Cryoballoon Ablation Versus Medical Therapy in Patients With Heart Failure and Atrial Fibrillation

Not Applicable

Recruiting

• Conditions: Atrial Fibrillation; Heart Failure; Heart Failure, Systolic; Heart Failure With Reduced Ejection Fraction
• Interventions: Procedure: Cryoballoon ablation

• Registration Number: NCT04342832
• Lead Sponsor: Maastricht University

Brief Summary

Rationale:

Atrial fibrillation (AF) and heart failure (HF) can cause each other and sustain each other. Combined, the two diseases negatively influence each other's prognosis and lead to higher mortality. Studies in HF patients in which the AF burden is reduced by AF ablation show promising results toward improved prognosis, but so far only one randomized trial is conducted that focused on major clinical endpoints. As the selected patients in this trial were not representative for the entire population and its ablation method varied from patient to patient, it is the aim of the present study to confirm that early invasive therapy consisting of a strict pulmonary vein isolation (PVI) protocol using cryoballoon therapy has positive effects on hard clinical endpoints in a wider variety of patients in the HF population.

Furthermore, there are no studies which compare cost-effectiveness of an early invasive strategy in this patient category. The investigators expect that avoided hospitalizations and healthcare resource utilizations lead to lower costs in the AF ablation group, despite initial higher costs of the procedure.

Objective:

To compare outcome and cost-effectiveness of early AF ablation by PVI using cryoballoon therapy with standard (medical) therapy in patients with heart failure with reduced ejection fraction.

Study design:

Multicenter, randomized, open label clinical trial.

Study population:

Symptomatic adult patients with heart failure with reduced ejection fraction (\<40%) and paroxysmal or persistent AF.

Intervention:

AF ablation (PVI) using cryoballoon therapy.

Outcome measures:

The primary endpoint is a combined endpoint of all-cause mortality, unplanned cardiovascular hospitalization, and stroke (time-to-event analysis).

Secondary endpoints of the trial are:

* A combined endpoint of mortality, number of unplanned cardiovascular hospitalizations, and stroke (recurrent-event analysis);

* A hierarchical endpoint of mortality, unplanned cardiovascular hospitalizations, stroke, and HF complaints;

* Cost-effectiveness. Key exploratory endpoints include individual components of the combined endpoints, days alive out of the hospital, hospitalizations for heart failure, recurrence of atrial arrhythmia, and quality of life.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-03-26
• Study First Submitted QC: 2020-04-08
• Study First Posted: 2020-04-13
• Study Start: 2020-07-16
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-16
• Last Update Posted: 2021-03-18
• Primary Completion: 2024-09-01
• Study Completion: 2024-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

• Patients aged 18-80;
• HF with ejection fraction <40%, as assessed by recent (<6 months) echocardiography or cardiovascular magnetic resonance imaging (CMR);
• AF, documented on standard ECG or Holter monitoring;
• Eligible for both treatment arms;
• Signed and dated informed consent prior to admission to the trial.

Exclusion Criteria

• End-stage heart failure: NYHA class IV, patients on waiting list for cardiac transplant and/or left ventricular assist device;
• Long-standing (> 1 year) persistent or permanent AF;
• Previous pulmonary vein isolation or surgical ablation;
• Left atrial diameter ≥60 mm or left atrial volume index ≥50 ml/m2;
• Impaired renal function, defined as estimated glomerular filtration rate (eGFR) ≤25 ml/min/1.73m2;
• Recent (<90 days) acute coronary syndrome, cardiac intervention1, or stroke/transient ischemic attack (TIA);
• Planned or expected cardiac surgery in the following year;
• Active infectious disease or malignancy;
• Women who are pregnant or planning to become pregnant during the trial;
• Contraindication for cryoballoon ablation or other condition that may prevent subjects from adhering to the trial protocol, in the opinion of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early invasive treatment (cryoballoon ablation)	Cryoballoon ablation	-

Primary Outcome Measures

Name	Time	Method
Composite of all-cause mortality, unplanned cardiovascular hospitalizations and stroke (time-to-event analysis)	Study duration (1-5 years, expected median follow-up duration 2 years)

Secondary Outcome Measures

Name	Time	Method
Combined endpoint of all-cause mortality	Study duration (1-5 years, expected median follow-up duration 2 years)
Total number of unplanned cardiovascular hospitalizations and stroke (recurrent-event analysis)	Study duration (1-5 years, expected median follow-up duration 2 years)
Hierarchal endpoint of all-cause mortality, unplanned cardiovascular hospitalizations, stroke and change in heart failure complaints (hierarchical endpoint analysis)	Study duration (1-5 years, expected median follow-up duration 2 years)
Cost-effectiveness	Study duration (1-5 years, expected median follow-up duration 2 years)
Budget impact	Study duration (1-5 years, expected median follow-up duration 2 years)

Trial Locations

Locations (2)

Radboudumc; 🇳🇱 Nijmegen, Gelderland, Netherlands

Maastricht UMC+; 🇳🇱 Maastricht, Limburg, Netherlands