Effects of Dronedarone on Atrial Fibrillation Burden in Subjects With Permanent Pacemakers

NCT01135017 | Terminated Phase 4 Results DMC

• 2 other identifiers: DRONE_L_04316U1111-1117-0024
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 92

Brief Summary

Primary objective was to evaluate the effects of dronedarone on Atrial Fibrillation (AF) burden (i.e. percent time in AF) as measured on electrogram (EGM) in subjects with a permanent pacemaker. Secondary objectives were to evaluate:

• the effects of dronedarone on AF pattern characteristics i.e. ventricular rate during AF;
• the effects of dronedarone on subject-perceived AF burden and symptom severity as reported by subjects using the Atrial Fibrillation Severity Scale (AFSS);
• the incidence of electrical cardioversion (or overdrive pacing) during treatment;
• the safety of dronedarone.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• Atrial Fibrillation (AF) Burden During the 12-week Treatment Period

  AF burden, defined as the percent time a subject is in AF, was evaluated centrally by a Pacemaker Core Lab based on pacemaker interrogation reports including Electrogram (EGM) data provided by the Investigator. AF burden during the 12-week treatment period was defined as the duration-weighted average of AF burden collected at Week 4 and Week 12. It was calculated from the single available measurement when one measurement was missing.

  Baseline (before randomization), 4 weeks and 12 weeks after randomization

Secondary Outcomes (4)

• AF Burden During the First 4 Weeks of Treatment and After 4-week Treatment

  4 weeks and 12 weeks after randomization

• Average Ventricular Rate During AF Episodes

  Baseline (before randomization), 4 weeks and 12 weeks after randomization

• Atrial Fibrillation Severity Scale (AFSS) Scores

  Baseline (before randomization) and 12 weeks after randomization

• Incidence Rate of Electrical Cardioversion (or Overdrive Pacing)

  12 weeks

Other Outcomes (1)

• Overview of Adverse Events (AE)

  from first study drug intake up to 10 days after the last study drug intake

Study Arms (2)

Dronedarone

EXPERIMENTAL

Dronedarone 400 mg twice a day for 12 weeks

Drug: Dronedarone

Placebo

PLACEBO COMPARATOR

Placebo (for Dronedarone) twice a day for 12 weeks

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:

• Paroxysmal AF or atrial flutter (AFL) documented by evidence of AF/AFL and sinus rhythm within the prior 6 months;
• AF burden ≥1% on pacemaker EGM interrogation at screening, with at least one episode of AF within the previous 28 days;
• Programmable dual chamber pacemaker with lead placement no less than 3 months before screening, a minimum capability of storing 3 months or more of EGM data, and an expected remaining battery life of 1 year or more.

You may not qualify if:

• AF burden \<1% on pacemaker EGM interrogation at screening;
• None of the following cardiovascular risk factors: Age ≥70 years, hypertension, diabetes mellitus, prior cardiovascular accident or systemic embolism, left atrium diameter ≥50 mm by M-mode or 2D echocardiography, or left ventricular ejection fraction ≤0.40 by M-mode or 2D echocardiography, cardiac catheterization, or nuclear cardiac imaging;
• Permanent AF;
• Evidence of persistent AF (continuous AF activity lasting longer than 7 days);
• Electrical cardioversion (or overdrive pacing) within 4 weeks prior to screening;
• Cardiac ablation procedure within 3 months prior to screening;
• Evidence of uncorrected atrial undersensing or oversensing documented in routine pacemaker evaluation at screening;
• Pacemaker programming requirements for the study not clinically feasible, contraindicated, or could have posed risk;
• Ongoing potentially dangerous symptoms when in AF/AFL such as angina pectoris, transient ischemic attacks, stroke, or syncope;
• 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;
• Evidence of clinical instability including hypotension, unstable angina and hemodynamically significant obstructive valvular disease, hemodynamically significant obstructive cardiomyopathy, a cardiac operation, or revascularization procedure within 4 weeks prior to screening;
• Noncardiovascular illness or disorder that could have precluded participation or severely limit survival including cancer with metastasis and organ transplantation requiring immune suppression;
• Planned noncardiac or cardiac surgery or procedures including surgery for valvular heart disease, coronary artery bypass graft, percutaneous coronary intervention, cardiac transplantation or electrical cardioversion for AF/AFL;
• Need for concomitant medication that were prohibited in this trial: Antiarrhythmics, drugs or products that are strong inhibitors of CYP3A, CYP3A inducers;
• Chronic use of amiodarone within the 4 weeks prior to screening;

Sponsors & Collaborators

• Sanofi: lead

Study Sites (92)

Investigational Site Number 840015

Birmingham, Alabama, 35235, United States

Location

Investigational Site Number 840087

Huntsville, Alabama, 35801, United States

Location

Investigational Site Number 840018

Mobile, Alabama, 36608, United States

Location

Investigational Site Number 840030

Mesa, Arizona, 85206, United States

Location

Investigational Site Number 840048

Phoenix, Arizona, 85006, United States

Location

Investigational Site Number 840072

Phoenix, Arizona, 85032, United States

Location

Investigational Site Number 840013

Tucson, Arizona, 85723, United States

Location

Investigational Site Number 840069

Hot Springs, Arkansas, 71913, United States

Location

Investigational Site Number 840121

Beverly Hills, California, 90211, United States

Location

Investigational Site Number 840090

Laguna Hills, California, 92653, United States

Location

Investigational Site Number 840068

Los Angeles, California, 90048, United States

Location

Investigational Site Number 840062

Mission Hills, California, 91345, United States

Location

Investigational Site Number 840070

Orange, California, 92868, United States

Location

Investigational Site Number 840021

Riverside, California, 92501, United States

Location

Investigational Site Number 840024

San Diego, California, 92103, United States

Location

Investigational Site Number 840001

Aurora, Colorado, 80012, United States

Location

Investigational Site Number 840089

Littleton, Colorado, 80120, United States

Location

Investigational Site Number 840029

Loveland, Colorado, 80538, United States

Location

Investigational Site Number 840108

Newark, Delaware, 19713, United States

Location

Investigational Site Number 840045

Washington D.C., District of Columbia, 20010-2975, United States

Location

Investigational Site Number 840106

Washington D.C., District of Columbia, 20037, United States

Location

Investigational Site Number 840010

Clearwater, Florida, 33756, United States

Location

Investigational Site Number 840020

Fort Myers, Florida, 33908, United States

Location

Investigational Site Number 840058

Inverness, Florida, 34452, United States

Location

Investigational Site Number 840043

Jacksonville, Florida, 32204, United States

Location

Investigational Site Number 840066

Jacksonville, Florida, 32216, United States

Location

Investigational Site Number 840128

Jacksonville, Florida, 32216, United States

Location

Investigational Site Number 840044

Jacksonville Beach, Florida, 32250, United States

Location

Investigational Site Number 840042

Orlando, Florida, 32803, United States

Location

Investigational Site Number 840016

Port Charlotte, Florida, 33952, United States

Location

Investigational Site Number 840080

Wellington, Florida, 33449, United States

Location

Investigational Site Number 840056

Gainesville, Georgia, 30501, United States

Location

Investigational Site Number 840092

Normal, Illinois, 61761, United States

Location

Investigational Site Number 840032

Oak Lawn, Illinois, 60453, United States

Location

Investigational Site Number 840046

Rockford, Illinois, 61107, United States

Location

Investigational Site Number 840051

Bloomington, Indiana, 47403, United States

Location

Investigational Site Number 840053

Kansas City, Kansas, 66160, United States

Location

Investigational Site Number 840110

Owensboro, Kentucky, 42303, United States

Location

Investigational Site Number 840102

Columbia, Maryland, 21044, United States

Location

Investigational Site Number 840017

Lansing, Michigan, 48910, United States

Location

Investigational Site Number 840081

Lapeer, Michigan, 48446, United States

Location

Investigational Site Number 840075

Petoskey, Michigan, 49770, United States

Location

Investigational Site Number 840027

Troy, Michigan, 48085, United States

Location

Investigational Site Number 840104

Saint Cloud, Minnesota, 56301, United States

Location

Investigational Site Number 840097

Tupelo, Mississippi, 38801, United States

Location

Investigational Site Number 840037

Columbia, Missouri, 65212, United States

Location

Investigational Site Number 840035

Kansas City, Missouri, 64111, United States

Location

Investigational Site Number 840060

St Louis, Missouri, 63122, United States

Location

Investigational Site Number 840055

St Louis, Missouri, 63141, United States

Location

Investigational Site Number 840067

Missoula, Montana, 59802, United States

Location

Investigational Site Number 840049

Reno, Nevada, 89502, United States

Location

Investigational Site Number 840054

Reno, Nevada, 89502, United States

Location

Investigational Site Number 840026

Bridgewater, New Jersey, 08807, United States

Location

Investigational Site Number 840093

Englewood, New Jersey, 07631, United States

Location

Investigational Site Number 840006

Buffalo, New York, 14215, United States

Location

Investigational Site Number 840077

Kingston, New York, 12401, United States

Location

Investigational Site Number 840096

Mineola, New York, 11501, United States

Location

Investigational Site Number 840041

Syracuse, New York, 13202, United States

Location

Investigational Site Number 840036

The Bronx, New York, 10467, United States

Location

Investigational Site Number 840086

Troy, New York, 12180, United States

Location

Investigational Site Number 840007

Williamsville, New York, 14221, United States

Location

Investigational Site Number 840084

Raleigh, North Carolina, 27610, United States

Location

Investigational Site Number 840061

Wilmington, North Carolina, 28401, United States

Location

Investigational Site Number 840065

Tulsa, Oklahoma, 74104, United States

Location

Investigational Site Number 840008

Camp Hill, Pennsylvania, 17011, United States

Location

Investigational Site Number 840009

Doylestown, Pennsylvania, 18901, United States

Location

Investigational Site Number 840004

Philadelphia, Pennsylvania, 19111, United States

Location

Investigational Site Number 840078

Phoenixville, Pennsylvania, 19460, United States

Location

Investigational Site Number 840105

Pittsburgh, Pennsylvania, 15236, United States

Location

Investigational Site Number 840130

Scranton, Pennsylvania, 18510, United States

Location

Investigational Site Number 840019

Unionville, Pennsylvania, 15401, United States

Location

Investigational Site Number 840023

Wyomissing, Pennsylvania, 19610, United States

Location

Investigational Site Number 840119

Greenville, South Carolina, 29607, United States

Location

Investigational Site Number 840002

Rapid City, South Dakota, 57701, United States

Location

Investigational Site Number 840114

Germantown, Tennessee, 38138, United States

Location

Investigational Site Number 840118

Corpus Christi, Texas, 78404, United States

Location

Investigational Site Number 840014

Dallas, Texas, 75390-8858, United States

Location

Investigational Site Number 840012

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 840125

Tyler, Texas, 75701, United States

Location

Investigational Site Number 840083

Salt Lake City, Utah, 84102, United States

Location

Investigational Site Number 840113

Danville, Virginia, 24541, United States

Location

Investigational Site Number 840082

Lynchburg, Virginia, 24501, United States

Location

Investigational Site Number 840088

Manassas, Virginia, 20109, United States

Location

Investigational Site Number 840099

Richmond, Virginia, 23219, United States

Location

Investigational Site Number 840112

Richmond, Virginia, 23230, United States

Location

Investigational Site Number 840003

Tacoma, Washington, 98405, United States

Location

Investigational Site Number 840107

Tacoma, Washington, 98405, United States

Location

Investigational Site Number 840123

Green Bay, Wisconsin, 54301-3505, United States

Location

Investigational Site Number 840022

Madison, Wisconsin, 53713, United States

Location

Investigational Site Number 840033

Milwaukee, Wisconsin, 53215, United States

Location

Investigational Site Number 840047

Milwaukee, Wisconsin, 53215, United States

Location

Investigational Site Number 840076

Milwaukee, Wisconsin, 53226, United States

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 smaller-than-planned number of participants (112 instead of 424), results should be cautiously interpreted. However, the power to detect large treatment effect remained high and the posthoc power to detect a 60% reduction in AF burden was 99%.

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: May 28, 2010
• First Posted: June 2, 2010
• Study Start: July 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 11, 2013
• Results First Posted: April 1, 2013

Record last verified: 2013-04

Locations

US (92)