Atrial Fibrillation
Conditions
Brief summary
The objective of this prospective multicenter randomized study is to establish the effectiveness of treatment of persistent atrial fibrillation by encircling the pulmonary veins with radiofrequency (RF) ablation and creating additional lines of block with the aid of the NAVISTAR® THERMOCOOL® catheter in conjunction with the CARTO™ EP Navigation System. Effectiveness will be determined by comparing the chronic success of ablation therapy versus antiarrhythmic drug therapy, defined as the absence of persistent tachyarrhythmias during the first 24 months after a run-in phase of 2 months.
Interventions
DEVICERF ablation
Catheter ablation with NAVISTAR® THERMOCOOL® Catheter in conjunction with CARTO™ EP Navigation System
Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Sponsors
Biosense Webster EMEA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 18-70 years * Written informed consent * One documented relapse of atrial fibrillation (AF) during antiarrhythmic drug therapy after an electrical cardioversion
Exclusion criteria
* Permanent atrial fibrillation * Patients who had tried \>1 antiarrhythmic drug (Class I or Class III). * AF was the sole rhythm for \>6 months before the enrollment. * Previous ablation for AF. * AF is deemed secondary to a transient or correctable abnormality including electrolyte imbalance, trauma, recent surgery, infection, toxic ingestion, and endocrinopathy. * Patients who have fibrillation episodes triggered by another uniform arrhythmia (eg, atrial flutter or atrial tachycardia). * Patients with intra-atrial thrombus, tumor, or another abnormality that precludes catheter introduction. * Patients with Wolf-Parkinson-White syndrome. * Patients awaiting cardiac transplantation. * Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-III-IV or ejection fraction (EF) \<40%. * Patients with unstable angina or acute myocardial infarction within 3 months. * Patients with cardiac revascularization or other cardiac surgery within 6 months. * Patients with heart disease in which corrective surgery is anticipated. * Patients in whom appropriate vascular access is precluded. * Pregnant women. * A separate requirement for antiarrhythmic drug treatment, which will require an antiarrhythmic drug not previously tried for AF suppression. * Prior atrial surgery. * Contraindication to treatment with warfarin or other bleeding diathesis. * Renal failure requiring dialysis. * Hepatic failure. * Participant in investigational clinical or device trial. * Unwilling or unable to give informed consent. * Inaccessible for follow-up. * Psychological problem that might limit compliance. * Active abuse of alcohol or other drugs which may be causative of AF. * An implanted device (pacemaker or cardioverter-defibrillator). * Left atrial diameter (anteroposterior) \>50 mm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Absence of Persistent Atrial Tachyarrhythmias Relapse During the First 24 Months After the run-in Phase (2 Months). | within first 24 months after a 2-month run-in phase | Persistent atrial tachyarrhythmia is defined as lasting 7 or more days per two consecutive transtelephonic monitoring or electrocardiogram recordings (obtained at least one week apart) with no cardioversions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Procedural Success | The day of the procedure | Procedural success was determined on the day of the procedure (Day 0) and was based on responses to the following: 1. Has a validation of the lesions been performed by taking 3 points inside each circular lesion? 2. If YES to #1, did you observe that none of them exceed 0.1 mV? 3. Did you observe any adverse event during the procedure? If the answers to (1 ) and (2 ) were YES and (3) was NO, then the procedure was determined a success. |
| Time to First Recurrence of Any Tachyarrhythmias Lasting 30 or More Seconds After the Run in Phase | day 61 through 790 | — |
| Percentage of Participants Achieving Clinical Success (Subjects Taking AADs That Remain Free From Any Tachyarrhythmias) in Association With Antiarrhythmic Drugs | at 26 months and at each patients last follow-up visit | — |
| Percentage of Participants With Total Absence of Any Documented Atrial Tachyarrhythmias Lasting Longer Than 30 Seconds During the First 24 Months After the run-in Phase (2 Months) | within first 24 months after a 2-month run-in phase | — |
| Health-economics Parameters (Days of Hospitalization) | at 26 months and at each patients last follow-up visit | — |
| Percentage of Participants With Normal Sinus Rhythm at the Last Follow-up Visit Measured by ECG and 24-hour Holter Monitor | at each patients last follow-up visit | — |
| Quality of Life | at 14, 26 and 38 months | — |
Participant flow
Recruitment details
One hundred twenty-nine (129) subjects were enrolled in the study at the time of termination. Ten of 13 study sites were in Italy, thus the majority of subjects were recruited from Italian sites. The sponsor's decision at study termination was to report primary and secondary endpoints for which meaningful data analysis was possible.
Participants by arm
| Arm | Count |
|---|---|
| Catheter Ablation Catheter Ablation | 87 |
| Antiarrhythmic Drug Treatment Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study | 42 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | study terminated early | 12 | 5 |
Baseline characteristics
| Characteristic | Catheter Ablation | Antiarrhythmic Drug Treatment | Total |
|---|---|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 8.9 | 64.3 years STANDARD_DEVIATION 4.7 | 59.6 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 17 Participants | 21 Participants | 38 Participants |
| Sex: Female, Male Male | 70 Participants | 21 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 87 | 3 / 42 |
| serious Total, serious adverse events | 25 / 87 | 22 / 42 |
Outcome results
Primary
Percentage of Participants With Absence of Persistent Atrial Tachyarrhythmias Relapse During the First 24 Months After the run-in Phase (2 Months).
