A Multicenter Randomized Trial Comparing Flecainide Acetate and Amiodarone Hydrochloride for Cardioversion of Paroxysmal Atrial Fibrillation in Coronary Artery Disease
- Trial ID
- 2024-519233-33-00
- Protocol
- FLECA-ED
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **superiority** of flecainide over amiodarone in achieving successful cardioversion of paroxysmal atrial fibrillation (AF) to sinus rhythm in the Emergency Department. Additionally, the study aims to establish that the safety profile of flecainide is non-inferior to that of amiodarone. This is clinically relevant as effective and safe conversion of paroxysmal AF is crucial in patients with coronary artery disease, without residual ischemia and a left ventricular ejection fraction greater than 35%, to prevent complications and improve patient outcomes.
Secondary objectives include proving the superiority of flecainide over amiodarone in:
- Reducing hospitalizations from the Emergency Department due to AF
- Decreasing the time required to successfully restore sinus rhythm
- Reducing the need for electrical cardioversion
Participants
The clinical trial involves participants aged **18 to 25 years** who are diagnosed with **paroxysmal atrial fibrillation** (AF) and have a history of coronary artery disease without residual ischemia. The study population includes both male and female subjects, and it is not focused on a vulnerable population. Participants must have a left ventricular ejection fraction greater than 35%, as documented by cardiac ultrasound. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Selection criteria include documented AF by a 12-lead ECG, with specific conditions regarding the onset of AF and anticoagulation therapy. Participants must have undergone angioplasty or coronary artery bypass surgery within specified timeframes or have a history of coronary artery stenosis greater than 60% without revascularization. All participants are required to provide a signed informed consent form. The trial does not emphasize any particular lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the safety and efficacy of **flecainide** compared to **amiodarone** for the conversion of paroxysmal atrial fibrillation in patients with coronary artery disease without residual ischemia and a left ventricular ejection fraction greater than 35%. The trial aims to demonstrate the superiority of flecainide in achieving successful cardioversion to sinus rhythm and to establish that its safety profile is non-inferior to that of amiodarone. The study is expected to run from April 2023 to June 2025, with participant involvement lasting up to 30 days.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-25 years), documented paroxysmal atrial fibrillation, history of coronary artery disease, and ejection fraction documentation. Following the screening, eligible participants will be randomized to receive either flecainide or amiodarone. The primary endpoint is the frequency of successful cardioversion to sinus rhythm within 6 hours of drug administration. Secondary endpoints include the frequency of discharges in sinus rhythm, time to restoration to sinus rhythm, and the occurrence of arrhythmias and adverse events over a 24-hour period and up to 30 days.
Follow-up visits will be conducted to monitor the participants' response to treatment and to assess any adverse events. The end-of-study visit will occur at the conclusion of the 30-day period or earlier if the participant experiences significant adverse events or if the primary endpoint is achieved. Conditions that may lead to early termination from the study include the development of severe adverse events or withdrawal of consent. The trial is structured to ensure rigorous monitoring and data collection to support the evaluation of the trial's objectives.
Treatment
The clinical trial involves the administration of two **antiarrhythmic drugs** for the treatment of paroxysmal atrial fibrillation in patients with coronary disease. The first experimental medication is **Angoron**, which contains the active substance **amiodarone hydrochloride**. This medication is provided in the form of a **solution for injection**. Each ampoule contains 150 mg of amiodarone hydrochloride in 3 ml of solution. The maximum daily dose is 1525 mg, and the administration is conducted via **injection**. The treatment period is limited to a maximum of one day. The medication is manufactured by SANOFI-AVENTIS MONOPROSOPI A.E.B.E and is authorized for use in Greece.
The comparator treatment in this trial is **FLECARDIA**, which contains the active substance **flecainide acetate**. This medication is also provided as a **solution for injection/infusion**. The maximum daily dose for flecainide acetate is 150 mg, administered via **injection**. Similar to Angoron, the treatment period is restricted to one day. FLECARDIA is produced by WIN MEDICA SA and is also authorized for use in Greece. Both medications are chemically derived and are not formulated for pediatric use. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the conversion of **paroxysmal atrial fibrillation** (AF) to sinus rhythm. The primary endpoints include the frequency of successful cardioversion to sinus rhythm and the combined frequency of premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (NSVT), supraventricular tachycardia (SVT), bradycardia with a heart rate less than 50 beats per minute, and systolic blood pressure below 90 mmHg. These parameters will be measured from the moment the drug is administered and for up to 6 hours.
