Brief 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.
Brief Title
Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial
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 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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Atrial Fibrillation
Arrhythmia
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Atrial Fibrillation
Left Atrial Ablation
Pulmonary Vein Isolation
Catheter Ablation
Antiarrhythmic Drug Therapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
90 Years
Minimum Age
18 Years
NCT Id
NCT00911508
Org Class
Other
Org Full Name
Mayo Clinic
Org Study Id
09-004616
Overall Status
Completed
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF.
Outcome Time Frame
From date of enrollment until time-to-first event over a median follow-up of 48.5 months.
Secondary Ids
Secondary Id
U01HL089709
Secondary Outcomes
Outcome Description
All deaths were reviewed and adjudicated by the Clinical Events Committee
Outcome Time Frame
From date of enrollment until date of death over a median follow-up of 48.5 months.
Outcome Measure
Number of Participants With All-cause Mortality
Outcome Description
Hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form.
Outcome Time Frame
From date of enrollment until time-to-first event of death or CV hospitalization over a median follow-up of 48.5 months.
Outcome Measure
Number of Participants With Mortality or Cardiovascular (CV) Hospitalization
Outcome Description
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.
Outcome Time Frame
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.
Outcome Measure
Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events)
Outcome Description
Cardiovascular death as determined by the Clinical Events Committee based on the available data provided by the Principal Investigator
Outcome Time Frame
From date of enrollment until date of a cardiovascular death over a median follow-up of 48.5 months.
Outcome Measure
Number of Participants With Cardiovascular Death
Outcome Description
Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2.
Outcome Time Frame
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.
Outcome Measure
Number of Participants With Cardiovascular Death or Disabling Stroke
Outcome Description
All deaths and cardiac arrest events were adjudicated by the Clinical Events Committee
Outcome Time Frame
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.
Outcome Measure
Number of Participants With an Arrhythmic Death or Cardiac Arrest
Outcome Description
All deaths were categorized and adjudicated by the Clinical Events Committee
Outcome Time Frame
From date of enrollment until date of heart failure death over a median follow-up of 48.5 months.
Outcome Measure
Number of Participants With Heart Failure Death
Outcome Description
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.
Outcome Time Frame
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.
Outcome Measure
Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period
Outcome Description
The reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form.
Outcome Time Frame
From date of enrollment until date of cardiovascular hospitalization over a median follow-up of 48.5 months.
Outcome Measure
Number of Participants With Cardiovascular Hospitalization
Outcome Description
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).
Outcome Time Frame
Baseline ,12 month, 5 years
Outcome Measure
Changes in Quality of Life Measures - AFEQT
Outcome Description
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).
Outcome Time Frame
Baseline, 12 Month, 5 Year
Outcome Measure
Changes in Quality of Life Measures - MAFSI Frequency Score
Outcome Description
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).
Outcome Time Frame
Baseline, 12 Month, 5 Year
Outcome Measure
Changes in Quality of Life Measures - MAFSI Severity Score
Outcome Description
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.
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.
Outcome Time Frame
From treatment start date to date of event over a median follow-up of 48.5 months.
Outcome Measure
Number of Participants With Adverse Events/Complications
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
90
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Eugen Palma
Investigator Email
eupalma@montefiore.org
Investigator Phone
Categories Mesh Debug
Heart/Cardiovascular --- ATRIAL FIBRILLATION
Heart/Cardiovascular --- ARRHYTHMIAS, CARDIAC
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
MeSH Terms
ATRIAL FIBRILLATION
ARRHYTHMIAS, CARDIAC
HEART DISEASES
CARDIOVASCULAR DISEASES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS