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

NCT01198873 | Terminated Phase 4 Results

• 1 other identifier: DRONE_L_04315
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 57

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.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Changes From Baseline in Left Atrial Function

  baseline (before randomization) and post-baseline (after 3-12 months of treatment)

• Changes From Baseline in Left Atrial Dimension

  baseline (before randomization) and post-baseline (after 3-12 months of treatment)

• Changes From Baseline in Left Ventricular Ejection Fraction (LVEF)

  baseline (before randomization) and post-baseline (after 3-12 months of treatment)

• Changes From Baseline in Left Ventricular Function

  baseline (before randomization) and post-baseline (after 3-12 months of treatment)

Study Arms (2)

Dronedarone

EXPERIMENTAL

Dronedarone 400 mg twice a day

Drug: Dronedarone

Placebo

PLACEBO COMPARATOR

Placebo (for Dronedarone) twice a day

Drug: Placebo (for Dronedarone)

Interventions

Dronedarone DRUG

Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)

Also known as: Multaq®, SR33589

Dronedarone

Placebo (for Dronedarone) DRUG

film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (57)

Investigational Site Number 840072

Phoenix, Arizona, 85006, United States

Location

Investigational Site Number 840015

Little Rock, Arkansas, 72204, United States

Location

Investigational Site Number 840086

Beverly Hills, California, 90211, United States

Location

Investigational Site Number 840018

Loma Linda, California, 92354, United States

Location

Investigational Site Number 840029

Merced, California, 95348, United States

Location

Investigational Site Number 840044

Redwood City, California, 94062, United States

Location

Investigational Site Number 840042

Santa Ana, California, 92704, United States

Location

Investigational Site Number 840060

Vista, California, 92083, United States

Location

Investigational Site Number 840057

Stamford, Connecticut, 06905, United States

Location

Investigational Site Number 840002

Newark, Delaware, 19713, United States

Location

Investigational Site Number 840063

Wilmington, Delaware, 19808, United States

Location

Investigational Site Number 840070

Bradenton, Florida, 34205, United States

Location

Investigational Site Number 840010

Jacksonville, Florida, 32216, United States

Location

Investigational Site Number 840071

Jupiter, Florida, 33458, United States

Location

Investigational Site Number 840061

Lakeland, Florida, 33805, United States

Location

Investigational Site Number 840096

Lauderdale Lakes, Florida, 33313, United States

Location

Investigational Site Number 840031

Ocala, Florida, 34471, United States

Location

Investigational Site Number 840074

Orlando, Florida, 32803, United States

Location

Investigational Site Number 840016

Ormond Beach, Florida, 32174, United States

Location

Investigational Site Number 840051

St. Petersburg, Florida, 33709, United States

Location

Investigational Site Number 840081

Roswell, Georgia, 30076, United States

Location

Investigational Site Number 840103

Jerseyville, Illinois, 62052, United States

Location

Investigational Site Number 840106

Peoria, Illinois, 61606, United States

Location

Investigational Site Number 840066

Elkhart, Indiana, 46514, United States

Location

Investigational Site Number 840099

Lexington, Kentucky, 40504, United States

Location

Investigational Site Number 840039

Owensboro, Kentucky, 42303, United States

Location

Investigational Site Number 840092

Baton Rouge, Louisiana, 70808, United States

Location

Investigational Site Number 840040

Auburn, Maine, 04210, United States

Location

Investigational Site Number 840077

Ayer, Massachusetts, 01432, United States

Location

Investigational Site Number 840050

Alpena, Michigan, 49707, United States

Location

Investigational Site Number 840041

Saginaw, Michigan, 48670, United States

Location

Investigational Site Number 840058

Minneapolis, Minnesota, 55422, United States

Location

Investigational Site Number 840101

Picayune, Mississippi, 39466, United States

Location

Investigational Site Number 840078

St Louis, Missouri, 63122, United States

Location

Investigational Site Number 840038

St Louis, Missouri, 63128, United States

Location

Investigational Site Number 840102

St Louis, Missouri, 63128, United States

Location

Investigational Site Number 840012

Kalispell, Montana, 59901, United States

Location

Investigational Site Number 840090

Lincoln, Nebraska, 68506, United States

Location

Investigational Site Number 840045

Buffalo, New York, 14215, United States

Location

Investigational Site Number 840055

Manhasset, New York, 11030, United States

Location

Investigational Site Number 840003

The Bronx, New York, 10468, United States

Location

Investigational Site Number 840004

Troy, New York, 12180, United States

Location

Investigational Site Number 840009

Maumee, Ohio, 43537, United States

Location

Investigational Site Number 840028

Camp Hill, Pennsylvania, 17011, United States

Location

Investigational Site Number 840067

Wyomissing, Pennsylvania, 19610, United States

Location

Investigational Site Number 840027

Wakefield, Rhode Island, 02879, United States

Location

Investigational Site Number 840046

Knoxville, Tennessee, 37917, United States

Location

Investigational Site Number 840014

Longview, Texas, 75605, United States

Location

Investigational Site Number 840068

Danville, Virginia, 24541, United States

Location

Investigational Site Number 840069

Manassas, Virginia, 20109, United States

Location

Investigational Site Number 840087

Richmond, Virginia, 23249, United States

Location

Investigational Site Number 840085

Winchester, Virginia, 22601, United States

Location

Investigational Site Number 840013

Burien, Washington, 98166, United States

Location

Investigational Site Number 840091

Spokane, Washington, 99204, United States

Location

Investigational Site Number 840080

Madison, Wisconsin, 53713, United States

Location

Investigational Site Number 840023

Milwaukee, Wisconsin, 53215, United States

Location

Investigational Site Number 124003

Cambridge, Ontario, Canada

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Dronedarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amiodarone; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

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).

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact_US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 10, 2010
• Study Start: September 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: February 12, 2013
• Results First Posted: February 12, 2013

Record last verified: 2013-01

Locations

US (56); CA (1)