Randomized Evaluation of fleCAinide safety vs. STandard of care in patients with coronary artery disease and Atrial Fibrillation (ReCAST AF).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-06-26

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Research Foundation – Flanders (FWO)

External identifiers

EU CT number

2025-525121-13-00

ClinicalTrials.gov

NCT07405671

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

To demonstrate that, in patients with atrial fibrillation and stable coronary artery disease, the safety profile of flecainide for rhythm control is non-inferior to that of class III antiarrhythmic drugs, as measured by the primary composite endpoint over a minimum follow-up of 1 year.

Secondary objectives 10

1. To compare the incidence of each individual component of the primary composite endpoint between treatment groups.
2. To compare the overall incidence, severity, and type of adverse events and serious adverse events between treatment groups.
3. To compare treatment discontinuation rates and reasons for discontinuation between treatment groups.
4. To evaluate treatment adherence and persistence over time in both treatment groups.
5. To compare the effectiveness of flecainide versus class III antiarrhythmic drugs in maintaining sinus rhythm and preventing atrial fibrillation recurrence.
6. To compare rates of unplanned cardiovascular hospitalisations beyond those included in the primary endpoint.
7. To evaluate changes in cardiac function and biomarkers (including natriuretic peptides and echocardiographic parameters) over time between treatment groups.
8. To assess patient-reported outcomes, including quality of life and symptom burden, and compare changes over time between treatment groups.
9. To compare healthcare resource utilisation between treatment groups, including outpatient visits, hospitalisations, and procedures.
10. To evaluate the cost-effectiveness of flecainide versus class III antiarrhythmic drugs from a healthcare system perspective.

Conditions and MedDRA coding

Coronary artery disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 (ICF)
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 of ischemia, defined as: a. Prior percutaneous coronary intervention; OR b. Prior revascularised ACS or coronary artery bypass surgery > 3 months at enrolment; OR c. Invasive coronary angiography demonstrating coronary atherosclerosis, defined as ≥50% diameter stenosis in at least one major epicardial coronary artery; OR d. 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. Left ventricular ejection fraction ≥ 45% documented on any imaging modality

Exclusion criteria 25

1. LVEF < 45%
2. Known channelopathy, including Brugada syndrome, long QT syndrome,…
3. Contra-indication to AV-slowing agents, including beta-blockers, diltiazem or verapamil
4. Atrial fibrillation due to reversible cause
5. Active intracardiac thrombus
6. Acute coronary syndrome during the 3-month period preceding the consent date
7. 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
8. Moderate or severe congenital heart disease as per 2020 ESC guidelines
9. Hypertrophic cardiomyopathy (septal or posterior wall thickness >1.5 cm)
10. Significant chronic kidney disease (eGFR <40 mL/min)
11. Life expectancy less than 1 year
12. NYHA class III or IV congestive heart failure
13. 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
14. 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.
15. Participation in an interventional Trial with an investigational medicinal product (IMP) or device
16. Active treatment with amiodarone
17. History of intolerance of flecainide or both sotalol and amiodarone
18. Unstable angina or inducible ischemia on exercise stress testing, myocardial perfusion imaging, stress cardiac MRI, or fractional flow reserve performed for clinical indications
19. Baseline QRS duration ≥ 120 ms, unless a functioning pacemaker is present
20. Baseline corrected QT interval (Fridericia) ≥ 500 ms
21. Pre-existing advanced AV block (second-, or third-degree)
22. Pre-existing sick sinus syndrome or sinus bradycardia <50 bpm
23. Clinically significant uncorrected hypokalemia or hypomagnesemia before initiation of trial treatment.
24. Evidence or history of thyroid dysfunction contraindicating amiodarone use, where amiodarone would be prescribed as standard of care treatment.
25. Hypersensitivity to the active substances or any excipients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A composite safety outcome including the following adverse events of interest: (1) All-cause mortality; (2) Severe adverse events leading to drug discontinuation; and (3) Unscheduled hospitalisation for heart failure or acute coronary syndrome

Secondary endpoints 11

1. Individual components of the primary safety endpoint
2. Freedom from fast atrial arrhythmia post-treatment (clinical recurrence of AF)
3. Major adverse cardiovascular events (MACE): cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke
4. Incidence of catheter ablation for AF during follow-up
5. Total number of days of cardiovascular hospitalisation
6. All adverse and serious adverse events (frequency and severity, proportion of participants experiencing at least one AE/SAE, specific drug-related adverse events)
7. Changes in cardiac function from baseline to follow-up (left ventricular ejection fraction, global longitudinal strain, left atrial volume index)
8. Change in N-terminal-pro-brain Natriuretic Peptide (NT-proBNP) from baseline
9. Change in QTc interval (ms) and QRS duration (ms) from baseline.
10. Patient-reported outcome measures, including: Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire; EuroQoL-5 dimension health utility index (EQ-5D-5L); Short Form-12 (SF-12) health survey; EHRA symptom score; Work Productivity and Activity Impairment (WPAI) questionnaire
11. Economic evaluation with within-trial healthcare resource utilization between the two treatment arms

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Prof. Dr. Joris Ector

Public contact point

Organisation

UZ Leuven

Contact name

Prof. Dr. Joris Ector

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications