Persistent Atrial Fibrillation
Conditions
Keywords
persistent atrial fibrillation - ablation procedure
Brief summary
The primary purpose of this study is to assess the effectiveness of using CARTOFINDER™ maps created by the RHYTHMFINDER-192 catheter and the CARTOFINDER™ Algorithm to terminate persistent atrial fibrillation (PsAF) to either Normal Sinus Rhythm or Atrial Tachycardia compared to pulmonary vein isolation (PVI) in treating PsAF. The RHYTHMFINDER-192 catheter is investigational, while the CARTOFINDER™ system is CE marked in Europe. All subjects with persistent AF who are scheduled to undergo a clinically indicated ablation procedure for management of their persistent AF will be the target population for screening. The study will enroll approximately 40-70 subjects. Subjects will undergo CARTOFINDER™ guided ablation (CFGA) followed by PVI. Subjects will have follow-up visits at 7 days, 3, 6 and 12 months postprocedure.
Interventions
PROCEDUREcartofinder guided ablation followed by PVI
cartofinder guided ablation followed by PVI
Sponsors
Biosense Webster, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \> 18 years. 2. Patients who have signed the Patient Informed Consent Form (ICF) 3. Scheduled to undergo a clinically-indicated catheter ablation procedure for treatment of 1. persistent atrial fibrillation (defined as continuous atrial fibrillation that is sustained beyond seven consecutive days). 2. drug-resistant atrial fibrillation. (failed 1 or more class I or III antiarrhythmic drugs) and demonstrating Persistent AF (requiring drugs or electrical shock to terminate AF) 4. In AF at the time of the baseline CARTOFINDER™ Map (spontaneous) 5. Left Atrium (LA) must demonstrate sufficient electrical activity to allow for the identification of ablation targets. 6. Able and willing to comply with all pre-, post-, and follow-up testing and requirements (e.g. patients not confined by a court ruling)
Exclusion criteria
1. Paroxysmal Atrial Fibrillation 2. Continuous AF \> 12 months (1-Year) (Longstanding Persistent AF) Subjects previously diagnosed as Long Standing Persistent (LSP) but have demonstrated the ability to maintain Normal Sinus Rhythm for \>30 days after cardioversion and have not been in AF greater than 1 year at the time of the procedure remain eligible for inclusion. 3. Previous ablation procedure for PsAF (defined as ablations involving more than only PV isolation) 4. Patients with a left atrial size \>55 mm (echocardiography, parasternal long axis view). 5. Inability to restore sinus rhythm for 30 seconds or longer in the opinion of the investigator. 6. Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study. 7. Atrial arrhythmia patients with structural atrial disease such as a prior history of atriotomy from prior atrial surgery, presence of an atrial septal defect, and/or presence of an atrial septal closure patch. 8. History of or current blood clotting or bleeding abnormalities, contraindication to systemic anticoagulation (i.e., heparin, warfarin, dabigatran, or a direct thrombin inhibitor). 9. significant pulmonary disease, cardiac surgeries, unstable angina, uncontrolled heart failure, acute illness or systemic infection, or any other disease or malfunction that would preclude treatment in the opinion of the investigator. 10. Current enrollment in a study evaluating another device or drug. 11. A complex arrhythmia secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause. 12. Any cardiac surgery within the past 60 days (2 months) (includes PCI) 13. Subjects that have ever undergone valvular cardiac surgical procedure (i.e., ventriculotomy, atriotomy, and valve repair or replacement and presence of a prosthetic valve) 14. Prior ICD or pacemaker implanted 15. Presence of intramural thrombus, tumor or other abnormality that precludes catheter introduction or manipulation. 16. Presence of a condition that precludes vascular access. 17. Subject has a contra-indication to the device under study per the IFU 18. Women of child bearing potential whom are pregnant, lactating, or planning to become pregnant during the course of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) Only (Before Pulmonary Vein Isolation [PVI] and Without Cardioversion). | Up to 7 days | Acute success defined as rate of conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial Tachycardia, after CARTOFINDER Guided Ablation (CFGA) only (before Pulmonary Vein Isolation \[PVI\] and without cardioversion). |
| Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) and Pulmonary Vein Isolation (PVI) Without Cardioversion | Up to 7 days | Acute success defined as rate of conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial Tachycardia, after CFGA and PVI without Cardioversion. |
| Percentage of Participants With Procedural Success | Up to 7 days | Procedural success defined as the conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial Tachycardia after overall ablation procedure, with or without the need for cardioversion. |
| Percentage of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, and Atrial Tachycardia Episodes of Greater Than or Equal to (>=) 30 Seconds to Measure the Effectiveness Success Rate for up to 12 Months | Up to 12 months | Documented AF/AT/AFL recurrence is defined as any occurrence of documented (symptomatic) atrial fibrillation, atrial flutter, and atrial tachycardia episodes \>= 30 seconds during the post-blanking period (Day 91-365). Here 'HM' signifies Holter monitoring. |
| Number of Participants With Early-onset Primary Adverse Events | Up to 7 days | Incidence of early-onset (within 7 days of the initial mapping and ablation procedure) Primary Adverse Events (PAEs) was reported. PAEs included death, Atria-Esophageal Fistula, Cardiac Tamponade/Perforation, Myocardial Infarction, Stroke/Cerebrovascular Accident, Thromboembolism, Transient Ischemic Attack, Diaphragmatic Paralysis, Pneumothorax, Heart Block, Pulmonary Vein Stenosis, Pulmonary Edema (Respiratory Insufficiency), Pericarditis and Major Vascular Access Complication/Bleeding. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Confirmed Entrance Block After Adenosine/Isoproterenol Challenge | Up to 12 months | Number of participants with confirmed entrance block after adenosine/isoproterenol challenge was reported. |
| Number of Participants With Procedural Related Serious Adverse Event and Non-serious Adverse Events | Up to 12 months | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with treatment and therefore can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal product, whether or not related to that medicinal product. TEAEs were defined as AEs that were reported or worsened on after start of study drug(s) dosing through safety follow-up visit. A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulting in any of following outcomes: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. |
| Change of Intra-cycle Length From Pre-CFGA (Baseline) to Post-CFGA and Post-PVI | Pre-CFGA (Baseline) to Post-CFGA and Post-PVI (Up to 7 days) | Change of intra-cycle length from pre-CFGA to post-CFGA and post-PVI is reported to measure the slowing for the overall Atrial Fibrillation rate in both atrium's. |
| Number of Participants With Serious Adverse Device Effects (SADEs) up to 12 Months | Up to 12 months | Any serious adverse event which was related to the device and/or the procedure was defined as a SADE. |
| Number of Participants With All Serious Adverse Events (SAEs) up to 12 Months | Up to 12 months | Number of participants with SAEs will be evaluated. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important, and may jeopardize participant or may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Number of Participants With Adverse Device Effects (ADEs) up to 12 Months | Up to 12 months | Number of participants with adverse device effects was reported. Adverse Device Effect (ADE's) are adverse events related to the use of an investigational medical device. This definition includes adverse events resulting from insufficient or inadequate instructions for use deployment, implantation, installation, or operation, or any malfunction of the investigational medical device. This definition includes any event resulting from use errors or from intentional misuse of the investigational medical device. |
Countries
Belgium, Canada, Czechia, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) Participants with PsAF and an ablation target on the CARTOFINDER (CF) map underwent CARTOFINDER-Guided Ablation (CFGA) followed by Pulmonary Vein Isolation (PVI) Wide Area Circumferential Ablation (WACA) ablation and followed-up at 7 days, 3 months, 6 months, and 12 months post ablation procedure. Participants not displaying an ablation target on CARTOFINDER were treated per investigator's standard of care and followed up until 7 days post-procedure. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Exited prior to procedure | 8 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Mapping Failure | 4 |
| Overall Study | Withdrew consent: 3-month FU visit | 1 |
Baseline characteristics
| Characteristic | Participants With Persistent Atrial Fibrillation (PsAF) | — |
|---|---|---|
| Age, Continuous | 61.6 Years STANDARD_DEVIATION 9.99 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 9 Participants | — |
| Sex: Female, Male Male | 51 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 52 |
| other Total, other adverse events | 6 / 52 |
| serious Total, serious adverse events | 10 / 52 |
Outcome results
Primary
Number of Participants With Early-onset Primary Adverse Events
Incidence of early-onset (within 7 days of the initial mapping and ablation procedure) Primary Adverse Events (PAEs) was reported. PAEs included death, Atria-Esophageal Fistula, Cardiac Tamponade/Perforation, Myocardial Infarction, Stroke/Cerebrovascular Accident, Thromboembolism, Transient Ischemic Attack, Diaphragmatic Paralysis, Pneumothorax, Heart Block, Pulmonary Vein Stenosis, Pulmonary Edema (Respiratory Insufficiency), Pericarditis and Major Vascular Access Complication/Bleeding.
