Clinical trial NCT06125925: Catheter Ablation in Atrial Fibrillation Patients With HFpEF (STABLE-SR IV Trial)
Official title: Catheter Ablation in Atrial Fibrillation Patients With Heart Failure With Preserved Ejection Fraction: an International, Prospective, Multi-center, Randomized Controlled Study (STABLE-SR IV Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
HFpEF - Heart Failure With Preserved Ejection Fraction
Keywords: atrial fibrillation
HFpEF
radiofrequency catheter ablation
drug therapy
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2023-11-09
Enrollment: 436
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate whether RFCA is superior to AADs in AF patients with HFpEF on the basis of optimized anti-heart-failure drug therapy regarding their longterm clinical outcomes.

Detailed description: Background: Atrial Fibrillation (AF) is a common cardiac rhythm disorder and radiofrequency catheter ablation (RFCA) has become the first-line therapy in the symptomatic AF patients. Heart failure is often the sister disease with AF. Recently, RFCA was found to be superior to antiarrhythmic drugs (AADs) in heart failure patients with AF and reduced ejection fraction (HFrEF), regarding all-cause mortality and hospitalization for worsening heart failure (HF). However, in heart failure patients with AF and preserved ejection fraction (HFpEF), it remains unknown whether RFCA is superior to AADs in an even larger population, despite several nonrandomized retrospective studies. Thus, this prospective, multi-center, randomized controlled trial aims to investigate whether RFCA could better improve the clinical outcome of AF patients with HFpEF than longterm AADs use.

Aim of this study: To investigate whether RFCA is superior to AADs in AF patients with HFpEF on the basis of optimized anti-heart-failure drug therapy regarding their longterm clinical outcomes.

Design: The STABLE-SR-IV trial is an international, prospective, multi-center, randomized controlled trial. In this trial, physical examination, echocardiogram, NT-proBNP and other blood test would be assessed before enrollment. Those who conform to all the inclusion criteria and absent from any exclusion criteria would enter into a run-in period of 5 weeks (±7 days). Anticoagulation and anti-heart-failure therapy for HFpEF must be optimized according to the current guideline. After the run-in period, inclusion and exclusion criteria would be reassessed. Thereafter, all the subjects enrolled would be randomized into RFCA arm and Medical Therapy arm with a 1:1 manner, namely 218 subjects in each arm. Each arm will follow the protocol of RFCA and medical therapy, respectively. Follow-up duration of this study is up to 2\~3 years (12 month enrollment).

Eligibility criteria: Inclusion Criteria:

* Symptomatic paroxysmal or persistent atrial fibrillation
* CHADS2-VASc score≥ 2
* Conform to the diagnosis of HFpEF

  1. NYHA II-IV level;
  2. Left ventricular ejection fraction (LVEF)≥ 50%;
  3. NT-proBNP≥ 300 pg/mL under sinus rhythm or NT-proBNP≥ 600 pg/mL under atrial fibrillation or flutter;
  4. Evidence of left ventricular diastolic dysfunction/raised left ventricular filling pressure on echocardiogram.
* Sign informed consent

Exclusion Criteria:

* A life expectancy below 2 years due to any non-cardiovascular condition
* Reversible atrial fibrillation, such as hyperthyroidism or hypokalemia-related atrial fibrillation
* Prior atrial fibrillation ablation
* Left atrial size≥ 55 mm
* Heart failure due to any of the following: known genetic hypertrophic cardiomyopathy, infiltrative cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, constrictive pericarditis, active myocarditis, cardiac tamponade, or uncorrected primary valvular disease
* Previous cardiac transplantation, complex congenital heart disease, rheumatic heart disease
* Any contraindication for radiofrequency catheter ablation, antiarrhythmic drugs or anticoagulation
* Acute coronary syndrome, cardiac surgery, angioplasty or cerebrovascular accident within 12 weeks before enrollment
* Severe hepatic and renal dysfunction
* Body mass index\> 50 kg/m2
* Female in period of pregnancy or breast-feeding
* Any conditions that, in the opinion of the investigator, may render the patient unable to complete the study
* Involved in other studies

The inclusion and exclusion criteria would be reassessed after run-in period and the cut-off of NT-proBNP would be set as \>125 pg/ml under sinus rhythm or \>365 pg/ml under AF/atrial flutter (AFL).

Primary outcomes:
measure: Composite endpoint of worsening heart failure requiring unplanned hospitalizations or urgent visits, and cardiovascular death (Time-to-first event analysis)
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
Secondary outcomes:
measure: Time to hospitalization or urgent visits for heart failure
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Time to hospitalization for heart failure
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Time to urgent visits for heart failure
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Time to cardiovascular death
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Time to all-cause death
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Time to cardiovascular hospitalization
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Total number of worsening heart failure events and cardiovascular deaths
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Change in quality of life - KCCQ score
timeFrame: Baseline, 3 months, 12 months
measure: Change in quality of life - MLWHFQ
timeFrame: Baseline, 3 months, 12 months
measure: Change in 6-minute walk test from baseline to Month 3 and Month 12
timeFrame: Baseline, 3months, 12 months
measure: Change in H2FPEF score from baseline to Month 3 and Month 12
timeFrame: Baseline, 3 months, 12 months
measure: Change in N-terminal pro-B type natriuretic peptide (NT-proBNP) from baseline to Month 3 and Month 12
timeFrame: Baseline, 3 months, 12 months
measure: Change in NYHA class from baseline to Month 3, 6 and 12
timeFrame: Baseline, 3 months, 12 months
measure: Time to change of diuretics
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
measure: Change in atrial fibrillation burden
timeFrame: Baseline, 12 months
measure: Time to Atrial Fibrillation recurrence (RFCA arm)
timeFrame: From randomization until completion of the planned follow-up, up to 36 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: the First Affiliated Hospital of Nanjing Medical University
Study officials:
References: