A Phase 3 interventional study of Βeta-Blockers discontinued (with tapering) in Heart Failure, sponsored by Assistance Publique - Hôpitaux de Paris. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-16.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Other
A significant proportion of patients initially diagnosed with heart failure and a reduced left ventricular ejection fraction (LVEF\<40%, HFrEF) presents a substantial improvement in response to evidence-based medical and device therapies. Some of these patients (estimated from 20 to 30%) even display a complete normalization of LVEF (i.e., >50%) and are now recognized as a specific sub-group of patients named Heart Failure with recovered Ejection Fraction (HFrecovEF). Different studies have shown that reverse remodeling with recovery of cardiac function and stabilization of HF symptoms are associated with improved clinical outcomes over the long-term. Whether these patients present a stable remission of HF and could benefit a therapeutic de-escalation is however unclear. Until novel data are provided, medical therapies are thus continued indefinitely in these stable patients with HFrecovEF. Current guidelines for the management of patients with heart failure and a reduced left ventricular ejection fraction recommends a comprehensive therapy, including 5 different therapeutic classes (RAAS blockers (with a preference for ARNi) + Beta-Blockers + SGLT2i + Mineraloreceptors Antagonists + or - Diuretics ).
None of these therapies (with the recent exception of one SGLT2i, i.e. Dapagliflozin) have been tested in patients with HFrecovEF. In addition, it is unclear whether the benefit of older therapies (notably beta-blockers) remains in patients receiving modern comprehensive therapy as newer drugs were tested as add-on therapies. This polypharmacy is lowering adherence and is creating a challenge for physicians and patients. Betablockers are notably associated with frequent side effects, a limited tolerance and a significant reduction of quality of life. Their efficacy on outcomes is not established in patients with normal LVEF. Pilot studies have suggested that Beta-blockers interruption in patients with HF and normal EF was associated with functional improvement.
BONFIRE is a National, Multicenter, Randomised, Open-label, Non-inferiority, Blinded endpoints prospective trial.
The study concerns HF patients with a history of reduced left ventricular ejection fraction (45% or below), but with a normalized LVEF (currently ≥ 50 % on cardiac echography) under an optimal medical therapy as recommended in European guidelines (including beta-blockers, RAAS blockade with ARNI or ACE-I or ARBs, SGLT2 inhibitors, MRA, + or - loop diuretics) AND with no or mild symptoms and no heart failure-related events within the last six months.
The patients fulfilling the full inclusion criteria and without exclusion criteria, that agree to participate the protocol and that have signed the informed consent will be randomized (1:1) into two groups:
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's planned enrollment of 1,300 is above the median of 76 across 4,049 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,592 studies on the registry; 1,033 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
And receiving the guideline-directed optimal medical therapy for at least 12 months (i.e., maximal tolerated dose of SGLT2 inhibitors, and of RAAS blocker (Angiotensin receptor neprilysin inhibitor OR Angiotensin-converting-enzyme-inhibitors OR Angiotensin II receptors blockers), and MRA if tolerated). Loop diuretics use is adjusted to congestive signs according to physicians' decision.
No initiation or major adjustment in heart failure therapies should have occurred during the 3 months prior to study inclusion.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Βeta-Blockers therapy will be discontinued (with tapering) while the remaining guideline-directed optimal medical therapy for HF is maintained
Drug: Βeta-Blockers discontinued (with tapering)
The patients will continue their usual guideline-directed optimal medical therapy for HF, including Βeta-Blockers therapy, without modification.
The experimental group will undergo discontinuation of their beta-blockers treatment during the study period. The tapering of beta-blocker will start on the day after randomisation and is based on a reduction by half-dose every 48 hours (1/2 maximally recommended dose for 48 hours, then ¼ maximally recommended dose for 48 hours) until reaching the minimal recommended dosage (1/8 maximally recommended dose) for 48 hours before complete interruption of treatment. Consequently, the tapering will not be needed in patients already receiving the minimal recommended dosage (i.e., 1/8 dose) at inclusion, and these patients will be instructed to stop taking beta-blockers the day after randomisation.
The primary endpoint of the study will be evaluated with one-year minimum follow-up and will be the composite of:
\- HF relapse (at any time during the study period): * drop in LVEF \>10% (expressed as absolute value) * relative increase in body surface area-indexed left ventricular end-diastolic volume (LVEDVi) \>10% * increase in NT-proBNP \>2x and ≥ 400 ng/L * worsening heart failure symptoms requiring hospitalization or urgent visits or out-of-hospital therapeutic management with diuretics (intra-venous or oral).
Time frame: Within 1 year minimum after randomization
death
All-cause death
Time frame: Within 1 year minimum after randomization
Hospitalisation for CV reason
\- Hospitalisation for CV reason (ACS or need for coronary catheterization +/- revascularization / supra-ventricular arrhythmias / ventricular arrhythmias / Syncope, Pace-Maker implantation / High blood pressure / Stroke).
