Heart FailurePhase 4TAPERED-HFNCT07513883
The Assessment of Partial Guideline-Directed Medical Therapy Down Titration in Heart Failure in Remission.
A Phase 4 study testing Down-titration and Continuation of guideline-directed heart failure therapy in people with Heart Failure, run by Ziekenhuis Oost-Limburg at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Down-titration and Continuation of guideline-directed heart failure therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteBelgium
- Study dates
- 16 Mar 2026to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
Ziekenhuis Oost-Limburg
Genk, 3600
Marnicq van Es, Medical Doctor, 089804033, marnicq.vanes@zol.be
About this study
Official title: 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.
- Conditions
- Heart Failure
- Being tested
- Down-titration, Continuation of guideline-directed heart failure therapy
- Keywords
- Heart failure in remission, Heart failure improvement, Guideline-recommended medical therapy, Heart failure recovery, Therapy withdrawal, Heart failure treatment
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Down-titrationDrug
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).
Continuation of guideline-directed heart failure therapyDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | 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). Receives: Drug: Continuation of guideline-directed heart failure therapy |
| Intervention | Experimental | 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. Receives: Drug: Down-titration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first occurrence of recurrent adverse remodeling, significant NT-proBNP increase or all-cause mortality.
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.
Measured: From enrollment to 2 year follow-up
Secondary outcomes (3)
Time to first occurrence of cardiovascular mortality or heart failure hospitalizations
Measured: From enrollment to 2 year follow-up
Change in quality of life
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.
Measured: From enrollment to 2 year follow-up
Proportion of patients requiring heart failure therapy re-initiation or intensification for any reason
Measured: From enrollment to 2 year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2026
- Study start16 Mar 2026
- Primary completionSep 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ziekenhuis Oost-Limburg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07513883
- Sponsor's protocol ID
- Z-2025058
- Acronym
- TAPERED-HF
- Status last verified
- Mar 2026
- First submitted
- 20 Mar 2026
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Controlled Clinical Pilot Trial Investigating the Partial Down-titration of Guideline-directed Medical Therapy in Patients With Heart Failure in Remission.
- ClinicalTrials.gov ID
- NCT07513883
- Acronym / sponsor ID
- TAPERED-HF / Z-2025058
- Conditions
- Heart Failure
- Keywords
- Heart failure in remission, Heart failure improvement, Guideline-recommended medical therapy, Heart failure recovery, Therapy withdrawal, Heart failure treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ziekenhuis Oost-LimburgUniversity, hospital or other
- Study start
- 16 Mar 2026 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 7 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Drug: Continuation of guideline-directed heart failure therapyContinuation 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). |
| Intervention | Experimental | Drug: Down-titrationDown-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Down-titrationThe 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). | Drug | Intervention |
| Continuation of guideline-directed heart failure therapyThe 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). | Drug | Control |
Primary outcome
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.
3 secondary outcomes
Time to first occurrence of cardiovascular mortality or heart failure hospitalizations
Time frame: From enrollment to 2 year follow-up
Change in quality of life
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Down-titration and Continuation of guideline-directed heart failure therapy in people with Heart Failure, run by Ziekenhuis Oost-Limburg at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.