Efficacy & Safety of Dronedarone Versus Amiodarone for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation (DIONYSOS)

Randomized Double Blind Trial to Evaluate the Efficacy and Safety of Dronedarone (400mg BID) Versus Amiodarone (600mg Daily for 28 Days, Then 200mg Daily Thereafter) for at Least 6 Months for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation (AF)

The objective of this study is to compare the efficacy and safety of dronedarone to that of amiodarone for the treatment of patients with atrial fibrillation.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: dronedarone (SR33589); Drug: amiodarone

• Study Type: Interventional
• Enrollment (Actual): 504
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Sanofi-Aventis Administrative Office
• Australia
  • Cove, Australia
    • Sanofi-Aventis Administrative Office
• Austria
  • Vienna, Austria
    • Sanofi-Aventis Administrative Office
• Belgium
  • Diegem, Belgium
    • Sanofi-Aventis Administrative Office
• Canada
  • Laval, Canada
    • Sanofi-Aventis Administrative Office
• Chile
  • Santiago, Chile
    • Sanofi-Aventis Administrative Office
• China
  • Shangaï, China
    • Sanofi-Aventis Administrative Office
• Czech Republic
  • Praha, Czech Republic
    • Sanofi-Aventis Administrative Office
• Estonia
  • Tallinn, Estonia
    • Sanofi-Aventis Administrative Office
• Finland
  • Helsinki, Finland
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Germany
  • Berlin, Germany
    • Sanofi-Aventis Administrative Office
• Italy
  • Milan, Italy
    • Sanofi-Aventis Administrative Office
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Sanofi-Aventis Administrative Office
• Mexico
  • Mexico, Mexico
    • Sanofi-Aventis Administrative Office
• Morocco
  • Casablanca, Morocco
    • Sanofi-Aventis Administrative Office
• Netherlands
  • Gouda, Netherlands
    • Sanofi-Aventis Administrative Office
• Poland
  • Warszawa, Poland
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office
• Sweden
  • Bromma, Sweden
    • Sanofi-Aventis Administrative Office
• Tunisia
  • Megrine, Tunisia
    • Sanofi-Aventis Administrative Office
• Turkey
  • Istanbul, Turkey
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with documented atrial fibrillation for more than 72 hours for whom cardioversion and antiarrhythmic treatment is indicated in the opinion of the investigator and under oral anticoagulation

Exclusion Criteria:

• Contraindication to oral anticoagulation
• Patient having received amiodarone in the past whatever the date (more than a total of twenty 200 mg tablets or more than 5 days intravenous)
• Patients known to have chronic AF, patients with atrial flutter or paroxysmal atrial fibrillation
• Severe congestive heart failure with New-York Heart Association (NYHA) class III or IV, severe bradycardia, high degree atrio-ventricular block, ongoing potentially dangerous symptoms when in AF such as angina pectoris, transient ischemic attacks, stroke, syncope, as judged by the investigator, first degree family history of sudden cardiac death below age 50 years in the absence of coronary heart disease, significant sinus node disease without a permanent pacemaker implanted
• History of torsades de pointes or long QT syndrome or QT- or QTc-interval ≥500 msecs before randomization
• Treatment with other class I or III antiarrhythmic drugs which cannot be discontinued
• Dysthyroidism or other contraindication to amiodarone

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dronedarone 400mg bid; dronedarone 400mg tablets administered twice a day (bid) and matching over-encapsulated tablets of placebo of amiodarone 200mg	Drug: dronedarone (SR33589); oral administration; Other Names: Multaq®
Active Comparator: Amiodarone 600mg/200mg od; over-encapsulated tablets of amiodarone 200mg (600mg daily for 28 days then 200mg daily) administered once daily (od) and matching placebo of dronedarone 400mg tablets	Drug: amiodarone; oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure	The primary event is the treatment failure defined as the first recurrence of atrial fibrillation or premature study drug discontinuation for intolerance or lack of efficacy according to the investigator judgement. The primary efficacy analysis is performed on the time from first study drug intake to this primary event. The "Measured Values" table below presents the numbers of patients with the event at the end of the study period.	minimum study duration is 6 months (+10 days); maximum is 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of the Main Safety Endpoint (MSE) Defined as Thyroid, Hepatic, Pulmonary, Neurological, Skin, Eye, or Gastrointestinal Specific Treatment Emergent Events or Premature Study Drug Discontinuation Following Any Adverse Event	The considered event is the occurrence of the MSE defined as thyroid, hepatic, pulmonary, neurological, skin, eye, or gastrointestinal specific treatment emergent events or premature study drug discontinuation following any adverse event (AE), whichever comes first. The analysis is performed on the time from first study drug intake to this event. The "Measured Values" table below presents the numbers of patients with the event at the end of the study period.	minimum study duration is 6 months (+10 days); maximum is 15 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of the MSE Excluding Gastrointestinal Specific Treatment Emergent Events Defined as Diarrhoea, Nausea, Vomiting	The considered event is the occurrence of the MSE excluding gastrointestinal specific treatment emergent events defined as diarrhoea, nausea, vomiting. The analysis is performed on the time from first study drug intake to this event. The "Measured Values" table below presents the numbers of patients with the event at the end of the study period.	minimum study duration is 6 months (+10 days); maximum is 15 months

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: International Clinical Development, Sanofi

Publications and helpful links

General Publications

• Le Heuzey JY, De Ferrari GM, Radzik D, Santini M, Zhu J, Davy JM. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol. 2010 Jun 1;21(6):597-605. doi: 10.1111/j.1540-8167.2010.01764.x. Epub 2010 Apr 6.
• Ezekowitz MD. Maintaining sinus rhythm--making treatment better than the disease. N Engl J Med. 2007 Sep 6;357(10):1039-41. doi: 10.1056/NEJMe078148. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: June 20, 2007
• First Submitted That Met QC Criteria: June 20, 2007
• First Posted (Estimate): June 21, 2007

Study Record Updates

• Last Update Posted (Estimate): February 18, 2010
• Last Update Submitted That Met QC Criteria: February 15, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; amiodarone; sinus rhythm
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Amiodarone; Dronedarone
• Other Study ID Numbers: EFC4968