Secondary endpoints will further assess efficacy by measuring the frequency of discharges from the Emergency Department in sinus rhythm, the frequency of successful cardioversion to sinus rhythm over a 24-hour period using 24-hour Holter monitoring, and the time to restoration to sinus rhythm within 6 hours. Additionally, the frequency of electrical cardioversion and the occurrence of arrhythmias, including the burden of PVCs, NSVT episodes, and SVT episodes, will be evaluated over a 24-hour period. The frequency, severity, and type of adverse events (AEs) will also be monitored from the moment the drug is administered and for up to 30 days.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age: 18-25 years old
- Paroxysmal atrial fibrillation (AF), documented by a 12-lead ECG, provided one of the following conditions is met: • Atrial Fibrillation onset less than 48 hours from the time of presentation to the Emergency Department, regardless of anticoagulation therapy. • Atrial Fibrillation onset between 48 hours and 7 days from the time of presentation to the Emergency Department, with anticoagulation therapy for at least 30 days.
- History of coronary artery disease without residual ischemia, defined by one of the following criteria: • The patient underwent angioplasty within the past year. • The patient underwent coronary artery bypass surgery within the last 3 years. • The patient had a negative imaging-based stress testing within the past year, and additionally: • The patient had angioplasty more than a year ago, or • The patient underwent coronary artery bypass surgery more than 3 years ago, or • The patient has a history of coronary artery stenosis >60% without revascularization.
- Ejection fraction > 35% (documented by cardiac ultrasound in the Emergency Department or within the last year).
- Signed informed consent form.
Exclusion Criteria
- Based on the ECG in the Emergency Department. • Atrial Flutter • Newly documented Left Bundle Branch Block (LBBB) • Newly documented Right Bundle Branch Block (RBBB) with QRS duration > 150 ms.
- Severe Chronic Kidney Disease (stage ≥ 4).
- Severe systemic disease, including neoplastic disease under any antineoplasmatic treatment, liver failure, infection with fever.
- Use of the "pill in the pocket" strategy pocket with flecainide (max 200 mg) or propafenone (max 600 mg) within 6 hours before the visit in the Emergency Department.
- Intolerance or known allergy to flecainide and amiodarone.
- Pregnancy and/or breastfeeding.
- Any previous 24-hour ECG halter monitoring with > 720 polymorphic PVCs / 24 hours, or non sustained ventricular tachycardia.
- No history of coronary artery disease.
- Myocardial infarction with ST-segment elevation.
- Myocardial infarction without ST-segment elevation • If the troponin level at t0 h is over the "low" criterion on the table of the cutoof values • If the change in troponin Delta (1-hour, Δtroponin at t1h ) is over the respective cutoff value at the table for the cutoff values.
- Unstable angina (myocardial ischemia at rest or with minimal effort, absence of acute injury/ myocardial cell necrosis).
- Known residual ischemia: • Positive imaging-based stress testing • Negative imaging-based stress testing ≥ 1 year, and : • The patient underwent vascularization more that one year ago , or • The patient underwent coronary artery bypass more than 3 years ago, or • The patient has a medical history of revascularization of stenosis coronary vessels more than 60%.
- History of acute coronary syndrome within one year.
- Severe aortic valve stenosis (mean pressure difference> 40 mmHg, AVA < 1 cm/m2).
- Participation in any other clinical trial.
- Life expectancy less than 1 year.
- Inapprooriate, unfit, or unwilling patient to follow the required protocol procedures.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Recruiting | 13 Apr 2023 | 200 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Angoron 150 mg/3 ml amp ενέσιμο διάλυμα | Comparator | AMP ΕΝΈΣΙμΟ ΔΙΆΛΥμΑ | INJECTION | 1525 | 1 | PRD435793 |
FLECARDIA Διάλυμα για ένεση/έχχυση | Test | ΔΙΆΛΥΜΑ ΓΙΑ ΈΝΕΣΗ/ΈΧΧΥΣΗ | INJECTION | 150 | 1 | PRD7419791 |