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

Atrial Fibrillation Clinical Trial

— ODYSSEUS  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01198873
• Other study ID #: DRONE_L_04315
• Status: Terminated
• Phase: Phase 4
• First received: September 9, 2010
• Last updated: January 10, 2013
• Start date: September 2010
• Est. completion date: January 2012

Study information

• Verified date: January 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 76
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion criteria:

• 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.

Exclusion criteria:

• 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;

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Dronedarone
Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)
• Placebo (for Dronedarone)
film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)

Locations

Country	Name	City	State
Canada	Investigational Site Number 124003	Cambridge	Ontario
United States	Investigational Site Number 840050	Alpena	Michigan
United States	Investigational Site Number 840040	Auburn	Maine
United States	Investigational Site Number 840077	Ayer	Massachusetts
United States	Investigational Site Number 840092	Baton Rouge	Louisiana
United States	Investigational Site Number 840086	Beverly Hills	California
United States	Investigational Site Number 840070	Bradenton	Florida
United States	Investigational Site Number 840003	Bronx	New York
United States	Investigational Site Number 840045	Buffalo	New York
United States	Investigational Site Number 840013	Burien	Washington
United States	Investigational Site Number 840028	Camp Hill	Pennsylvania
United States	Investigational Site Number 840068	Danville	Virginia
United States	Investigational Site Number 840066	Elkhart	Indiana
United States	Investigational Site Number 840010	Jacksonville	Florida
United States	Investigational Site Number 840103	Jerseyville	Illinois
United States	Investigational Site Number 840071	Jupiter	Florida
United States	Investigational Site Number 840012	Kalispell	Montana
United States	Investigational Site Number 840046	Knoxville	Tennessee
United States	Investigational Site Number 840061	Lakeland	Florida
United States	Investigational Site Number 840096	Lauderdale Lakes	Florida
United States	Investigational Site Number 840099	Lexington	Kentucky
United States	Investigational Site Number 840090	Lincoln	Nebraska
United States	Investigational Site Number 840015	Little Rock	Arkansas
United States	Investigational Site Number 840018	Loma Linda	California
United States	Investigational Site Number 840014	Longview	Texas
United States	Investigational Site Number 840080	Madison	Wisconsin
United States	Investigational Site Number 840069	Manassas	Virginia
United States	Investigational Site Number 840055	Manhasset	New York
United States	Investigational Site Number 840009	Maumee	Ohio
United States	Investigational Site Number 840029	Merced	California
United States	Investigational Site Number 840023	Milwaukee	Wisconsin
United States	Investigational Site Number 840058	Minneapolis	Minnesota
United States	Investigational Site Number 840002	Newark	Delaware
United States	Investigational Site Number 840031	Ocala	Florida
United States	Investigational Site Number 840074	Orlando	Florida
United States	Investigational Site Number 840016	Ormond Beach	Florida
United States	Investigational Site Number 840039	Owensboro	Kentucky
United States	Investigational Site Number 840106	Peoria	Illinois
United States	Investigational Site Number 840072	Phoenix	Arizona
United States	Investigational Site Number 840101	Picayune	Mississippi
United States	Investigational Site Number 840044	Redwood City	California
United States	Investigational Site Number 840087	Richmond	Virginia
United States	Investigational Site Number 840081	Roswell	Georgia
United States	Investigational Site Number 840041	Saginaw	Michigan
United States	Investigational Site Number 840042	Santa Ana	California
United States	Investigational Site Number 840091	Spokane	Washington
United States	Investigational Site Number 840038	St Louis	Missouri
United States	Investigational Site Number 840078	St Louis	Missouri
United States	Investigational Site Number 840051	St Petersburg	Florida
United States	Investigational Site Number 840102	St. Louis	Missouri
United States	Investigational Site Number 840057	Stamford	Connecticut
United States	Investigational Site Number 840004	Troy	New York
United States	Investigational Site Number 840060	Vista	California
United States	Investigational Site Number 840027	Wakefield	Rhode Island
United States	Investigational Site Number 840063	Wilmington	Delaware
United States	Investigational Site Number 840085	Winchester	Virginia
United States	Investigational Site Number 840067	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline (before randomization) and post-baseline (after 3-12 months of treatment)	No
Secondary	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.	baseline (before randomization) and post-baseline (after 3-12 months of treatment)	No
Secondary	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.	baseline (before randomization) and post-baseline (after 3-12 months of treatment)	No
Secondary	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.	baseline (before randomization) and post-baseline (after 3-12 months of treatment)	No
Secondary	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.	baseline (before randomization) and post-baseline (after 3-12 months of treatment)	No