STEPwise De-escalation and Optimizing Withdrawal of ARNI and SGLT2i in Normalized Heart Failure

ConditionsHeart Failure With Reduced Ejection Fraction Heart Failure Ventricular Dysfunction, Left

Trial statusNot yet recruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age19+

SponsorKyungsub Song

About this trial

This is a multicenter, randomized, open-label pilot study to evaluate whether stepwise withdrawal of two heart failure medications-angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitor (SGLT2i)-is safe in patients with Heart Failure with improved Ejection Fraction (HFimpEF) whose underlying structural cause (valvular heart disease or ischemic cardiomyopathy) has been completely corrected by surgery or intervention.

Eighty adult patients (40 per arm) whose left ventricular ejection fraction (LVEF) has recovered to 50% or higher and whose NT-proBNP is ≤ 250 ng/L will be randomized 1:1 to either (1) stepwise withdrawal of ARNI followed by SGLT2i over one month under close echocardiographic monitoring, or (2) continuation of their current guideline-directed medical therapy.

The primary outcome is the change in LVEF at 12 months, with non-inferiority of the withdrawal strategy declared if the LVEF decline is within 5 percentage points of the continuation arm. Secondary outcomes include cardiovascular death, heart failure hospitalization, NT-proBNP, quality of life (KCCQ-12), 6-minute walk distance, and adverse events.

Results from this pilot will inform the design and sample size of a subsequent definitive non-inferiority trial and may provide initial evidence to guide deprescribing decisions in clinical practice.

Eligibility criteria

Qualifiers

Adults aged 19 years or older

Prior left ventricular ejection fraction (LVEF) ≤40% before surgery or intervention, with recovery to ≥50% (normalized range) at the time of enrollment

N-terminal pro-B-type natriuretic peptide (NT-proBNP) <250 ng/L

Complete correction of a reversible underlying cause of heart failure: surgical or transcatheter correction of valvular heart disease (mitral regurgitation, aortic stenosis, aortic regurgitation), or percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for ischemic cardiomyopathy

Disqualifiers

Heart failure due to irreversible etiology (e.g., idiopathic dilated cardiomyopathy, toxic cardiomyopathy, genetic cardiomyopathy)

For valvular disease: moderate or greater paravalvular leak, or residual moderate or greater mitral or aortic regurgitation

For ischemic disease: incomplete revascularization or graft occlusion on post-operative coronary CT

Chronic kidney disease stage 4 or higher (eGFR <30 mL/min/1.73 m²)

Trial design

Treatments tested in this trial

Stepwise Withdrawal of ARNI and SGLT2i
Continued Guideline-Directed Medical Therapy

Treatment groups

80 Participants

are divided into 2 treatment groups

Sponsors and collaborators

Kyungsub Song

Lead sponsor

Keimyung University Dongsan Medical Center

Sponsor institution

Seoul National University Bundang Hospital

Collaborator

Ajou University Hospital, Suwon, South Korea

Collaborator

Korea University Anam Hospital

Collaborator

Pusan National University Yangsan Hospital

Collaborator

Source ClinicalTrials.gov