Clinical trial NCT01135017: Effects of Dronedarone on Atrial Fibrillation Burden in Subjects With Permanent Pacemakers
Official title: A Placebo-Controlled, Double-Blind, Randomized, Multi-Center Study to Assess the Effects of Dronedarone 400 mg BID for 12 Weeks on Atrial Fibrillation Burden in Subjects With Permanent Pacemakers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Atrial Fibrillation
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-06-02
Enrollment: 112
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 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.

Detailed description: The maximum duration of the study period for a participant was 18 weeks (approximatively 4.5 months) including up to 4 weeks screening, 12-week Treatment period and a post-treatment follow-up of 2 weeks.

Eligibility criteria: Inclusion criteria:

* 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.

Exclusion criteria:

* 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;
* Use of Class I or Class III antiarrhythmics (other than amiodarone) within 5-half lives prior to screening;
* Use of St John's wort, grapefruit juice, or drugs that prolong the QT interval and might have increased the risk of torsade de pointes;
* Inability or unwillingness to comply with oral anticoagulation therapy, if indicated;
* Bazett corrected QT interval interval ≥500 msec at screening (if in sinus rhythm);
* Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥ 100mmHg) at screening;
* Uncorrected hypokalemia (serum potassium \<3.5 mEq/L)
* Severe hepatic impairment (ie, Child-Pugh Class C), abnormal liver function test defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin \>2 X upper limit of normal (ULN), or renal impairment defined as serum creatinine \>2.0 mg/dL at screening;
* Uncontrolled diabetes mellitus (documented history of HbA1c \>10% at the most recent assessment prior to screening);
* Pregnant woman or woman of childbearing potential not on adequate birth control;
* Breastfeeding woman;
* Previous (within 2 months prior to screening) or current participation in another clinical trial with an investigational drug (under development) or investigational device.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Atrial Fibrillation (AF) Burden During the 12-week Treatment Period
timeFrame: Baseline (before randomization), 4 weeks and 12 weeks after randomization
Secondary outcomes:
measure: AF Burden During the First 4 Weeks of Treatment and After 4-week Treatment
timeFrame: 4 weeks and 12 weeks after randomization
measure: Average Ventricular Rate During AF Episodes
timeFrame: Baseline (before randomization), 4 weeks and 12 weeks after randomization
measure: Atrial Fibrillation Severity Scale (AFSS) Scores
timeFrame: Baseline (before randomization) and 12 weeks after randomization
measure: Incidence Rate of Electrical Cardioversion (or Overdrive Pacing)
timeFrame: 12 weeks
Other outcomes:
measure: Overview of Adverse Events (AE)
timeFrame: from first study drug intake up to 10 days after the last study drug intake
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840015
state: Alabama
city: Huntsville
country: United States
facility: Investigational Site Number 840087
state: Alabama
city: Mobile
country: United States
facility: Investigational Site Number 840018
state: Alabama
city: Mesa
country: United States
facility: Investigational Site Number 840030
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 840048
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 840072
state: Arizona
city: Tucson
country: United States
facility: Investigational Site Number 840013
state: Arizona
city: Hot Springs
country: United States
facility: Investigational Site Number 840069
state: Arkansas
city: Beverly Hills
country: United States
facility: Investigational Site Number 840121
state: California
city: Laguna Hills
country: United States
facility: Investigational Site Number 840090
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840068
state: California
city: Mission Hills
country: United States
facility: Investigational Site Number 840062
state: California
city: Orange
country: United States
facility: Investigational Site Number 840070
state: California
city: Riverside
country: United States
facility: Investigational Site Number 840021
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840024
state: California
city: Aurora
country: United States
facility: Investigational Site Number 840001
state: Colorado
city: Littleton
country: United States
facility: Investigational Site Number 840089
state: Colorado
city: Loveland
country: United States
facility: Investigational Site Number 840029
state: Colorado
city: Newark
country: United States
facility: Investigational Site Number 840108
state: Delaware
city: Washington
country: United States
facility: Investigational Site Number 840045
state: District of Columbia
city: Washington
country: United States
facility: Investigational Site Number 840106
state: District of Columbia
city: Clearwater
country: United States
facility: Investigational Site Number 840010
state: Florida
city: Ft. Myers
country: United States
facility: Investigational Site Number 840020
state: Florida
city: Inverness
country: United States
facility: Investigational Site Number 840058
state: Florida
city: Jacksonville Beach
country: United States
facility: Investigational Site Number 840044
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840043
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840066
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840128
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 840042
state: Florida
city: Port Charlotte
country: United States
facility: Investigational Site Number 840016
state: Florida
city: Wellington
country: United States
facility: Investigational Site Number 840080
state: Florida
city: Gainesville
country: United States
facility: Investigational Site Number 840056
state: Georgia
city: Normal
country: United States
facility: Investigational Site Number 840092
state: Illinois
city: Oak Lawn
country: United States
facility: Investigational Site Number 840032
state: Illinois
city: Rockford
country: United States
facility: Investigational Site Number 840046
state: Illinois
city: Bloomington
country: United States
facility: Investigational Site Number 840051
state: Indiana
city: Kansas City
country: United States
facility: Investigational Site Number 840053
state: Kansas
city: Owensboro
country: United States
facility: Investigational Site Number 840110
state: Kentucky
city: Columbia
country: United States
facility: Investigational Site Number 840102
state: Maryland
city: Lansing
country: United States
facility: Investigational Site Number 840017
state: Michigan
city: Lapeer
country: United States
facility: Investigational Site Number 840081
state: Michigan
city: Petoskey
country: United States
facility: Investigational Site Number 840075
state: Michigan
city: Troy
country: United States
facility: Investigational Site Number 840027
state: Michigan
city: St Cloud
country: United States
facility: Investigational Site Number 840104
state: Minnesota
city: Tupelo
country: United States
facility: Investigational Site Number 840097
state: Mississippi
city: Columbia
country: United States
facility: Investigational Site Number 840037
state: Missouri
city: Kansas City
country: United States
facility: Investigational Site Number 840035
state: Missouri
city: St Louis
country: United States
facility: Investigational Site Number 840060
state: Missouri
city: St. Louis
country: United States
facility: Investigational Site Number 840055
state: Missouri
city: Missoula
country: United States
facility: Investigational Site Number 840067
state: Montana
city: Reno
country: United States
facility: Investigational Site Number 840049
state: Nevada
city: Reno
country: United States
facility: Investigational Site Number 840054
state: Nevada
city: Bridgewater
country: United States
facility: Investigational Site Number 840026
state: New Jersey
city: Englewood
country: United States
facility: Investigational Site Number 840093
state: New Jersey
city: Bronx
country: United States
facility: Investigational Site Number 840036
state: New York
city: Buffalo
country: United States
facility: Investigational Site Number 840006
state: New York
city: Kingston
country: United States
facility: Investigational Site Number 840077
state: New York
city: Mineola
country: United States
facility: Investigational Site Number 840096
state: New York
city: Syracuse
country: United States
facility: Investigational Site Number 840041
state: New York
city: Troy
country: United States
facility: Investigational Site Number 840086
state: New York
city: Williamsville
country: United States
facility: Investigational Site Number 840007
state: New York
city: Raleigh
country: United States
facility: Investigational Site Number 840084
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 840061
state: North Carolina
city: Tulsa
country: United States
facility: Investigational Site Number 840065
state: Oklahoma
city: Camp Hill
country: United States
facility: Investigational Site Number 840008
state: Pennsylvania
city: Doylestown
country: United States
facility: Investigational Site Number 840009
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigational Site Number 840004
state: Pennsylvania
city: Phoenixville
country: United States
facility: Investigational Site Number 840078
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Investigational Site Number 840105
state: Pennsylvania
city: Scranton
country: United States
facility: Investigational Site Number 840130
state: Pennsylvania
city: Unionville
country: United States
facility: Investigational Site Number 840019
state: Pennsylvania
city: Wyomissing
country: United States
facility: Investigational Site Number 840023
state: Pennsylvania
city: Greenville
country: United States
facility: Investigational Site Number 840119
state: South Carolina
city: Rapid City
country: United States
facility: Investigational Site Number 840002
state: South Dakota
city: Germantown
country: United States
facility: Investigational Site Number 840114
state: Tennessee
city: Corpus Christi
country: United States
facility: Investigational Site Number 840118
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840014
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840012
state: Texas
city: Tyler
country: United States
facility: Investigational Site Number 840125
state: Texas
city: Salt Lake City
country: United States
facility: Investigational Site Number 840083
state: Utah
city: Danville
country: United States
facility: Investigational Site Number 840113
state: Virginia
city: Lynchburg
country: United States
facility: Investigational Site Number 840082
state: Virginia
city: Manassas
country: United States
facility: Investigational Site Number 840088
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840099
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840112
state: Virginia
city: Tacoma
country: United States
facility: Investigational Site Number 840003
state: Washington
city: Tacoma
country: United States
facility: Investigational Site Number 840107
state: Washington
city: Green Bay
country: United States
facility: Investigational Site Number 840123
state: Wisconsin
city: Madison
country: United States
facility: Investigational Site Number 840022
state: Wisconsin
city: Milwaukee
country: United States
facility: Investigational Site Number 840033
state: Wisconsin
city: Milwaukee
country: United States
facility: Investigational Site Number 840047
state: Wisconsin
city: Milwaukee
country: United States
facility: Investigational Site Number 840076
state: Wisconsin
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: