Clinical trial NCT01198873: Effects of Dronedarone on Cardiac Geometry and Function in Patients With Atrial Fibrillation and Left Atrial Enlargement
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Atrial Fibrillation
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-09-10
Enrollment: 76
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Change From Baseline in Left Atrial Volume Index (LAVi)
timeFrame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Secondary outcomes:
measure: Changes From Baseline in Left Atrial Function
timeFrame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
measure: Changes From Baseline in Left Atrial Dimension
timeFrame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
measure: Changes From Baseline in Left Ventricular Ejection Fraction (LVEF)
timeFrame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
measure: Changes From Baseline in Left Ventricular Function
timeFrame: baseline (before randomization) and post-baseline (after 3-12 months of treatment)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Investigational Site Number 840072
state: Arizona
city: Little Rock
country: United States
facility: Investigational Site Number 840015
state: Arkansas
city: Beverly Hills
country: United States
facility: Investigational Site Number 840086
state: California
city: Loma Linda
country: United States
facility: Investigational Site Number 840018
state: California
city: Merced
country: United States
facility: Investigational Site Number 840029
state: California
city: Redwood City
country: United States
facility: Investigational Site Number 840044
state: California
city: Santa Ana
country: United States
facility: Investigational Site Number 840042
state: California
city: Vista
country: United States
facility: Investigational Site Number 840060
state: California
city: Stamford
country: United States
facility: Investigational Site Number 840057
state: Connecticut
city: Newark
country: United States
facility: Investigational Site Number 840002
state: Delaware
city: Wilmington
country: United States
facility: Investigational Site Number 840063
state: Delaware
city: Bradenton
country: United States
facility: Investigational Site Number 840070
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840010
state: Florida
city: Jupiter
country: United States
facility: Investigational Site Number 840071
state: Florida
city: Lakeland
country: United States
facility: Investigational Site Number 840061
state: Florida
city: Lauderdale Lakes
country: United States
facility: Investigational Site Number 840096
state: Florida
city: Ocala
country: United States
facility: Investigational Site Number 840031
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 840074
state: Florida
city: Ormond Beach
country: United States
facility: Investigational Site Number 840016
state: Florida
city: St Petersburg
country: United States
facility: Investigational Site Number 840051
state: Florida
city: Roswell
country: United States
facility: Investigational Site Number 840081
state: Georgia
city: Jerseyville
country: United States
facility: Investigational Site Number 840103
state: Illinois
city: Peoria
country: United States
facility: Investigational Site Number 840106
state: Illinois
city: Elkhart
country: United States
facility: Investigational Site Number 840066
state: Indiana
city: Lexington
country: United States
facility: Investigational Site Number 840099
state: Kentucky
city: Owensboro
country: United States
facility: Investigational Site Number 840039
state: Kentucky
city: Baton Rouge
country: United States
facility: Investigational Site Number 840092
state: Louisiana
city: Auburn
country: United States
facility: Investigational Site Number 840040
state: Maine
city: Ayer
country: United States
facility: Investigational Site Number 840077
state: Massachusetts
city: Alpena
country: United States
facility: Investigational Site Number 840050
state: Michigan
city: Saginaw
country: United States
facility: Investigational Site Number 840041
state: Michigan
city: Minneapolis
country: United States
facility: Investigational Site Number 840058
state: Minnesota
city: Picayune
country: United States
facility: Investigational Site Number 840101
state: Mississippi
city: St Louis
country: United States
facility: Investigational Site Number 840078
state: Missouri
city: St Louis
country: United States
facility: Investigational Site Number 840038
state: Missouri
city: St. Louis
country: United States
facility: Investigational Site Number 840102
state: Missouri
city: Kalispell
country: United States
facility: Investigational Site Number 840012
state: Montana
city: Lincoln
country: United States
facility: Investigational Site Number 840090
state: Nebraska
city: Bronx
country: United States
facility: Investigational Site Number 840003
state: New York
city: Buffalo
country: United States
facility: Investigational Site Number 840045
state: New York
city: Manhasset
country: United States
facility: Investigational Site Number 840055
state: New York
city: Troy
country: United States
facility: Investigational Site Number 840004
state: New York
city: Maumee
country: United States
facility: Investigational Site Number 840009
state: Ohio
city: Camp Hill
country: United States
facility: Investigational Site Number 840028
state: Pennsylvania
city: Wyomissing
country: United States
facility: Investigational Site Number 840067
state: Pennsylvania
city: Wakefield
country: United States
facility: Investigational Site Number 840027
state: Rhode Island
city: Knoxville
country: United States
facility: Investigational Site Number 840046
state: Tennessee
city: Longview
country: United States
facility: Investigational Site Number 840014
state: Texas
city: Danville
country: United States
facility: Investigational Site Number 840068
state: Virginia
city: Manassas
country: United States
facility: Investigational Site Number 840069
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840087
state: Virginia
city: Winchester
country: United States
facility: Investigational Site Number 840085
state: Virginia
city: Burien
country: United States
facility: Investigational Site Number 840013
state: Washington
city: Spokane
country: United States
facility: Investigational Site Number 840091
state: Washington
city: Madison
country: United States
facility: Investigational Site Number 840080
state: Wisconsin
city: Milwaukee
country: United States
facility: Investigational Site Number 840023
state: Wisconsin
city: Cambridge
country: Canada
facility: Investigational Site Number 124003
state: Ontario
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: