Stopping aldosterone-blocker (MRA) medicine in stable heart failure with improved ejection fraction

Simplification of Treatment by Withdrawal of Medications in Stable Heart Failure With Improved Left Ventricular Ejection Fraction

This trial will test whether stopping mineralocorticoid receptor antagonists (MRAs) is safe for people with stable heart failure whose ejection fraction has improved.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital de Clinicas de Porto Alegre (other)
• Locations: 1 site (Porto Alegre, Rio Grande do Sul)
• Trial ID: NCT07489547 on ClinicalTrials.gov

What this trial studies

Adults with heart failure who previously had reduced ejection fraction but now have an improved LVEF will be randomized to either stop their MRA (placebo) or continue it and followed for 24 weeks. Visitors include scheduled clinic visits with echocardiography to measure LVEF and blood draws for NT-proBNP at each visit, plus one sample for genetic analysis. The main outcomes are a drop in LVEF of more than 10% to below 40% and a relative rise in NT-proBNP of more than 50% above age-adjusted thresholds. The design tests whether MRA withdrawal can be performed without clinical or biomarker signs of heart-failure relapse in a selected, stable population.

Who should consider this trial

Good fit: Ideal candidates are clinically stable adults with prior HFrEF who now have LVEF ≥40 with a sustained absolute improvement >10%, have been on MRAs and an ACE inhibitor/ARB/ARNI for at least 12 months, are NYHA class I–II, and have low age-adjusted natriuretic peptide levels.

Not a fit: Patients who are recently unstable, have persistent elevated BNP/NT-proBNP, LVEF under 40, abnormal left-ventricular dimensions, or require frequent diuretic increases are unlikely to benefit from MRA withdrawal.

Why it matters

Potential benefit: If successful, some patients with recovered ejection fraction could safely stop MRAs and reduce their medication burden and side effects while keeping good heart function.

How similar studies have performed: Prior withdrawal research in recovered cardiomyopathy (for example TRED-HF) showed a substantial relapse rate after stopping heart-failure therapies, so targeted MRA-only withdrawal is relatively novel and needs testing.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of heart failure (HF) and use of MRAs and an ACE inhibitor/ARB/ARNI for at least 12 months
* Left ventricular ejection fraction (LVEF) ≥40%, improved from a prior value ≤35%, with a sustained absolute increase \>10%
* Left ventricular end-diastolic diameter within normal limits according to predefined criteria (≤59 mm for men and ≤53 mm for women)
* NYHA functional class I or II
* BNP levels \<100 pg/mL, or NT-proBNP levels within age-adjusted thresholds: ≥450 pg/mL for individuals \<50 years, ≥900 pg/mL for those 50-75 years, and ≥1800 pg/mL for individuals \>75 years
* In cases of atrial fibrillation, NT-proBNP thresholds should be doubled
* Clinical stability defined as no hospitalizations or need for increased diuretic therapy due to congestion within the previous 12 months
* Optimized heart failure medications with no modifications for at least 3 months
* Maximum allowed dose of furosemide of 80 mg/day
* Acceptable etiologies: HF following cardiac resynchronization therapy (CRT); non-ischemic HF after myocarditis; non-ischemic HF due to tachycardiomyopathy; non-ischemic HF due to alcoholic cardiomyopathy; non-ischemic HF due to cardiotoxicity; non-ischemic HF due to peripartum cardiomyopathy; non-ischemic HF after correction or intervention for valvular disease; ischemic HF after revascularization

Exclusion Criteria:

* Acute coronary syndrome within the past 12 months
* Arrhythmia requiring therapy within the past 12 months
* Syncope or appropriate device therapy (if ICD present) within the past 12 months
* Uncorrected moderate to severe valvular disease
* Severe unrevascularized coronary artery disease, defined as \>50% stenosis of the left main coronary artery (LMCA) or \>70% stenosis of the left anterior descending artery (LAD), circumflex artery (LCx), or right coronary artery (RCA)

Where this trial is running

Porto Alegre, Rio Grande do Sul

• Hospital de Clínicas de Porto Alegre — Porto Alegre, Rio Grande do Sul, Brazil (RECRUITING)

Study contacts

• Principal investigator: Luis E. Rohde, Full Professor — Hospital de Clínicas de Porto Alegre
• Study coordinator: Lucas C Petersen, Dr

Conditions: Heart Failure