Time frame: Up to 7 days
Population: The safety participants population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted, regardless if CARTOFINDER-guided ablation was performed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Pneumothorax | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Myocardial Infarction | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Cardiac tamponade / Perforation | 2 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Major vascular access complications / bleeding | 2 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Pericarditis | 1 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Atrio-Esophageal Fistula | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Death | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Diaphragmatic Paralysis | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Heart Block | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Pulmonary Edema (Respiratory Insufficiency) | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Pulmonary Vein Stenosis | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Stroke / Cerebrovascular Accident | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Thromboembolism | 0 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Early-onset Primary Adverse Events | Transient Ischemic Attack | 0 Participants |
Primary
Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) and Pulmonary Vein Isolation (PVI) Without Cardioversion
Acute success defined as rate of conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial Tachycardia, after CFGA and PVI without Cardioversion.
Time frame: Up to 7 days
Population: The evaluable participant population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted and where CARTOFINDER-guided ablation was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) and Pulmonary Vein Isolation (PVI) Without Cardioversion | 33.3 Percentage of participants |
Primary
Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) Only (Before Pulmonary Vein Isolation [PVI] and Without Cardioversion).
Acute success defined as rate of conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial Tachycardia, after CARTOFINDER Guided Ablation (CFGA) only (before Pulmonary Vein Isolation \[PVI\] and without cardioversion).
Time frame: Up to 7 days
Population: The evaluable participant population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted and where CARTOFINDER-guided ablation was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) Only (Before Pulmonary Vein Isolation [PVI] and Without Cardioversion). | 22.9 Percentage of participants |
Primary
Percentage of Participants With Procedural Success
Procedural success defined as the conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial Tachycardia after overall ablation procedure, with or without the need for cardioversion.
Time frame: Up to 7 days
Population: The evaluable participant population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted and where CARTOFINDER-guided ablation was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Percentage of Participants With Procedural Success | 97.9 Percentage of participants |
Primary
Percentage of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, and Atrial Tachycardia Episodes of Greater Than or Equal to (>=) 30 Seconds to Measure the Effectiveness Success Rate for up to 12 Months
Documented AF/AT/AFL recurrence is defined as any occurrence of documented (symptomatic) atrial fibrillation, atrial flutter, and atrial tachycardia episodes \>= 30 seconds during the post-blanking period (Day 91-365). Here 'HM' signifies Holter monitoring.
Time frame: Up to 12 months
Population: Evaluable population:enrolled participants who had RHYTHMFINDER 192 Catheter inserted, where CFGA performed. 'N' (Number of participants analyzed):number of participants who completed 12 months follow-up(post initial ablation) or data collected from ElectroCardioGram, HM, or Post Procedure Arrhythmia Log forms beyond 337 days post index procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Percentage of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, and Atrial Tachycardia Episodes of Greater Than or Equal to (>=) 30 Seconds to Measure the Effectiveness Success Rate for up to 12 Months | 72.3 Percentage of participants |
Secondary
Change of Intra-cycle Length From Pre-CFGA (Baseline) to Post-CFGA and Post-PVI
Change of intra-cycle length from pre-CFGA to post-CFGA and post-PVI is reported to measure the slowing for the overall Atrial Fibrillation rate in both atrium's.
