Efficacy and Safety Study of F373280
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: 1g of F373280; Placebo
Intervention description: Oral administration, one capsule each evening with dinner.; Oral administration, one capsule each evening with dinner.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 135.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cardiovascular diseases; Chronic Heart Failure

Summary:

      The purpose of this study is to assess the efficacy of F373280 on the maintenance of normal
      cardiac rhythm after direct electric cardioversion in patients with persistent atrial
      fibrillation and cardiac failure.
    

Eligibility criteria:

        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