Trial Outcomes & Findings for Effects of Dronedarone on Atrial Fibrillation Burden in Subjects With Permanent Pacemakers (NCT NCT01135017)

Last Updated: 2013-04-11

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

112 participants

Primary outcome timeframe

Baseline (before randomization), 4 weeks and 12 weeks after randomization

Results posted on

2013-04-11

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone Dronedarone 400 mg twice a day for 12 weeks
Overall Study STARTED	55	57
Overall Study Treated	55	57
Overall Study Evaluable for Efficacy	55	55
Overall Study COMPLETED	49	45
Overall Study NOT COMPLETED	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone Dronedarone 400 mg twice a day for 12 weeks
Overall Study Adverse Event	3	8
Overall Study Other than above	3	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=55 Participants Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone n=57 Participants Dronedarone 400 mg twice a day for 12 weeks	Total n=112 Participants Total of all reporting groups
Age Continuous	74.5 years STANDARD_DEVIATION 9.5 • n=5 Participants	77.3 years STANDARD_DEVIATION 8.6 • n=7 Participants	75.9 years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	28 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	29 Participants n=7 Participants	67 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (before randomization), 4 weeks and 12 weeks after randomization

Population: 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).

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone n=55 Participants Dronedarone 400 mg twice a day for 12 weeks
Atrial Fibrillation (AF) Burden During the 12-week Treatment Period Baseline	8.77 percent time in AF Interval 6.413 to 12.006	10.14 percent time in AF Interval 7.167 to 14.354
Atrial Fibrillation (AF) Burden During the 12-week Treatment Period 12-week treatment period	9.90 percent time in AF Interval 6.633 to 14.772	4.63 percent time in AF Interval 2.61 to 8.198

SECONDARY outcome

Timeframe: 4 weeks and 12 weeks after randomization

Population: Modified intent-to-treat population as previously defined

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

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone n=55 Participants Dronedarone 400 mg twice a day for 12 weeks
AF Burden During the First 4 Weeks of Treatment and After 4-week Treatment Week 1 - 4 (n =54, 49)	8.99 percent time in AF Interval 5.901 to 13.705	3.62 percent time in AF Interval 1.806 to 7.258
AF Burden During the First 4 Weeks of Treatment and After 4-week Treatment Week 5 - 12 (n =54, 54)	9.37 percent time in AF Interval 5.938 to 14.786	4.28 percent time in AF Interval 2.388 to 7.673

SECONDARY outcome

Timeframe: Baseline (before randomization), 4 weeks and 12 weeks after randomization

Population: Modified intent-to-treat population as previously defined

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.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone n=55 Participants Dronedarone 400 mg twice a day for 12 weeks
Average Ventricular Rate During AF Episodes Baseline (n =49, 47)	93.02 beats/min Standard Deviation 16.74	90.68 beats/min Standard Deviation 19.80
Average Ventricular Rate During AF Episodes Week 1-12 (n =49, 48)	95.67 beats/min Standard Deviation 17.43	91.28 beats/min Standard Deviation 20.30
Average Ventricular Rate During AF Episodes --- Week 1-4 (n =44, 41)	96.80 beats/min Standard Deviation 20.09	91.93 beats/min Standard Deviation 21.89
Average Ventricular Rate During AF Episodes --- Week 5-12 (n =47, 42)	95.58 beats/min Standard Deviation 18.72	88.56 beats/min Standard Deviation 20.69

SECONDARY outcome

Timeframe: Baseline (before randomization) and 12 weeks after randomization

Population: Modified intent-to-treat population as previously defined

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.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone n=55 Participants Dronedarone 400 mg twice a day for 12 weeks
Atrial Fibrillation Severity Scale (AFSS) Scores AF burden at baseline (n =45, 34)	13.72 units on a scale Standard Deviation 4.59	12.76 units on a scale Standard Deviation 4.62
Atrial Fibrillation Severity Scale (AFSS) Scores AF burden after 12-week treatment (n =38, 31)	13.30 units on a scale Standard Deviation 5.40	12.48 units on a scale Standard Deviation 5.45
Atrial Fibrillation Severity Scale (AFSS) Scores AF symptoms at baseline (n =55, 55)	8.47 units on a scale Standard Deviation 6.97	8.36 units on a scale Standard Deviation 6.83
Atrial Fibrillation Severity Scale (AFSS) Scores AF symptoms after 12-week treatment (n =54, 53)	8.06 units on a scale Standard Deviation 7.11	7.42 units on a scale Standard Deviation 7.48

