Efficacy & Safety of Dronedarone Versus Amiodarone for th... | NCT00489736

Label	Type	Description	Intervention Names
Dronedarone 400mg bid	Experimental	dronedarone 400mg tablets administered twice a day (bid) and matching over-encapsulated tablets of placebo of amiodarone 200mg	Drug: dronedarone (SR33589)
Amiodarone 600mg/200mg od	Active Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
dronedarone (SR33589)	Drug	oral administration	Dronedarone 400mg bid

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

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.

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.

Name	Affiliation	Role
International Clinical Development	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Sanofi-Aventis Administrative Office		Bridgewater	New Jersey	08807	United States
Sanofi-Aventis Administrative Office

PubMed Identifier	Type	Citation	Retractions
20384650	Derived	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.
17804851

ID	Title	Description
FG000	Dronedarone 400mg Bid	dronedarone tablets 400mg twice daily (bid)
FG001	Amiodarone 600mg/200mg od	amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)

ID	Title	Description
BG000	Dronedarone 400mg Bid	dronedarone tablets 400mg twice daily (bid)
BG001	Amiodarone 600mg/200mg od	amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000249 BG001255 BG002504

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

All randomized and treated patients (receiving at least one dose of study drug) were included in the efficacy analysis according to the treatment received.

Posted

Number

participants

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

ID	Title	Description
OG000	Dronedarone 400mg Bid	dronedarone tablets 400mg twice daily (bid)
OG001	Amiodarone 600mg/200mg od	amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)

Units	Counts
Participants	OG000249 OG001255

Title

Denominators

Categories

Title	Measurements
	OG000184(37.0 to 45.0) OG001141(99.0 to 275.0)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		<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	1.28	1.98			The 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.	No	Superiority or Other

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.

All randomized and treated patients (receiving at least one dose of study drug) were included in the safety analysis according to the treatment received.

Posted

Number

participants

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

ID	Title	Description
OG000	Dronedarone 400mg Bid	dronedarone tablets 400mg twice daily (bid)
OG001	Amiodarone 600mg/200mg od	amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)

Units	Counts

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.

All randomized and treated patients (receiving at least one dose of study drug) were included in the safety analysis according to the treatment received.

Posted

Number

participants

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

ID	Title	Description
OG000	Dronedarone 400mg Bid	dronedarone tablets 400mg twice daily (bid)
OG001	Amiodarone 600mg/200mg od	amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0006 affected249 at risk EG0011 affected255 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0016 affected255 at risk
Bradycardia	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0012 affected255 at risk
Angina pectoris	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0011 affected255 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Diastolic dysfunction	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Pericarditis	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Sick sinus syndrome	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Lung squamous cell carcinoma stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0011 affected255 at risk
Anaplastic thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Carcinoma in situ of bladder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Adrenal adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Gastrointestinal stromal tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Small cell lung cancer stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Pneumonia	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0002 affected249 at risk EG0010 affected255 at risk
Diverticulitis	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0011 affected255 at risk
Bronchitis	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0012 affected255 at risk
Cellulitis	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Ear infection	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Escherichia sepsis	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Gastroenteritis	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Septic shock	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Syncope	Nervous system disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0012 affected255 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Gastrointestinal necrosis	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Therapeutic agent toxicity	Injury, poisoning and procedural complications	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0013 affected255 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0012 affected255 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Blood creatinine increased	Investigations	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0011 affected255 at risk
Electrocardiogram PR prolongation	Investigations	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
International normalised ratio increased	Investigations	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0012 affected255 at risk
Death	General disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Oedema peripheral	General disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Chest pain	General disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Sudden death	General disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Mixed liver injury	Hepatobiliary disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Diabetic foot	Metabolism and nutrition disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Hypoprothrombinaemia	Blood and lymphatic system disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Symphysiolysis	Musculoskeletal and connective tissue disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Haematuria	Renal and urinary disorders	MedDRA 11.0	Non-systematic Assessment	EG0001 affected249 at risk EG0010 affected255 at risk
Urinary retention	Renal and urinary disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk
Pelvic venous thrombosis	Vascular disorders	MedDRA 11.0	Non-systematic Assessment	EG0000 affected249 at risk EG0011 affected255 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Any Gastrointestinal disorders	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG00054 affected249 at risk EG00144 affected255 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG00023 affected249 at risk EG0018 affected255 at risk
Nausea	Gastrointestinal disorders	MedDRA 11.0	Non-systematic Assessment	EG00013 affected249 at risk EG0019 affected255 at risk
Any Infections and infestations	Infections and infestations	MedDRA 11.0	Non-systematic Assessment	EG00035 affected249 at risk EG00135 affected255 at risk
Any Investigations	Investigations	MedDRA 11.0	Non-systematic Assessment	EG00033 affected249 at risk EG00135 affected255 at risk
Any Cardiac disorders	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG00021 affected249 at risk EG00136 affected255 at risk
Bradycardia	Cardiac disorders	MedDRA 11.0	Non-systematic Assessment	EG0004 affected249 at risk EG00114 affected255 at risk
Any Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	MedDRA 11.0	Non-systematic Assessment	EG00021 affected249 at risk EG00122 affected255 at risk
Any Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Non-systematic Assessment	EG00021 affected249 at risk EG00121 affected255 at risk
Any Skin and subcutaneous tissue disorders	Skin and subcutaneous tissue disorders	MedDRA 11.0	Non-systematic Assessment	EG00018 affected249 at risk EG00123 affected255 at risk
Any Nervous system disorders	Nervous system disorders	MedDRA 11.0	Non-systematic Assessment	EG00017 affected249 at risk EG00139 affected255 at risk
Dizziness	Nervous system disorders	MedDRA 11.0	Non-systematic Assessment	EG0008 affected249 at risk EG00116 affected255 at risk
Any General disorders and administration site conditions	General disorders	MedDRA 11.0	Non-systematic Assessment	EG00014 affected249 at risk EG00126 affected255 at risk
Oedema peripheral	General disorders	MedDRA 11.0	Non-systematic Assessment	EG0006 affected249 at risk EG00113 affected255 at risk
Any Vascular disorders	Vascular disorders	MedDRA 11.0	Non-systematic Assessment	EG0009 affected249 at risk EG00123 affected255 at risk
Hypertension	Vascular disorders	MedDRA 11.0	Non-systematic Assessment	EG0007 affected249 at risk EG00116 affected255 at risk
Any Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	MedDRA 11.0	Non-systematic Assessment	EG0008 affected249 at risk EG00117 affected255 at risk
Any Metabolism and nutrition disorders	Metabolism and nutrition disorders	MedDRA 11.0	Non-systematic Assessment	EG0008 affected249 at risk EG00115 affected255 at risk
Any Psychiatric disorders	Psychiatric disorders	MedDRA 11.0	Non-systematic Assessment	EG0006 affected249 at risk EG00123 affected255 at risk
Sleep disorder	Psychiatric disorders	MedDRA 11.0	Non-systematic Assessment	EG0003 affected249 at risk EG00119 affected255 at risk
Any Eye disorders	Eye disorders	MedDRA 11.0	Non-systematic Assessment	EG0006 affected249 at risk EG00113 affected255 at risk
Any Endocrine disorders	Endocrine disorders	MedDRA 11.0	Non-systematic Assessment	EG0003 affected249 at risk EG00114 affected255 at risk

ID	Term
D001145	Arrhythmias, Cardiac
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D001572	Benzofurans
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dronedarone 400mg Bid	dronedarone tablets 400mg twice daily (bid)			34	249	146	249
EG001	Amiodarone 600mg/200mg od	amiodarone 600mg once daily (od) for 28 days, then amiodarone 200mg once daily (od)			37	255	165	255