Atrial Fibrillation
Conditions
Keywords
paroxysmal, persistent, targeted, generalized, CFAE
Brief summary
This study will be a multicenter, open, prospective, randomized trial. Patients with either paroxysmal or persistent atrial fibrillation will be considered for the study. (For US, only paroxysmal atrial fibrillation will be considered.) Eligible subjects will be randomized into one of two arms in the study: (1) targeted CFAE ablation or (2) generalized CFAE ablation. Both techniques will then be followed by PVAI (pulmonary vein antral isolation) as part of a hybrid ablation strategy. The nature of the ablation procedures does not allow physicians to be blinded to the randomization.
Detailed description
The purpose of this study is to compare a strategy of targeted CFAE ablation, focusing on regions of continuous electrical activity versus a strategy of generalized CFAE ablation in terms of (1) acute effects on AFCL (atrial fibrillation cycle length), AF regularization, and AF termination; (2) number and distribution of lesion sets delivered; and (3) long term effects on procedural outcome when combined with PVAI as a hybrid strategy.
Interventions
PROCEDURECFAE ablation
CFAE ablation (targeted vs. generalized)
Sponsors
Biosense Webster, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Candidates for this study must meet ALL of the following criteria: * Age ≥ 18 years old * First-time ablation procedure for AF * Symptomatic AF which has been refractory to at least one antiarrhythmic medication (AAD). Symptomatic patients are those who have been aware of their AF anytime within the last 5 years. Symptoms may include, but are not restricted to, palpitations, shortness of breath, chest pain, fatigue, or other symptoms, or any combination of the above * One of the following must apply: * AF must either be PERSISTENT AF (non-US sites only) or HIGH BURDEN PAROXYSMAL AF - High burden paroxysmal AF is defined as episodes that terminate within 30 days and meet any ONE of the following criteria: * More than 1 episode of AF per month in the preceding 6 months with at least 1 episode lasting \>24 hours by symptoms, * LA size of \>/= 48 mm in the PLAX (parasternal long axis) view on echocardiography * LA volume \>/= 100 cc * Total AF history \>/= 10 years * At least one episode of AF must have been documented by ECG, Holter, TTM, or telemetry strip within 24 months of inclusion in the study. * Patients must be able and willing to provide written informed consent to participate in the study. * Able and willing to comply with all pre-, post- and follow-up testing and requirements.
Exclusion criteria
Candidates will be excluded from the study if any of the following conditions apply: * Patients with long-standing persistent AF \>1 year for which cardioversion (pharmacologic or electrical) has failed or will never be attempted. * Patients with AF felt to be secondary to an obvious reversible cause. * Patients with contraindications to systemic anticoagulation with heparin or Coumadin. * Patients who have previously undergone atrial fibrillation ablation. * Patients who are pregnant (by history of menses or pregnancy test if history is considered unreliable. * Left atrial size ≥55 mm (PLAX view on echocardiography).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Were Free From Atrial Arrhythmia at One Year. | From day 91 to day 365 post first ablation procedure | Proportion of subjects who were free from atrial arrhythmia (no recurrence of atrial fibrillation, atrial flutter, and atrial tachycardia (AF/AFL/AT)) between Day 91 and Day 365 post first ablation procedure. |
| Total Radio-frequency (RF) Delivery Time During CFAE | Duration of an Atrial Fibrillation RF ablation procedure (up to about 5 hours) | Total RF delivery time (minutes) is defined as the duration of the RF delivered per ablation site and totaled for each procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Ablation Procedure | Duration of ablation procedure (up to about 5 hours) | Duration of ablation procedure includes three components: Access time - Time from first stick to tracking of the NAVISTAR catheter to the chamber of interest; Mapping time - Creation of first workable map; Ablation and verification time - Creation and verification of all ablation points including pulmonary vein isolation and complex fractionated electrograms. |
| Fluoroscopy Time | Duration of an Atrial Fibrillation RF ablation procedure (up to about 5 hours) | Fluoroscopy time is divided into: Fluoroscopy time for access - Time to track the NAVISTAR catheter to the chamber of interest; Fluoroscopy time to map - Creation of first workable map, ablation, and verification time; Fluoroscopy to create and verify all ablation points including pulmonary vein isolation and complex fractionated electrograms. Fluoroscopy time for access is independent of the strategies and will not be included in comparative analysis. |
| Change in Atrial Fibrillation Cycle Length From Baseline to the End of the Ablation Procedure for Each Target | Duration of an Atrial Fibrillation RF ablation procedure (up to 5 hours) | Change in atrial fibrillation cycle length from baseline to the end of the ablation procedure for each target |
| Incidence of Atrial Fibrillation (AF) Termination/Regularization | Duration of an Atrial Fibrillation RF ablation procedure (up to about 5 hours) | Incidence of Atrial Fibrillation (AF) termination/regularization is defined as AF terminates during a complex fractionated atrial electrograms (CFAE) procedure. |
Countries
Australia, Canada, United States
Participant flow
Recruitment details
The first subject of the study was consented on August 17, 2009. The final follow-up was performed on November 14, 2011. The total study duration was approximately 27 months. A total of 86 subjects were enrolled from 7 participating sites; 2 sites in the United States (US), 4 sites in Canada, and 1 site in Australia.
