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CompletedNCT00489736DIONYSOSUpdated Feb 18, 2010Results posted

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

A Phase 3 interventional study of dronedarone (SR33589) and amiodarone in Atrial Fibrillation, sponsored by Sanofi. Completed at 23 sites in 23 countries. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2010-02-18.

Sponsored by Sanofi · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
504
Allocation
Randomized
Ages
21 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Atrial Fibrillation

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Keywords

  • Atrial Fibrillation
  • sinus rhythm
  • amiodarone
03

In context

Atrial Fibrillation

3,870 studies on the registry are indexed under Atrial Fibrillation; 924 are open to participants now.

This study's enrollment of 504 is above the median of 144 across 2,380 interventional studies indexed under Atrial Fibrillation.

Browse Atrial Fibrillation studies →

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
504 participants (actual)

Study arms

  • 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)

  • 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

Interventions

  • Drugdronedarone (SR33589)

    oral administration

    Also known as: Multaq®

  • Drugamiodarone

    oral administration

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: minimum study duration is 6 months (+10 days); maximum is 15 months

Secondary outcomes

  1. 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.

    Time frame: minimum study duration is 6 months (+10 days); maximum is 15 months

Other outcomes

  1. 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.

    Time frame: minimum study duration is 6 months (+10 days); maximum is 15 months

07

Results

Posted Nov 9, 2009

Participant flow

Enrollment of patients started on June 12, 2007 and was completed on October 3, 2008. The study was conducted in 112 centers in 23 countries. Minimum duration of treatment was 6 months. Minimum duration of observation was last patient's randomization plus 190 days.

Participant flow — Overall Study
MilestoneDronedarone 400mg BidAmiodarone 600mg/200mg od
Started249255
Completed153186
Not completed9669
Withdrew: Lack of efficacy5314
Withdrew: Adverse event3245
Withdrew: Poor compliance62
Withdrew: Not coded/ not pre-specified58

Outcome measures

PrimaryTreatment 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.

Time frame:
minimum study duration is 6 months (+10 days); maximum is 15 months
Reported as:
Number · participants
Treatment Failure
participantsDronedarone 400mg BidAmiodarone 600mg/200mg od
Treatment Failure184 (37.0 to 45.0)141 (99.0 to 275.0)
Statistical analysis
  • Dronedarone 400mg Bid vs Amiodarone 600mg/200mg od · Log Rank · p = <0.0001 (Cumulative incidence functions in each treatment group were calculated using time-to-event non-parametric Kaplan-Meier estimate. The primary comparison was performed at the 5% level using a 2-sided Log rank test.) · Hazard ratio (hr): 1.59 · 95% CI 1.28 to 1.98The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It provides the relative hazard of treatment failure for the dronedarone group compared with the amiodarone group.
SecondaryOccurrence 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.

Time frame:
minimum study duration is 6 months (+10 days); maximum is 15 months
Reported as:
Number · participants
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
participantsDronedarone 400mg BidAmiodarone 600mg/200mg od
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 Event83107
Statistical analysis
  • Dronedarone 400mg Bid vs Amiodarone 600mg/200mg od · Log Rank · p = 0.13 (Cumulative incidence functions in each treatment group were calculated using time-to-event non-parametric Kaplan-Meier estimate. The comparison was performed at the 5% level using a 2-sided Log rank test.) · Hazard ratio (hr): 0.80 · 95% CI 0.60 to 1.07The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It provides the relative hazard of main safety event occurrence for the dronedarone group compared with the amiodarone group.
Other pre-specifiedOccurrence 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.

Time frame:
minimum study duration is 6 months (+10 days); maximum is 15 months
Reported as:
Number · participants
Occurrence of the MSE Excluding Gastrointestinal Specific Treatment Emergent Events Defined as Diarrhoea, Nausea, Vomiting
participantsDronedarone 400mg BidAmiodarone 600mg/200mg od
Occurrence of the MSE Excluding Gastrointestinal Specific Treatment Emergent Events Defined as Diarrhoea, Nausea, Vomiting6199
Statistical analysis
  • Dronedarone 400mg Bid vs Amiodarone 600mg/200mg od · Log Rank · p = 0.002 (Cumulative incidence functions in each treatment group were calculated using time-to-event non-parametric Kaplan-Meier estimate. The comparison was performed at the 5% level using a 2-sided Log rank test.) · Hazard ratio (hr): 0.61 · 95% CI 0.44 to 0.84The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It provides the relative hazard of MSE occurrence excluding gastrointestinal events, for the dronedarone group compared with the amiodarone group.

Adverse events

Collected over From first to last study drug intake +10 days i.e. end of the study.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dronedarone 400mg Bid—34/249 (13.7%)146/249 (58.6%)
Amiodarone 600mg/200mg od—37/255 (14.5%)165/255 (64.7%)
Most frequent serious events
Showing 10 of 74
Most frequent serious events
EventDronedarone 400mg BidAmiodarone 600mg/200mg od
Cardiac failureCardiac disorders6/2491/255
Cardiac failure congestiveCardiac disorders1/2496/255
Therapeutic agent toxicityInjury, poisoning and procedural complications1/2493/255
PneumoniaInfections and infestations2/2490/255
BradycardiaCardiac disorders1/2492/255
BronchitisInfections and infestations0/2492/255
SyncopeNervous system disorders0/2492/255
Accidental overdoseInjury, poisoning and procedural complications0/2492/255
International normalised ratio increasedInvestigations0/2492/255
Angina pectorisCardiac disorders1/2491/255
Most frequent other events
Showing 10 of 22
Most frequent other events
EventDronedarone 400mg BidAmiodarone 600mg/200mg od
Any Gastrointestinal disordersGastrointestinal disorders54/24944/255
Any Nervous system disordersNervous system disorders17/24939/255
Any Cardiac disordersCardiac disorders21/24936/255
Any Infections and infestationsInfections and infestations35/24935/255
Any InvestigationsInvestigations33/24935/255
Any General disorders and administration site conditionsGeneral disorders14/24926/255
DiarrhoeaGastrointestinal disorders23/2498/255
Any Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders18/24923/255
Any Vascular disordersVascular disorders9/24923/255
Any Psychiatric disordersPsychiatric disorders6/24923/255

Baseline characteristics

Age, Customized
Age, Customized(participants)Dronedarone 400mg BidAmiodarone 600mg/200mg odTotal
18 to < 65 years125138263
65 to < 75 years7670146
>= 75 years484795
Age Continuous
Age Continuous(years)Dronedarone 400mg BidAmiodarone 600mg/200mg odTotal
Mean64.4 ± 10.863.7 ± 10.664.0 ± 10.7
Sex: Female, Male
Sex: Female, Male(Participants)Dronedarone 400mg BidAmiodarone 600mg/200mg odTotal
Female7373146
Male176182358
08

Study locations

23 sites
  • Sanofi-Aventis Administrative Office
    Bridgewater, New Jersey 08807, United States
  • Sanofi-Aventis Administrative Office
    Buenos Aires, Argentina
  • Sanofi-Aventis Administrative Office
    Cove, Australia
  • Sanofi-Aventis Administrative Office
    Vienna, Austria
  • Sanofi-Aventis Administrative Office
    Diegem, Belgium
  • Sanofi-Aventis Administrative Office
    Laval, Canada
  • Sanofi-Aventis Administrative Office
    Santiago, Chile
  • Sanofi-Aventis Administrative Office
    Shangaï, China
  • Sanofi-Aventis Administrative Office
    Praha, Czech Republic
  • Sanofi-Aventis Administrative Office
    Tallinn, Estonia
  • Sanofi-Aventis Administrative Office
    Helsinki, Finland
  • Sanofi-Aventis Administrative Office
    Paris, France
  • Sanofi-Aventis Administrative Office
    Berlin, Germany
  • Sanofi-Aventis Administrative Office
    Milan, Italy
  • Sanofi-Aventis Administrative Office
    Seoul, Korea, Republic of
  • Sanofi-Aventis Administrative Office
    Mexico, Mexico
  • Sanofi-Aventis Administrative Office
    Casablanca, Morocco
  • Sanofi-Aventis Administrative Office
    Gouda, Netherlands
  • Sanofi-Aventis Administrative Office
    Warszawa, Poland
  • Sanofi-Aventis Administrative Office
    Moscow, Russian Federation
  • Sanofi-Aventis Administrative Office
    Bromma, Sweden
  • Sanofi-Aventis Administrative Office
    Megrine, Tunisia
  • Sanofi-Aventis Administrative Office
    Istanbul, Turkey
09

References and documents

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. PubMed 20384650 ↗
  • 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. PubMed 17804851 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 18, 2010, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00489736
Lead sponsor
Sanofi
First posted
Jun 21, 2007
Start date
Jun 2007
Primary completion
Oct 2008
Completion
Oct 2008
Results posted
Nov 9, 2009
Last update
Feb 18, 2010

Study contacts

International Clinical Development
study director · Sanofi

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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