Trial Outcomes & Findings for Efficacy & Safety of Dronedarone Versus Amiodarone for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation (NCT NCT00489736)

Last Updated: 2010-02-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

504 participants

Primary outcome timeframe

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

Results posted on

2010-02-18

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.

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.

Participant milestones

Participant milestones
Measure	Dronedarone 400mg Bid dronedarone tablets 400mg twice daily (bid)	Amiodarone 600mg/200mg od amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)
Overall Study STARTED	249	255
Overall Study COMPLETED	153	186
Overall Study NOT COMPLETED	96	69

Reasons for withdrawal

Reasons for withdrawal
Measure	Dronedarone 400mg Bid dronedarone tablets 400mg twice daily (bid)	Amiodarone 600mg/200mg od amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)
Overall Study Lack of Efficacy	53	14
Overall Study Adverse Event	32	45
Overall Study Poor compliance	6	2
Overall Study Not coded/ Not pre-specified	5	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dronedarone 400mg Bid n=249 Participants dronedarone tablets 400mg twice daily (bid)	Amiodarone 600mg/200mg od n=255 Participants amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)	Total n=504 Participants Total of all reporting groups
Age, Customized 18 to < 65 years	125 participants n=5 Participants	138 participants n=7 Participants	263 participants n=5 Participants
Age, Customized 65 to < 75 years	76 participants n=5 Participants	70 participants n=7 Participants	146 participants n=5 Participants
Age, Customized >= 75 years	48 participants n=5 Participants	47 participants n=7 Participants	95 participants n=5 Participants
Age Continuous	64.4 years STANDARD_DEVIATION 10.8 • n=5 Participants	63.7 years STANDARD_DEVIATION 10.6 • n=7 Participants	64.0 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	73 Participants n=7 Participants	146 Participants n=5 Participants
Sex: Female, Male Male	176 Participants n=5 Participants	182 Participants n=7 Participants	358 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dronedarone 400mg Bid n=249 Participants dronedarone tablets 400mg twice daily (bid)	Amiodarone 600mg/200mg od n=255 Participants amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)
Treatment Failure	184 participants Interval 37.0 to 45.0	141 participants Interval 99.0 to 275.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Dronedarone 400mg Bid n=249 Participants dronedarone tablets 400mg twice daily (bid)	Amiodarone 600mg/200mg od n=255 Participants amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (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	83 participants	107 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Dronedarone 400mg Bid n=249 Participants dronedarone tablets 400mg twice daily (bid)	Amiodarone 600mg/200mg od n=255 Participants amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)
Occurrence of the MSE Excluding Gastrointestinal Specific Treatment Emergent Events Defined as Diarrhoea, Nausea, Vomiting	61 participants	99 participants

Adverse Events

Dronedarone 400mg Bid

Serious events: 34 serious events

Other events: 146 other events

Deaths: 0 deaths

Amiodarone 600mg/200mg od

Serious events: 37 serious events

Other events: 165 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

International Clinical Development, Clinical Study Director

sanofi-aventis

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such publication for comment at least 45 days before any submission for publication. If requested by the Sponsor, any submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dronedarone 400mg Bid n=249 participants at risk dronedarone tablets 400mg twice daily (bid)	Amiodarone 600mg/200mg od n=255 participants at risk amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)
Gastrointestinal disorders Any Gastrointestinal disorders	21.7% 54/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	17.3% 44/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Gastrointestinal disorders Diarrhoea	9.2% 23/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	3.1% 8/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Gastrointestinal disorders Nausea	5.2% 13/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	3.5% 9/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Infections and infestations Any Infections and infestations	14.1% 35/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	13.7% 35/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Investigations Any Investigations	13.3% 33/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	13.7% 35/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Cardiac disorders Any Cardiac disorders	8.4% 21/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	14.1% 36/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Cardiac disorders Bradycardia	1.6% 4/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	5.5% 14/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Musculoskeletal and connective tissue disorders Any Musculoskeletal and connective tissue disorders	8.4% 21/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	8.6% 22/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Respiratory, thoracic and mediastinal disorders Any Respiratory, thoracic and mediastinal disorders	8.4% 21/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	8.2% 21/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Skin and subcutaneous tissue disorders Any Skin and subcutaneous tissue disorders	7.2% 18/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	9.0% 23/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Nervous system disorders Any Nervous system disorders	6.8% 17/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	15.3% 39/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Nervous system disorders Dizziness	3.2% 8/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	6.3% 16/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
General disorders Any General disorders and administration site conditions	5.6% 14/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	10.2% 26/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
General disorders Oedema peripheral	2.4% 6/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	5.1% 13/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Vascular disorders Any Vascular disorders	3.6% 9/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	9.0% 23/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Vascular disorders Hypertension	2.8% 7/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	6.3% 16/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Injury, poisoning and procedural complications Any Injury, poisoning and procedural complications	3.2% 8/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	6.7% 17/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Metabolism and nutrition disorders Any Metabolism and nutrition disorders	3.2% 8/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	5.9% 15/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Psychiatric disorders Any Psychiatric disorders	2.4% 6/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	9.0% 23/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Psychiatric disorders Sleep disorder	1.2% 3/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	7.5% 19/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Eye disorders Any Eye disorders	2.4% 6/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	5.1% 13/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.
Endocrine disorders Any Endocrine disorders	1.2% 3/249 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.	5.5% 14/255 • From first to last study drug intake +10 days i.e. end of the study. The safety population was the "All randomized and treated patients" population.