Pre-assignment details
Among the 86 consented subjects, two were excluded prior to randomization; one was excluded due to thrombus found on pre-procedure echo. Hence only 83 subjects were randomized to the two treatment arms and underwent radio-frequency ablation
Participants by arm
| Arm | Count |
|---|---|
| Targeted CFAE Ablation Targeted complex fractionated atrial electrograms (CFAE) ablation focuses on highly selective regions of continuous electrical activity (CEA) that are critical to Atrial Fibrillation (AF) perpetuation. In the Targeted arm, the cardiac mapping system collects the abnormal electrical heart signals that are displayed in another specific color when the abnormal electrical signal is above the normal for more than the specified percentage of time over a pre-specified length of time. | 42 |
| Generalized CFAE Ablation Generalized complex fractionated atrial electrograms (CFAE) ablation focused on all repetitive CAFE, which was defined as interval confidence level (ICL) \> 5. In the Generalized arm, the cardiac mapping system collects the abnormal electrical heart signals and displays in a specific color when the number of electrical signals are more than the specified number over a pre-specified length of time. | 40 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incomplete CFAE Procedures | 3 | 3 |
Baseline characteristics
| Characteristic | Targeted CFAE Ablation | Generalized CFAE Ablation | Total |
|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 9.8 | 61.5 years STANDARD_DEVIATION 9.2 | 61.6 years STANDARD_DEVIATION 9.4 |
| Atrial fibrillation type High Burden Paroxysmal | 11 participants | 19 participants | 30 participants |
| Atrial fibrillation type Persistent | 31 participants | 21 participants | 52 participants |
| Duration of Atrial fibrillation diagnosis (Year) | 5.8 years STANDARD_DEVIATION 5.7 | 5.2 years STANDARD_DEVIATION 5.2 | 5.5 years STANDARD_DEVIATION 5.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) White | 37 Participants | 32 Participants | 69 Participants |
| Sex: Female, Male Female | 13 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Male | 29 Participants | 31 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 42 | 31 / 41 |
| serious Total, serious adverse events | 15 / 42 | 11 / 41 |
Outcome results
Primary
Proportion of Subjects Who Were Free From Atrial Arrhythmia at One Year.
Proportion of subjects who were free from atrial arrhythmia (no recurrence of atrial fibrillation, atrial flutter, and atrial tachycardia (AF/AFL/AT)) between Day 91 and Day 365 post first ablation procedure.
Time frame: From day 91 to day 365 post first ablation procedure
Population: Per-protocol population - subjects who underwent repeat ablation procedures within six months of initial procedures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Targeted CFAE Ablation | Proportion of Subjects Who Were Free From Atrial Arrhythmia at One Year. | With recurrence AF/AFL/AT | 29 participants |
| Targeted CFAE Ablation | Proportion of Subjects Who Were Free From Atrial Arrhythmia at One Year. | Without recurrence AF/AFL/AT | 10 participants |
| Generalized CFAE Ablation | Proportion of Subjects Who Were Free From Atrial Arrhythmia at One Year. | Without recurrence AF/AFL/AT | 18 participants |
| Generalized CFAE Ablation | Proportion of Subjects Who Were Free From Atrial Arrhythmia at One Year. | With recurrence AF/AFL/AT | 20 participants |
Comparison: The null hypothesis is that rates of free from atrial arrhythmia for the two arms, Targeted and Generalized, are the same. The alternative hypothesis is that the rates are not the same. Due to the lack of literature data comparing these endpoints between two randomization groups, the sample size is not statistically powered to support statistical inferences.p-value: 0.048Fisher Exact
Primary
Total Radio-frequency (RF) Delivery Time During CFAE
Total RF delivery time (minutes) is defined as the duration of the RF delivered per ablation site and totaled for each procedure.
Time frame: Duration of an Atrial Fibrillation RF ablation procedure (up to about 5 hours)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Targeted CFAE Ablation | Total Radio-frequency (RF) Delivery Time During CFAE | 23.2 Minutes | Standard Deviation 19.7 |
| Generalized CFAE Ablation | Total Radio-frequency (RF) Delivery Time During CFAE | 37.8 Minutes | Standard Deviation 20.1 |
Comparison: The null hypothesis is that the total RF delivery times for both arms are equal. The alternative hypothesis is that the total RF delivery times are not equal. Due to the lack of literature data comparing these endpoints between two randomization groups, the sample size is not statistically powered to support statistical inferences.p-value: 0.002t-test, 2 sided
Secondary
Change in Atrial Fibrillation Cycle Length From Baseline to the End of the Ablation Procedure for Each Target
Change in atrial fibrillation cycle length from baseline to the end of the ablation procedure for each target
Time frame: Duration of an Atrial Fibrillation RF ablation procedure (up to 5 hours)
Population: Per-protocol population with available outcome data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Targeted CFAE Ablation | Change in Atrial Fibrillation Cycle Length From Baseline to the End of the Ablation Procedure for Each Target | 23.3 Milliseconds | Standard Deviation 33.3 |
| Generalized CFAE Ablation | Change in Atrial Fibrillation Cycle Length From Baseline to the End of the Ablation Procedure for Each Target | 25.4 Milliseconds | Standard Deviation 32.8 |
Secondary
Duration of Ablation Procedure
Duration of ablation procedure includes three components: Access time - Time from first stick to tracking of the NAVISTAR catheter to the chamber of interest; Mapping time - Creation of first workable map; Ablation and verification time - Creation and verification of all ablation points including pulmonary vein isolation and complex fractionated electrograms.
Time frame: Duration of ablation procedure (up to about 5 hours)
Population: Per-protocol population with available outcome data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Targeted CFAE Ablation | Duration of Ablation Procedure | Total Procedure Time | 220.6 Minutes | Standard Deviation 59.4 |
| Targeted CFAE Ablation | Duration of Ablation Procedure | Procedure Time to Mapping | 35.7 Minutes | Standard Deviation 26.5 |
| Targeted CFAE Ablation | Duration of Ablation Procedure | Procedure Time to Access Site | 42.7 Minutes | Standard Deviation 20.8 |
| Targeted CFAE Ablation | Duration of Ablation Procedure | Procedure Time to Ablation and Verification | 132.8 Minutes | Standard Deviation 43 |
| Generalized CFAE Ablation | Duration of Ablation Procedure | Procedure Time to Access Site | 45.4 Minutes | Standard Deviation 22.4 |
| Generalized CFAE Ablation | Duration of Ablation Procedure | Total Procedure Time | 226.1 Minutes | Standard Deviation 52 |
| Generalized CFAE Ablation | Duration of Ablation Procedure | Procedure Time to Ablation and Verification | 149.9 Minutes | Standard Deviation 47.7 |
| Generalized CFAE Ablation | Duration of Ablation Procedure | Procedure Time to Mapping | 27.4 Minutes | Standard Deviation 10.5 |
Secondary
Fluoroscopy Time
Fluoroscopy time is divided into: Fluoroscopy time for access - Time to track the NAVISTAR catheter to the chamber of interest; Fluoroscopy time to map - Creation of first workable map, ablation, and verification time; Fluoroscopy to create and verify all ablation points including pulmonary vein isolation and complex fractionated electrograms. Fluoroscopy time for access is independent of the strategies and will not be included in comparative analysis.
Time frame: Duration of an Atrial Fibrillation RF ablation procedure (up to about 5 hours)
Population: Per-protocol population with available outcome data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Targeted CFAE Ablation | Fluoroscopy Time | Total Fluoroscopy Time | 57.4 Minutes | Standard Deviation 20.2 |
| Targeted CFAE Ablation | Fluoroscopy Time | Fluoroscopy Time to Gain Access | 9.7 Minutes | Standard Deviation 8.3 |
| Targeted CFAE Ablation | Fluoroscopy Time | Fluoroscopy Time to Mapping | 15.5 Minutes | Standard Deviation 12.6 |
| Targeted CFAE Ablation | Fluoroscopy Time | Fluoroscopy Time to Ablation and Verification | 36.9 Minutes | Standard Deviation 10.9 |
| Generalized CFAE Ablation | Fluoroscopy Time | Fluoroscopy Time to Ablation and Verification | 41.5 Minutes | Standard Deviation 22.1 |
| Generalized CFAE Ablation | Fluoroscopy Time | Total Fluoroscopy Time | 60.1 Minutes | Standard Deviation 19.3 |
| Generalized CFAE Ablation | Fluoroscopy Time | Fluoroscopy Time to Mapping | 13.8 Minutes | Standard Deviation 11.1 |
| Generalized CFAE Ablation | Fluoroscopy Time | Fluoroscopy Time to Gain Access | 11.8 Minutes | Standard Deviation 11.6 |
Secondary
Incidence of Atrial Fibrillation (AF) Termination/Regularization
Incidence of Atrial Fibrillation (AF) termination/regularization is defined as AF terminates during a complex fractionated atrial electrograms (CFAE) procedure.
Time frame: Duration of an Atrial Fibrillation RF ablation procedure (up to about 5 hours)
Population: Per-protocol population with available outcome data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Targeted CFAE Ablation | Incidence of Atrial Fibrillation (AF) Termination/Regularization | 11 participants |
| Generalized CFAE Ablation | Incidence of Atrial Fibrillation (AF) Termination/Regularization | 14 participants |