Flecainide Safety in Patients With Coronary Artery Disease and Atrial Fibrillation (ReCAST AF)

Randomized Evaluation of fleCAinide Safety Versus STandard of Care in Patients With Coronary Artery Disease and Atrial Fibrillation

The goal of this clinical trial is to learn whether the antiarrhythmic drug flecainide can be used as safely as standard rhythm-control drugs in people with atrial fibrillation (AF) and stable coronary artery disease (CAD). The study includes adults aged 18 years and older who have AF and known but stable coronary artery disease.

The main questions this study aims to answer are:

• Is treatment with flecainide as safe as standard rhythm-control drugs (sotalol or amiodarone) in this patient group?
• Does flecainide lead to similar or fewer serious side effects, hospitalisations, or deaths compared with standard treatment?

Researchers will compare patients treated with flecainide to patients treated with standard rhythm-control therapy (sotalol or amiodarone) to see whether flecainide is not worse in terms of safety outcomes.

Participants will:

• Be randomly assigned to receive either flecainide or standard rhythm-control medication
• Take the assigned medication as part of routine clinical care
• Attend regular follow-up visits at the hospital and have additional follow-up by telephone
• Undergo routine heart tests such as electrocardiograms and echocardiography
• Complete questionnaires about symptoms, quality of life, and daily functioning

This study follows patients for at least one year and collects information on safety, heart rhythm outcomes, quality of life, and healthcare use.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Atrial Fibrillation (AF)
• Intervention / Treatment: Drug: flecainide; Drug: Sotalol or Amiodarone

• Study Type: Interventional
• Enrollment (Estimated): 988
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Joris Ector, MD PhD; Phone Number: +32 16 34 14 87; Email: Joris.Ector@UZLeuven.be
• Study Contact Backup: Name: Bert Vandenberk, MD PhD MSc; Email: bert.vandenberk@uzleuven.be

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. At least 18 years of age at the time of signing the Informed Consent Form
3. Non-permanent atrial fibrillation or ectopic atrial tachycardia with rhythm control strategy, documented on any modality in the 1 year preceding the consent date

4. Stable coronary artery disease without argument, defined as:

   1. Prior percutaneous coronary intervention; OR
   2. Prior revascularised ACS or coronary artery bypass surgery > 3 months at enrolment; OR
   3. Invasive coronary angiography demonstrating coronary atherosclerosis, defined as ≥50% diameter stenosis in at least one major epicardial coronary artery; OR
   4. Coronary CT scan showing coronary stenosis CAD-RADS stage ≥ 3 on, including CAD-RADS stages 4 and 5 in the absence of ischemia on exercise testing, myocardial perfusion imaging (MIBI), stress cardiac MRI, or fractional flow reserve.
5. LVEF ≥ 45% documented on any imaging modality*

Exclusion Criteria:

