Efficacy and safety study of F373280 for maintenance of sinus rhythm after electrical cardioversion in patients with persistent Atrial Fibrillation and Chronic Heart Failure.

Phase 1

Conditions: F373280 is a new therapy based on DHA delivery (pro-drug) developed for the maintenance of sinus rhythm after electrical cardioversion in persistent Atrial Fibrillation (AF) patients with chronic hearth failure. The results of pharmacological studies performed in animals evidenced that DHA reduces the duration of Atrial Fibrillation (AF) induced by burst pacing.
MedDRA version: 14.1Level: PTClassification code 10061024Term: Cardiac disorderSystem Organ Class: 10007541 - Cardiac disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2012-003487-48-IT

Lead Sponsor: Pierre Fabre Medicament

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 135

Inclusion Criteria

1.Men or women aged more than 18 years (inclusive),
2.Patients with persistent AF between 7 days and 6 months duration for whom electrical cardioversion is warranted.
3.History of first documented persistent AF less than 1 year
4.History of ischemic or non ischemic heart failure
5.NYHA class I or II chronic heart failure at selection and at inclusion
6.Reduced left ventricular ejection fraction between 30% and 45% inclusive (using the two-dimensional echocardiography biplane Simpson’s rule) ) at selection and at inclusion
7.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
8.Left atrial area ? 40 cm² ) at selection and at inclusion
9.Patients treated or having to be treated by anti-vitamin K
10.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

11.For female patient of child-bearing potential: negative urine pregnancy test at inclusion
12.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 a month 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 a month after the end of the study.
13.Having signed his/her written informed consent,
14.Affiliated to a social security system, or is beneficiary (if applicable in the national regulation)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 122
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1.History of first documented episode of persistent AF more than 1 year
2.More than two successful cardioversions (electrical or pharmacological) in the last 6 months
3.Secondary Atrial Fibrillation due to alcohol or severe valvular heart disease (grade III to IV)
4.NYHA class III or IV heart failure at selection or at inclusion
5.Thyroid disease uncontrolled by treatment: TSH ± T4L ± T3L to be checked in case of treatment for thyroid disease
6.Myocardial infarction or unstable angina or presence of unstable ischemic coronaropathy assessed by coronarography or cardiac stress test (Echo stress, exercice stress test, nuclear or MR perfusion evaluation methods) within 6 months before selection
7.Severe chronic kidney disease (creatinine ? 25 mg/L or estimated glomerular filtration rate < 30 mL/min) at selection
8.Bradycardia (HR ? 50 bpm)
9.Hyperkalemia or hypokalemia (K>5.5 mEq/L or K < 3.5 mEq/L) at selection
10.Cardiac surgery within 3 months before selection or planned during the study duration
11.Previously ineffective pharmacological or electrical cardioversion
12.Concomitant treatment with any anti-arrhythmic drug (within 7 days prior to selection), except stable dose of digoxin, betablockers, calcium-blockers
13.Previous treatment with oral amiodarone within 12 months prior to inclusion
14.Previous treatment with intravenous amiodarone within 6 months prior to inclusion
15.Patient requiring a cardiac resynchronization therapy (CRT) or having undergone CRT implantation within the last 6 months
16.Treatment with any Polyunsaturated Fatty Acid (PUFA) within the last 3 months
17.Dietary supplement with ?3 or ?6 according to investigator’s judgement
18.Having undergone any form of ablation therapy for AF
19.Patient treated with other anticoagulant treatment than antivitamin K: thrombin inhibitor such as Dabigatran or treated with antiaggregant P2Y12 inhibitors such as Clopidogrel or Prasugrel
20.Patient liable not to comply with protocol instructions and/or with treatment, in the investigator’s opinion
21.Patient having taken part in a clinical trial in the preceding 2 months or taking part in a trial at the time of selection
22.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
23.Patient family member or work associate (secretary, nurse, technician,..) of the Investigator
24.Patient having forfeited his / her freedom by administrative or legal award or being under guardianship
25.Breastfeeding female patient

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary:<br>Efficacy of F373280 on the maintenance of sinus rhythm after electrical cardioversion in persistent Atrial Fibrillation patients with chronic hearth failure.;Secondary Objective: Secondary:<br>- Efficacy of F373280 on the efficency of direct electrical cardioversion <br>- Effect of F373280 on echocardiographic paramenters<br>- Safety and tolerability of F373280;Primary end point(s): Efficacy;Timepoint(s) of evaluation of this end point: Time to first atrial fibrillation recurrence defined by the first episode of atrial fibrillation lasting for at least 10 minutes.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Safety;Timepoint(s) of evaluation of this end point: Adverse Events<br>Vital Signs<br>Physical Examination<br>Standard 12-lead ECG<br>Haematology<br>Biochemistry<br>Coagulation parameters

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