SECONDARY outcome

Timeframe: 12 weeks

Population: Modified intent-to-treat population as previously defined

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.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone n=55 Participants Dronedarone 400 mg twice a day for 12 weeks
Incidence Rate of Electrical Cardioversion (or Overdrive Pacing)	1 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: from first study drug intake up to 10 days after the last study drug intake

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

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

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo (for Dronedarone) twice a day for 12 weeks	Dronedarone n=57 Participants Dronedarone 400 mg twice a day for 12 weeks
Overview of Adverse Events (AE) Any AE	31 participants	37 participants
Overview of Adverse Events (AE) - Any serious AE	7 participants	7 participants
Overview of Adverse Events (AE) - Any AE leading to death	0 participants	0 participants
Overview of Adverse Events (AE) - Any AE leading to treatment discontinuation	3 participants	8 participants

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 9 other events

Deaths: 0 deaths

Dronedarone

Serious events: 7 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=55 participants at risk Placebo (for dronedarone) twice a day for 12 weeks	Dronedarone n=57 participants at risk Dronedarone 400 mg twice a day for 12 weeks
Infections and infestations Lobar pneumonia	1.8% 1/55 • 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. 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.	0.00% 0/57 • 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. 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.
Nervous system disorders Neuropathy peripheral	0.00% 0/55 • 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. 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.	1.8% 1/57 • 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. 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.
Nervous system disorders Presyncope	0.00% 0/55 • 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. 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.	1.8% 1/57 • 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. 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.
Eye disorders Ocular discomfort	0.00% 0/55 • 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. 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.	1.8% 1/57 • 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. 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.
Cardiac disorders Cardiac failure congestive	0.00% 0/55 • 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. 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.	5.3% 3/57 • 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. 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.
Cardiac disorders Cardiomyopathy	0.00% 0/55 • 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. 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.	1.8% 1/57 • 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. 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.
Cardiac disorders Intracardiac thrombus	1.8% 1/55 • 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. 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.	0.00% 0/57 • 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. 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.
Respiratory, thoracic and mediastinal disorders Asthma	1.8% 1/55 • 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. 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.	0.00% 0/57 • 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. 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.
Gastrointestinal disorders Diarrhoea	1.8% 1/55 • 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. 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.	0.00% 0/57 • 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. 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.
Gastrointestinal disorders Melaena	1.8% 1/55 • 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. 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.	0.00% 0/57 • 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. 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.
Musculoskeletal and connective tissue disorders Arthralgia	1.8% 1/55 • 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. 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.	0.00% 0/57 • 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. 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.
General disorders Non-cardiac chest pain	1.8% 1/55 • 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. 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.	0.00% 0/57 • 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. 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.
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/55 • 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. 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.	1.8% 1/57 • 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. 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.

Other adverse events

Other adverse events
Measure	Placebo n=55 participants at risk Placebo (for dronedarone) twice a day for 12 weeks	Dronedarone n=57 participants at risk Dronedarone 400 mg twice a day for 12 weeks
Nervous system disorders Dizziness	3.6% 2/55 • 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. 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.	5.3% 3/57 • 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.5% 3/55 • 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. 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.	3.5% 2/57 • 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. 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.
Gastrointestinal disorders Diarrhoea	7.3% 4/55 • 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. 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.	12.3% 7/57 • 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. 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.
Gastrointestinal disorders Nausea	1.8% 1/55 • 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. 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.	12.3% 7/57 • 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. 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.
General disorders Fatigue	1.8% 1/55 • 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. 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.	5.3% 3/57 • 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. 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.

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER