Ablation Versus Anti-Arrhythmic (AA) Drug Therapy for AF - Pivotal Trial - Full Text View

Sponsor:	Mayo Clinic
Collaborators:	National Heart, Lung, and Blood Institute (NHLBI) Duke University St. Jude Medical Biosense Webster, Inc.
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00911508

Purpose

The CABANA Trial has the overall goal of establishing the appropriate roles for medical and ablative intervention for atrial fibrillation (AF). The CABANA Trial is designed to test the hypothesis that the treatment strategy of left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) will be superior to current state-of-the-art therapy with either rate control or rhythm control drugs for reducing total mortality in patients with untreated or incompletely treated AF.

Condition	Intervention	Phase
Atrial Fibrillation Arrhythmia Stroke Prevention Mortality	Device: Left atrial ablation Drug: Rate or Rhythm Control Therapy	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial

Resource links provided by NLM:

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome

MedlinePlus related topics: Arrhythmia Atrial Fibrillation

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

Percutaneous left atrial catheter ablation for the purpose of eliminating AF is superior to current state-of-the-art therapy with either rate or rhythm control drugs for reducing total mortality in patients with untreated or incompletely treated AF. [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Decrease the composite endpoint of total mortality, disabling stroke, serious bleeding, and cardiac arrest in patients with untreated or incompletely treated AF warranting therapy. [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
Total mortality, disabling stroke, serious bleeding, or cardiac arrest [ Time Frame: 6 month intervals, length of trial ] [ Designated as safety issue: Yes ]
Total mortality or cardiovascular hospitalization [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
Cardiovascular death [ Time Frame: 6 month intervals, length of trial ] [ Designated as safety issue: Yes ]
Cardiovascular death or disabling stroke [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
Arrhythmic death or cardiac arrest [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
Heart failure deathLA size, morphology and function [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
Freedom from recurrent AF [ Time Frame: Monitored monthly for trial duration ] [ Designated as safety issue: No ]
Cardiovascular hospitalization [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
Medical costs, resource utilization, and cost effectiveness [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: No ]
Quality of Life [ Time Frame: At months 3, 6, 12, 18, 24, 30, 36 ] [ Designated as safety issue: No ]
Composite adverse events [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
Left atrial size, morphology and function [ Time Frame: Baseline and 3 months post therapy initiation ] [ Designated as safety issue: No ]

Estimated Enrollment:	3000
Study Start Date:	August 2009
Estimated Study Completion Date:	September 2015
Estimated Primary Completion Date:	March 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Ablation: Active Comparator Pulmonary vein isolation using a circumferential ablative approach in the left atrium. Ablation may be performed using circular mapping catheter-guided ablation, antral isolation using a circular guided approach, or wide area circumferential ablation.	Device: Left atrial ablation St. Jude: Livewire, Therapy Dual/Thermocouple Biosense Webster: NAVI-STAR Thermo-cool,NAVI-STAR/NAVI-STAR DS, Celsius Braided Tip CryoCath Technologies: Freezor/Freezor Max Bard: Stinger Boston Scientific: Blazer II RF/RPM/SteeroCath/XP, Chilli Cooled.
Rate or Rhythm Control Therapy: Active Comparator Current state-of-the-art drug therapy for atrial fibrillation (rate control or rhythm control). Treating physicians will be encouraged to follow the American College of Cardiology / American Heart Association / European Society of Cardiology Atrial Fibrillation Guidelines with regard to drug therapy for atrial fibrillation. The specific choice of rate control versus rhythm control drug therapy and the specific drugs to be used will ultimately be left to the discretion of the treating physician.	Drug: Rate or Rhythm Control Therapy Rate control: Metoprolol 50-100mg, Atenolol 50-100mg, Propranolol 40-80mg, Acebutolol 200-300mg, Carvedilol 6.25-25mg, Diltiazem 180-240mg, Verapamil 180-240mg, Digoxin 0.125-0.25mg Rhythm control: Propafenone 450-625mg, Flecainide 200-300mg, Sotalol 240-320mg, Dofetilide 500-1000mcg, Amiodarone 200-400mg, Quinidine 600-900mg

Arms

Assigned Interventions

Ablation: Active Comparator

Pulmonary vein isolation using a circumferential ablative approach in the left atrium. Ablation may be performed using circular mapping catheter-guided ablation, antral isolation using a circular guided approach, or wide area circumferential ablation.

