Heart Diseases, Arrhythmia, Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, Paroxysmal Atrial Fibrillation
Brief summary
This trial compares the safety and effectiveness of catheter ablation for PAF with antiarrhythmic drug therapy. The investigational catheter being studied is the NAVISTAR® THERMOCOOL® irrigated-tip catheter. At the time of this study, the NAVISTAR® THERMOCOOL® catheter was FDA-approved for commercial distribution in the U.S. for treating patients with Type I atrial flutter and drug refractory monomorphic ventricular tachycardia post myocardial infarction. The catheter was approved for use in Europe for endocardial ablation for treating cardiac arrhythmias.
Interventions
The Biosense Webster NAVISTAR® THERMOCOOL® Diagnostic/Ablation Deflectable Tip Catheter is a luminal catheter with a deflectable tip designed to facilitate electrophysiological mapping of the heart and to transmit radiofrequency current to the catheter tip electrode for ablation purposes.
Subjects randomized to the antiarrhythmic drug (control) arm will be prescribed to a not previously administered class I or class III antiarrhythmic drug that is currently approved in the U.S. for treating atrial fibrillation.
Sponsors
Biosense Webster, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
You may be eligible to participate in this study if you: Have failed to respond to drug treatment for your AFib, or find the side effects of your medication intolerable. Inclusion Criteria * Patients with symptomatic PAF who have had three (3) AF episodes in the six (6) months prior to randomization, one of which must be documented. Documentation may include electrocardiogram (ECG), transtelephonic monitor (TTM), Holter monitor (HM), or telemetry strip. * Failure of at least one AAD for PAF \[class I or III or AV nodal blocking agents such as beta blockers (BB) and calcium channel blockers (CCB)\] as evidenced by recurrent symptomatic PAF, or intolerable side effects due to AAD. * Signed Patient Informed Consent Form. * Age 18 years or older. * Able and willing to comply with all pre-, post- and follow-up testing and requirements.
Exclusion criteria
* Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause. * Previous ablation for atrial fibrillation. * Patients on amiodarone therapy at any time during the previous six (6) months. * AF episodes that last longer than 30 days and are terminated via cardioversion. * Any valvular cardiac surgical procedure. * CABG procedure within the last 180 days (six months). * Awaiting cardiac transplantation or other cardiac surgery within the next 360 days (12 months). * Documented left atrial thrombus on imaging (e.g. TEE). * History of a documented thromboembolic event within the past one (1) year. * Diagnosed atrial myxoma. * Presence of implanted ICD. * Significant pulmonary disease, (e.g. restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms. * Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study. * Women who are pregnant (by history of menstrual period or pregnancy test if the history is considered unreliable). * Acute illness or active systemic infection or sepsis. * Unstable angina. * Myocardial infarction within the previous 60 days (two months). * LVEF \< 40%. * History of blood clotting or bleeding abnormalities. * Contraindication to anticoagulation (i.e. heparin or warfarin). * Contraindication to CT/MRA procedure. * Life expectancy less than 360 days (12 months). * Enrollment in an investigational study evaluating another device or drug. * Uncontrolled heart failure or NYHA class III or IV heart failure. * Presence of intramural thrombus, tumor or other abnormality that precludes catheter introduction or manipulation. * Presence of a condition that precludes vascular access. * Left atrial size ≥ 50 mm
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Chronic Success of the NAVISTAR THERMOCOOL Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (PAF) | The evaluation time frame for the THERMOCOOL catheter subjects is 91-361 days (12 months) post procedure; for Antiarrhythmic Drug Therapy subjects the time frame is 15-285 days (9 months) post procedure. | Chronic success was defined as freedom of documented symptomatic Atrial Fibrillation episodes based on electrocardiographic data and no changes in antiarrhythmic drugs (AAD) regimen during comparable evaluation periods for the THERMOCOOL and AAD (Control) groups through 12 and 9 months of follow-up, respectively. |
| The Percentage of Subjects Who Experienced Incidences of Early Onset (Within 7 Days of Ablation Procedure) Serious Catheter-related Adverse Events | Within 7 Days of Ablation Procedure | Catheter-related adverse events include death, myocardial infarction, pulmonary vein stenosis,diaphragmatic paralysis, atrio-esophageal fistula,transient ischemic attack,stroke,cerebrovascular accident, thromboembolism, pericarditis, cardiac tamponade,pericardial effusion,pneumothorax,atrial perforation,vascular access complications,pulmonary edema,hospitalization (initial and prolonged), and heart block. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Who Achieved Acute Success. | 90 days post study procedure | Acute success was defined as confirmation of entrance block in all targeted pulmonary veins. The study protocol considered subjects that had more than 2 AF ablation procedures within the 90 day blanking period immediately following their index study procedure or subjects that had additional ablation procedures greater than 80 days following their original study ablation procedure as acute failures. |
| Percentage of Subjects Who Experienced Atrial Fibrillation Recurrence During the Two-year Follow up. | During the two years of post procedure | At the 2 year follow-up visit, Atrial Fibrillation recurrence was assessed by subject interview without documentation. |
| Percentage of Subjects Responded to Each of the Four Health Status Categories. | During the two years of post procedure | At the 2 year follow-up visit, Atrial Fibrillation recurrence was assessed by subject interview without documentation. |
Countries
Brazil, Canada, Czechia, Italy, United States
Participant flow
Recruitment details
This pivotal study was closed to enrollment on October 12, 2007 with a total of 167 subjects enrolled at 19 investigational sites (15 US and 4 outside US).
Participants by arm
| Arm | Count |
|---|---|
| NAVISTAR® THERMOCOOL® Catheter Subjects who were randomized to the THERMOCOOL group, i.e., to receive NAVISTAR® THERMOCOOL® Catheter at randomization. The Biosense Webster NAVISTAR® THERMOCOOL® Diagnostic/Ablation Deflectable Tip Catheter is a luminal catheter with a deflectable tip designed to facilitate electrophysiological mapping of the heart and to transmit radiofrequency current to the catheter tip electrode for ablation purposes. | 106 |
| Antiarrhythmic Drug The antiarrhythmic drug (control group) is defined as class I, class III or atrioventricular nodal blocking agents such as beta blocking agents (BB) or calcium channel blockers (CCB). During the two-week dosing period, the subject's medication was titrated up for maximum efficacy for the treatment of paroxysmal atrial fibrillation. The subject was maintained on the same drug for the rest of study time frame OR underwent a study ablation procedure after failing the effectiveness endpoint. | 61 |
| Total | 167 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not meet inclusion criteria | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Total | NAVISTAR® THERMOCOOL® Catheter | Antiarrhythmic Drug |
|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 10.7 | 55.5 years STANDARD_DEVIATION 9.3 | 56.1 years STANDARD_DEVIATION 12.8 |
| Number of documented symptomatic Atrial Fibrillation episodes | 63.24 Number of episodes STANDARD_DEVIATION 93 | 62.3 Number of episodes STANDARD_DEVIATION 89.2 | 64.9 Number of episodes STANDARD_DEVIATION 98 |
| Race/Ethnicity, Customized Arab ethnicity | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 164 Participants | 103 Participants | 61 Participants |
| Region of Enrollment Brazil | 12 participants | 7 participants | 5 participants |
| Region of Enrollment Canada | 8 participants | 5 participants | 3 participants |
| Region of Enrollment Czech Republic | 27 participants | 17 participants | 10 participants |
| Region of Enrollment Italy | 50 participants | 31 participants | 19 participants |
| Region of Enrollment United States | 70 participants | 46 participants | 24 participants |
| Sex: Female, Male Female | 56 Participants | 33 Participants | 23 Participants |
| Sex: Female, Male Male | 111 Participants | 73 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 139 | 0 / 25 |
| serious Total, serious adverse events | 25 / 139 | 0 / 25 |
Outcome results
Primary
The Percentage of Chronic Success of the NAVISTAR THERMOCOOL Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (PAF)
Chronic success was defined as freedom of documented symptomatic Atrial Fibrillation episodes based on electrocardiographic data and no changes in antiarrhythmic drugs (AAD) regimen during comparable evaluation periods for the THERMOCOOL and AAD (Control) groups through 12 and 9 months of follow-up, respectively.
Time frame: The evaluation time frame for the THERMOCOOL catheter subjects is 91-361 days (12 months) post procedure; for Antiarrhythmic Drug Therapy subjects the time frame is 15-285 days (9 months) post procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NAVISTAR® THERMOCOOL® Catheter | The Percentage of Chronic Success of the NAVISTAR THERMOCOOL Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (PAF) | 66 Percentage of participants |
| Antiarrhythmic Drug | The Percentage of Chronic Success of the NAVISTAR THERMOCOOL Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (PAF) | 16 Percentage of participants |
Comparison: The study null hypothesis is that the chronic success rates for the THERMOCOOL and AAD groups are equal.p-value: <0.001Log Rank
Primary
The Percentage of Subjects Who Experienced Incidences of Early Onset (Within 7 Days of Ablation Procedure) Serious Catheter-related Adverse Events
Catheter-related adverse events include death, myocardial infarction, pulmonary vein stenosis,diaphragmatic paralysis, atrio-esophageal fistula,transient ischemic attack,stroke,cerebrovascular accident, thromboembolism, pericarditis, cardiac tamponade,pericardial effusion,pneumothorax,atrial perforation,vascular access complications,pulmonary edema,hospitalization (initial and prolonged), and heart block.
Time frame: Within 7 Days of Ablation Procedure
Population: Analysis population includes those enrolled subjects undergoing a study ablation procedure. A total of 139 underwent the procedure, including 36 AAD (control) group subjects who underwent the procedure after failing the effectiveness endpoint. The remaining 25 AAD (control) subjects didn't have the ablation procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NAVISTAR® THERMOCOOL® Catheter | The Percentage of Subjects Who Experienced Incidences of Early Onset (Within 7 Days of Ablation Procedure) Serious Catheter-related Adverse Events | 10.1 Percentage of Participants |
| Antiarrhythmic Drug | The Percentage of Subjects Who Experienced Incidences of Early Onset (Within 7 Days of Ablation Procedure) Serious Catheter-related Adverse Events | 0.0 Percentage of Participants |
Secondary
Percentage of Subjects Responded to Each of the Four Health Status Categories.
At the 2 year follow-up visit, Atrial Fibrillation recurrence was assessed by subject interview without documentation.
Time frame: During the two years of post procedure
Population: Subjects who completed the two-year health survey.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NAVISTAR® THERMOCOOL® Catheter | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Improved | 65.2 Percentage of Participants |
| NAVISTAR® THERMOCOOL® Catheter | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Unchanged | 29.3 Percentage of Participants |
| NAVISTAR® THERMOCOOL® Catheter | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Worsened | 5.4 Percentage of Participants |
| NAVISTAR® THERMOCOOL® Catheter | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Missing | 0.0 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Missing | 0.0 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Improved | 60.0 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Worsened | 2.9 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Unchanged | 37.1 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Missing | 6.7 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Unchanged | 33.3 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Worsened | 6.7 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Responded to Each of the Four Health Status Categories. | Two-Year Health Status: Improved | 53.3 Percentage of Participants |
Secondary
Percentage of Subjects Who Experienced Atrial Fibrillation Recurrence During the Two-year Follow up.
At the 2 year follow-up visit, Atrial Fibrillation recurrence was assessed by subject interview without documentation.
Time frame: During the two years of post procedure
Population: Subjects who completed two years follow up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NAVISTAR® THERMOCOOL® Catheter | Percentage of Subjects Who Experienced Atrial Fibrillation Recurrence During the Two-year Follow up. | 29.3 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Who Experienced Atrial Fibrillation Recurrence During the Two-year Follow up. | 28.6 Percentage of Participants |
| Antiarrhythmic Drug | Percentage of Subjects Who Experienced Atrial Fibrillation Recurrence During the Two-year Follow up. | 53.3 Percentage of Participants |
Secondary
The Percentage of Subjects Who Achieved Acute Success.
Acute success was defined as confirmation of entrance block in all targeted pulmonary veins. The study protocol considered subjects that had more than 2 AF ablation procedures within the 90 day blanking period immediately following their index study procedure or subjects that had additional ablation procedures greater than 80 days following their original study ablation procedure as acute failures.
Time frame: 90 days post study procedure
Population: This analysis population is based on the first study ablation procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NAVISTAR® THERMOCOOL® Catheter | The Percentage of Subjects Who Achieved Acute Success. | 100 Percentage of participants |
| Antiarrhythmic Drug | The Percentage of Subjects Who Achieved Acute Success. | 94 Percentage of participants |