Efficacy and Safety Study of F373280

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Cardiovascular diseases, Chronic Heart Failure Read More

Inclusion Criteria:

• Men or women aged more than 18 years (inclusive)
• Patients with current episode of persistent Atrial Fibrillation (AF) between 7 days and 6 months duration for whom electrical cardioversion is warranted
• Previous history of first documented episode of persistent AF.
• Previous history of ischemic or non ischemic heart failure
• New York Heart Association (NYHA) class I or II chronic heart failure at selection and at inclusion

• Left ventricular systolic dysfunction defined at selection and at inclusion by a reduced left ventricular ejection fraction (LVEF) ≥ 30% and ≤ 45% or for patients with a LVEF > 45%:

  • an increased left ventricular end-diastolic size (diameter ≥ 60 mm and/or > 32 mm/m² and/or volume > 97 ml/m²)
  • and/or an increased left ventricular end-systolic size (diameter > 45 mm and/or > 25 mm/m² and/or volume > 43 ml/m²)
  • and/or a reduced left ventricular outflow tract velocity time integral < 15 cm
• On appropriate, stable medical treatments for heart failure, including a diuretic and/or angiotensin-converting enzyme, and/or angiotensin-receptor blocker and/or mineralocorticoid receptor (MR) antagonists, and/or betablockers
• Left atrial area ≤ 40 cm² at selection and at inclusion
• Patients treated or having to be treated by vitamin K antagonist

• For female patient of child-bearing potential:

  • In all the countries except Italy:
• Use of an effective method of contraception (hormonal contraception or intra-uterine device) assessed by the investigator, for at least 2 months before the selection in the study, and agreement to go on using it during the whole duration of the study and up to 1 month after the last dose of the study treatment

• Documented as surgically sterilized

  • In Italy only:
• Absolute abstention from sexual intercourse during the whole duration of the study and for a month after the end of the study or
• Use of double barrier contraception method (use of effective medical contraception method) from at least 2 months before the start of the study to the entire duration of the study and for a month after the end of the study or
• Documented as surgically sterilized.
• For female patient of child-bearing potential: negative urine pregnancy test at inclusion
• For male with a child-bearing potential partner (In Italy only):
• Absolute abstention from sexual intercourse during the whole duration of the study and for 3 months after the end of the study or
• Use of double barrier contraception method (use of condom for male and effective contraception method for the partner) from the entire duration of the study to 3 months after the end of the study.

Ethical / legal considerations:

• Having signed his/her written informed consent,
• Affiliated to a social security system, or is beneficiary (if applicable in the national regulation)

Exclusion Criteria:

• No previous history of first documented episode of persistent AF
• More than two successful cardioversions (electrical or pharmacological) in the last 6 months
• Secondary Atrial Fibrillation due to alcohol or severe valvular heart disease (grade III to IV)
• NYHA class III or IV heart failure at selection or at inclusion
• Thyroid disease uncontrolled by treatment: TSH ± T4L ± T3L to be checked in case of treatment for thyroid disease
• Myocardial infarction or unstable angina or presence of unstable ischemic coronaropathy assessed by coronarography or cardiac stress test (Echo stress, exercise stress test, nuclear or MR perfusion evaluation methods) within 6 months before selection
• Severe chronic kidney disease (creatinine ≥ 25 mg/L or estimated glomerular filtration rate < 30 ml/min) at selection
• Bradycardia (HR ≤ 50 bpm)
• Hyperkalemia or hypokalemia (according to the standards of local laboratories) at selection
• Cardiac surgery within 3 months before selection or planned during the study duration

Criteria related to treatments:

• Previously ineffective pharmacological or electrical cardioversion
• Concomitant treatment with ranolazine or any antiarrhythmic drug (within 7 days prior to selection), except amiodarone, dronedarone and stable dose of digoxin, betablockers, calcium-blockers
• Concomitant treatment with oral amiodarone or dronedarone from selection
• Concomitant treatment with intravenous amiodarone from selection
• Patient requiring a cardiac resynchronization therapy (CRT) or having undergone CRT implantation within the last 6 months
• Treatment with any Polyunsaturated Fatty Acid (PUFA) within the last 3 months
• Dietary supplement with ω 3 or ω 6 according to investigator's judgement
• Having undergone any form of ablation therapy for AF
• Patient treated with oral anticoagulant treatment other than vitamin K antagonist: new oral anticoagulants (dabigatran, rivaroxaban, apixaban), or treated with irreversible antiplatelet agents P2Y12 inhibitors such as ticlopidine, clopidogrel or prasugrel

Other criteria:

• Patient liable not to comply with protocol instructions and/or with treatment, in the investigator's opinion
• Patient having taken part in a clinical trial in the preceding 2 months or taking part in a trial at the time of selection
• Patient linguistically or mentally unable to understand the nature, objectives and possible consequences of the trial, or refusing to patient himself/herself to its constraints
• Patient family member or work associate (secretary, nurse, technician,..) of the Investigator
• Patient having forfeited his / her freedom by administrative or legal award or being under guardianship
• Breastfeeding female patient