Clinical trial NCT01831856: Efficacy and Safety Study of F373280
Official title: Efficacy and Safety Study of F373280 for Maintenance of Sinus Rhythm After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation and Chronic Heart Failure. International, Multicentric, Randomised, Double-blind, Placebo Controlled Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Keywords: Cardiovascular diseases
Chronic Heart Failure
Lead sponsor: Pierre Fabre Medicament
Sponsor class: INDUSTRY
First posted: 2013-04-15
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Time to First Atrial Fibrillation (AF) Recurrence or Atrial Flutter Emergence Defined by the Time to First Episode of AF or Atrial Flutter Lasting for at Least 10 Minutes During the 20-week Follow-up After Visit 3 (Electrical Cardioversion (ECV) Visit).
timeFrame: from electrical cardioversion (Visit 3) to last follow-up visit (W24)
Secondary outcomes:
Other outcomes:
Locations:
city: Karlovy Vary
country: Czechia
city: Praha 2
country: Czechia
city: Praha 5 - Motol
country: Czechia
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Augusta
country: Italy
city: Brescia
country: Italy
city: Foggia
country: Italy
city: Terni
country: Italy
city: Verona
country: Italy
city: Grodzisk Mazowiecki
country: Poland
city: Radom
country: Poland
city: Sandomierz
country: Poland
city: Warszawa
country: Poland
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Santiago de Compostela
country: Spain
city: Tarragona
country: Spain
Study officials:
affiliation: PierreFabre Medicamment
name: Karim Keddad, MD
role: STUDY_DIRECTOR
References: