HF that could be utilised as a comparator. All patients will be treated according to local guidelines on standard of care treatment for patients with HFrEF and post PCI, focusing on treatment of HF symptoms (e.g. diuretics) and comorbidities (including treatment for high blood pressure, ischaemic heart disease).

Treatment:

Drug: Guideline-directed medical therapy