Time frame: Pre-CFGA (Baseline) to Post-CFGA and Post-PVI (Up to 7 days)
Population: Evaluable participant included all enrolled participants who had RHYTHMFINDER 192 Catheter inserted, where CARTOFINDER-guided ablation was performed. Here 'n' (number analyzed) included participants analyzed at specified categories for post-CFGA and post PVI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Change of Intra-cycle Length From Pre-CFGA (Baseline) to Post-CFGA and Post-PVI | Left Atrium: Change post-CFGA | 64.0 milliseconds | Standard Deviation 273.62 |
| Participants With Persistent Atrial Fibrillation (PsAF) | Change of Intra-cycle Length From Pre-CFGA (Baseline) to Post-CFGA and Post-PVI | Left Atrium: Change post-PVI | 464.0 milliseconds | Standard Deviation 1009.44 |
| Participants With Persistent Atrial Fibrillation (PsAF) | Change of Intra-cycle Length From Pre-CFGA (Baseline) to Post-CFGA and Post-PVI | Right Atrium: Change post-CFGA | 33.3 milliseconds | Standard Deviation 103.58 |
| Participants With Persistent Atrial Fibrillation (PsAF) | Change of Intra-cycle Length From Pre-CFGA (Baseline) to Post-CFGA and Post-PVI | Right Atrium: Change post-PVI | 525.2 milliseconds | Standard Deviation 1120.7 |
Secondary
Number of Participants With Adverse Device Effects (ADEs) up to 12 Months
Number of participants with adverse device effects was reported. Adverse Device Effect (ADE's) are adverse events related to the use of an investigational medical device. This definition includes adverse events resulting from insufficient or inadequate instructions for use deployment, implantation, installation, or operation, or any malfunction of the investigational medical device. This definition includes any event resulting from use errors or from intentional misuse of the investigational medical device.
Time frame: Up to 12 months
Population: The safety participants population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted, regardless if CARTOFINDER-guided ablation was performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Adverse Device Effects (ADEs) up to 12 Months | 20 Participants |
Secondary
Number of Participants With All Serious Adverse Events (SAEs) up to 12 Months
Number of participants with SAEs will be evaluated. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important, and may jeopardize participant or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Up to 12 months
Population: The safety participants population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted, regardless if CARTOFINDER-guided ablation was performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With All Serious Adverse Events (SAEs) up to 12 Months | 10 Participants |
Secondary
Number of Participants With Confirmed Entrance Block After Adenosine/Isoproterenol Challenge
Number of participants with confirmed entrance block after adenosine/isoproterenol challenge was reported.
Time frame: Up to 12 months
Population: Evaluable participant population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted and where CARTOFINDER-guided ablation was performed. Here 'N' number of participants analyzed included participants with adenosine/isoproterenol challenge and non-missing confirmation of entry block data collected from the PVI form.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Confirmed Entrance Block After Adenosine/Isoproterenol Challenge | 15 Participants |
Secondary
Number of Participants With Procedural Related Serious Adverse Event and Non-serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with treatment and therefore can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal product, whether or not related to that medicinal product. TEAEs were defined as AEs that were reported or worsened on after start of study drug(s) dosing through safety follow-up visit. A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulting in any of following outcomes: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
Time frame: Up to 12 months
Population: The safety participants population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted, regardless if CARTOFINDER-guided ablation was performed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Procedural Related Serious Adverse Event and Non-serious Adverse Events | Serious Adverse event | 6 Participants |
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Procedural Related Serious Adverse Event and Non-serious Adverse Events | Adverse event | 14 Participants |
Secondary
Number of Participants With Serious Adverse Device Effects (SADEs) up to 12 Months
Any serious adverse event which was related to the device and/or the procedure was defined as a SADE.
Time frame: Up to 12 months
Population: The safety participants population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted, regardless if CARTOFINDER-guided ablation was performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Persistent Atrial Fibrillation (PsAF) | Number of Participants With Serious Adverse Device Effects (SADEs) up to 12 Months | 6 Participants |