Atrial Fibrillation (AF) Ablation to Prevent Disease Progression of AF-induced Atrial Cardiomyopathy in Women and Men (RACE X)

The goal of clinical trial is to compare AF ablation to pharmacological rhythm management (being rate or rhythm control) in AF patients with signs of atrial cardiomyopathy (as defined by left atrial volume index >34 ml/m2) The main objective it aims to answer is to determine whether AF ablation compared to pharmacological rhythm management in ACMP patients with AF reduces the incidence of the composite primary endpoint of CV death and first CV hospitalization/urgent visit.

Study Overview

• Status: Recruiting
• Conditions: Fibrillation, Atrial; Atrial Cardiomyopathy
• Intervention / Treatment: Procedure: Pulmonary vein isolation; Drug: Pharmacological rhythm management

Detailed Description

The RACE X trial investigates the impact of atrial cardiomyopathy (ACMP) and ablation timing on adverse outcomes in atrial fibrillation (AF) patients. ACMP leads to an atrial substrate less responsive to rhythm control, exacerbating AF recurrence and progression. This trial assesses whether AF ablation versus pharmacological rhythm management reduces the combined primary endpoint of cardiovascular (CV) death and hospitalization in ACMP and AF patients. Secondary objectives include measuring ACMP progression, ACMP-related outcomes, mortality, hospitalizations, AF symptoms, quality of life, and healthcare costs. Exploratory goals involve various additional measurements. This prospective, multicenter, open-label, blinded-endpoint, phase IIIb trial randomizes patients with ACMP and AF to receive either AF ablation or pharmacological rhythm management. Follow-up involves mobile health (mHealth) applications, questionnaires, and heart rhythm monitoring across 13 Dutch hospitals. Ineligible patients undergoing AF ablation join an observational registry. The trial population consists of patients aged 65-80 years with confirmed ACMP and ECG-confirmed AF. With 604 patients and a median 2.5-year follow-up, the trial aims to assign patients equally to each intervention. The primary endpoint is a composite of CV death and hospitalization. Catheter ablation, a safe and efficient technique, minimizes patient burden, and remote follow-up through mHealth reduces site visits. Additional study procedures are integrated into routine care, ensuring a streamlined process.

• Study Type: Interventional
• Enrollment (Estimated): 604
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michiel Rienstra, Prof. dr.; Phone Number: +31503616161; Email: m.rienstra@umcg.nl
• Study Contact Backup: Name: Nick L van Vreeswijk, Drs.; Phone Number: 0624678451; Email: nickvanvreeswijk@gmail.com

Study Locations

• Netherlands
  • Groningen, Netherlands, 9715BS
    • Recruiting
    • UMCG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Confirmed ACMP (LAVI >34 ml/m2)
• ECG-confirmed AF
• Age: 65-80 years old
• Patients eligible for both treatment strategies judged by the treating physician signed and dated informed consent prior to admission to the trial

Exclusion criteria

• Longstanding (>1 year) persistent or permanent (accepted) AF
• Previous left atrial (LA) ablation or LA surgery
• AF due to a reversible cause (e.g. hyperthyroidism, post-operative AF)
• Recent (<90 days) acute coronary syndrome, stroke/TIA or cardiac intervention (Cardiac interventions include percutaneous coronary intervention, coronary artery bypass grafting, and heart valve repair or replacement (endovascular or surgical))
• Intracardiac thrombus
• HF NYHA III/IV
• Impaired renal function, defined as estimated glomerular filtration rate ≤25 ml/min/1.73m2
• Presence of (or scheduled for) mechanical assist device or heart transplant
• Severe aortic or mitral valve disease
• Complex congenital heart disease
• Life expectancy <1 year
• Currently enrolled in another clinical randomized trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AF ablation; These patients will undergo Pulmonary vein isolation (PVI) (only)	Procedure: Pulmonary vein isolation; Pulmonary vein isolation using pulsed field ablation (PFA), cryoballoon or radiofrequency ablation (RFA); Other Names: AF ablation
Active Comparator: Pharmacological rhythm management; These patients will take rate control medication. If this therapy fails, pharmacological rhythm control and AF ablation are 2nd and 3rd line options respectively within this arm,	Drug: Pharmacological rhythm management; 1st line: rate control, 2nd line: pharmacological rhythm management. 3rd line: AF ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A composite of cardiovascular (CV) death and first CV hospitalisation/urgent visit.	Atrial cardiomyopathy (ACMP)-associated complications	through study completion, a median of 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACMP progression or regression	As measured by LAVI (left atrial volume index) increase or decrease	through study completion, a median of 2.5 years
Hospitalisations/urgent visits for AF, atrial flutter (AFL) or atrial tachycardia (AT)	Hospitalisations/urgent visits for AF, AFL or AT	through study completion, a median of 2.5 years
Hospitalisations/urgent visits for heart failure (HF)	Hospitalisations/urgent visits for heart failure	through study completion, a median of 2.5 years
Hospitalisations/urgent visits for ischemic stroke (including transient ischemic attack (TIA))	Hospitalisations/urgent visits for ischemic stroke (including TIA)	through study completion, a median of 2.5 years
Cardiovascular death	Cardiovascular death	through study completion, a median of 2.5 years
All-cause mortality	All-cause mortality	through study completion, a median of 2.5 years
Symptoms and improve quality of life (QoL) measured by EuroQol-5D-5L questionnaire. (higher score indicating a better QoL)		through study completion, a median of 2.5 years
Symptoms and improve quality of life (QoL) measured by Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire (higher score indicating less symptoms and a better QoL)		through study completion, a median of 2.5 years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Michiel Rienstra, Prof. dr., University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2024
• Primary Completion (Estimated): July 25, 2029
• Study Completion (Estimated): July 25, 2029

Study Registration Dates

• First Submitted: December 1, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: atrial fibrillation; mHealth; AF ablation; pulmonary vein isolation; atrial cardiomyopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Disease Progression; Atrial Fibrillation; Cardiomyopathies
• Other Study ID Numbers: RACE X trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No