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

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.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Dronedarone; Drug: Placebo (for 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 Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Cambridge, Ontario, Canada
      • Investigational Site Number 124003
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Investigational Site Number 840072
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Investigational Site Number 840015
  • California
    • Beverly Hills, California, United States, 90211
      • Investigational Site Number 840086
    • Loma Linda, California, United States, 92354
      • Investigational Site Number 840018
    • Merced, California, United States, 95348
      • Investigational Site Number 840029
    • Redwood City, California, United States, 94062
      • Investigational Site Number 840044
    • Santa Ana, California, United States, 92704
      • Investigational Site Number 840042
    • Vista, California, United States, 92083
      • Investigational Site Number 840060
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Investigational Site Number 840057
  • Delaware
    • Newark, Delaware, United States, 19713
      • Investigational Site Number 840002
    • Wilmington, Delaware, United States, 19808
      • Investigational Site Number 840063
  • Florida
    • Bradenton, Florida, United States, 34205
      • Investigational Site Number 840070
    • Jacksonville, Florida, United States, 32216
      • Investigational Site Number 840010
    • Jupiter, Florida, United States, 33458
      • Investigational Site Number 840071
    • Lakeland, Florida, United States, 33805
      • Investigational Site Number 840061
    • Lauderdale Lakes, Florida, United States, 33313
      • Investigational Site Number 840096
    • Ocala, Florida, United States, 34471
      • Investigational Site Number 840031
    • Orlando, Florida, United States, 32803
      • Investigational Site Number 840074
    • Ormond Beach, Florida, United States, 32174
      • Investigational Site Number 840016
    • St Petersburg, Florida, United States, 33709
      • Investigational Site Number 840051
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Investigational Site Number 840081
  • Illinois
    • Jerseyville, Illinois, United States, 62052
      • Investigational Site Number 840103
    • Peoria, Illinois, United States, 61606
      • Investigational Site Number 840106
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Investigational Site Number 840066
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Investigational Site Number 840099
    • Owensboro, Kentucky, United States, 42303
      • Investigational Site Number 840039
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Investigational Site Number 840092
  • Maine
    • Auburn, Maine, United States, 04210
      • Investigational Site Number 840040
  • Massachusetts
    • Ayer, Massachusetts, United States, 01432
      • Investigational Site Number 840077
  • Michigan
    • Alpena, Michigan, United States, 49707
      • Investigational Site Number 840050
    • Saginaw, Michigan, United States, 48670
      • Investigational Site Number 840041
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Investigational Site Number 840058
  • Mississippi
    • Picayune, Mississippi, United States, 39466
      • Investigational Site Number 840101
  • Missouri
    • St Louis, Missouri, United States, 63122
      • Investigational Site Number 840078
    • St Louis, Missouri, United States, 63128
      • Investigational Site Number 840038
    • St. Louis, Missouri, United States, 63128
      • Investigational Site Number 840102
  • Montana
    • Kalispell, Montana, United States, 59901
      • Investigational Site Number 840012
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Investigational Site Number 840090
  • New York
    • Bronx, New York, United States, 10468
      • Investigational Site Number 840003
    • Buffalo, New York, United States, 14215
      • Investigational Site Number 840045
    • Manhasset, New York, United States, 11030
      • Investigational Site Number 840055
    • Troy, New York, United States, 12180
      • Investigational Site Number 840004
  • Ohio
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 840009
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Investigational Site Number 840028
    • Wyomissing, Pennsylvania, United States, 19610
      • Investigational Site Number 840067
  • Rhode Island
    • Wakefield, Rhode Island, United States, 02879
      • Investigational Site Number 840027
  • Tennessee
    • Knoxville, Tennessee, United States, 37917
      • Investigational Site Number 840046
  • Texas
    • Longview, Texas, United States, 75605
      • Investigational Site Number 840014
  • Virginia
    • Danville, Virginia, United States, 24541
      • Investigational Site Number 840068
    • Manassas, Virginia, United States, 20109
      • Investigational Site Number 840069
    • Richmond, Virginia, United States, 23249
      • Investigational Site Number 840087
    • Winchester, Virginia, United States, 22601
      • Investigational Site Number 840085
  • Washington
    • Burien, Washington, United States, 98166
      • Investigational Site Number 840013
    • Spokane, Washington, United States, 99204
      • Investigational Site Number 840091
  • Wisconsin
    • Madison, Wisconsin, United States, 53713
      • Investigational Site Number 840080
    • Milwaukee, Wisconsin, United States, 53215
      • Investigational Site Number 840023

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dronedarone; Dronedarone 400 mg twice a day	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	Drug: Placebo (for Dronedarone); film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: September 9, 2010
• First Submitted That Met QC Criteria: September 9, 2010
• First Posted (Estimate): September 10, 2010

Study Record Updates

• Last Update Posted (Estimate): February 12, 2013
• Last Update Submitted That Met QC Criteria: January 10, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anti-Arrhythmia Agents; Dronedarone
• Other Study ID Numbers: DRONE_L_04315