Mitral Valve ProlapsePhase 3FLECAPRONCT05631730
Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
A Phase 3 study testing Flecainide and Metoprolol in people with Mitral Valve Prolapse and Ventricular Arrhythmias and Cardiac Arrest, run by Oslo University Hospital at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mitral Valve Prolapse, Ventricular Arrhythmias and Cardiac Arrest
- What is being tested?
- Flecainide and Metoprolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteNorway
- Study dates
- 4 Jan 2023to Aug 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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
- Pregnancy
- Not willing to use a mandatory contraceptive method for the duration of the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Investigator-Initiated Prospective Randomized Open-Label Blinded-Endpoint Crossover Trial Comparing the Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
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.
Read the detailed 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.
- Being tested
- Flecainide, Metoprolol
- Keywords
- arrhythmic mitral valve prolapse, mitral annular disjunction, ventricular arrhythmia
- Medical subject headings
- Mitral Valve Prolapse, Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlecainideDrug
Also called C01B C04
Flecainide is mainly used for pharmacological conversion in patients with atrial tachyarrhythmias and to suppress ventricular arrhythmias in patients with structurally normal hearts.
MetoprololDrug
Also called C07A B02
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Metoprolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (4)
Burden of premature ventricular complexes
First hierarchical key secondary outcome. Assessed by 24-hour Holter monitoring. Intention-to-treat, superiority
Measured: 12 months
Change in health-related quality of life
Second hierarchical key secondary outcome. Number of patients with ≥5-point increase in Short Form 36 overall summary score. Intention-to-treat, superiority
Measured: 12 months
Number of severe ventricular tachycardias
Third hierarchical key secondary outcome. Sum of (i) non-sustained ventricular tachycardia with syncope, (ii) sustained ventricular tachycardia and (iii) ventricular fibrillation. Intention-to-treat, superiority
Measured: 12 months
Safety composite
Sum of (i) number of adverse events, (ii) number of serious adverse events, and (iii) higher degree atrioventricular (AV)-block (Mobitz type 2 or 3rd-degree AV-block). Safety population.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2022
- Study start4 Jan 2023
- Primary completionAug 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitral Valve ProlapseStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover prospective randomized open-label blinded-endpoint (PROBE) trial.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Research Council of Norway, University of Oslo
- Responsible party
- Principal investigator, Eivind Westrum Aabel, Oslo University Hospital
- Investigators
- Eivind W Aabel, MD PhD, Principal investigator, Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05631730
- Sponsor's protocol ID
- 2022-500814-24-00
- Other IDs
- 2022-500814-24-00
- Acronym
- FLECAPRO
- Status last verified
- Nov 2026
- First submitted
- 8 Nov 2022
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share anonymized data sets with the medical community via the medical journal upon submitting the manuscript.
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-Initiated Prospective Randomized Open-Label Blinded-Endpoint Crossover Trial Comparing the Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
- ClinicalTrials.gov ID
- NCT05631730
- Acronym / sponsor ID
- FLECAPRO / 2022-500814-24-00
- Keywords
- arrhythmic mitral valve prolapse, mitral annular disjunction, ventricular arrhythmia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- The Research Council of Norway, University of Oslo
- Study start
- 4 Jan 2023 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 30 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Crossover prospective randomized open-label blinded-endpoint (PROBE) trial.
| Arm | Type | Receives |
|---|---|---|
| Flecainide and Metoprolol | Experimental | Drug: Flecainide, Drug: MetoprololParticipants 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. |
| Metoprolol Alone | Active comparator | Drug: MetoprololParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FlecainideAlso: C01B C04Flecainide is mainly used for pharmacological conversion in patients with atrial tachyarrhythmias and to suppress ventricular arrhythmias in patients with structurally normal hearts. | Drug | Flecainide and Metoprolol |
| MetoprololAlso: C07A B02Metoprolol 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. | Drug | Flecainide and Metoprolol, Metoprolol Alone |
Primary outcome
Number of ventricular tachyarrhythmias
Time frame: 12 months
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.
4 secondary outcomes
Burden of premature ventricular complexes
Time frame: 12 months
Change in health-related quality of life
Time frame: 12 months
Number of severe ventricular tachycardias
Time frame: 12 months
Safety composite
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- European Union Clinical Trial Information System (CTIS) applicationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. We will share anonymized data sets with the medical community via the medical journal upon submitting the manuscript.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eivind W Aabel, MD PhD principal investigator
Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Flecainide and Metoprolol in people with Mitral Valve Prolapse and Ventricular Arrhythmias and Cardiac Arrest, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of ventricular tachyarrhythmias (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.