Device: Left atrial ablation

St. Jude: Livewire, Therapy Dual/Thermocouple

Biosense Webster: NAVI-STAR Thermo-cool,NAVI-STAR/NAVI-STAR DS, Celsius Braided Tip

CryoCath Technologies: Freezor/Freezor Max

Bard: Stinger

Boston Scientific: Blazer II RF/RPM/SteeroCath/XP, Chilli Cooled.

Rate or Rhythm Control Therapy: Active Comparator

Current state-of-the-art drug therapy for atrial fibrillation (rate control or rhythm control). Treating physicians will be encouraged to follow the American College of Cardiology / American Heart Association / European Society of Cardiology Atrial Fibrillation Guidelines with regard to drug therapy for atrial fibrillation. The specific choice of rate control versus rhythm control drug therapy and the specific drugs to be used will ultimately be left to the discretion of the treating physician.

Drug: Rate or Rhythm Control Therapy

Rate control: Metoprolol 50-100mg, Atenolol 50-100mg, Propranolol 40-80mg, Acebutolol 200-300mg, Carvedilol 6.25-25mg, Diltiazem 180-240mg, Verapamil 180-240mg, Digoxin 0.125-0.25mg

Rhythm control: Propafenone 450-625mg, Flecainide 200-300mg, Sotalol 240-320mg, Dofetilide 500-1000mcg, Amiodarone 200-400mg, Quinidine 600-900mg

Detailed Description:

The need for this trial arises out of 1) the rapidly increasing number of pts > 60 years of age with AF accompanied by symptoms and morbidity, 2) the failure of anti-arrhythmic drug therapy to maintain sinus rhythm and reduce mortality, 3) the rapidly increasing application of radio-frequency catheter ablation without appropriate evidence-based validation, and 4) the expanding impact of AF on health care costs.

This study will randomize 3000 patients to a strategy of catheter ablation versus pharmacologic therapy with rate or rhythm control drugs. Each pt will have 1) characteristics similar to AFFIRM pts (≥65 yo or <65 with >1 risk factor for stroke, 2) Documented AF warranting treatment, and 3) Eligibility for both catheter ablation and ≥2 anti-arrhythmic or ≥3 rate control drugs. Pts will be followed every 6 months for >2 yrs and will undergo repeat trans-telephonic monitor, Holter monitor, and CT/MR studies to assess the impact of treatment.

The CABANA trial will disclose the role of medical and non-pharmacologic therapies for AF, establish the cost and impact of therapy on quality of life and will help determine if AF is a modifiable risk factor for increased mortality.

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Have the capacity to understand and sign an informed consent form
Be ≥18 years of age.
Have documented AF episodes ≥1 hour in duration; with ≥2 episodes over 4 months with electrocardiographic documentation of 1 episode or at least 1 episode of AF lasting more than 1 week
Warrant active therapy beyond simple ongoing observation
Be eligible for both catheter ablation and ≥2 sequential rhythm control and/or ≥3 rate control drugs.
Be ≥65 yrs of age, or <65 yrs with one or more of the following risk factors for stroke: Hypertension, Diabetes, Congestive heart failure, Prior stroke or TIA, LA size ≥5.0 cm (or volume index ≥40 cc/m2), or EF ≥35. Subjects <65 yrs of age whose only risk factor is hypertension must have a second risk factor or LV hypertrophy to qualify.

