Flecainide in Idiopathic Premature Ventricular Contractions and Related Cardiomyopathy

NCT ID: NCT06949748

Last Updated: 2025-07-02

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-04-26
• Study Completion Date: 2027-12-01

Brief Summary

The UNIFLECA study is a prospective, single-arm, observational cohort evaluating the efficacy, safety, and tolerability of flecainide (in the form of Sanocard) in adults with frequent idiopathic premature ventricular contractions (PVCs) and suspected PVC-induced cardiomyopathy (PVCi-CMP). Frequent PVCs-defined as a burden >5% on two separate 24-hour Holter recordings-are increasingly recognized as a cause of reversible systolic dysfunction in patients without structural heart disease.

Participants undergo a comprehensive baseline evaluation including echocardiography, occasionally cardiac MRI, and coronary angiography or equivalent testing to confirm the absence of structural abnormalities. Patients are enrolled only if they are ineligible or unwilling to undergo catheter ablation, and have no contraindications to flecainide.

Flecainide therapy is initiated at a starting dose of 100 mg/day and titrated up to 200 mg/day, guided by ECG findings, symptom response, and QRS duration. Regular follow-up occurs at three-month intervals over three years, with periodic 24-hour Holter monitoring and assessment of symptoms, LVEF, and adverse events.

The primary outcome is the reduction in PVC burden. Secondary outcomes include improvement in LVEF, symptom relief (measured by structured questionnaires), adverse effects, and long-term treatment adherence. The study aims to generate real-world data on the non-invasive management of PVCs with flecainide and explore its role as an alternative to ablation in carefully selected patients.

Detailed Description

The UNIFLECA study is a prospective, single-arm, non-randomized observational cohort designed to evaluate the long-term efficacy and safety of flecainide (in the form of Sanocard) in adult patients with frequent idiopathic premature ventricular contractions (PVCs) and suspected PVC-induced cardiomyopathy (PVCi-CMP). Despite being considered benign in structurally normal hearts, a persistently high PVC burden-particularly above 10%-is increasingly recognized as a cause of reversible left ventricular dysfunction and a potential trigger for cardiomyopathy. This condition is frequently underdiagnosed and may lead to unnecessary treatments or delayed intervention.

The study targets a unique population: symptomatic patients with idiopathic PVCs who have structurally normal hearts and have either declined catheter ablation or are ineligible for invasive procedures. Each patient undergoes comprehensive baseline cardiac evaluation, including transthoracic echocardiography, cardiac magnetic resonance imaging (CMR) to exclude late gadolinium enhancement or myocardial scar, and coronary angiography or non-invasive equivalent to rule out ischemic heart disease. Two 24-hour Holter ECG recordings, taken at least 30 days apart, are used to confirm persistent high PVC burden (>5%).

Flecainide, a Class IC antiarrhythmic agent with sodium channel-blocking properties, is administered as monotherapy. The initial dose is 100 mg/day and may be titrated up to 200 mg/day based on clinical response, patient tolerability, and QRS interval monitoring. Beta-blockers are discontinued unless used for unrelated comorbidities such as hypertension. Patients are monitored with serial 12-lead ECGs, Holter recordings, and echocardiograms at baseline and every three months over a total follow-up period of three years.

The primary endpoint is the percentage reduction in PVC burden as measured by 24-hour Holter ECG. Secondary endpoints include (1) improvement in left ventricular ejection fraction (LVEF), (2) symptom relief as assessed by structured patient questionnaires focusing on palpitations, bradysphygmia, fatigue, dizziness, and exercise intolerance, (3) incidence of adverse events including proarrhythmia, conduction disturbances, and neurological side effects, and (4) adherence to long-term flecainide therapy, including need for dose modifications or drug discontinuation.

This investigator-initiated study is being conducted across tertiary arrhythmia centers in Greece. It aims to fill a significant evidence gap in the long-term pharmacologic management of idiopathic PVCs and PVCi-CMP. Preliminary results indicate significant PVC burden reduction and symptomatic improvement, supporting the potential utility of flecainide as an effective non-invasive therapeutic option in appropriately selected patients. Data from this study will contribute to optimizing treatment strategies for idiopathic ventricular arrhythmias in the absence of structural heart disease, supporting the use of personalized medicine and risk stratification.

Conditions

Premature Ventricular Beats; Premature Ventricular Complexes; Premature Ventricular Contraction (PVC); Arrhythmia Ventricular; Ventricular Dysfunction, Left; Ventricular Dysfunction; Cardiomyopathies, Secondary; Cardiomyopathies

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

High PVC Burden Cohort

Persistent, high PVC Burden (\>5%) in 24h Holter Monitoring

Flecainide (monotherapy)

Intervention Type: DRUG

• Medication: Flecainide acetate, administered orally.

• Initial Dosing and Titration:
• Patients were started on an appropriate dose based on body weight and renal function.
• The typical starting dose was 100-150 mg per day, split into two doses.
• Dosing was titrated as needed, depending on patient response and tolerability, under close ECG and clinical monitoring.
• Monitoring Protocol:
• Continuous ECG monitoring during drug initiation (especially in-hospital or via Holter).
• Regular outpatient follow-up visits, including:
• 12-lead ECGs
• Holter monitoring
• Echocardiography (to monitor LVEF and assess for reverse remodeling)
• ECG parameters (QRS width, QTc interval) were closely monitored for proarrhythmic changes.

Interventions

Flecainide (monotherapy)

• Medication: Flecainide acetate, administered orally.

• Initial Dosing and Titration:
• Patients were started on an appropriate dose based on body weight and renal function.
• The typical starting dose was 100-150 mg per day, split into two doses.
• Dosing was titrated as needed, depending on patient response and tolerability, under close ECG and clinical monitoring.
• Monitoring Protocol:
• Continuous ECG monitoring during drug initiation (especially in-hospital or via Holter).
• Regular outpatient follow-up visits, including:
• 12-lead ECGs
• Holter monitoring
• Echocardiography (to monitor LVEF and assess for reverse remodeling)
• ECG parameters (QRS width, QTc interval) were closely monitored for proarrhythmic changes.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Frequent idiopathic PVCs (burden >5% on multiple 24-hour Holter ECG recordings)
• Normal cardiac structure and function on echocardiography
• No late gadolinium enhancement or myocardial scar on cardiac MRI
• Normal coronary angiography (excluding ischemic cardiomyopathy)
• Normal serum electrolytes and renal function
• Willingness to comply with follow-up schedule and drug titration

Exclusion Criteria

• Structural heart disease
• Ischemic heart disease (confirmed by angiography)
• History of sustained ventricular arrhythmias
• Left ventricular ejection fraction (LVEF) <40% at baseline
• Brugada syndrome, long QT syndrome, or other channelopathies
• Contraindications to class IC agents
• Use of concurrent antiarrhythmics or proarrhythmic drugs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institute for Study, Research, Education and Therapy of Vascular, Heart, Brain and Kidney Nosologies

UNKNOWN

Sponsor Role: collaborator

University of Patras

OTHER

Sponsor Role: collaborator

University of Crete Medical School - University Hospital of Heraklion

UNKNOWN

Sponsor Role: collaborator

Aristotle University Of Thessaloniki

OTHER

Sponsor Role: collaborator

Uni-Pharma

INDUSTRY

Sponsor Role: collaborator

University of Athens

OTHER

Sponsor Role: lead

Responsible Party

Tsiachris Dimitrios

MD, PhD, Assistant Professor of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dimitrios Tsiachris, MD, PhD

Role: STUDY_CHAIR

University of Athens

Locations

Cardiology Clinic, University Hospital of Patras

Pátrai, Achaia, Greece

Site Status: RECRUITING

1st Cardiology Clinic, National and Kapodistrian University of Athens

Athens, Attica, Greece

Site Status: RECRUITING

Cardilogy Clinic, University of Crete

Heraklion, , Greece

Site Status: RECRUITING

2nd Cardiology Clinic, University of Ioannina

Ioannina, , Greece

Site Status: ACTIVE_NOT_RECRUITING

2nd Cardiology Clinic, Aristotle University of Thessaloniki

Thessaloniki, , Greece

Site Status: ACTIVE_NOT_RECRUITING

3rd Cardiology Clinic, Aristotle University of Thessaloniki

Thessaloniki, , Greece

Site Status: ACTIVE_NOT_RECRUITING

Countries

Greece

Central Contacts

Dimitrios Tsiachris, MD, PhD

Role: CONTACT

dtsiachris@yahoo.com

+306944849926

Sotirios Kotoulas, MD, MBA

Role: CONTACT

soter96@icloud.com

+306945012410

Facility Contacts

Dimitrios Tsiachris, MD, PhD

Role: primary

dtsiachris@yahoo.com

+306944849926

Sotirios Kotoulas, MD, MBA

Role: backup

Eleftherios Kallergis, MD, PhD

Role: primary

eleftherioskallergis@gmail.com

+306941509898

Other Identifiers

8014/25-04-2024

Identifier Type: -

Identifier Source: org_study_id