Clinical trial NCT06949748: Flecainide in Idiopathic Premature Ventricular Contractions and Related Cardiomyopathy
Official title: UNIFLECA Study: Prospective Cohort Study on Flecainide's Impact on Persistent High Premature Ventricular Contraction Burden and PVC-Induced Cardiomyopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Premature Ventricular Beats
Premature Ventricular Complexes
Premature Ventricular Contraction (PVC)
Arrhythmia Ventricular
Ventricular Dysfunction, Left
Ventricular Dysfunction
Cardiomyopathies, Secondary
Cardiomyopathies
Keywords: Flecainide
Sanocard
UNIFLECA
PVC induced CMP
PVC
Premature Ventricular Contraction
Outflow Tract PVC
NonOutflow Tract PVC
Lead sponsor: University of Athens
Sponsor class: OTHER
Collaborators: name: UNIPHARMA. Universal Pharmaceutical Industries
name: Institute for Study, Research, Education and Therapy of Vascular, Heart, Brain and Kidney Nosologies
name: University of Patras
name: University of Crete Medical School - University Hospital of Heraklion
name: Aristotle University Of Thessaloniki
First posted: 2025-04-29
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population in the UNIFLECA trial consisted of adult patients with frequent idiopathic premature ventricular contractions (PVCs), defined by a PVC burden greater than 5% on multiple 24-hour Holter monitoring. All participants had structurally normal hearts, confirmed by comprehensive imaging including echocardiography, cardiac MRI if necessary, and coronary angiography to exclude cardiomyopathy or ischemic heart disease.

Eligible individuals were required to have no contraindications to flecainide therapy and no history of sustained ventricular arrhythmias, significant conduction abnormalities, or inherited channelopathies. Patients were selected based on the presence of symptoms such as palpitations or fatigue and a clinical suspicion of PVC-induced cardiomyopathy, without the use of other antiarrhythmic drugs.

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.

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

Primary outcomes:
measure: PVC Burden Reduction
timeFrame: 3 years
Secondary outcomes:
measure: Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: 3 years
measure: Safety and tolerability of flecainide
timeFrame: 3 years
measure: Symptom improvement (Questionnaire Score)
timeFrame: 3 years
measure: Treatment Adherence and Dose Adjustments
timeFrame: 3 years
Other outcomes:
Locations:
city: Patras
country: Greece
facility: Cardiology Clinic, University Hospital of Patras
state: Achaia
city: Athens
country: Greece
facility: 1st Cardiology Clinic, National and Kapodistrian University of Athens
state: Attika
city: Heraklion
country: Greece
facility: Cardilogy Clinic, University of Crete
city: Ioannina
country: Greece
facility: 2nd Cardiology Clinic, University of Ioannina
city: Thessaloniki
country: Greece
facility: 2nd Cardiology Clinic, Aristotle University of Thessaloniki
city: Thessaloniki
country: Greece
facility: 3rd Cardiology Clinic, Aristotle University of Thessaloniki
Study officials:
affiliation: University of Athens
name: Dimitrios Tsiachris, MD, PhD
role: STUDY_CHAIR
References: