Efficacy and Safety Study of F373280

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.

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: 1g of F373280; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Karlovy Vary, Czechia
  • Praha 2, Czechia, 128 08
  • Praha 5 - Motol, Czechia
• Hungary
  • Budapest, Hungary, 1122
  • Budapest, Hungary, 1032
  • Budapest, Hungary, 1096
  • Budapest, Hungary, 1023
• Italy
  • Augusta, Italy
  • Brescia, Italy
  • Foggia, Italy
  • Terni, Italy
  • Verona, Italy
• Poland
  • Grodzisk Mazowiecki, Poland
  • Radom, Poland
  • Sandomierz, Poland
  • Warszawa, Poland, 03-242
• Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Santiago de Compostela, Spain
  • Tarragona, Spain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral administration, one capsule each evening with dinner.
Experimental: F373280	Drug: 1g of F373280; Oral administration, one capsule each evening with dinner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Time to first Atrial Fibrillation (AF) recurrence defined by the first episode of Atrial Fibrillation lasting for at least 10 minutes. AF recurrences or atrial flutter emergences: 7-day continuous electrocardiogram (ECG; 5-leads/2 or 3 channels) ambulatory recording (Holter ECG) between Visit 3 (Electrical Cardioversion Visit) and Visit 4 (Week 5). Then, the follow-up was documented using the Transtelephonic ECG monitor (TTEM): one transmission every two days from Week 9 to Week 24. For randomised patients with spontaneous cardioversion before Electrical Cardioversion, the recurrence of AF or the emergence of atrial flutter was assessed after Visit 3 (from Week 5). Moreover, during this TTEM period, if the patient experienced any AF or atrial flutter symptoms, it was recorded and documented using the TTEM.	from electrical cardioversion (Visit 3) to last follow-up visit (W24)

Collaborators and Investigators

• Sponsor: Pierre Fabre Medicament
• Investigators: Study Director: Karim Keddad, MD, PierreFabre Medicamment

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2013
• Primary Completion (Actual): April 3, 2017
• Study Completion (Actual): June 21, 2017

Study Registration Dates

• First Submitted: April 11, 2013
• First Submitted That Met QC Criteria: April 12, 2013
• First Posted (Estimate): April 15, 2013

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Cardiovascular diseases; Chronic Heart Failure
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: F373280 CA 2 01; 2012-003487-48 (EudraCT Number)