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

Last updated: July 26, 2024
Sponsor: Oslo University Hospital
Overall Status: Active - Recruiting

Phase

3

Condition

Chest Pain

Heart Defect

Circulation Disorders

Treatment

Metoprolol

Flecainide

Clinical Study ID

NCT05631730
2022-500814-24-00
2022-500814-24-00
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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

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

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

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

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

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

Exclusion

Exclusion Criteria:

  • Strict contraindications to flecainide or metoprolol use

  • Heart failure (signs or symptoms, elevated N-terminal proBNP)

  • Abnormal liver or kidney function (Aspartate aminotransferase (AST)/Alanineaminotransferase (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 atnight in young athletes or 1st-degree AV block that disappears during exercise)

  • Bundle branch block (QRS duration >120 ms) or intraventricular conduction defectwith 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

  • Pregnancy

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

Study Design

Total Participants: 50
Treatment Group(s): 2
Primary Treatment: Metoprolol
Phase: 3
Study Start date:
January 04, 2023
Estimated Completion Date:
February 28, 2026

Study Description

Mitral valve prolapse (MVP) is a common condition characterized by bulging one or both mitral leaflets into the left atrium. Although mainly a benign cardiac condition, a subgroup of patients develop severe ventricular arrhythmias that are a significant cause of sudden cardiac death in young adults. Arrhythmic MVP is defined as the presence of mitral valve prolapse with or without mitral annulus disjunction (MAD) combined with frequent ventricular ectopy, complex ectopy or sustained ventricular arrhythmia in the absence of another well-defined arrhythmic substrate. In these patients, ventricular arrhythmias most commonly originate from the mitral annulus, papillary muscles and outflow tracts. Several risk markers have been proposed, but clinical risk stratification remains challenging. Ventricular arrhythmias in patients with arrhythmic mitral valve prolapse are associated with excess long-term mortality.

There is no established medical therapy to suppress ventricular arrhythmias and relieve arrhythmic symptoms in these patients, and conventional beta-blocker therapy is often unsuccessful for both. Invasive catheter ablation can suppress ventricular arrhythmias, and thus relieve symptoms, in a subset of patients. However, many patients have multifocal ventricular ectopy, often originating from deep in the myocardium or papillary muscles and not easily accessible for catheter ablation. Furthermore, recurrence of ventricular arrhythmias is common despite initial successful catheter ablation procedures. The only strategy to prevent sudden cardiac death for high-risk patients is to implant an implantable cardioverter defibrillator (ICD), but this approach does not provide any symptomatic relief. Thus, most patients with arrhythmic mitral valve prolapse lack effective treatment options with proven efficacy in clinical trials.

Flecainide is a class 1c antiarrhythmic drug with a potent sodium channel-blocking effect frequently used in atrial tachyarrhythmias. Flecainide was developed as a treatment for ventricular arrhythmias, but its use subsided due to safety concerns when used in patients with acute myocardial infarction. However, this knowledge stems from a patient population before modern revascularization strategies after myocardial infarction and is extrapolated to patients with other structural heart diseases. Lately, flecainide has been shown to be safe in patients with stable coronary artery disease. Furthermore, flecainide reduces ventricular arrhythmias in patients with premature ventricular complex (PVC)-mediated cardiomyopathy, arrhythmogenic cardiomyopathy and catecholaminergic polymorphic ventricular tachycardia without short-term adverse effects. However, flecainide has not been studied in arrhythmic mitral valve prolapse patients.

The main goal of FLECAPRO is to evaluate 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. We hypothesize that a flecainide-based strategy is superior to a beta blocker-based strategy to suppress ventricular arrhythmias in patients with arrhythmic mitral valve prolapse.

Connect with a study center

  • Oslo University Hospital Rikshospitalet

    Oslo, 0372
    Norway

    Active - Recruiting

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