The Assessment of Partial Guideline-Directed Medical Therapy Down Titration in Heart Failure in Remission. (TAPERED-HF)

April 1, 2026 updated by: Ziekenhuis Oost-Limburg

A Prospective, Randomized, Controlled Clinical Pilot Trial Investigating the Partial Down-titration of Guideline-directed Medical Therapy in Patients With Heart Failure in Remission.

Heart failure (HF) is a chronic condition that is characterized by a weakened and enlarged heart. It typically causes symptoms such as breathlessness and swelling of the legs, and it is a serious illness that shortens life expectancy. In recent years, new medicines have been developed that can improve heart function and help patients with HF live longer. HF patients with reduced heart function typically are recommended to take four different medicines for the rest of their lives. Some patients respond so well to treatment that their heart function and symptoms appear to recover; this is called HF in remission. While the four standard medicines have proven to increase lifespan in patients with heart failure with reduced heart function, it is not known whether they all need to be continued lifelong after recovery of the heart. Current guidelines recommend treating patients lifelong, yet this is based on limited scientific evidence. Lifelong therapy comes with disadvantages: it carries considerable costs for patients and health care systems, causes potential side effects, and makes it harder for patients to keep up with all their other medications. This study will test whether carefully reducing certain HF medicines is safe compared to continuing them. Patients with heart failure in remission will be randomly assigned to either: (1) continue all standard therapies, or (2) gradually reduce medicines to just two per day under close medical supervision. Patients will followed for two years to see whether their heart function remains stable. This will be measured by looking at echograms of the heart (echocardiograms), blood tests, and whether patients experience serious events such as hospitalizations or death. This study will investigate whether partial therapy discontinuation is safe and feasible.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Genk, Belgium, 3600
        • Recruiting
        • Ziekenhuis Oost-Limburg
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed and dated written informed consent prior to randomization
  • Age ≥ 18 years
  • Prior diagnosis of heart failure with reduced ejection fraction (left ventricular ejection fraction < 40%)
  • Heart failure remission (defined as a quantified improvement in LVEF to ≥50% or described as a "normalized" or "recovered" LVEF on echocardiography or cardiac MRI at least 6 months prior; a normal LVESVi and LVEF during screening; no residual functional limitations caused by heart failure; a NT-proBNP < 250 pg/mL during screening)
  • Treatment with at least three heart failure therapies (ACE inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, or sodium-glucose cotransporter-2 inhibitors), consistent with international heart failure guidelines, at maximally tolerated dose and stable for at least 6 months before screening.

Exclusion Criteria:

  • Severe kidney disease: chronic kidney disease with significant albuminuria, defined as an eGFR (creatinine or cystatin C-based using the 2021 CKD-EPI formula) < 60 mL/min/1,73m2 and a urine-albumine creatinine ratio ≥ 200 mg/g, or requiring dialysis, or a history of kidney transplantation.
  • Recent major cardiovascular events, including acute coronary syndromes, coronary artery bypass surgery, stroke, or TIA, in the 90 days before screening.
  • Uncontrolled hypertension, defined as a systolic blood pressure above 160 mmHg and/or a diastolic blood pressure above 100 mmHg despite three antihypertensive agents, assessed during a 24-hour blood pressure measurement during screening.
  • Atrial fibrillation or atrial flutter with a resting heart rate > 110 beats per minute during screening
  • Suboptimal biventricular pacing in those treated with cardiac synchronization therapy, defined as a biventricular pacing percentage under 98% during screening.
  • Any concomitant current or future class I indication for the use SGLT2i beside heart failure: diabetes mellitus type II with ASCVD, or at least two major risk factors (i.e., obesity, hypertension, smoking, dyslipidemia or albuminuria) during screening.
  • Any sustained ventricular arrhythmias in the six months before screening.
  • Any untreated valvular heart disease of moderate or greater severity during screening.
  • Presence of any other disease with a life expectancy of less than two years.
  • Pregnant or lactating women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Control
Continuation of guideline-recommended medical therapy for heart failure with reduced ejection fraction (e.g., an ACE inhibitor/angiotensin-receptor blocker/angiotensin-receptor and neprilysin inhibitor, SGLT2 inhibitor, beta blocker, and/or mineralocorticoid receptor blocker).
Drug: Continuation of guideline-directed heart failure therapy

The comparator involves the continuation of the maximally tolerated dose of guideline-recommended medical therapy (e.g., ACEi/ARB/ARNI, MRA, SGLT2i, and/or beta blocker) the patient is using at the time of screening.

The formulations per drug class may differ according to treatment regimen at randomization, but may include:

  • ARNI: sacubitril/valsartan (at the maximally tolerated dose, according to the respective drug SmPC)
  • ACE inhibitor: enalapril, lisinopril, ramipril, captopril or trandolapril (at the maximally tolerated dose, according to the respective drug SmPC).
  • ARB: valsartan, losartan or candesartan (at the maximally tolerated dose, according to the respective drug SmPC).
  • Beta blocker: carvedilol, metroprolol, bisoprolol or nebivolol (at the maximally tolerated dose, according to the respective drug SmPC).
  • SGLT2 inhibitor: dapagliflozin or empagliflozin at 10 mg per day.
  • MRA: spironolactone or eplerenone (at the maximally tolerated dose, according to the SmPC).
Experimental: Intervention
Down-titration of guideline-recommended medical therapy for heart failure with reduced ejection fraction to a combination of an ACE inhibitor or angiotensin-receptor blocker and a beta blocker.
Drug: Down-titration

The intervention involves a 3-month therapy down-titration period, during which the SGLT2 inhibitor and minerolocorticoid receptor antagonist are withdrawn, and the angiotensin receptor-neprilysin inhibitor is replaced by an ACE inhibitor or angiotensin receptor blocker.

The drug formulations used per drug class correspond with the ESC guideline recommendations:

  • ACE inhibitor: enalapril, lisinopril, ramipril, captopril or trandolapril (at the maximally tolerated dose, according to the respective drug SmPC).
  • ARB (second line alternative to ACEi): valsartan, losartan or candesartan (at the maximally tolerated dose, according to the respective drug SmPC).
  • Beta blocker: carvedilol, metroprolol, bisoprolol or nebivolol (at the maximally tolerated dose, according to the respective drug SmPC).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to first occurrence of recurrent adverse remodeling, significant NT-proBNP increase or all-cause mortality.
Time Frame: From enrollment to 2 year follow-up
The primary outcome is a composite of (1) adverse remodeling, defined as an LVESVi increase of more than 20% from baseline using echocardiography, (2) a significant biomarker increase, defined as an NT-proBNP increase to more than 500 pg/mL, or (3) all-cause mortality.
From enrollment to 2 year follow-up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to first occurrence of cardiovascular mortality or heart failure hospitalizations
Time Frame: From enrollment to 2 year follow-up
From enrollment to 2 year follow-up
Change in quality of life
Time Frame: From enrollment to 2 year follow-up
Measured as the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score. It provides a 0-100 summary score (higher is better) assessing physical limitations, symptom frequency, social limitations, and quality of life. A 5-point difference is clinically significant, with 75-100 indicating good health.
From enrollment to 2 year follow-up
Proportion of patients requiring heart failure therapy re-initiation or intensification for any reason
Time Frame: From enrollment to 2 year follow-up
From enrollment to 2 year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ziekenhuis Oost-Limburg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 16, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 20, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 7, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 7, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Z-2025058

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure

Clinical Trials on Continuation of guideline-directed heart failure therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings