Medication Withdrawal in Stable HF With Improved LVEF

NCT07489547 | Recruiting Phase 2

• 1 other identifier: 2024-0387
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety and feasibility of withdrawing mineralocorticoid antagonists (MRA) in patients with stable heart failure with improved left ventricular ejection fraction (HFimpEF). The main questions it aims to answer are: Does withdrawal of MRAs lead to a reduction in left ventricular ejection fraction greater than 10%, resulting in a final LVEF below 40%? Does withdrawal of MRAs cause a relative increase in NT-proBNP levels greater than 50% above age-adjusted thresholds? Researchers will compare MRAs withdrawal (placebo) with continuation of therapy to determine whether medication withdrawal can be performed safely without worsening heart failure status. Participants will: Attend scheduled clinical visits over a 24-week follow-up period; Undergo echocardiographic evaluation of left ventricular ejection fraction before study visits; Provide blood samples for NT-proBNP measurement at each visit; Provide one blood sample for genetic analysis of polymorphisms related to the renin-angiotensin-aldosterone system; Receive either continued MRA therapy or placebo as part of a double-blind randomized design; Be monitored for clinical stability, symptoms of heart failure, and potential adverse events during follow-up.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (2)

• Change in Left Ventricular Ejection Fraction

  Decrease from baseline in left ventricular ejection fraction (LVEF) of greater than 10%, resulting in a final LVEF below 40%.

  6 months

• Change in NT-proBNP Levels

  Increase from baseline in NT-proBNP levels of greater than 50%, with age-specific cut-off values: 450 pg/mL for participants younger than 50 years, 900 pg/mL for those between 50 and 75 years, and 1800 pg/mL for participants older than 75 years.

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

A placebo is an inactive substance that has no therapeutic effect.

Drug: Discontinuation of MRAs

Continue MRAs

ACTIVE COMPARATOR

Drug: Continue MRAs

Interventions

Discontinuation of MRAs DRUG

Participants assigned to the intervention group will undergo discontinuation of MRAs as part of a treatment simplification strategy in patients with stable heart failure with improved left ventricular ejection fraction. All other guideline-directed medical therapies will be maintained according to the treating physician's judgment. Participants will be clinically monitored during follow-up to assess stability, potential recurrence of heart failure symptoms, and other clinical outcomes after withdrawal of MRAs.

Placebo

Continue MRAs DRUG

Participants assigned to the control group will continue MRAs as part of their guideline-directed medical therapy for heart failure with improved left ventricular ejection fraction. All other heart failure medications will be maintained according to standard clinical practice and the treating physician's judgment. Participants will be clinically monitored during follow-up to assess clinical stability, heart failure symptoms, and other relevant outcomes.

Continue MRAs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

RECRUITING

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Luis E. Rohde, Full Professor

  Hospital de Clínicas de Porto Alegre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lucas C Petersen, Dr

CONTACT

555196950660; lpetersen@hcpa.edu.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 24, 2026
• Study Start: March 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)