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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase IV, Double-blind, Placebo-controlled, Canadian Multicentre Study Comparing Two Treatment Strategies of Dronedarone Administration Following ELECTive caRdioversion for Prevention of Symptomatic Atrial Fibrillation (AF) Recurrence

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Dronedarone
* Drug: Placebo (for dronedarone)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dronedarone pre-cardioversion<br>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 | Drug: Dronedarone<br>* Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)<br>* Other names: SR33589;|
| Placebo Comparator: Placebo pre-cardioversion<br>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 | Drug: Dronedarone<br>* Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)<br>* Other names: SR33589;Drug: Placebo (for dronedarone)<br>* film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with at least one symptomatic, ECG confirmed, AF recurrence |  | 6 months from initial cardioversion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Symptomatic AF Recurrences/Patient/6 Months (With or Without ECG Confirmation) |  | up to 6 months from initial cardioversion | 
| Characteristics of Symptomatic AF Recurrence (Frequency, Duration of Episodes, Type, Number, and Severity of AF Symptoms) |  | up to 6 months from initial cardioversion | 
| Proportion of Participants With Early Recurrence of AF (i.e. From 5 Minutes to to 7 Days Following Cardioversion) |  | up to 7 days following initial cardioversion | 
| Proportion of Participants With Symptomatic AF Recurrences (With or Without ECG Confirmation) |  | up to 6 months from initial cardioversion | 
| Number of Electrical Cardioversions Per Patient |  | up to 6 months from intial cardioversion | 
| Number of Shocks Required During Initial Cardioversion |  | during the initial cardioversion | 
| Cumulative Amount of Energy Delivered and Shock Failure |  | during the initial cardioversion | 
| Proportion of Participants With Immediate Recurrence of AF (From 5 Seconds to 5 Minutes After Electrical Shock) |  | during the initial cardioversion | 
| Number of CV Hospitalizations |  | up to 6 months from initial cardioversion | 
| Quality of Life, as Measured by Atrial Fibrillation Severity Scale (AFSS) and Atrial Fibrillation Effect on Quality of Life (AFEQT) Questionnaires |  | Baseline and 6 months after initial cardioversion |