Clinical trial NCT06560047: Danish Evaluation of Early Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure
Official title: Danish Evaluation of Early Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure - The DanAblate-HF Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Heart Failure
Keywords: Heart failure
Atrial fibrillation
Catheter ablation
Treatment
Outcome
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Odense University Hospital
name: Aarhus University Hospital
name: Zealand University Hospital
name: Herlev and Gentofte Hospital
First posted: 2024-08-19
Enrollment: 1616
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The DanAblate-HF trial is a pragmatic, investigator-initiated, prospective, multicenter, open-labeled, randomized, controlled trial. Patients will be randomized 1:1 to either early catheter ablation or standard treatment.
Primary purpose: TREATMENT

Brief summary: The DanAblate-HF trial will investigate whether early catheter ablation treatment for atrial fibrillation in patients with heart failure is superior to standard treatment.

Detailed description: Atrial fibrillation (AF) is the most common arrhythmia in patients with heart failure (HF), with rates ranging between 20-65%, depending on age, severity of HF, subtypes of HF and duration of HF. The two conditions have an intricate and often overlapping pathophysiology, with each condition leading to development of the other, as well as progression of disease. Studies have shown that the presence of AF in HF patients is associated with increased morbidity and mortality, deterioration in HF, exacerbated HF symptoms, and reduced quality of life. The optimal treatment of AF in the presence of HF remains unknown. Currently, there is a pull towards catheter ablation as first-line therapy for AF in HF patients. However, there is no solid scientific evidence to support this approach. Furthermore, it is unknown whether early rhythm control by catheter ablation in HF patients is beneficial.

The investigators aim to conduct a pragmatic, randomized clinical trial designed to evaluate the efficacy and safety of early catheter ablation for AF in patients with HF compared with standard treatment.

Eligible patients with HF and AF will be prospectively screened from all Danish hospitals and randomized 1:1 to early catheter ablation with pulmonary vein isolation (within 6 weeks) or standard guideline directed treatment for AF. Patients with reversible causes for AF, conditions that preclude the use of catheter ablation or previous catheter ablation for AF will be excluded from the study. Randomization and follow-up will be conducted at six specialized sites in Denmark. There will be one scheduled on-site 12-months follow-up visit after randomization. All clinical follow-up will be conducted at the patient's local hospital, according to standard practice and out of trial setting. Information regarding hospital visits/admissions, events, adverse events, changes in medication, cross-over, heart rhythm and rate, and results of relevant blood-work will be ascertained through systematic patient chart-review at pre-specified time-points. The results from this trial will mold future treatment of AF in HF patients. The investigators hypothesize that early catheter ablation reduces the risk of HF hospitalizations and mortality when compared with standard treatment, thereby significantly improving the clinical prognosis for patients with HF and AF.

Eligibility criteria: Inclusion Criteria:

1. HF patients with AF within the past 12 months

   HF is defined as all of the below (all must apply)
   * Clinically assessed Heart Failure with Reduced Ejection Fraction (HFrEF)
   * An indication for initiation or ongoing guideline directed medical therapy for HFrEF, according to current Heart Failure guidelines
   * LVEF \< 50% at any point during the past 12 months

   AF is defined as one or more of the following:

   A. Symptomatic AF, documented by ECG, Holter of CIED

   B. Asymptomatic AF with one or more of the following:
   * Clinical indication for rhythm or rate control (documented by ECG, telemetry, Holter, CIED)
   * ≥2 ECG detected AF episodes within 3 months (on separate dates)
   * Holter detected AF with a continuous duration of more than 6 hours
   * CIED detected AF with continuous duration \>24 hours
2. 18 years ≤ Age \<80 years
3. Optimal medical therapy for HFrEF or planned/current uptitration in guideline directed medical therapy for HFrEF
4. Treatment with anticoagulation for stroke prevention, initiated according to guidelines for treatment of AF

Exclusion Criteria:

1. Life-expectancy \< 1 year
2. BMI \> 40
3. Contraindications or unacceptable side effects to rate limiting drugs AND amiodarone
4. LA size (indexed for BSA) \> 60 ml/m2 (volume) on echo within the last year
5. Documented persistent/permanent AF \> 1 year
6. Previous AF ablation/surgery
7. Reversible causes of AF (including, but not limited to, infection within 14 days, untreated thyroid disease, surgery)
8. Severe valvular disease
9. Acute myocardial infarction, cardiothoracic surgery or stroke within the past 3 months
10. Planned cardiothoracic surgery
11. Listed for heart transplant
12. Contraindications for anticoagulation therapy or catheter ablation
13. Severe kidney disease (CKD≥5)
14. Pregnancy
15. Patient unwilling to try medical therapy for AF
16. Patient unwilling/unable to give informed consent for study participation

Primary outcomes:
measure: Time to hospitalization for worsening HF or cardiovascular death
timeFrame: From baseline to study completion, with a minimum of 1 year
Secondary outcomes:
measure: Time to cardiovascular death
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to all-cause mortality
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to first heart failure hospitalization
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to first-time AF hospitalization
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to primary outcome stratified by age
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to primary outcome stratified by sex
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to primary outcome stratified by symptomatic and asymptomatic AF
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to primary outcome stratified by paroxysmal or persistent AF
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to primary outcome stratified by left ventricular ejection fraction (LVEF)
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Change in Quality of Life
timeFrame: From baseline to 12 months
measure: Change in self-assessed health
timeFrame: From baseline to 12 months
measure: Change in New York Heart Association (NYHA) class
timeFrame: From baseline to 12 months
measure: Change in European Heart Rhythm Association score of atrial fibrillation (EHRA class)
timeFrame: From baseline to 12 months
Other outcomes:
measure: Change in LVEF
timeFrame: From baseline to 12 months
measure: Change in left ventricular (LV) volume
timeFrame: From baseline to 12 months
measure: Change in left atrial (LA) volume
timeFrame: From baseline to 12 months
measure: Change in NT-pro-BNP
timeFrame: From baseline to 12 months
measure: Time to hospitalization or death due to stroke
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Cumulative heart failure hospitalization
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Cumulative hospitalizations for AF
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Time to first-time all-cause hospitalization
timeFrame: From baseline to study completion, with a minimum of 1 year
measure: Cumulative all-cause hospitalizations
timeFrame: From baseline to study completion, with a minimum of 1 year
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital, Department of Cardiology
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Cardiology, Rigshospitalet
city: Hellerup
country: Denmark
facility: Department of Cardiology, Herlev-Gentofte University Hospital
city: Odense
country: Denmark
facility: Department of Cardiology, Odense University Hospital
city: Roskilde
country: Denmark
facility: Department of Cardiology, Zealand University Hospital
Study officials:
affiliation: Department of Cardiology, Aalborg Univeristy Hospital
name: Sam Riahi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: