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

NCT05631730 | Recruiting Phase 3 DMC

• 1 other identifier: 2022-500814-24-00
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mitral Valve Prolapse; Ventricular Arrhythmias and Cardiac Arrest

Keywords

arrhythmic mitral valve prolapse; mitral annular disjunction; ventricular arrhythmia

Outcome Measures

Primary Outcomes (1)

• Number of ventricular tachyarrhythmias

  Sum of ventricular fibrillation and ventricular tachycardia (broad complex tachycardia with heart rate \>140/min) on implantable loop recorder during 12 months. Intention-to-treat, superiority.

  12 months

Secondary Outcomes (4)

• Burden of premature ventricular complexes

  12 months

• Change in health-related quality of life

  12 months

• Number of severe ventricular tachycardias

  12 months

• Safety composite

  12 months

Other Outcomes (13)

• Number of ventricular tachycardias

  12 months

• Number of ventricular fibrillations

  12 months

• Burden of premature ventricular complexes

  12 months

Study Arms (2)

Flecainide and Metoprolol

EXPERIMENTAL

Participants will receive flecainide 50 mg twice daily (BID), with a dosage target of 100 mg BID. The maximum daily dose of flecainide will not exceed 300 mg. The first dose of flecainide will be initiated in-hospital with a 12-lead electrocardiogram (ECG) taken after 3 hours. If the ECG is considered normal after flecainide treatment, the participant will continue with 50 mg BID from the next day. Participants will receive a dosage of Metoprolol taking into consideration prior beta-blocker use and concomitant medications. The maximum daily dose of metoprolol will not exceed 200 mg. Within the run-in period, the dosage of both Flecainide and Metoprolol will be increased to the maximum tolerable dose. The Study Team can change the immediate-release formulation of Flecainide to controlled release at the same daily dose of flecainide. Whether metoprolol sustained release will be dosed once daily (QD) or BID, will be up to the investigator and patient preference.

Drug: Flecainide; Drug: Metoprolol

Metoprolol Alone

ACTIVE COMPARATOR

Participants will receive a dosage of Metoprolol taking into consideration prior beta-blocker use and concomitant medications. Within the run-in period, the dosage will be increased to the maximum tolerable dose. Whether metoprolol sustained release will be dosed QD or BID, will be up to the investigator and patient preference. The maximum daily dose of metoprolol will not exceed 200 mg.

Drug: Metoprolol

Interventions

Flecainide DRUG

Flecainide is mainly used for pharmacological conversion in patients with atrial tachyarrhythmias and to suppress ventricular arrhythmias in patients with structurally normal hearts.

Also known as: C01B C04

Flecainide and Metoprolol

Metoprolol DRUG

Metoprolol is a beta-blocker and class II antiarrhythmic drug considered standard care in most cardiac diseases predisposing to ventricular arrhythmias, including arrhythmic mitral valve prolapse.

Also known as: C07A B02

Flecainide and Metoprolol; Metoprolol Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Strict contraindications to flecainide or metoprolol use
• Heart failure (signs or symptoms, elevated N-terminal proBNP)
• Abnormal liver or kidney function (Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) three times upper normal, estimated glomerular filtration (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/inducers, (ii) class I, III or IV antiarrhythmic drugs, (iii) clozapine, quinidine, cimetidine, bupropion, or (iii) monoamineoxidase (MAO) inhibitors

Sponsors & Collaborators

• Oslo University Hospital: lead
• The Research Council of Norway: collaborator
• University of Oslo: collaborator

Study Sites (1)

Oslo University Hospital Rikshospitalet

Oslo, 0372, Norway

RECRUITING

Related Links

• European Union Clinical Trial Information System (CTIS) application

MeSH Terms

Conditions

Mitral Valve Prolapse; Heart Arrest

Interventions

Flecainide; Metoprolol

Condition Hierarchy (Ancestors)

Heart Valve Prolapse; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Eivind W Aabel, MD PhD

  Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eivind W Aabel, MD PhD

CONTACT

41243148; eivind.westrum.aabel@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Separate endpoint adjudication committee blinded to randomized allocation of patients to treatment groups
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Crossover prospective randomized open-label blinded-endpoint (PROBE) trial.

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 30, 2022
• Study Start: January 4, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Will be made available with the publication of the primary analysis and remain available for 1 year. Thereafter, it can be made available upon request.
• Access Criteria: Researchers and clinicians with valid medical questions to be addressed. The data will not be available for commercial use.

Locations

NO (1)