Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06128980 |
| Other study ID # |
WEAN-HF |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
January 2024 |
| Est. completion date |
January 2032 |
Study information
| Verified date |
November 2023 |
| Source |
Herlev and Gentofte Hospital |
| Contact |
Emil Wolsk, MD |
| Phone |
+4538683868 |
| Email |
emil.wolsk[@]regionh.dk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
New onset heart failure (HF) is observed in up to 25% of patients with incident atrial
fibrillation or flutter (AF). Current guidelines suggest that both conditions (AF & HF) be
addressed with guideline directed medical therapy (GDMT) for HF and rate or rhythm control of
AF. Hence, patients with both conditions are subjected to extensive polypharmacy with
possible prognostic benefits, but also possible side effects, such as decreased renal
function, dizziness, tiredness and hypotension, as well as the financial burden on both the
individual patients and society, in addition to the stigma of having a HF diagnosis.
Guidelines do not inform how to manage long-term patients with HF, who following control of
the incident tachycardia (e.g. AF), show full recovery from their HF condition.
This investigator-initiated, open-label, randomized, non-inferiority trial will test whether
incremental weaning of GDMT in patients following full cardiac recovery and AF control is
non-inferior compared to continuous GDMT with respect to the primary endpoint of freedom from
heart failure deterioration. Furthermore, this study seeks to extensively phenotype these
patients (genetic testing, advanced imaging, biomarkers etc.) in order to establish whether
certain phenotypes are at lesser or greater risk of deterioration once remission is
established. This novel approach of a personalized treatment regimen depending on e.g.
genetic profiling could lead to an aggressive treatment in patients at high risk of
deterioration and conversely spare patients with a negligible risk, a life-long intensive
treatment regimen.
All HF clinics located in Zealand, Denmark, with a catchment area of >2 million citizens,
have agreed to participate in the WEAN-HF trial. A total of 348 patients will be randomized.
Patients are followed up the 1st year after randomization with clinical examination,
biomarkers and echocardiography, and are subsequently followed via Danish nationwide
registries for 10 years.
Description:
Background:
Heart failure (HF) is a disease that affects more than 60000 patients in Denmark and millions
across the world. The prognosis of HF is comparable to many types of cancer. New onset HF is
observed in up to 25% of patients with incident atrial fibrillation or flutter (AF). The
persistent tachycardia caused by AF is believed to exert the heart to a point where it causes
HF. Whether AF is the cause of HF, or conversely that the detrimental effects of HF has
induced AF, is difficult to ascertain upon the initial presentation. Current guidelines
suggest that both conditions (AF & HF) be addressed with guideline directed medical therapy
(GDMT) for HF and rate or rhythm control of AF. GDMT for HF consists of at least 4 different
types of medication which is combined with management for AF (anticoagulant and often
antiarrhythmic medication or ablation procedures). Hence, patients with both conditions are
subjected to polypharmacy with at least 6 different types of medication in addition to their
usual medication regimen. This may have prognostic benefits, but also possible side effects,
such as decreased renal function, dizziness, tiredness and hypotension, as well as the
financial burden on both the individual patients and society, in addition to the stigma of
having a heart failure diagnosis.
Gaps in knowledge Data are lacking on how to optimally manage patients long-term with heart
failure suspected to be tachycardia-induced, who following cessation or control of the
incident AF, show full recovery from their heart failure condition. Guidelines do not suggest
whether GDMT for heart failure should continue lifelong, cease or be weaned. In the TRED-HF
study, 51 non-ischemic HF patients with LVEF recovery who were seemingly clinically stable
were weaned from GDMT. Approximately 40% of patients showed signs of deterioration after 6
months of incremental GDMT weaning. Where TRED-HF patients had verified longstanding chronic
HF, the situation for patients experiencing an incident episode of AF subsequently leading to
acute heart failure may represent a different phenotype with a better prognosis once AF is
terminated or controlled as suggested by observational data. Currently there is no data
supporting how to manage GDMT in this population of heart failure patients with recovery
following control of their AF episode.
Objective:
To observe whether incremental weaning of GDMT in patients following full cardiac recovery
and AF control is non-inferior compared to continuous GDMT.
Furthermore, using an extensive phenotypic profiling, to investigate if one or more
biomarkers can predict which patients are at an increased risk of cardiac deterioration in
both intervention groups.
Hypothesis:
The investigators hypothesize that patients weaned from GDMT will experience similar rates of
deterioration as patients on continuous GDMT.
Perspective The chance of remission after a heart failure diagnosis differs greatly depending
on the etiology of heart failure. Although dramatic differences in remission rates depending
on etiology have been established, patients with heart failure are in general committed to
the same regimen of GDMT. For example, in patients with alcohol-induced heart failure,
removing the cardiotoxic substance (alcohol) through abstinence leads to recovery in >50% of
cases. Genetic profiling reveals that changes in mutations leading to alterations in cardiac
structural proteins - titin - are very prevalent in patients with alcohol-induced heart
failure. It appears that patients may be at increased risk of heart failure if they both have
a genetic disposition combined with a cardiotoxic stimulus (e.g. alcohol, tachycardia).
Interestingly, mutations in the same titin gene has also been found in many patients with
atrial fibrillation. Therefore, it is plausible that if the detrimental effects of prolonged
tachycardia could be stopped a continuous HF remission in our cohort would be observed. This
study seeks to extensively phenotype patients with tachycardia-induced heart failure in order
to establish whether certain phenotypes are at lesser or greater risk of deterioration once
remission is established. This novel approach of a personalized heart failure treatment
regimen depending on genetic profiling and advanced imaging could lead to an aggressive
treatment in patients at high risk of deterioration and conversely spare patients with a
negligible risk of deterioration a life-long intensive treatment regimen.
Primary endpoint:
Patients free from heart failure deterioration 1 year after randomization
Secondary endpoints 1 year after randomization:
- Changes in Minnesota Living with Heart Failure Questionnaire from baseline (min. score 0
- max. score 105, where higher scores indicates worse quality of life)
- Hospitalization for heart failure
- Cardiovascular (CV) hospitalizations
- Non-CV hospitalizations
- CV death
- All-cause death
- Patients in need of initiation of loop diuretics or doubling of dosage
- Changes in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from baseline
- Patients needing changes in medication for AF (uptitration of current medication or
change in/addition of new medication) or re-do ablation for AF
- Patients with signs of AF that persistently exceed 110 bpm despite best practice Adverse
events will be summarized;
- Patients with renal deterioration, hypotension, dizziness.
- Patients with signs of new onset liver affection and/or thyroid dysfunction
Methods:
This is an investigator-initiated, open-label, randomized, non-inferiority trial. This
clinical trial complies with the Declaration of Helsinki, modified in 2013. This study has
been approved by both the ethical committee (H-23010220) and the Knowledge Centre on Data
Protection Compliance in the Capital Region of Denmark (P-2023-111). This trial will adhere
to good clinical practice guidelines (GCP).
Patients with HF who are followed in HF clinics on Zealand including the greater Copenhagen
region are screened. This area covers >2 million citizens (approximately 1/3 of all citizens
in Denmark). All patients fulfilling criteria for participation will be invited to
participate. HF specialists at each HF clinic will assess eligibility based on a review of
the medical chart and an individual assessment. Patients can be rescreened for inclusion
repeatedly throughout the inclusion period.
Collaborators:
This trial is executed, analyzed and published by the main applicant and nested at
Herlev-Gentofte Hospital. A collaboration between the applicant and heart failure clinics is
pivotal in order to ensure timely inclusion of a generalizable heart failure population and
to swiftly implement the findings into clinical practice.
