Dronedarone Pattern of Use in Patients Scheduled for Elective Cardioversion (ELECTRA)

• Number of Symptomatic AF Recurrences/Patient/6 Months (With or Without ECG Confirmation) [ Time Frame: up to 6 months from initial cardioversion ] [ Designated as safety issue: No ]
• Characteristics of Symptomatic AF Recurrence (Frequency, Duration of Episodes, Type, Number, and Severity of AF Symptoms) [ Time Frame: up to 6 months from initial cardioversion ] [ Designated as safety issue: No ]
• Proportion of Participants With Early Recurrence of AF (i.e. From 5 Minutes to to 7 Days Following Cardioversion) [ Time Frame: up to 7 days following initial cardioversion ] [ Designated as safety issue: No ]
• Proportion of Participants With Symptomatic AF Recurrences (With or Without ECG Confirmation) [ Time Frame: up to 6 months from initial cardioversion ] [ Designated as safety issue: No ]
• Number of Electrical Cardioversions Per Patient [ Time Frame: up to 6 months from intial cardioversion ] [ Designated as safety issue: No ]
• Number of Shocks Required During Initial Cardioversion [ Time Frame: during the initial cardioversion ] [ Designated as safety issue: No ]
• Cumulative Amount of Energy Delivered and Shock Failure [ Time Frame: during the initial cardioversion ] [ Designated as safety issue: No ]
• Proportion of Participants With Immediate Recurrence of AF (From 5 Seconds to 5 Minutes After Electrical Shock) [ Time Frame: during the initial cardioversion ] [ Designated as safety issue: No ]
• Number of CV Hospitalizations [ Time Frame: up to 6 months from initial cardioversion ] [ Designated as safety issue: No ]
• Quality of Life, as Measured by Atrial Fibrillation Severity Scale (AFSS) and Atrial Fibrillation Effect on Quality of Life (AFEQT) Questionnaires [ Time Frame: Baseline and 6 months after initial cardioversion ] [ Designated as safety issue: No ]

• Number of electrical cardioversions per patient [ Time Frame: Month 3, Month 6 ] [ Designated as safety issue: No ]
• Number of shocks required [ Time Frame: during the first cardioversion ] [ Designated as safety issue: No ]
• Presence of immediate recurrence of AF (IRAF: immediate recurrence of atrial fibrillation) after the initial cardioversion [ Time Frame: after 5 seconds and less than 5 minutes after electrical shock ] [ Designated as safety issue: No ]
• Number of CV hospitalizations, taking into account when the hospitalization occurred, and duration of hospital stay [ Time Frame: Month 3, Month 6 ] [ Designated as safety issue: No ]
• Quality of Life, as measured by AFSS questionnaire [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
• Number of symptomatic AF recurrences/patient/6 months with and without ECG confirmation [ Time Frame: Month 3, Month 6 ] [ Designated as safety issue: No ]
• Characteristics of symptomatic AF recurrence in the two treatment arms (frequency, duration of episodes, type, number, and severity of AF symptoms per patient) [ Time Frame: Month 3, Month 6 ] [ Designated as safety issue: No ]
• Rates of early recurrences of AF (ERAF not IRAF) between the two treatment strategies [ Time Frame: 5 minutes to 7 days following cardioversion ] [ Designated as safety issue: No ]
• Difference in proportion of patients with symptomatic AF recurrences (with and without ECG confirmation) between the two treatment strategies [ Time Frame: Month 3, Month 6 ] [ Designated as safety issue: No ]
• Cumulative amount of energy delivered, shock failure [ Time Frame: during the first cardioversion ] [ Designated as safety issue: No ]

Primary Objective:

To determine whether daily administration of dronedarone started 5-7 days before cardioversion is superior to dronedarone started only after cardioversion with respect to the absence of symptomatic, ECG confirmed, atrial fibrillation (AF) recurrence over 6 months in adult patients with persistent AF, for whom cardioversion is clinically indicated and planned to reduce symptoms and antiarrhythmic treatment is clinically indicated to reduce the risk of cardiovascular hospitalization due to AF.

Secondary Objectives:

Main Secondary :

• To assess the number of symptomatic AF recurrences/patient/6 months with and without ECG confirmation;
• To assess characteristics of symptomatic AF recurrence in the two treatment arms (frequency, duration of episodes, type, number, and severity of AF symptoms per patient);
• To compare the rates of early recurrences of AF between the two treatment strategies;

Other secondary:

• To assess whether there is a difference in proportion of patients with symptomatic AF recurrences (with and without ECG confirmation) between the two treatment strategies;
• To assess whether there is a difference in number of electrical cardioversions per patient between the two treatment strategies;
• To assess the impact of the two strategies on number of shocks, cumulative amount of energy delivered, shock failure, and immediate success of cardioversion;
• To assess whether there is a difference in rate of cardiovascular (CV) hospitalizations and length of hospital stay between the two treatment strategies;
• To assess whether there is a difference in quality of life between the two treatment strategies.

The study period of approximatively 6 months consisted in:

• Double-blind treatment period (placebo or dronedarone) for 5-7 days prior to cardioversion;
• Electrical cardioversion;
• Open-label treatment period with dronedarone for 6 months after cardioversion.

• Drug: Dronedarone

  Film-coated tablet

  Oral administration under fed conditions (during breakfast and dinner)

  Other Names:

  • MULTAQ
  • SR33589
• Drug: Placebo (for dronedarone)

  film-coated tablet strictly identical in appearance

  Oral administration under fed conditions (during breakfast and dinner)

• Experimental: Dronedarone pre-cardioversion
  Dronedarone 400 mg twice a day for 5-7 days prior to cardioversion, then dronedarone 400 mg twice a day for 6 months after cardioversion
  Intervention: Drug: Dronedarone
• Placebo Comparator: Placebo pre-cardioversion
  Placebo (for dronedarone) twice a day for 5-7 days prior to cardioversion, then dronedarone 400 mg twice a day for 6 months after cardioversion
  Interventions:

  • Drug: Dronedarone
  • Drug: Placebo (for dronedarone)

Inclusion criteria:

- Adult patients with persistent AF (current episode at the screening visit >72 hrs and <12 month duration), for whom cardioversion was clinically indicated and planned to reduce symptoms and antiarrhythmic treatment was clinically indicated to reduce the risk of cardiovascular hospitalization due to AF.

Exclusion criteria:

• Severe congestive heart failure (NYHA Class IV) and other unstable hemodynamic conditions;
• Bradycardia <50 bpm;
• QTc Bazett interval ≥500 ms;
• Second- or third- degree atrio-ventricular (AV) block, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker);
• Severe hepatic impairment;
• Pregnancy and lactation;
• History of hypersensitivity reactions to dronedarone or any of its excipients or component of the container.

Concomitant drugs:

• Antiarrhythmic drugs (AADs) other than dronedarone should not be administered during the study and should be withdrawn for at least five plasma half-lives prior to the first study drug administration;
• Dronedarone should not be co-administered with strong CYP3A4 inhibitors;
• Dronedarone should not be co-administered with drugs inducing torsades de pointes.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.