Atrial FibrillationPhase 4ODYSSEUSNCT01198873

Effects of Dronedarone on Cardiac Geometry and Function in Patients With Atrial Fibrillation and Left Atrial Enlargement

A Phase 4 study testing Dronedarone in people with Atrial Fibrillation, run by Sanofi at 57 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

Primary Objective: Evaluate the effect of dronedarone versus placebo (standard therapy) in slowing the progression of adverse left atrial remodeling in patients with atrial fibrillation (AF) following 12 months of treatment. Read more about this study

Who is it for?: Ages 21 years and older
Conditions the study is for: Atrial Fibrillation
What is being tested?: Dronedarone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 76 participants
Where: 57 sitesin 2 countries
Study dates: Sep 2010to Jan 2012
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed written informed consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization;
Nonpermanent AF or AF/Atrial Flutter (AFL) documented electrocardiographically by both AF (or AF/AFL) and sinus rhythm within the prior 12 months;
At screening, sinus rhythm and Left Atrial Volume index (LAVi) ≥32 mL/m2 based on 2D-echocardiography;
At least one of the following cardiovascular (CV) risk factors: Age >70 years at start of screening, hypertension, diabetes mellitus, prior CV accident (stroke or transient ischemic attack) or systemic embolism, or left ventricular ejection fraction <0.40.

Who cannot join

Permanent AF defined as continuous AF for 6 months or longer;
Persistent AF defined as sustained AF >7 days duration and/or requiring cardioversion in the 4 weeks before screening;
Prior valvular heart surgery or significant valvular heart disease including rheumatic heart disease or acquired valvular heart disease;
Aortic or mitral regurgitation greater than mild (>1+) or any degree of mitral stenosis at the screening echocardiogram;
Myocardial infarction within the 6 months prior to screening or stroke within 2 months prior to screening;
Pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy devices placed within the 6 months prior to screening or at anytime during the study;

Show all 16Show fewer

Ongoing potentially dangerous symptoms when in AF/AFL such as angina pectoris, transient ischemic attacks, stroke, syncope as judged by the Investigator;
Cardiac ablative procedure or cardiac surgery within 3 months prior to screening, or percutaneous coronary intervention within 4 weeks prior to screening;
Need for concomitant medication that is prohibited in this trial, and would preclude the use of the study drug during the planned study period including the following:
Antiarrhythmics (eg, amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol);
Drugs or products that are strong inhibitors of CYP3A (eg, ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, ritonavir, and grapefruit juice);
Drugs that are inducers of CYP3A (eg, rifampin, phenobarbital, carbamazepine, phenytoin, and St John's wort);
QTc Bazett interval ≥500 msec on the screening ECG;
Bradycardia <50 bpm and/or PR interval ≥0.28 sec on the screening ECG unless the patient has a functional pacemaker;
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.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial locations and contacts

57 sites in 2 countries.

Country

City, postcode or hospital

57 sites in 2 countries

United States56 sites

Investigational Site Number 840050
Alpena, Michigan, 49707
Investigational Site Number 840040
Auburn, Maine, 04210
Investigational Site Number 840077
Ayer, Massachusetts, 01432
Investigational Site Number 840092
Baton Rouge, Louisiana, 70808
Investigational Site Number 840086
Beverly Hills, California, 90211
Investigational Site Number 840070
Bradenton, Florida, 34205
Investigational Site Number 840045
Buffalo, New York, 14215
Investigational Site Number 840013
Burien, Washington, 98166
Investigational Site Number 840028
Camp Hill, Pennsylvania, 17011
Investigational Site Number 840068
Danville, Virginia, 24541
Investigational Site Number 840066
Elkhart, Indiana, 46514
Investigational Site Number 840010
Jacksonville, Florida, 32216
Investigational Site Number 840103
Jerseyville, Illinois, 62052
Investigational Site Number 840071
Jupiter, Florida, 33458
Investigational Site Number 840012
Kalispell, Montana, 59901
Investigational Site Number 840046
Knoxville, Tennessee, 37917
Investigational Site Number 840061
Lakeland, Florida, 33805
Investigational Site Number 840096
Lauderdale Lakes, Florida, 33313
Investigational Site Number 840099
Lexington, Kentucky, 40504
Investigational Site Number 840090
Lincoln, Nebraska, 68506
Investigational Site Number 840015
Little Rock, Arkansas, 72204
Investigational Site Number 840018
Loma Linda, California, 92354
Investigational Site Number 840014
Longview, Texas, 75605
Investigational Site Number 840080
Madison, Wisconsin, 53713
Investigational Site Number 840069
Manassas, Virginia, 20109
Investigational Site Number 840055
Manhasset, New York, 11030
Investigational Site Number 840009
Maumee, Ohio, 43537
Investigational Site Number 840029
Merced, California, 95348
Investigational Site Number 840023
Milwaukee, Wisconsin, 53215
Investigational Site Number 840058
Minneapolis, Minnesota, 55422
Investigational Site Number 840002
Newark, Delaware, 19713
Investigational Site Number 840031
Ocala, Florida, 34471
Investigational Site Number 840074
Orlando, Florida, 32803
Investigational Site Number 840016
Ormond Beach, Florida, 32174
Investigational Site Number 840039
Owensboro, Kentucky, 42303
Investigational Site Number 840106
Peoria, Illinois, 61606
Investigational Site Number 840072
Phoenix, Arizona, 85006
Investigational Site Number 840101
Picayune, Mississippi, 39466
Investigational Site Number 840044
Redwood City, California, 94062
Investigational Site Number 840087
Richmond, Virginia, 23249
Investigational Site Number 840081
Roswell, Georgia, 30076
Investigational Site Number 840041
Saginaw, Michigan, 48670
Investigational Site Number 840042
Santa Ana, California, 92704
Investigational Site Number 840091
Spokane, Washington, 99204
Investigational Site Number 840078
St Louis, Missouri, 63122
Investigational Site Number 840038
St Louis, Missouri, 63128
Investigational Site Number 840102
St Louis, Missouri, 63128
Investigational Site Number 840051
St. Petersburg, Florida, 33709
Investigational Site Number 840057
Stamford, Connecticut, 06905
Investigational Site Number 840003
The Bronx, New York, 10468
Investigational Site Number 840004
Troy, New York, 12180
Investigational Site Number 840060
Vista, California, 92083
Investigational Site Number 840027
Wakefield, Rhode Island, 02879
Investigational Site Number 840063
Wilmington, Delaware, 19808
Investigational Site Number 840085
Winchester, Virginia, 22601
Investigational Site Number 840067
Wyomissing, Pennsylvania, 19610

Other trials in United States

Canada1 site

Investigational Site Number 124003
Cambridge, Ontario

Other trials in Canada

About this study

Official title: A Placebo-Controlled, Double-Blind, Randomized, Multi-center Study to Assess the Effects of Dronedarone 400 mg BID on Cardiac Geometry and Function in Patients With Atrial Fibrillation and Left Atrial Enlargement

Primary Objective:

Evaluate the effect of dronedarone versus placebo (standard therapy) in slowing the progression of adverse left atrial remodeling in patients with atrial fibrillation (AF) following 12 months of treatment.

Secondary Objectives:

Evaluate the effects of dronedarone versus placebo on left atrial function;
Evaluate the effects of dronedarone versus placebo on left atrial dimension;
Evaluate the effects of dronedarone versus placebo on left ventricular function (LVEF, E, E', A, E/E')
Evaluate the safety and tolerability of dronedarone.

Read the detailed description

The planned total study period per participant was 12 months and 3 weeks broken down as follows:

Screening period: up to 1 week;
Treatment period: 12 months;
Follow-up period: 2 weeks.

Conditions: Atrial Fibrillation
Being tested: Dronedarone, Placebo (for Dronedarone)
Medical subject headings: Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DronedaroneDrug
Also called Multaq®, SR33589
Film-coated tablet
Oral administration under fed conditions (during breakfast and dinner)
Placebo (for Dronedarone)Drug
film-coated tablet strictly identical in appearance
Oral administration under fed conditions (during breakfast and dinner)

Study groups in NCT01198873
Study group	Role	What they receive
Dronedarone	Experimental	Dronedarone 400 mg twice a day Receives: Drug: Dronedarone
Placebo	Placebo comparator	Placebo (for Dronedarone) twice a day Receives: Drug: Placebo (for Dronedarone)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Left Atrial Volume Index (LAVi)
Left Atrial Volume index (LAVi) was assessed at baseline and after 12 months treatment using 2-D echocardiography and interpreted blindly via a central Echocardiography Core Lab.
Participants who discontinued after completing at least 3 months of treatment were assessed after last study drug intake and data were included in the analysis.
Measured: baseline (before randomization) and post-baseline (after 3-12 months of treatment)

Secondary outcomes (4)

Changes From Baseline in Left Atrial Function
left atrial (LA) function was assessed at baseline and after 12 months treatment using 2-D echocardiography and interpreted blindly via a central Echocardiography Core Lab.
Participants who discontinued after completing at least 3 months of treatment were assessed after last study drug intake and data were included in the analysis.
Measured: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Changes From Baseline in Left Atrial Dimension
Maximal left atrial diameter in the anteroposterior dimension was assessed at baseline and after 12 months treatment using 2-D echocardiography and interpreted blindly via a central Echocardiography Core Lab.
Participants who discontinued after completing at least 3 months of treatment were assessed after last drug intake and data were included in the analysis.
Measured: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Changes From Baseline in Left Ventricular Ejection Fraction (LVEF)
Left Ventricular Ejection Fraction (LVEF) was assessed at baseline and after 12 months treatment using 2-D echocardiography and interpreted blindly via a central Echocardiography Core Lab.
Participants who discontinued after completing at least 3 months of treatment were assessed after last drug intake and data were included in the analysis.
Measured: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Changes From Baseline in Left Ventricular Function
left ventricular (LV) function was assessed at baseline and after 12 months treatment using 2-D echocardiography and interpreted blindly via a central Echocardiography Core Lab.
Participants who discontinued after completing at least 3 months of treatment were assessed after last study drug intake and data were included in the analysis.
Measured: baseline (before randomization) and post-baseline (after 3-12 months of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2010Jan 2012

First posted10 Sep 2010 (estimated)
Study startSep 2010
Primary completionJan 2012
Study completionJan 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Atrial FibrillationStudies of the same condition, open and under way.
More trials run by SanofiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 76 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01198873
Sponsor's protocol ID: DRONE_L_04315
Acronym: ODYSSEUS
Status last verified: Jan 2013
First submitted: 9 Sep 2010
Last updated: 12 Feb 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

All Atrial Fibrillation trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Placebo-Controlled, Double-Blind, Randomized, Multi-center Study to Assess the Effects of Dronedarone 400 mg BID on Cardiac Geometry and Function in Patients With Atrial Fibrillation and Left Atrial Enlargement
ClinicalTrials.gov ID: NCT01198873
Acronym / sponsor ID: ODYSSEUS / DRONE_L_04315
Conditions: Atrial Fibrillation
Phase: Phase 4
Study type: Interventional
Recruitment status: Terminated
Enrolment: 76 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Study start: Sep 2010
Primary completion: Jan 2012 (actual)
Study completion: Jan 2012 (actual)
First posted: 10 Sep 2010 (estimated)
Results: Posted 12 Feb 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Primary Objective:

Evaluate the effect of dronedarone versus placebo (standard therapy) in slowing the progression of adverse left atrial remodeling in patients with atrial fibrillation (AF) following 12 months of treatment.

Secondary Objectives:

Evaluate the effects of dronedarone versus placebo on left atrial function;
Evaluate the effects of dronedarone versus placebo on left atrial dimension;
Evaluate the effects of dronedarone versus placebo on left ventricular function (LVEF, E, E', A, E/E')
Evaluate the safety and tolerability of dronedarone.

Detailed description

The planned total study period per participant was 12 months and 3 weeks broken down as follows:

Screening period: up to 1 week;
Treatment period: 12 months;
Follow-up period: 2 weeks.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Dronedarone	Experimental	Drug: DronedaroneDronedarone 400 mg twice a day
Placebo	Placebo comparator	Drug: Placebo (for Dronedarone)Placebo (for Dronedarone) twice a day

Who may qualify

Ages: 21 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Signed written informed consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization;
Nonpermanent AF or AF/Atrial Flutter (AFL) documented electrocardiographically by both AF (or AF/AFL) and sinus rhythm within the prior 12 months;
At screening, sinus rhythm and Left Atrial Volume index (LAVi) ≥32 mL/m2 based on 2D-echocardiography;
At least one of the following cardiovascular (CV) risk factors: Age >70 years at start of screening, hypertension, diabetes mellitus, prior CV accident (stroke or transient ischemic attack) or systemic embolism, or left ventricular ejection fraction <0.40.

Key exclusion criteria (16 listed)

Permanent AF defined as continuous AF for 6 months or longer;
Persistent AF defined as sustained AF >7 days duration and/or requiring cardioversion in the 4 weeks before screening;
Prior valvular heart surgery or significant valvular heart disease including rheumatic heart disease or acquired valvular heart disease;
Aortic or mitral regurgitation greater than mild (>1+) or any degree of mitral stenosis at the screening echocardiogram;
Myocardial infarction within the 6 months prior to screening or stroke within 2 months prior to screening;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DronedaroneAlso: Multaq®, SR33589Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)	Drug	Dronedarone
Placebo (for Dronedarone)film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)	Drug	Placebo

Primary outcome

Change From Baseline in Left Atrial Volume Index (LAVi)
Time frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Left Atrial Volume index (LAVi) was assessed at baseline and after 12 months treatment using 2-D echocardiography and interpreted blindly via a central Echocardiography Core Lab. Participants who discontinued after completing at least 3 months of treatment were assessed after last study drug intake and data were included in the analysis.

4 secondary outcomes

Changes From Baseline in Left Atrial Function
Time frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Changes From Baseline in Left Atrial Dimension
Time frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Changes From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Changes From Baseline in Left Ventricular Function
Time frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)

Results and safety

Results posted to the registry on 12 Feb 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	41	4
Dronedarone	35	3

Primary outcome: Change From Baseline in Left Atrial Volume Index (LAVi)

Time frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment). Mean (Standard Deviation). Unit: mililiters/m2

Measure	Placebo n = 33	Dronedarone n = 26
Baseline (n =33, 26)	37.555 (5.899)	37.715 (6.597)
Post-baseline (n =32, 26)	29.191 (5.994)	30.823 (5.364)
Change from baseline (n =32, 26)	-8.438 (4.743)	-6.892 (5.759)

Population analysed: The analysis included all randomized and treated participants with at least one post-baseline echocardiographic assessment. Participants were included in the treatment group to which they were randomized (Modified Intent-to-treat analysis). The quality of the post-baseline echocardiography was inadequate for determining LAVi in one participant.

4 secondary outcomes are reported in the full results.

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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 41 (2.4%)	5 of 41 (12.2%)	Not reported
Dronedarone	5 of 35 (14.3%)	14 of 35 (40%)	Not reported

Limitations and caveats (from the sponsor): Due to the early termination of the study, results should be cautiously interpreted. Indeed the number of participants was lower than planned (76 instead of 334) and the treatment period was shorter than planned (6 months instead of 12 months).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Atrial Fibrillation

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Sciences & Operations study director

Sanofi

57 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dronedarone in people with Atrial Fibrillation, run by Sanofi at 57 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Left Atrial Volume Index (LAVi) (time frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01198873.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2013.