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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01198873
First received: September 9, 2010
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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.

Condition Intervention Phase
Atrial Fibrillation
Drug: Dronedarone
Drug: Placebo (for Dronedarone)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 on Cardiac Geometry and Function in Patients With Atrial Fibrillation and Left Atrial Enlargement

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change From Baseline in Left Atrial Volume Index (LAVi) [ Time Frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Changes From Baseline in Left Atrial Function [ Time Frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment) ] [ Designated as safety issue: No ]

    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.


  • Changes From Baseline in Left Atrial Dimension [ Time Frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment) ] [ Designated as safety issue: No ]

    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.


  • Changes From Baseline in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment) ] [ Designated as safety issue: No ]

    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.


  • Changes From Baseline in Left Ventricular Function [ Time Frame: baseline (before randomization) and post-baseline (after 3-12 months of treatment) ] [ Designated as safety issue: No ]

    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.



Enrollment: 76
Study Start Date: September 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)


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.
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198873

  Show 57 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01198873     History of Changes
Other Study ID Numbers: DRONE_L_04315
Study First Received: September 9, 2010
Results First Received: January 10, 2013
Last Updated: January 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Atrial Fibrillation
Hypertrophy
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Pathological Conditions, Anatomical
Amiodarone
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on August 21, 2014