Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse

• Status: Not yet recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

Summary

FLECAPRO is a randomized controlled crossover trial assessing the effect and safety of adding flecainide to standard beta-blocker therapy to reduce the burden of ventricular arrhythmias in patients with arrhythmic mitral valve prolapse. The primary endpoint of will be assessed using an implantable loop recorder with blinded endpoint adjudication.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oslo University Hospital
• Collaborators: The Research Council of Norway; University of Oslo
• Treatments: Flecainide; Metoprolol

Criteria

Inclusion Criteria:

• Participants must be 18 years of age or older at the time of signing the informed consent.

• Participants must have mitral valve prolapse evident by echocardiography or cardiac magnetic resonance imaging, defined as more than or equal to 2 mm atrial displacement of any part of the mitral leaflets.

• Participants must have ventricular arrhythmias, defined as at least one of the following (i) premature ventricular complex burden ≥3% per 24 hours by Holter monitoring, (ii) premature ventricular complex burden ≥1% per 24 hours if multifocal or occurring in bi-/trigemini and/or couplets by Holter monitoring, (iii) sustained or non-sustained ventricular tachycardia, (iv) aborted cardiac arrest.

• Participants must have a clinical indication for antiarrhythmic treatment due to ventricular arrhythmias.

• Participants must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).

• Participants (only women of childbearing) must accede to mandatory use of a contraceptive method for the duration of the trial and until 3 days after discontinuation of study medication.

Exclusion Criteria:

• Strict contraindications to flecainide or metoprolol use

• Heart failure (signs or symptoms, elevated NT-proBNP) according to ICD10

• Abnormal liver or kidney function (AST/ALT three times upper normal, eGRF <60)

• Prior myocardial infarction or ischemic heart disease

• Ion channelopathy, including Brugada syndrome and long QT syndrome

• Genetic cardiomyopathy (hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, dilated cardiomyopathy, including genotype positive phenotype negative individuals)

• Atrial flutter or permanent atrial fibrillation

• Sinus node dysfunction

• Ongoing electrolyte disorders

• More than moderate valvular disease according to international guidelines

• Pre-excitation

• Any degree of AV-block, except due to enhanced vagal tone (e.g. Wenckebach-block at night in young athletes or 1st-degree AV block that disappears during exercise)

• Bundle branch block (QRS duration >120 ms) or intraventricular conduction defect with QRS >120 ms.

• Prior flecainide therapy.

• Concomitant use of the following medications (i) CYP2D6 inhibitors/mediators, (ii) class I, III or IV antiarrhythmic drugs, (iii) clozapine, quinidine, cimetidine, bupropion, or (iii) monoamineoxidase (MAO) inhibitors

• Pregnancy

• Not willing to use a mandatory contraceptive method for the duration of the trial.