Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial

Atrial Fibrillation Clinical Trial

— CABANA  

Official title:

Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00911508
• Other study ID #: 09-004616
• Secondary ID: U01HL089709
• Status: Completed
• Phase: N/A
• Start date: November 13, 2009
• Est. completion date: December 31, 2017

Study information

• Verified date: April 2021
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The (Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) 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 decreasing the incidence of the composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest in patients with untreated or incompletely treated AF.

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 up to 2200 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 ≥2 rate control drugs. Pts will be followed every 6 months for an average of approximately 5 years 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2204
• Est. completion date: December 31, 2017
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Over the preceding 6 months have:

1. =2 paroxysmal (electrocardiographic documentation of at least 1) atrial fibrillation (AF) episodes lasting =1 hour in duration: (that terminate spontaneously within 7 days or cardioversion is performed within 48h of AF onset): or

2. electrocardiographic documentation of 1 persistent AF episode: (sustained for =7 days or cardioversion is performed more than 48h after AF onset): or

3. electrocardiographic documentation of 1 longstanding persistent AF episode:

(continuous AF of duration >1 year).

• Warrant active therapy (within the past 3 months) beyond simple ongoing observation

• Be eligible for catheter ablation and =2 sequential rhythm control and/or =2 rate control drugs.

• Be =65 yrs of age, or <65 yrs with one or more of the following risk factors for stroke: Hypertension (treated and/or defined as a blood pressure >140/90 mmHg) [90], Diabetes (treated and/or defined as a fasting glucose =126 mg/dl) [91], Congestive heart failure (including systolic or diastolic heart failure), Prior stroke, transient ischemic attack or systemic emboli, Atherosclerotic vascular disease (previous myocardial infarction (MI), peripheral arterial disease or aortic plaque), left atrial (LA) size >5.0 cm (or volume index =40 cc/m2), or ejection fraction (EF) =35.

• Have the capacity to understand and sign an informed consent form.

• Be =18 years of age.

• NOTE- Subjects <65 yrs of age whose only risk factor is hypertension must have a second risk factor or left ventricular (LV) hypertrophy to qualify.Patients receiving new drug therapy initiated within the previous 3 months may continue that therapy if randomized to the drug therapy arm. Patients may have documented atrial flutter in addition to atrial fibrillation and remain eligible for enrollment.

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 or side effects (Table 5.2.2)

• An efficacy failure of full dose amiodarone treatment >8 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, percutaneous intervention (PCI), or valve or bypass surgery in the preceding 3 months

• Hypertrophic obstructive cardiomyopathy (outflow track)

• Class IV angina or Class IV congestive heart failure (CHF) (including past or planned heart transplantation)

• Other arrhythmias mandating anti-arrhythmic drug therapy (i.e. ventricular tachycardia (VT), ventricular fibrillation (VF))

• 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 appropriate anti-coagulation therapy

• 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 (Participation in other non-mortality trials should be reviewed with the clinical trial management center)

• Unable to give informed consent

• NOTE- Prior ablation of the cavo-tricuspid isthmus alone is not an exclusion if the patient develops subsequent recurrent AF. Planned atrial flutter ablation in combination with the left atrial ablation is not an exclusion.

Related Conditions & MeSH terms

• Arrhythmia
• Atrial Fibrillation

Intervention

Device:
• Left atrial ablation
St. Jude: Livewire TC™ , Therapy™ Dual / Thermocouple, Safire,Therapy Cool Path Biosense Webster: NAVI-STAR, NAVI-STAR/NAVI-STAR DS, Celsius Braided/Long Tip, NAVI-STAR™ and Celsius™ ThermoCool, NAVI-STAR® RMT, Celsius® RMT, ThermoCool® SF Medtronic CryoCath LP: Freezor®/Freezor MAX®, Artic Front®, Cardiac Ablation System Bard: Stinger Boston Scientific: Blazer II RF/XP, Blazer RPM, Chilli II Cooled, SteeroCath