Time frame: Within 1 year minimum after randomization
HF relapse defined by:
* Reduction in LVEF by more than 10% (absolute value) * A relative increase in LVEDVi by more than 10% * A two-fold rise in baseline NT-pro-BNP concentration and to more than 400 ng/L. * Clinical evidence of heart failure, based on signs and symptoms as adjudicated by the research team. * Hospitalization for worsening HF
Time frame: At each visit from randomization through study completion, an average of 4 years
Death
All-cause Death
Time frame: At each visit from randomization through study completion, an average of 4 years
All individual reasons for Hospitalisation, as follows:
* ACS or need for coronary catheterisation +/-revascularization * Recurrent ischemia * Supra-ventricular or ventricular arrhythmias * Syncope, PM implantation * High blood pressure * Stroke
Time frame: At each visit from randomization through study completion, an average of 4 years
Cardiovascular death
All-cause cardiovascular death
Time frame: At each visit from randomization through study completion, an average of 4 years
Number of patients with reduction in LVEF
Number of patients with reduction in LVEF by more than 10% (absolute value) and to less than 50%.
Time frame: At each visit from randomization through study completion, an average of 4 years
Number of patients with a relative increase in LVEDVi
Number of patients with a relative increase in LVEDVi by more than 10% and to higher than the normal range.
Time frame: At each visit from randomization through study completion, an average of 4 years
Number of patients hospitalized
Number of patients hospitalized for worsening HF
Time frame: At each visit from randomization through study completion, an average of 4 years
Number of patients needing loop diuretics
Number of patients needing loop diuretics for congestive symptoms, during hospitalization and/or in out-of-hospital settings
Time frame: At each visit from randomization through study completion, an average of 4 years
Changes in NYHA Class
Changes in NYHA Class
Time frame: At each visit from randomization through study completion, an average of 4 years
Absolute values of NT-pro-BNP concentrations at the different visits
Absolute values of NT-pro-BNP concentrations at the different visits
Time frame: At each visit from randomization through study completion, an average of 4 years
Proportion of patients with changes in NT-proBNP concentrations to more than 400 ng/L.
Proportion of patients with changes in NT-proBNP concentrations to more than 400 ng/L.
Time frame: At each visit from randomization through study completion, an average of 4 years
Number of patients needing beta-blocker re-introduction in the experimental group or beta-blocker discontinuation in the control group
Number of patients needing beta-blocker re-introduction in the experimental group or beta-blocker discontinuation in the control group
Time frame: At each visit from randomization through study completion, an average of 4 years
Occurrence of arrhythmic events (any types, i.e., supra-ventricular and/or ventricular arrhythmias & requiring hospitalization or not) in all participants
Occurrence of arrhythmic events (any types, i.e., supra-ventricular and/or ventricular arrhythmias \& requiring hospitalization or not) in all participants
Time frame: At each visit from randomization through study completion, an average of 4 years
Occurrence of infra-clinic supra-ventricular and/or ventricular arrhythmias in patients implanted with ICD before participating the study
Occurrence of infra-clinic supra-ventricular and/or ventricular arrhythmias in patients implanted with ICD before participating the study
Time frame: At each visit from randomization through study completion, an average of 4 years
Quality of life (QoL) evaluated by the auto-questionnaire (EQ5D)
Quality of life (QoL) evaluated by the auto-questionnaire (EQ5D)
Time frame: At each visit from randomization through study completion, an average of 4 years
Quality of life with heart failure, evaluated by the auto-questionnaire KCCQ-12 filled by the patients himself.
Quality of life with heart failure, evaluated by the auto-questionnaire KCCQ-12 filled by the patients himself.
Time frame: At each visit from randomization through study completion, an average of 4 years
Anxiety
questionnaire HADS (Hospital Anxiety and Depression Scale), score de 0 à 21, higher scores indicate the presence of anxiety or depression
Time frame: At each visit from randomization through study completion, an average of 4 years
Erectile dysfunction (in men only)
Erectile dysfunction (in men only) by the questionnaire IIEF5 (International Index of Erectile Function).
Time frame: At each visit from randomization through study completion, an average of 4 years
Absolute values of heart rate at the different visits
Absolute values of heart rate at the different visits and relative change as compared to baseline values (first year)
Time frame: At each visit from randomization through study completion, an average of 4 years
Evaluation of Side effects: Questionnaire on the Presence of Blury Vision
Questionnaire on the Presence of Blury Vision
Time frame: At each visit from randomization through study completion, an average of 4 years
Evaluation of Side effects: Sensation of cold hands and feet
Sensation of cold hands and feet
Time frame: At each visit from randomization through study completion, an average of 4 years
Evaluation of Side effects : Insomnia
Insomnia
Time frame: At each visit from randomization through study completion, an average of 4 years
Occurrence of Palpitations
Occurrence of Palpitations
Time frame: At each visit from randomization through study completion, an average of 4 years
Syncope / Dizziness requiring a consultation
Syncope / Dizziness requiring a consultation
Time frame: At each visit from randomization through study completion, an average of 4 years
Evaluation of adherence to therapies evaluated by self-questionnaire
Evaluation of adherence to therapies evaluated by self-questionnaire
Time frame: At each visit from randomization through study completion, an average of 4 years
Exercise capacity by 6M walk test (in participating centers)
Exercise capacity by 6M walk test (in participating centers)
Time frame: At each visit from randomization through study completion, an average of 4 years
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