HESTIA: Effects of Dronedarone on Atrial Fibrillation Burden in Subjects With Permanent Pacemakers

• Sponsor: Sanofi (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01135017
• Collaborator: (none)
• Enrollment: 112
• Locations: 92
• Arms: 2
• Duration (Months): 19.1
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary objective was to evaluate the effects of dronedarone on Atrial Fibrillation (AF) burden (i.e. percent time in AF) as measured on electrogram (EGM) in subjects with a permanent pacemaker.

Secondary objectives were to evaluate:

• the effects of dronedarone on AF pattern characteristics i.e. ventricular rate during AF;

• the effects of dronedarone on subject-perceived AF burden and symptom severity as reported by subjects using the Atrial Fibrillation Severity Scale (AFSS);

• the incidence of electrical cardioversion (or overdrive pacing) during treatment;

• the safety of dronedarone.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Dronedarone; Drug: Placebo (for Dronedarone)	Phase 4

Detailed Description

The maximum duration of the study period for a participant was 18 weeks (approximatively 4.5 months) including up to 4 weeks screening, 12-week Treatment period and a post-treatment follow-up of 2 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled, Double-Blind, Randomized, Multi-Center Study to Assess the Effects of Dronedarone 400 mg BID for 12 Weeks on Atrial Fibrillation Burden in Subjects With Permanent Pacemakers
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dronedarone Dronedarone 400 mg twice a day for 12 weeks	Drug: Dronedarone; Film-coated tablet Oral administration under fed conditions (during breakfast and dinner); Other Names: Multaq® SR33589
Placebo Comparator: Placebo Placebo (for Dronedarone) twice a day for 12 weeks	Drug: Placebo (for Dronedarone); Film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)

Outcome Measures

Primary Outcome Measures

1. Atrial Fibrillation (AF) Burden During the 12-week Treatment Period [Baseline (before randomization), 4 weeks and 12 weeks after randomization]

   AF burden, defined as the percent time a subject is in AF, was evaluated centrally by a Pacemaker Core Lab based on pacemaker interrogation reports including Electrogram (EGM) data provided by the Investigator. AF burden during the 12-week treatment period was defined as the duration-weighted average of AF burden collected at Week 4 and Week 12. It was calculated from the single available measurement when one measurement was missing.

Secondary Outcome Measures

1. AF Burden During the First 4 Weeks of Treatment and After 4-week Treatment [4 weeks and 12 weeks after randomization]

   AF burden at each pacemaker interrogation as evaluated centrally by the Pacemaker Core Lab

2. Average Ventricular Rate During AF Episodes [Baseline (before randomization), 4 weeks and 12 weeks after randomization]

   Ventricular rates of AF episodes were obtained from pacemaker interrogation and EGM review. The average ventricular rate during AF episodes in the 12-week treatment period was defined as the duration-weighted average of the ventricular rates collected at Week 4 and Week 12. It was calculated from the single available measurement when one measurement was missing.

3. Atrial Fibrillation Severity Scale (AFSS) Scores [Baseline (before randomization) and 12 weeks after randomization]

   The University of Toronto Atrial Fibrillation Severity Scale is an instrument to assess the subject-perceived AF burden and AF symptom severity. It consists in a questionnaire plus a scoring algorithm. AF Burden score ranges from 3 to 30 and higher scores indicate greater AF burden. AF symptoms severity score ranges from 0 to 35 and higher scores indicate extremely severe AF symptoms.

4. Incidence Rate of Electrical Cardioversion (or Overdrive Pacing) [12 weeks]

   Electrical cardioversion is a procedure in which an electric shock is used to restore normal heart rhythm. Overdrive pacing is a procedure in which an artificial cardiac pacemaker is used to increase the heart rate in order to suppress certain arrhythmias. Incidence rate of electrical cardioversion (or overdrive pacing) is expressed as the number of participants that was cardioverted or paced during the study.

Other Outcome Measures

1. Overview of Adverse Events (AE) [from first study drug intake up to 10 days after the last study drug intake]

   AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Paroxysmal AF or atrial flutter (AFL) documented by evidence of AF/AFL and sinus rhythm within the prior 6 months;

• AF burden ≥1% on pacemaker EGM interrogation at screening, with at least one episode of AF within the previous 28 days;

• Programmable dual chamber pacemaker with lead placement no less than 3 months before screening, a minimum capability of storing 3 months or more of EGM data, and an expected remaining battery life of 1 year or more.

Exclusion criteria:

• AF burden <1% on pacemaker EGM interrogation at screening;

• None of the following cardiovascular risk factors: Age ≥70 years, hypertension, diabetes mellitus, prior cardiovascular accident or systemic embolism, left atrium diameter ≥50 mm by M-mode or 2D echocardiography, or left ventricular ejection fraction ≤0.40 by M-mode or 2D echocardiography, cardiac catheterization, or nuclear cardiac imaging;

• Permanent AF;

• Evidence of persistent AF (continuous AF activity lasting longer than 7 days);

• Electrical cardioversion (or overdrive pacing) within 4 weeks prior to screening;

• Cardiac ablation procedure within 3 months prior to screening;

• Evidence of uncorrected atrial undersensing or oversensing documented in routine pacemaker evaluation at screening;

• Pacemaker programming requirements for the study not clinically feasible, contraindicated, or could have posed risk;

• Ongoing potentially dangerous symptoms when in AF/AFL such as angina pectoris, transient ischemic attacks, stroke, or syncope;

• New York Heart Association (NYHA) Class IV heart failure or NYHA Class II or III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within 4 weeks prior to screening;

• Evidence of clinical instability including hypotension, unstable angina and hemodynamically significant obstructive valvular disease, hemodynamically significant obstructive cardiomyopathy, a cardiac operation, or revascularization procedure within 4 weeks prior to screening;

• Noncardiovascular illness or disorder that could have precluded participation or severely limit survival including cancer with metastasis and organ transplantation requiring immune suppression;

• Planned noncardiac or cardiac surgery or procedures including surgery for valvular heart disease, coronary artery bypass graft, percutaneous coronary intervention, cardiac transplantation or electrical cardioversion for AF/AFL;

• Need for concomitant medication that were prohibited in this trial: Antiarrhythmics, drugs or products that are strong inhibitors of CYP3A, CYP3A inducers;

• Chronic use of amiodarone within the 4 weeks prior to screening;

• Use of Class I or Class III antiarrhythmics (other than amiodarone) within 5-half lives prior to screening;

• Use of St John's wort, grapefruit juice, or drugs that prolong the QT interval and might have increased the risk of torsade de pointes;

• Inability or unwillingness to comply with oral anticoagulation therapy, if indicated;

• Bazett corrected QT interval interval ≥500 msec at screening (if in sinus rhythm);

• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥ 100mmHg) at screening;

• Uncorrected hypokalemia (serum potassium <3.5 mEq/L)

• Severe hepatic impairment (ie, Child-Pugh Class C), abnormal liver function test defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin >2 X upper limit of normal (ULN), or renal impairment defined as serum creatinine >2.0 mg/dL at screening;

• Uncontrolled diabetes mellitus (documented history of HbA1c >10% at the most recent assessment prior to screening);

• Pregnant woman or woman of childbearing potential not on adequate birth control;

• Breastfeeding woman;

• Previous (within 2 months prior to screening) or current participation in another clinical trial with an investigational drug (under development) or investigational device.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840015	Birmingham	Alabama	United States	35235
2	Investigational Site Number 840087	Huntsville	Alabama	United States	35801
3	Investigational Site Number 840018	Mobile	Alabama	United States	36608
4	Investigational Site Number 840030	Mesa	Arizona	United States	85206
5	Investigational Site Number 840048	Phoenix	Arizona	United States	85006
6	Investigational Site Number 840072	Phoenix	Arizona	United States	85032
7	Investigational Site Number 840013	Tucson	Arizona	United States	85723
8	Investigational Site Number 840069	Hot Springs	Arkansas	United States	71913
9	Investigational Site Number 840121	Beverly Hills	California	United States	90211
10	Investigational Site Number 840090	Laguna Hills	California	United States	92653
11	Investigational Site Number 840068	Los Angeles	California	United States	90048
12	Investigational Site Number 840062	Mission Hills	California	United States	91345
13	Investigational Site Number 840070	Orange	California	United States	92868
14	Investigational Site Number 840021	Riverside	California	United States	92501
15	Investigational Site Number 840024	San Diego	California	United States	92103
16	Investigational Site Number 840001	Aurora	Colorado	United States	80012
17	Investigational Site Number 840089	Littleton	Colorado	United States	80120
18	Investigational Site Number 840029	Loveland	Colorado	United States	80538
19	Investigational Site Number 840108	Newark	Delaware	United States	19713
20	Investigational Site Number 840045	Washington	District of Columbia	United States	20010-2975
21	Investigational Site Number 840106	Washington	District of Columbia	United States	20037
22	Investigational Site Number 840010	Clearwater	Florida	United States	33756
23	Investigational Site Number 840020	Ft. Myers	Florida	United States	33908
24	Investigational Site Number 840058	Inverness	Florida	United States	34452
25	Investigational Site Number 840044	Jacksonville Beach	Florida	United States	32250
26	Investigational Site Number 840043	Jacksonville	Florida	United States	32204
27	Investigational Site Number 840066	Jacksonville	Florida	United States	32216
28	Investigational Site Number 840128	Jacksonville	Florida	United States	32216
29	Investigational Site Number 840042	Orlando	Florida	United States	32803
30	Investigational Site Number 840016	Port Charlotte	Florida	United States	33952
31	Investigational Site Number 840080	Wellington	Florida	United States	33449
32	Investigational Site Number 840056	Gainesville	Georgia	United States	30501
33	Investigational Site Number 840092	Normal	Illinois	United States	61761
34	Investigational Site Number 840032	Oak Lawn	Illinois	United States	60453
35	Investigational Site Number 840046	Rockford	Illinois	United States	61107
36	Investigational Site Number 840051	Bloomington	Indiana	United States	47403
37	Investigational Site Number 840053	Kansas City	Kansas	United States	66160
38	Investigational Site Number 840110	Owensboro	Kentucky	United States	42303
39	Investigational Site Number 840102	Columbia	Maryland	United States	21044
40	Investigational Site Number 840017	Lansing	Michigan	United States	48910
41	Investigational Site Number 840081	Lapeer	Michigan	United States	48446
42	Investigational Site Number 840075	Petoskey	Michigan	United States	49770
43	Investigational Site Number 840027	Troy	Michigan	United States	48085
44	Investigational Site Number 840104	St Cloud	Minnesota	United States	56301
45	Investigational Site Number 840097	Tupelo	Mississippi	United States	38801
46	Investigational Site Number 840037	Columbia	Missouri	United States	65212
47	Investigational Site Number 840035	Kansas City	Missouri	United States	64111
48	Investigational Site Number 840060	St Louis	Missouri	United States	63122
49	Investigational Site Number 840055	St. Louis	Missouri	United States	63141
50	Investigational Site Number 840067	Missoula	Montana	United States	59802
51	Investigational Site Number 840049	Reno	Nevada	United States	89502
52	Investigational Site Number 840054	Reno	Nevada	United States	89502
53	Investigational Site Number 840026	Bridgewater	New Jersey	United States	08807
54	Investigational Site Number 840093	Englewood	New Jersey	United States	07631
55	Investigational Site Number 840036	Bronx	New York	United States	10467
56	Investigational Site Number 840006	Buffalo	New York	United States	14215
57	Investigational Site Number 840077	Kingston	New York	United States	12401
58	Investigational Site Number 840096	Mineola	New York	United States	11501
59	Investigational Site Number 840041	Syracuse	New York	United States	13202
60	Investigational Site Number 840086	Troy	New York	United States	12180
61	Investigational Site Number 840007	Williamsville	New York	United States	14221
62	Investigational Site Number 840084	Raleigh	North Carolina	United States	27610
63	Investigational Site Number 840061	Wilmington	North Carolina	United States	28401
64	Investigational Site Number 840065	Tulsa	Oklahoma	United States	74104
65	Investigational Site Number 840008	Camp Hill	Pennsylvania	United States	17011
66	Investigational Site Number 840009	Doylestown	Pennsylvania	United States	18901
67	Investigational Site Number 840004	Philadelphia	Pennsylvania	United States	19111
68	Investigational Site Number 840078	Phoenixville	Pennsylvania	United States	19460
69	Investigational Site Number 840105	Pittsburgh	Pennsylvania	United States	15236
70	Investigational Site Number 840130	Scranton	Pennsylvania	United States	18510
71	Investigational Site Number 840019	Unionville	Pennsylvania	United States	15401
72	Investigational Site Number 840023	Wyomissing	Pennsylvania	United States	19610
73	Investigational Site Number 840119	Greenville	South Carolina	United States	29607
74	Investigational Site Number 840002	Rapid City	South Dakota	United States	57701
75	Investigational Site Number 840114	Germantown	Tennessee	United States	38138
76	Investigational Site Number 840118	Corpus Christi	Texas	United States	78404
77	Investigational Site Number 840014	Dallas	Texas	United States	75390-8858
78	Investigational Site Number 840012	San Antonio	Texas	United States	78229
79	Investigational Site Number 840125	Tyler	Texas	United States	75701
80	Investigational Site Number 840083	Salt Lake City	Utah	United States	84102
81	Investigational Site Number 840113	Danville	Virginia	United States	24541
82	Investigational Site Number 840082	Lynchburg	Virginia	United States	24501
83	Investigational Site Number 840088	Manassas	Virginia	United States	20109
84	Investigational Site Number 840099	Richmond	Virginia	United States	23219
85	Investigational Site Number 840112	Richmond	Virginia	United States	23230
86	Investigational Site Number 840003	Tacoma	Washington	United States	98405
87	Investigational Site Number 840107	Tacoma	Washington	United States	98405
88	Investigational Site Number 840123	Green Bay	Wisconsin	United States	54301-3505
89	Investigational Site Number 840022	Madison	Wisconsin	United States	53713
90	Investigational Site Number 840033	Milwaukee	Wisconsin	United States	53215
91	Investigational Site Number 840047	Milwaukee	Wisconsin	United States	53215
92	Investigational Site Number 840076	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01135017
• Other Study ID Numbers: DRONE_L_04316; U1111-1117-0024
• First Posted: Jun 2, 2010
• Last Update Posted: Apr 11, 2013
• Last Verified: Apr 1, 2013

• Additional relevant MeSH terms: Atrial Fibrillation; Dronedarone

Study Results

Participant Flow

Recruitment Details	Recruitment initiated in July 2010 was discontinued in December, 2011 due to significantly lower than planned enrollment with no feasibility to complete the trial within reasonable, meaningful timelines and despite a protocol amendment that extended the recruitment period and reduced the sample size from 424 to 286 participants.
Pre-assignment Detail	After signature of the informed consent and after eligibility was confirmed, group assignment was made at site in a 1:1 ratio using a treatment code list generated centrally by Sanofi. Participants were considered as randomized as soon as the assignment was made. Only 112 patients were randomized at 62 sites.

Arm/Group Title	Placebo	Dronedarone
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks
Period Title: Overall Study
STARTED	55	57
Treated	55	57
Evaluable for Efficacy	55	55
COMPLETED	49	45
NOT COMPLETED	6	12

Baseline Characteristics

Arm/Group Title	Placebo	Dronedarone	Total
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks	Total of all reporting groups
Overall Participants	55	57	112
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.5 (9.5)	77.3 (8.6)	75.9 (9.1)
Sex: Female, Male (Count of Participants)
Female	17 30.9%	28 49.1%	45 40.2%
Male	38 69.1%	29 50.9%	67 59.8%

Outcome Measures

1. Primary Outcome

Title	Atrial Fibrillation (AF) Burden During the 12-week Treatment Period
Description	AF burden, defined as the percent time a subject is in AF, was evaluated centrally by a Pacemaker Core Lab based on pacemaker interrogation reports including Electrogram (EGM) data provided by the Investigator. AF burden during the 12-week treatment period was defined as the duration-weighted average of AF burden collected at Week 4 and Week 12. It was calculated from the single available measurement when one measurement was missing.
Time Frame	Baseline (before randomization), 4 weeks and 12 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis included all randomized and treated participants with post-baseline AF burden assessment. Participants were included in the treatment group to which they were randomized (Modified Intent-to-treat analysis).

Arm/Group Title	Placebo	Dronedarone
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks
Measure Participants	55	55
Baseline	8.77	10.14
12-week treatment period	9.90	4.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dronedarone
	Comments	The planned sample size of 286 participants was estimated to have 70% power to detect a reduction in mean AF burden of 30% relative to the placebo group. Due to the smaller-than-planned sample size, the power to detect this difference was estimated to be only 44%, based on the original assumption. However, the power to detect larger treatment effects (>40% reduction) remained high and the posthoc power to detect a 60% reduction in AF burden was 99%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	No adjustment for multiplicity was made. The priori threshold for statistical significance was ≤0.05.
	Method	ANCOVA
	Comments	ANCOVA model on log-transformed AF burden data with treatment arm as a fixed effect term and baseline log-transformed AF burden as a covariate
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean difference
	Estimated Value	-59.13
	Confidence Interval	(2-Sided) 95%; -76.322 to -29.457
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.275
	Estimation Comments	Percent change in AF burden with dronedarone relative to placebo LS Mean difference from the ANCOVA model on log-transformed AF burden data was exponentiated to convert back to percent change.

2. Secondary Outcome

Title	AF Burden During the First 4 Weeks of Treatment and After 4-week Treatment
Description	AF burden at each pacemaker interrogation as evaluated centrally by the Pacemaker Core Lab
Time Frame	4 weeks and 12 weeks after randomization

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population as previously defined

Arm/Group Title	Placebo	Dronedarone
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks
Measure Participants	55	55
Week 1 - 4 (n =54, 49)	8.99	3.62
Week 5 - 12 (n =54, 54)	9.37	4.28

3. Secondary Outcome

Title	Average Ventricular Rate During AF Episodes
Description	Ventricular rates of AF episodes were obtained from pacemaker interrogation and EGM review. The average ventricular rate during AF episodes in the 12-week treatment period was defined as the duration-weighted average of the ventricular rates collected at Week 4 and Week 12. It was calculated from the single available measurement when one measurement was missing.
Time Frame	Baseline (before randomization), 4 weeks and 12 weeks after randomization

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population as previously defined

Arm/Group Title	Placebo	Dronedarone
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks
Measure Participants	55	55
Baseline (n =49, 47)	93.02 (16.74)	90.68 (19.80)
Week 1-12 (n =49, 48)	95.67 (17.43)	91.28 (20.30)
--- Week 1-4 (n =44, 41)	96.80 (20.09)	91.93 (21.89)
--- Week 5-12 (n =47, 42)	95.58 (18.72)	88.56 (20.69)

4. Secondary Outcome

Title	Atrial Fibrillation Severity Scale (AFSS) Scores
Description	The University of Toronto Atrial Fibrillation Severity Scale is an instrument to assess the subject-perceived AF burden and AF symptom severity. It consists in a questionnaire plus a scoring algorithm. AF Burden score ranges from 3 to 30 and higher scores indicate greater AF burden. AF symptoms severity score ranges from 0 to 35 and higher scores indicate extremely severe AF symptoms.
Time Frame	Baseline (before randomization) and 12 weeks after randomization

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population as previously defined

Arm/Group Title	Placebo	Dronedarone
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks
Measure Participants	55	55
AF burden at baseline (n =45, 34)	13.72 (4.59)	12.76 (4.62)
AF burden after 12-week treatment (n =38, 31)	13.30 (5.40)	12.48 (5.45)
AF symptoms at baseline (n =55, 55)	8.47 (6.97)	8.36 (6.83)
AF symptoms after 12-week treatment (n =54, 53)	8.06 (7.11)	7.42 (7.48)

5. Secondary Outcome

Title	Incidence Rate of Electrical Cardioversion (or Overdrive Pacing)
Description	Electrical cardioversion is a procedure in which an electric shock is used to restore normal heart rhythm. Overdrive pacing is a procedure in which an artificial cardiac pacemaker is used to increase the heart rate in order to suppress certain arrhythmias. Incidence rate of electrical cardioversion (or overdrive pacing) is expressed as the number of participants that was cardioverted or paced during the study.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population as previously defined

Arm/Group Title	Placebo	Dronedarone
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks
Measure Participants	55	55
Number [participants]	1 1.8%	0 0%

6. Other Pre-specified Outcome

Title	Overview of Adverse Events (AE)
Description	AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time Frame	from first study drug intake up to 10 days after the last study drug intake

Outcome Measure Data

Analysis Population Description

All randomized and treated participants. Participants were considered according to the treatment actually received.

Arm/Group Title	Placebo	Dronedarone
Arm/Group Description	Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone 400 mg twice a day for 12 weeks
Measure Participants	55	57
Any AE	31 56.4%	37 64.9%
- Any serious AE	7 12.7%	7 12.3%
- Any AE leading to death	0 0%	0 0%
- Any AE leading to treatment discontinuation	3 5.5%	8 14%

Adverse Events

Time Frame	All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug in the period spanning from signature of the Informed Consent Form up to the last visit.
Adverse Event Reporting Description	The analysis included all randomized participants who received at least one dose of study drug and all AE that developed or worsened from randomization up to 10 days after last study drug intake. Participants were considered according to the treatment actually received regardless the amount of treatment administered.
Arm/Group Title	Placebo		Dronedarone
Arm/Group Description	Placebo (for dronedarone) twice a day for 12 weeks		Dronedarone 400 mg twice a day for 12 weeks
All Cause Mortality
	Placebo		Dronedarone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Dronedarone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/55 (12.7%)		7/57 (12.3%)
Cardiac disorders
Cardiac failure congestive	0/55 (0%)		3/57 (5.3%)
Cardiomyopathy	0/55 (0%)		1/57 (1.8%)
Intracardiac thrombus	1/55 (1.8%)		0/57 (0%)
Eye disorders
Ocular discomfort	0/55 (0%)		1/57 (1.8%)
Gastrointestinal disorders
Diarrhoea	1/55 (1.8%)		0/57 (0%)
Melaena	1/55 (1.8%)		0/57 (0%)
General disorders
Non-cardiac chest pain	1/55 (1.8%)		0/57 (0%)
Infections and infestations
Lobar pneumonia	1/55 (1.8%)		0/57 (0%)
Injury, poisoning and procedural complications
Muscle rupture	0/55 (0%)		1/57 (1.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/55 (1.8%)		0/57 (0%)
Nervous system disorders
Neuropathy peripheral	0/55 (0%)		1/57 (1.8%)
Presyncope	0/55 (0%)		1/57 (1.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/55 (1.8%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Dronedarone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/55 (16.4%)		16/57 (28.1%)
Gastrointestinal disorders
Diarrhoea	4/55 (7.3%)		7/57 (12.3%)
Nausea	1/55 (1.8%)		7/57 (12.3%)
General disorders
Fatigue	1/55 (1.8%)		3/57 (5.3%)
Nervous system disorders
Dizziness	2/55 (3.6%)		3/57 (5.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/55 (5.5%)		2/57 (3.5%)

Limitations/Caveats

Due to smaller-than-planned number of participants (112 instead of 424), results should be cautiously interpreted. However, the power to detect large treatment effect remained high and the posthoc power to detect a 60% reduction in AF burden was 99%.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months after trial completion, the Investigator can present or publish trial results. A copy is submitted to the Sponsor for review and comment at least 45 days in advance of the submission to journal (20 days for abstracts). The Sponsor can require to delay the communication for a period not exceeding 90 days to allow for filing a patent application or such other measures as Sponsor deems appropriate to establish and preserve its proprietary rights.