1. LVEF < 45%
2. NYHA class III or IV congestive heart failure
3. Active treatment with amiodarone
4. History of intolerance of flecainide or both sotalol and amiodarone
5. Unstable angina or inducible ischemia on exercise stress testing, myocardial perfusion imaging, stress cardiac MRI, or fractional flow reserve performed for clinical indications
6. Baseline QRS duration ≥ 120 ms, unless a functioning pacemaker is present
7. Baseline corrected QT interval (Fridericia) ≥ 500 ms
8. Pre-existing advanced AV block (second-, or third-degree)
9. Pre-existing sick sinus syndrome or sinus bradycardia <50 bpm
10. Known channelopathy
11. Contra-indication to AV-slowing agents, including beta-blockers, diltiazem or verapamil
12. Atrial fibrillation due to reversible cause
13. Active intracardiac thrombus
14. Acute coronary syndrome during the 3-month period preceding the consent date
15. Cardiac surgery, including coronary artery bypass surgery, during the 3-month period preceding the consent date or planned at a future date at the time of consent
16. Moderate or severe congenital heart disease as per 2020 ESC guidelines
17. Hypertrophic cardiomyopathy (septal or posterior wall thickness >1.5 cm)
18. Significant chronic kidney disease (eGFR <40 mL/min)
19. Life expectancy less than 1 year
20. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
21. Inability to provide written informed consent, including decision-making incapacity due to cognitive impairment or other medical or psychiatric conditions that preclude adequate understanding of the study and its procedures.
22. Participation in an interventional Trial with an investigational medicinal product (IMP) or device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flecainide; Flecainide, a class Ic anti-arrhythmic drug.	Drug: flecainide; Flecainide, a class Ic anti-arrhythmic drug Recommended starting dose of 100 to 150 mg per day per os, either spread in 2 equal doses BID or in 1 dose OD with controlled release formulation. Flecainide will always be combined with an AV nodal blocker (beta-blocker or diltiazem/verapamil).
Active Comparator: Sotalol or Amiodarone; Class III anti-arrhythmic drug: sotalol or amiodarone as per physician preference.	Drug: Sotalol or Amiodarone; Class III anti-arrhythmic drug: Sotalol or amiodarone as per physician preference. Recommended starting doses: Sotalol: 80 mg BID per os, with a dose adjustment to once daily if the eGFR is between 40 and 60 mL/min.; Amiodarone: loading dose of 600 mg daily per os in divided doses for 1 week, followed by 400 mg daily per os in divided doses for 1 week, and subsequently 200 mg per os once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite safety outcome	The primary outcome measure is a composite safety outcome including all-cause mortality, severe adverse events leading to drug discontinuation, and unscheduled hospitalisation for heart failure or acute coronary syndrome. Each of these individual components is assessed as secondary outcome.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Death from any cause	1 year
Severe adverse events leading to drug discontinuation	Any severe AE leading to intervention discontinuation, including bradyarrhythmias, ventricular arrhythmias, atrial flutter with 1:1 conduction, QT/QRS prolongation, serious extra-cardiac adverse events	1 year
Unscheduled hospitalisation for heart failure or acute coronary syndrome	Unscheduled hospitalisation for heart failure or acute coronary syndrome	1 year
AF recurrence	Freedom from fast atrial arrhythmia post-treatment (clinical recurrence of AF)	1 year
Major adverse cardiovascular events	Composite of cardiovascular death, myocardial infarction, stroke	1 year
Catheter ablation	Incidence of catheter ablation for AF during follow-up	1 year
Cardiovascular hospitalisation duration	Total number of days of cardiovascular hospitalisation	1 year
Treatment-related adverse events	All serious adverse events and adverse events: Frequency and severity of all treatment-emergent adverse events; Proportion of participants experiencing at least one AE/SAE.; Specific drug-related adverse events (e.g., QT prolongation, proarrhythmia, bradycardia, hypotension, fatigue, gastrointestinal disturbances).	1 year
Cardiac function - LVEF	Changes in cardiac function assessed by left ventricular ejection fraction expressed in percentages (%) from baseline measured by echocardiography	3 months
NT-proBNP	Change in N-terminal-pro-brain Natriuretic Peptide (NT-proBNP) at 3 months from baseline	3 months
QTc	Change in QTc interval (ms) and QRS duration (ms) from baseline	1 year
Healthcare resource utilization	Total within-trial healthcare resource utilization expressed in Euro (€)	1 year
Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire	Change in patient reported outcomes assessed by the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire. The AFEQT questionnaire is a 20-item, disease-specific, patient-reported outcome measure ranging from 0 to 100 with a higher value corresponding to a better quality of life.	1 year
EuroQoL-5 dimension health utility index (EQ-5D-5L)	Change in patient-reported outcome as assessed by the EuroQoL-5 dimension health utility index (EQ-5D-5L) questionnaire. The EQ-5D-5L measures health-related quality of life across five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) on five severity levels (1=no problem to 5=extreme problem). Results are interpreted via a 5-digit health state profile (e.g., 11211), a calculated utility index (ranging from <0 to 1, where 1=full health), and a 0-100 Visual Analog Scale (VAS). A higher score corresponds to a better quality of life.	1 year
Short Form-12 (SF-12) health survey	Change in patient-reported outcome as assessed by the Short Form-12 (SF-12) health survey. The Short Form-12 (SF-12) health survey is interpreted by calculating two main, norm-based scores-the Physical Component Summary (PCS) and Mental Component Summary (MCS)-where a score of 50 represents the average for the general population. Scores above 50 indicate better-than-average health-related quality of life, while scores below 50 indicate below-average health.	1 year
EHRA symptom score	Change in patient-reported outcome as assessed by the European Heart Rhythm Association (EHRA) symptom score. The EHRA symptom score is a standardized, four-level classification system used to quantify the severity of symptoms in patients with atrial fibrillation based on how they impact daily activities. EHRA Symptom Score Classification (I-IV): EHRA I (Asymptomatic): No symptoms are experienced. EHRA II (Mild Symptoms): Normal daily activity is not affected. EHRA III (Severe Symptoms): Normal daily activity is affected. EHRA IV (Disabling Symptoms): Normal daily activity is discontinued.	1 year
Work Productivity and Activity Impairment (WPAI) questionnaire	Change in patient-reported outcome as assessed by the Work Productivity and Activity Impairment (WPAI) questionnaire. The WPAI questionnaire is interpreted by calculating four key impairment percentages over the past 7 days, with higher scores (0-100%) indicating greater impairment and lower productivity. It measures absenteeism (time missed), presenteeism (impairment while working), overall work loss, and daily activity impairment, using a 0-10 scale for productivity.	1 year

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Research Foundation Flanders

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: February 4, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: atrial fibrillation; stable coronary artery disease; amiodarone; flecainide; rhythm control; sotalol
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Coronary Artery Disease; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amines; Piperidines; Alcohols; Amino Alcohols; Ethanolamines; Benzofurans; Amiodarone; Sotalol; Flecainide
• Other Study ID Numbers: S69367; 2025-525121-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Starting 12 months after publication
• IPD Sharing Access Criteria: Upon reasonable request to the Principal Investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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