Persistent atrial tachyarrhythmia is defined as lasting 7 or more days per two consecutive transtelephonic monitoring or electrocardiogram recordings (obtained at least one week apart) with no cardioversions.
Time frame: within first 24 months after a 2-month run-in phase
Population: Intention to treat (ITT) analysis includes subjects with available transtelephonic monitoring data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catheter Ablation | Percentage of Participants With Absence of Persistent Atrial Tachyarrhythmias Relapse During the First 24 Months After the run-in Phase (2 Months). | 36.0 percentage of participants |
| Antiarrhythmic Drug Treatment | Percentage of Participants With Absence of Persistent Atrial Tachyarrhythmias Relapse During the First 24 Months After the run-in Phase (2 Months). | 45.9 percentage of participants |
Secondary
Health-economics Parameters (Days of Hospitalization)
Time frame: at 26 months and at each patients last follow-up visit
Population: Data not analyzed due to study termination - insufficient data to identify meaningful differences and draw significant conclusions.
Secondary
Percentage of Participants Achieving Clinical Success (Subjects Taking AADs That Remain Free From Any Tachyarrhythmias) in Association With Antiarrhythmic Drugs
Time frame: at 26 months and at each patients last follow-up visit
Population: Study termination due to randomization imbalance. Data not analyzed since enrollment limited and therefore insufficient data to identify meaningful differences and draw significant conclusions. The 0 below represents not available.
Secondary
Percentage of Participants With Normal Sinus Rhythm at the Last Follow-up Visit Measured by ECG and 24-hour Holter Monitor
Time frame: at each patients last follow-up visit
Population: Intention to Treat (ITT)analysis of sinus rhythm was performed for subjects with available Holter Monitor data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catheter Ablation | Percentage of Participants With Normal Sinus Rhythm at the Last Follow-up Visit Measured by ECG and 24-hour Holter Monitor | 75.6 percentage of participants |
| Antiarrhythmic Drug Treatment | Percentage of Participants With Normal Sinus Rhythm at the Last Follow-up Visit Measured by ECG and 24-hour Holter Monitor | 51.3 percentage of participants |
Secondary
Percentage of Participants With Total Absence of Any Documented Atrial Tachyarrhythmias Lasting Longer Than 30 Seconds During the First 24 Months After the run-in Phase (2 Months)
Time frame: within first 24 months after a 2-month run-in phase
Population: Intention to treat (ITT) analysis includes subjects with available transtelephonic monitoring data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catheter Ablation | Percentage of Participants With Total Absence of Any Documented Atrial Tachyarrhythmias Lasting Longer Than 30 Seconds During the First 24 Months After the run-in Phase (2 Months) | 16.0 percentage of participants |
| Antiarrhythmic Drug Treatment | Percentage of Participants With Total Absence of Any Documented Atrial Tachyarrhythmias Lasting Longer Than 30 Seconds During the First 24 Months After the run-in Phase (2 Months) | 24.3 percentage of participants |
Secondary
Percentage of Procedural Success
Procedural success was determined on the day of the procedure (Day 0) and was based on responses to the following: 1. Has a validation of the lesions been performed by taking 3 points inside each circular lesion? 2. If YES to #1, did you observe that none of them exceed 0.1 mV? 3. Did you observe any adverse event during the procedure? If the answers to (1 ) and (2 ) were YES and (3) was NO, then the procedure was determined a success.
Time frame: The day of the procedure
Population: Procedural success was only calculated for the catheter ablation group. Intention to Treat (ITT) analysis of procedural success for the catheter ablation group was performed using available data. The 0 below the Antiarrhythmic Drug treatment group represents not available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catheter Ablation | Percentage of Procedural Success | 70.2 percentage of participants |
Secondary
Quality of Life
Time frame: at 14, 26 and 38 months
Population: Study termination due to randomization imbalance. Data not analyzed since enrollment limited and therefore insufficient data to identify meaningful differences and draw significant conclusions. The 0 below represents not available.
Secondary
Time to First Recurrence of Any Tachyarrhythmias Lasting 30 or More Seconds After the Run in Phase
Time frame: day 61 through 790
Population: Intention to treat (ITT) analysis includes subjects with available transtelephonic monitoring data. The upper bound of the confidence interval for the drug treatment group could not be calculated because of the high censoring rate. Therefore, NA is more appropriate in place of the maximum duration of follow-up (790.0) as the upper bound.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Catheter Ablation | Time to First Recurrence of Any Tachyarrhythmias Lasting 30 or More Seconds After the Run in Phase | 302.0 days |
| Antiarrhythmic Drug Treatment | Time to First Recurrence of Any Tachyarrhythmias Lasting 30 or More Seconds After the Run in Phase | 328.0 days |