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

Sponsor
Kyungsub Song
Study ID
NCT07631156
Phase
PHASE4
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
19 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Stepwise Withdrawal of ARNI and SGLT2i — DRUG
    Sequential discontinuation of angiotensin receptor-neprilysin inhibitor (ARNI; e.g., sacubitril/valsartan) and sodium-glucose cotransporter-2 inhibitor (SGLT2i; e.g., dapagliflozin or empagliflozin). ARNI is discontinued first; after a 1-month observation with echocardiographic and biomarker assessment, SGLT2i is discontinued if no signs of deterioration are observed. Concomitant MRA and beta-blocker therapy is continued.
  • Continued Guideline-Directed Medical Therapy — DRUG
    Continuation of currently prescribed ARNI and SGLT2i, together with any concomitant MRA and beta-blocker, at the doses being received at enrollment, per current guideline-directed medical therapy.

Study Details

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.

Key Dates

First listed
Jun 5, 2026
Start date
Aug 12, 2026
Status verified
Aug 2026
Primary completion
Jun 30, 2029
Completion
Dec 30, 2029

Study Design

Enrollment
80 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Stepwise Withdrawal
    Stepwise discontinuation of ARNI followed by SGLT2i. ARNI is withdrawn first; if no echocardiographic deterioration (LVEF drop \<10 percentage points) and NT-proBNP remains ≤250 ng/L after 1 month, SGLT2i is then withdrawn. MRA and beta-blockers, if previously prescribed, are continued. Intensive echocardiographic monitoring is performed at 1 and 3 months.
  • Active Comparator: Continuation
    Continuation of all current heart-failure medications including ARNI and SGLT2i per guideline-directed medical therapy, with standard follow-up.

Primary Outcome Measure

Change in Left Ventricular Ejection Fraction (LVEF) at 12 Months [ Time Frame: Baseline to 12 months ]

Central Contacts

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