Withdrawal of Treatment for Heart Failure Patients With Recovery From Tachycardia-induced Cardiomyopathy

NCT06128980 | Recruiting Phase 2

• 1 other identifier: WEAN-HF
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure With Reduced Ejection Fraction; Heart Rhythm Disorder

Outcome Measures

Primary Outcomes (1)

• Patients free from heart failure deterioration 1 year after randomization

  Heart failure deterioration is defined as following; a reduction in LVEF of more than 10% and less than 50%, and/or increase in LVEDV by more than 10% and to higher than the normal range (indexed for body surface area), and/or hospitalization for heart failure and/or arrhythmia, and/or clinical evidence of heart failure.

  1 year after randomization

Secondary Outcomes (10)

• Changes in Minnesota Living with Heart Failure Questionnaire from baseline

  1 year after randomization

• Cardiovascular (CV) hospitalizations

  1 year after randomization

• Non-CV hospitalizations

  1 year after randomization + 10 year follow-up

• CV death

  1 year after randomization + 10 year follow-up

• All-cause death

  1 year after randomization + 10 year follow-up

Other Outcomes (2)

• Patients with renal deterioration, hypotension, dizziness.

  1 year after randomization

• Patients with signs of new onset liver affection and/or thyroid dysfunction

  1 year after randomization

Study Arms (2)

Standard of Care

NO INTERVENTION

Patients will be treated with GDMT for heart failure during the trial follow-up of 1 year.

Weaning

ACTIVE COMPARATOR

Patients will be weaned from GDMT in a sequential order.

Drug: GDMT

Interventions

GDMT DRUG

Sequential weaning starting with SGLT2i - MRA - BB - ACEi/ARB/ARNi

Weaning

Eligibility Criteria

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

You may qualify if:

• Patients with new onset heart failure (ambulatory or hospital) with reduced ejection fraction (LVEF≤40% assessed by echocardiography) and NYHA ≥2 and atrial fibrillation or atrial flutter with ventricular rate ≥110 bpm (ECG monitoring, hospital telemetry or Holter monitoring) that following GDMT - while AF is terminated (e.g. ablation or conversion) or controlled (HR\<110 on resting ECG) - experience LVEF remission (LVEF ≥50%), normalization of indexed LV volume, and normal ECG (no bundle branch block, ST segment deviations or T-wave inversion) and NT-proBNP \<250 pg/ml.

You may not qualify if:

• years or older and able to consent
• Former ablation procedures and inability to tolerate antiarrhythmic drugs
• Pregnancy
• Congenital heart disease (congenital defects with no hemodyamic effects are not excluded)
• Previously genotyped positive for genes known to cause cardiomyopathy
• Probable hypertrophic, restrictive or non-compaction cardiomyopathy
• Moderate/severe valvular disease
• Suspicion of or known cardiac amyloidosis, sarcoidosis, or other storage/inflammatory disease
• More than 10% PVCs or documented sustained ventricular arrhythmias
• History of persistent or permanent AF with ventricular rates \>110 before incident HF despite best standard of care
• eGFR \< 30 ml/min/1.73 m2
• Acute myocardial infarction at index
• Probable medication-, alcohol- or illicit drug use induced AF and/or HF
• Systolic blood pressure \>160 mmHg (at multiple measurements) at index or history of uncontrollable hypertension
• Myocarditis

Sponsors & Collaborators

• Nordsjaellands Hospital: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator
• Zealand University Hospital: collaborator
• Copenhagen University Hospital, Hvidovre: collaborator
• Herlev and Gentofte Hospital: lead

Study Sites (1)

Herlev-Gentofte Hospital

Copenhagen, 2730, Denmark

RECRUITING

Study Officials

• Emil Wolsk, MD

  Herlev and Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emil Wolsk, MD

CONTACT

+4538683868; emil.wolsk@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Heart Failure, Principal investigator

Model Details: Randomized, non-inferiority study

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: November 13, 2023
• Study Start: January 9, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2032
• Last Updated: February 23, 2026

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)