Exclusion Criteria:

Lone AF in the absence of risk factors for stroke in patients <65 years of age
Patients who in the opinion of the managing clinician should not yet receive any therapy for AF
Patients who have failed ≥2 membrane active anti-arrhythmic drugs at a therapeutic dose due to inefficacy
More than one week of amiodarone treatment in the past 3 months
An efficacy failure of full dose amiodarone treatment ≥12 weeks duration at any time
Reversible causes of AF including thyroid disorders, acute alcohol intoxication, recent major surgical procedures, or trauma
Recent cardiac events including MI, PCI, or valve or bypass surgery in the preceding 3 months
Hypertrophic obstructive cardiomyopathy
Class IV angina or Class IV CHF (including past or planned heart transplantation)
Other mandated anti-arrhythmic drug therapy
Heritable arrhythmias or increased risk for torsade de pointes with class I or III drugs
Prior LA catheter ablation with the intention of treating AF
Prior surgical interventions for AF such as the MAZE procedure
Prior AV nodal ablation
Patients with other arrhythmias requiring ablative therapy
Contraindication to warfarin anti-coagulation
Renal failure requiring dialysis
Medical conditions limiting expected survival to <1 year
Women of childbearing potential (unless post-menopausal or surgically sterile)
Participation in any other clinical mortality trial
Unable to give informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00911508

Contacts

Contact: Kristi H. Monahan, RN, BSM	507-255-6676	CABANA@mayo.edu
Contact: Shari Rolbiecki	507-538-4358	CABANA@mayo.edu

Locations

United States, Alabama
University of Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35294
Principal Investigator: Neal Kay, M.D.
United States, California
Good Samaritan hospital	Recruiting
Los Angeles, California, United States, 90017
Contact: Young Park 213-977-4175
Principal Investigator: Anil Bhandari, M.D.
United States, Illinois
Loyola University Medical Center	Recruiting
Maywood, Illinois, United States, 60153
Contact: Jean Del Priori, RN 708-216-2644
Principal Investigator: David Wilber, M.D.
United States, Iowa
Iowa Heart Center	Recruiting
West Des Moines, Iowa, United States, 50226
Principal Investigator: Steven Bailin, M.D.
United States, Maryland
Johns Hopkins Hospital	Recruiting
Baltimore, Maryland, United States, 21287
Principal Investigator: Hugh Calkins, M.D.
United States, Massachusetts
Brigham and Womens Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Christine Pellegrini, MSN 617-732-5241
Principal Investigator: William Stevenson, M.D.
United States, Minnesota
Mayo Clinic Rochester	Recruiting
Rochester, Minnesota, United States, 55905
Contact: HRS Research Office 507-255-7456
Principal Investigator: Douglas L. Packer, M.D.
Sub-Investigator: David Bradley, M.D.
United States, Ohio
Ohio State University Medical Center	Recruiting
Columbus, Ohio, United States, 43210
Contact: Jennifer Bremer, BSN 614-293-4967
Principal Investigator: John Hummel, M.D.
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Francis Marchlinski, M.D.
United States, Utah
LDS Hospital	Recruiting
Salt Lake City, Utah, United States, 84143
Principal Investigator: John Day, MD

Sponsors and Collaborators

Mayo Clinic

National Heart, Lung, and Blood Institute (NHLBI)

Duke University

St. Jude Medical

Biosense Webster, Inc.

Investigators

Principal Investigator:	Douglas L. Packer, M.D.	Mayo Clinic
Principal Investigator:	Kerry L. Lee, Ph.D.	Duke University
Principal Investigator:	Daniel B. Mark, M.D., MPH	Duke University
Principal Investigator:	Rich A. Robb, Ph.D. Phy	Mayo Clinic
Study Chair:	Alice M. Mascette, M.D.	NIH/NHLBI

More Information

Additional Information:

Mayo Clinic Clinical Trials This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Mayo Clinic Rochester ( Douglas L. Packer, M.D. )
Study ID Numbers:	08-007043 09-004616, U01HL089709
Study First Received:	May 28, 2009
Last Updated:	December 21, 2009
ClinicalTrials.gov Identifier:	NCT00911508 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Federal Government

Keywords provided by Mayo Clinic:

Atrial Fibrillation
Left Atrial Ablation
Pulmonary Vein Isolation
Catheter Ablation
Antiarrhythmic Drug Therapy

Additional relevant MeSH terms:

Pathologic Processes
Heart Diseases
Therapeutic Uses
Cardiovascular Diseases
Cardiovascular Agents

Anti-Arrhythmia Agents
Atrial Fibrillation
Pharmacologic Actions
Arrhythmias, Cardiac

ClinicalTrials.gov processed this record on February 08, 2010