Clinical trial NCT04342832: Cryoballoon Ablation Versus Medical Therapy in Patients With Heart Failure and Atrial Fibrillation
Official title: CRyoballoon Ablation Versus mediCal thErapy in Patients With Heart Failure and Atrial Fibrillation: A Multicenter Randomized Clinical Trial, the RACE-8-HF Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atrial Fibrillation
Heart Failure
Heart Failure With Reduced Ejection Fraction
Heart Failure, Systolic
Keywords: Pulmonary vein isolation
Cryoballoon ablation
Atrial fibrillation
Heart failure
Lead sponsor: Maastricht University
Sponsor class: OTHER
First posted: 2020-04-13
Enrollment: 600
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: Multicenter randomized clinical trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Composite of all-cause mortality, unplanned cardiovascular hospitalizations and stroke (time-to-event analysis)
timeFrame: Study duration (1-5 years, expected median follow-up duration 2 years)
Secondary outcomes:
measure: Combined endpoint of all-cause mortality
timeFrame: Study duration (1-5 years, expected median follow-up duration 2 years)
measure: Total number of unplanned cardiovascular hospitalizations and stroke (recurrent-event analysis)
timeFrame: Study duration (1-5 years, expected median follow-up duration 2 years)
measure: Hierarchal endpoint of all-cause mortality, unplanned cardiovascular hospitalizations, stroke and change in heart failure complaints (hierarchical endpoint analysis)
timeFrame: Study duration (1-5 years, expected median follow-up duration 2 years)
measure: Cost-effectiveness
timeFrame: Study duration (1-5 years, expected median follow-up duration 2 years)
measure: Budget impact
timeFrame: Study duration (1-5 years, expected median follow-up duration 2 years)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
state: Limburg
Study officials:
affiliation: Maastricht UMC+, Radboudumc
name: Kevin Vernooy, MD PhD
role: STUDY_CHAIR
affiliation: UMC Groningen
name: Michiel Rienstra, MD PhD
role: STUDY_CHAIR
References: