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

Atrial Fibrillation Clinical Trial

— HESTIA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01135017
• Other study ID #: DRONE_L_04316
• Secondary ID: U1111-1117-0024
• Status: Terminated
• Phase: Phase 4
• First received: May 28, 2010
• Last updated: April 5, 2013
• Start date: July 2010
• Est. completion date: February 2012

Study information

• Verified date: April 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 112
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Dronedarone
Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)
• Placebo (for Dronedarone)
Film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)

Locations

Country	Name	City	State
United States	Investigational Site Number 840001	Aurora	Colorado
United States	Investigational Site Number 840121	Beverly Hills	California
United States	Investigational Site Number 840015	Birmingham	Alabama
United States	Investigational Site Number 840051	Bloomington	Indiana
United States	Investigational Site Number 840026	Bridgewater	New Jersey
United States	Investigational Site Number 840036	Bronx	New York
United States	Investigational Site Number 840006	Buffalo	New York
United States	Investigational Site Number 840008	Camp Hill	Pennsylvania
United States	Investigational Site Number 840010	Clearwater	Florida
United States	Investigational Site Number 840037	Columbia	Missouri
United States	Investigational Site Number 840102	Columbia	Maryland
United States	Investigational Site Number 840118	Corpus Christi	Texas
United States	Investigational Site Number 840014	Dallas	Texas
United States	Investigational Site Number 840113	Danville	Virginia
United States	Investigational Site Number 840009	Doylestown	Pennsylvania
United States	Investigational Site Number 840093	Englewood	New Jersey
United States	Investigational Site Number 840020	Ft. Myers	Florida
United States	Investigational Site Number 840056	Gainesville	Georgia
United States	Investigational Site Number 840114	Germantown	Tennessee
United States	Investigational Site Number 840123	Green Bay	Wisconsin
United States	Investigational Site Number 840119	Greenville	South Carolina
United States	Investigational Site Number 840069	Hot Springs	Arkansas
United States	Investigational Site Number 840087	Huntsville	Alabama
United States	Investigational Site Number 840058	Inverness	Florida
United States	Investigational Site Number 840043	Jacksonville	Florida
United States	Investigational Site Number 840066	Jacksonville	Florida
United States	Investigational Site Number 840128	Jacksonville	Florida
United States	Investigational Site Number 840044	Jacksonville Beach	Florida
United States	Investigational Site Number 840035	Kansas City	Missouri
United States	Investigational Site Number 840053	Kansas City	Kansas
United States	Investigational Site Number 840077	Kingston	New York
United States	Investigational Site Number 840090	Laguna Hills	California
United States	Investigational Site Number 840017	Lansing	Michigan
United States	Investigational Site Number 840081	Lapeer	Michigan
United States	Investigational Site Number 840089	Littleton	Colorado
United States	Investigational Site Number 840068	Los Angeles	California
United States	Investigational Site Number 840029	Loveland	Colorado
United States	Investigational Site Number 840082	Lynchburg	Virginia
United States	Investigational Site Number 840022	Madison	Wisconsin
United States	Investigational Site Number 840088	Manassas	Virginia
United States	Investigational Site Number 840030	Mesa	Arizona
United States	Investigational Site Number 840033	Milwaukee	Wisconsin
United States	Investigational Site Number 840047	Milwaukee	Wisconsin
United States	Investigational Site Number 840076	Milwaukee	Wisconsin
United States	Investigational Site Number 840096	Mineola	New York
United States	Investigational Site Number 840062	Mission Hills	California
United States	Investigational Site Number 840067	Missoula	Montana
United States	Investigational Site Number 840018	Mobile	Alabama
United States	Investigational Site Number 840108	Newark	Delaware
United States	Investigational Site Number 840092	Normal	Illinois
United States	Investigational Site Number 840032	Oak Lawn	Illinois
United States	Investigational Site Number 840070	Orange	California
United States	Investigational Site Number 840042	Orlando	Florida
United States	Investigational Site Number 840110	Owensboro	Kentucky
United States	Investigational Site Number 840075	Petoskey	Michigan
United States	Investigational Site Number 840004	Philadelphia	Pennsylvania
United States	Investigational Site Number 840048	Phoenix	Arizona
United States	Investigational Site Number 840072	Phoenix	Arizona
United States	Investigational Site Number 840078	Phoenixville	Pennsylvania
United States	Investigational Site Number 840105	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840016	Port Charlotte	Florida
United States	Investigational Site Number 840084	Raleigh	North Carolina
United States	Investigational Site Number 840002	Rapid City	South Dakota
United States	Investigational Site Number 840049	Reno	Nevada
United States	Investigational Site Number 840054	Reno	Nevada
United States	Investigational Site Number 840099	Richmond	Virginia
United States	Investigational Site Number 840112	Richmond	Virginia
United States	Investigational Site Number 840021	Riverside	California
United States	Investigational Site Number 840046	Rockford	Illinois
United States	Investigational Site Number 840083	Salt Lake City	Utah
United States	Investigational Site Number 840012	San Antonio	Texas
United States	Investigational Site Number 840024	San Diego	California
United States	Investigational Site Number 840130	Scranton	Pennsylvania
United States	Investigational Site Number 840104	St Cloud	Minnesota
United States	Investigational Site Number 840060	St Louis	Missouri
United States	Investigational Site Number 840055	St. Louis	Missouri
United States	Investigational Site Number 840041	Syracuse	New York
United States	Investigational Site Number 840003	Tacoma	Washington
United States	Investigational Site Number 840107	Tacoma	Washington
United States	Investigational Site Number 840027	Troy	Michigan
United States	Investigational Site Number 840086	Troy	New York
United States	Investigational Site Number 840013	Tucson	Arizona
United States	Investigational Site Number 840065	Tulsa	Oklahoma
United States	Investigational Site Number 840097	Tupelo	Mississippi
United States	Investigational Site Number 840125	Tyler	Texas
United States	Investigational Site Number 840019	Unionville	Pennsylvania
United States	Investigational Site Number 840045	Washington	District of Columbia
United States	Investigational Site Number 840106	Washington	District of Columbia
United States	Investigational Site Number 840080	Wellington	Florida
United States	Investigational Site Number 840007	Williamsville	New York
United States	Investigational Site Number 840061	Wilmington	North Carolina
United States	Investigational Site Number 840023	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overview of Adverse Events (AE)	AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.	from first study drug intake up to 10 days after the last study drug intake	Yes
Primary	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	No
Secondary	AF Burden During the First 4 Weeks of Treatment and After 4-week Treatment	AF burden at each pacemaker interrogation as evaluated centrally by the Pacemaker Core Lab	4 weeks and 12 weeks after randomization	No
Secondary	Average Ventricular Rate During AF Episodes	Ventricular rates of AF episodes were obtained from pacemaker interrogation and EGM review.; The average ventricular rate during AF episodes in the 12-week treatment period was defined as the duration-weighted average of the ventricular rates 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	No
Secondary	Atrial Fibrillation Severity Scale (AFSS) Scores	The University of Toronto Atrial Fibrillation Severity Scale is an instrument to assess the subject-perceived AF burden and AF symptom severity. It consists in a questionnaire plus a scoring algorithm.; AF Burden score ranges from 3 to 30 and higher scores indicate greater AF burden.; AF symptoms severity score ranges from 0 to 35 and higher scores indicate extremely severe AF symptoms.	Baseline (before randomization) and 12 weeks after randomization	No
Secondary	Incidence Rate of Electrical Cardioversion (or Overdrive Pacing)	Electrical cardioversion is a procedure in which an electric shock is used to restore normal heart rhythm. Overdrive pacing is a procedure in which an artificial cardiac pacemaker is used to increase the heart rate in order to suppress certain arrhythmias.; Incidence rate of electrical cardioversion (or overdrive pacing) is expressed as the number of participants that was cardioverted or paced during the study.	12 weeks	No