Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, sinus rhythm, amiodarone
Brief 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.
Interventions
oral administration
DRUGamiodarone
oral administration
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Failure | minimum study duration is 6 months (+10 days); maximum is 15 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | minimum study duration is 6 months (+10 days); maximum is 15 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of the MSE Excluding Gastrointestinal Specific Treatment Emergent Events Defined as Diarrhoea, Nausea, Vomiting | minimum study duration is 6 months (+10 days); maximum is 15 months | 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. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, China, Czechia, Estonia, Finland, France, Germany, Italy, Mexico, Morocco, Netherlands, Poland, Russia, South Korea, Sweden, Tunisia, Turkey (Türkiye), United States
Participant flow
Recruitment details
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.
Pre-assignment details
Planned sample size was 472. Six hundred and eighteen patients (618) were screened of which 113 did not verify one or more selection criteria. One eligible patient received a placebo capsule (morning intake in the amiodarone group) but was not randomized in the trial. This patient did not report any adverse event and was excluded from all analyses.
Participants by arm
| Arm | Count |
|---|---|
| Dronedarone 400mg Bid dronedarone tablets 400mg twice daily (bid) | 249 |
| Amiodarone 600mg/200mg od amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od) | 255 |
| Total | 504 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 32 | 45 |
| Overall Study | Lack of Efficacy | 53 | 14 |
| Overall Study | Not coded/ Not pre-specified | 5 | 8 |
| Overall Study | Poor compliance | 6 | 2 |
Baseline characteristics
| Characteristic | Total | Amiodarone 600mg/200mg od | Dronedarone 400mg Bid |
|---|---|---|---|
| Age Continuous | 64.0 years STANDARD_DEVIATION 10.7 | 63.7 years STANDARD_DEVIATION 10.6 | 64.4 years STANDARD_DEVIATION 10.8 |
| Age, Customized 18 to < 65 years | 263 participants | 138 participants | 125 participants |
| Age, Customized 65 to < 75 years | 146 participants | 70 participants | 76 participants |
| Age, Customized >= 75 years | 95 participants | 47 participants | 48 participants |
| Sex: Female, Male Female | 146 Participants | 73 Participants | 73 Participants |
| Sex: Female, Male Male | 358 Participants | 182 Participants | 176 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 146 / 249 | 165 / 255 |
| serious Total, serious adverse events | 34 / 249 | 37 / 255 |
Outcome results
Primary
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
Population: All randomized and treated patients (receiving at least one dose of study drug) were included in the efficacy analysis according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dronedarone 400mg Bid | Treatment Failure | 184 participants |
| Amiodarone 600mg/200mg od | Treatment Failure | 141 participants |
p-value: <0.000195% CI: [1.28, 1.98]Log Rank
Secondary
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
Population: All randomized and treated patients (receiving at least one dose of study drug) were included in the safety analysis according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dronedarone 400mg Bid | 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 | 83 participants |
| Amiodarone 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 Event | 107 participants |
p-value: 0.1395% CI: [0.6, 1.07]Log Rank
Other Pre-specified
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
Population: All randomized and treated patients (receiving at least one dose of study drug) were included in the safety analysis according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dronedarone 400mg Bid | Occurrence of the MSE Excluding Gastrointestinal Specific Treatment Emergent Events Defined as Diarrhoea, Nausea, Vomiting | 61 participants |
| Amiodarone 600mg/200mg od | Occurrence of the MSE Excluding Gastrointestinal Specific Treatment Emergent Events Defined as Diarrhoea, Nausea, Vomiting | 99 participants |
p-value: 0.00295% CI: [0.44, 0.84]Log Rank