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, Dronedarone 800mg

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Canada	University of Calgary	Calgary	Alberta
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	University of Western Ontario - London Health Sciences Centre	London	Ontario
Canada	Southlake Regional Health Centre	Newmarket	Ontario
China	Beijing Anzhen Hospital	Beijing
China	Fuwai Hospital	Beijing
China	First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
Czechia	Saint Anne's University Hospital, ICRC	Brno
Czechia	Charles University	Prague 2
Czechia	Clinic of Cardiology IKEM Medical Institute	Prague 4
Czechia	Na Homolce Hospital	Prague 5	Hlavni Mesto Praha
Germany	Kerckhoff Klinik	Bad Nauheim
Germany	Herz-und Diabeteszentrum NRW	Bad Oeynhausen	Nordrhein-Westfalen
Germany	Klinikum Coburg	Coburg	Bayern
Germany	Praxisklinik Herz and GefaBe	Dresden
Germany	Technische Universitat Dresden	Dresden	Saxony
Germany	CCB - Cardioaniologisches Centrum Bethanien	Frankfurt
Germany	Georg-August-University	Gottingen
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitares Herrzentrum Hamburg	Hamburg	Freie-Hansestadt Hamburg
Germany	Saint Vincentius-Kliniken	Karlsruhe
Germany	Herzzentrum Leipzig	Leipzig
Germany	University Hospital of Mannheim	Mannheim	Baden-Wurttemberg
Germany	Universitat Rostock	Rostock
Italy	Policlinico Multimedical Cardiology and Arrhythmia Centre	Milan
Italy	Policlinico San Donato Center of Clinical Arrhythmia and Electrophysiology	San Donato Milanese	Lombardia
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Yonsei University Severance Hospital	Seoul
Russian Federation	Bakoulev Scientific Center for Cardiovascular Surgery	Moscow
Russian Federation	Clinical Hospital # 83 under the Federal Medical and Biological Agency	Moscow
Russian Federation	Research Institute of Circulation of Pathology	Novosibirsk	Novosibirskaya Oblast
Russian Federation	Scientific Research Institute of Cardiology of Ministry of Health of Russian Foundation	Tomsk
United Kingdom	Golden Jubilee Hospital	Glasgow
United Kingdom	Saint Bartholomew's Hospital	London
United Kingdom	Saint George's Hospital Medical School	London
United Kingdom	Saint Mary's Hospital	London
United States	Albany Associates in Cardiology	Albany	New York
United States	Georgia Regents University	Augusta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Texas Cardiac Arrhythmia	Austin	Texas
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Alexian Brothers Medical Center	Barrington	Illinois
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The Sanger Clinic, PA	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Memorial Health Care System	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Penrose Saint Francis Health Services	Colorado Springs	Colorado
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Geisinger Wyoming Valley Medical Center	Danville	Pennsylvania
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	NorthShore University Health System	Evanston	Illinois
United States	Virginia Hospital Center - Arlington	Falls Church	Virginia
United States	Baylor All Saints Medical Center	Fort Worth	Texas
United States	Greenville Hospital System University Medical Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Hartford Hospital	Hartford	Connecticut
United States	Penn State University Cardiovascular Center	Hershey	Pennsylvania
United States	University of Texas Health Science Center	Houston	Texas
United States	Jackson Heart Clinic	Jackson	Mississippi
United States	Arkansas Cardiology, PA	Little Rock	Arkansas
United States	Good Samaritan Hospital	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	Georgia Arrhythmia Consultants & Research Institute	Macon	Georgia
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami Hospital	Miami	Florida
United States	Minneapolis V.A. Medical Center	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Florida Hospital	Orlando	Florida
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	V.A. Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	The Heart Hospital Baylor Plano	Plano	Texas
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of California Davis Medical Center	Sacramento	California
United States	Saint John's Mercy Heart Health Center	Saint Louis	Missouri
United States	Saint Louis Heart and Vascular	Saint Louis	Missouri
United States	Park Nicollet Methodist Hospital	Saint Louis Park	Minnesota
United States	Northside Hospital and Heart Institute	Saint Petersburg	Florida
United States	Intermountain Medical Center-LDS Hospital	Salt Lake City	Utah
United States	South Texas Cardiovascular Consultants	San Antonio	Texas
United States	University of California at San Francisco Medical Center	San Francisco	California
United States	Swedish Medical Center - Providence Campus	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	Stony Brook University Hospital and Medical Center	Stony Brook	New York
United States	Cardiac Study Center	Tacoma	Washington
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	Florida Heart Rhythm-University of South Florida College of Medicine	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Oklahoma Heart Institute	Tulsa	Oklahoma
United States	George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Mercy Medical Center-Iowa Heart Center	West Des Moines	Iowa
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Lankenau Hospital	Wynnewood	Pennsylvania
United States	Saint Joseph Mercy Hospital	Ypsilanti	Michigan

Sponsors (4)

Lead Sponsor	Collaborator
Mayo Clinic	Abbott Medical Devices, Biosense Webster, Inc., National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Czechia,  Germany,  Italy,  Korea, Republic of,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF.	All events for each component of the primary endpoint were reviewed and adjudicated in a blinded fashion by an independent clinical events committee using prospectively determined event definitions. Death was defined as all-cause mortality, disabling stroke (including intracranial bleeding) as an irreversible physical limitation defined by a Rankin Stroke Scale =2, and serious bleeding as bleeding accompanied by hemodynamic compromise that required surgical intervention or a transfusion of =3 units of blood.	From date of enrollment until time-to-first event over a median follow-up of 48.5 months.
Secondary	Number of Participants With All-cause Mortality	All deaths were reviewed and adjudicated by the Clinical Events Committee	From date of enrollment until date of death over a median follow-up of 48.5 months.
Secondary	Number of Participants With Mortality or Cardiovascular (CV) Hospitalization	Hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form.	From date of enrollment until time-to-first event of death or CV hospitalization over a median follow-up of 48.5 months.
Secondary	Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events)	Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale =2 and the reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form.	From date of enrollment until time-to-first event of death, stroke, or CV hospitalization (for heart failure or acute ischemic event) over a median follow-up of 48.5 months.
Secondary	Number of Participants With Cardiovascular Death	Cardiovascular death as determined by the Clinical Events Committee based on the available data provided by the Principal Investigator	From date of enrollment until date of a cardiovascular death over a median follow-up of 48.5 months.
Secondary	Number of Participants With Cardiovascular Death or Disabling Stroke	Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale =2.	From date of enrollment until time-to-first event of a cardiovascular death or disabling stroke over a median follow-up of 48.5 months.
Secondary	Number of Participants With an Arrhythmic Death or Cardiac Arrest	All deaths and cardiac arrest events were adjudicated by the Clinical Events Committee	From date of enrollment until time-to-first event for an arrhythmic death or cardiac arrest over a median follow-up of 48.5 months.
Secondary	Number of Participants With Heart Failure Death	All deaths were categorized and adjudicated by the Clinical Events Committee	From date of enrollment until date of heart failure death over a median follow-up of 48.5 months.
Secondary	Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period	Data from patients using the study provided ECG event recording system were analyzed. A 30-second episode of AF in either group, confirmed through blinded review by an ECG Core Lab Committee was used for defining the endpoint of recurrent AF.	From date of therapy initiation until date of first AF recurrence following a 90 day wait (blanking) period over a median follow-up of 48.5 months.
Secondary	Number of Participants With Cardiovascular Hospitalization	The reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form.	From date of enrollment until date of cardiovascular hospitalization over a median follow-up of 48.5 months.
Secondary	Changes in Quality of Life Measures - AFEQT	Atrial Fibrillation Effect on Quality of Life (AFEQT) Overall Score (Scale: 0 = complete disability, 100 = no disability). The AFEQT is a 21-item AF-specific, health-related QOL questionnaire designed to assess the effect of atrial fibrillation on patient quality of life. The AFEQT has an Overall Score (calculated from 18 of the questions) and subscale scores in three domains: symptoms, daily activities, and treatment concern. Overall and subscale scores range from 0 (corresponds to complete disability) to 100 (no AF-related disability).	Baseline ,12 month, 5 years
Secondary	Changes in Quality of Life Measures - MAFSI Frequency Score	The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI frequency of symptoms over the past month was recorded as 0 (never), 1 (rarely), 2 (sometimes), 3 (often), and 4 (always) for each of the 10 items listed in the questionnaire. The 10 item responses were summed for a total Frequency Score that ranged from 0 (no AF symptoms) to 40 (worst score).	Baseline, 12 Month, 5 Year
Secondary	Changes in Quality of Life Measures - MAFSI Severity Score	The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI severity scores over the past month were recorded as 1 (mild), 2 (moderate), and 3 (extreme) for each of the 10 items listed in the questionnaire. The 10 items items were then summed for the total Severity Score that ranged from 0 (no AF symptoms) to 30 (most severe AF symptoms).	Baseline, 12 Month, 5 Year
Secondary	Number of Participants With Adverse Events/Complications	Comparing individual non-endpoint adverse events between ablative and drug therapy is difficult due to the substantial difference in the types of adverse events expected.; Ablation-related events were counted among all patients that were randomized to and received an ablation.; Drug-related events were counted among all patients that were randomized to and received drug therapy.	From treatment start date to date of event over a median follow-up of 48.5 months.

External Links

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