Atrial Fibrillation
Conditions
Keywords
Interventional, Irreversible electroporation, Paroxysmal atrial fibrillation
Brief summary
To demonstrate the safety and 12-month effectiveness of the VARIPULSE™ Catheter when used in conjunction with the TRUPULSE™ Generator for pulmonary vein isolation (PVI) in the treatment of subjects with symptomatic paroxysmal atrial fibrillation.
Detailed description
This is a prospective, non-randomized, multi-center, clinical evaluation of the Biosense Webster IRE Ablation system to demonstrate safety and long-term effectiveness for the treatment of drug refractory symptomatic PAF. The BWI IRE Ablation System consists of the VARIPULSE™ Catheter and TRUPULSE™ Generator. In conjunction with CARTO™ 3 system, it is indicated for PVI of patients with drug refractory paroxysmal atrial fibrillation.
Interventions
DEVICEPulse Field Ablation
PFA ablation using a circular multi-electrode pulsed electrical field catheter and multichannel generator
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 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosed with Symptomatic Paroxysmal Atrial Fibrillation with 1. At least two symptomatic AF episodes within last six months from enrollment. 2. At least one ectrocardiographically documented AF episode within twelve (12) months prior to enrollment. * Failed at least one Class I or Class III antiarrhythmic drug.
Exclusion criteria
* Previously diagnosed with persistent AF (\> 7 days in duration). * AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause. * Previous surgical or catheter ablation for AF. * Patients known to require ablation outside the PV region * Documented severe dilatation of the LA (LAD \>50mm) antero-posterior diameter on imaging within 6 months prior to enrollment. * Documented LA thrombus by imaging within 48 hours of the procedure. * Documented severely compromised LVEF (\<40%) by imaging within 6 months prior to enrollment * Uncontrolled heart failure or New York Heart Association Class III or IV * History of blood clotting, bleeding abnormalities or contraindication to anticoagulation (heparin, warfarin, or dabigatran), * Documented thromboembolic event (including TIA) within the past 12 months * Previous PCI/MI within the past 2 months * Coronary Artery Bypass Grafting (CABG) surgery within the past 6 months (180 days) * Valvular cardiac surgical/percutaneous procedure * Unstable angina within 6 months * Anticipated cardiac transplantation, cardiac surgery, or other major surgery within the next 12 months. * Significant pulmonary disease or any other disease or malfunction of the lungs or respiratory system that produces severe chronic symptoms. * Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study * Prior diagnosis of pulmonary vein stenosis * Pre-existing hemi diaphragmatic paralysis * Acute illness, active systemic infection, or sepsis * Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or patch or other abnormality that precludes catheter introduction or manipulation. * Severe mitral regurgitation * Presence of implanted pacemaker or Implantable Cardioverter-Defibrillator (ICD) or other implanted metal cardiac device that may interfere with the IRE energy field. * Presence of a condition that precludes vascular access * Current enrollment in an investigational study evaluating another device or drug. * Women who are pregnant, lactating, or who are of child-bearing age and plan on becoming pregnant during the course of the clinical investigation. * Life expectancy less than 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pivotal Main Phase Modified Intent-To-Treat (mITT) Analysis Set: Number of Participants With Primary Adverse Events (PAEs) | From Day 0 to Day 7 post catheter insertion on Day 0 | An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. PAEs included the following AEs: Phrenic Nerve Paralysis (permanent), Stroke/Cerebrovascular accident (CVA), Major Vascular Access Complication/Bleeding, Thromboembolism, Myocardial Infarction, Transient Ischemic Attack (TIA), Pericarditis, Pulmonary Edema (Respiratory Insufficiency), Heart Block, and Vagal Nerve Injury/ Gastroparesis. |
| Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Primary Adverse Events (PAEs) | From Day 0 to Day 7 post catheter insertion on Day 0 | An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. PAEs included the following AEs: Phrenic Nerve Paralysis (permanent), Stroke/CVA, Major Vascular Access Complication/Bleeding, Thromboembolism, Myocardial Infarction, Transient Ischemic Attack (TIA), Pericarditis, Pulmonary Edema (Respiratory Insufficiency), Heart Block, and Vagal Nerve Injury/ Gastroparesis. |
| Pivotal Main Phase Per-Protocol (PP) Analysis Set: Number of Participants With Freedom of Documented Atrial Tachyarrhythmia | Day 91 to Day 365 post catheter insertion on Day 0 | Number of Participants With freedom from documented (symptomatic and asymptomatic) atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial tachycardia \[AT\], or atrial flutter \[AFL\] of unknown origin positive) episodes based on electrocardiographic data (greater than or equal to \[\>=\] 30 seconds on an electrocardiogram \[ECG\], sponsor-provided cardiac event monitor \[CEM\], or Holter device) during the effectiveness evaluation period (Day 91-365 post catheter insertion procedure) and freedom from the following failure modes: acute procedural failure, repeat ablation failure, non-study catheter failure, AAD failure, continuous AF/AT/AFL of unknown origin on ECG, any Direct Current Cardioversion (DCCV) procedure were reported. |
| Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Freedom of Documented Atrial Tachyarrhythmia | Day 91 to Day 365 post catheter insertion on Day 0 | Number of Participants With freedom from documented (symptomatic and asymptomatic) atrial tachyarrhythmia (AF, AT, or AFL of unknown origin positive) episodes based on electrocardiographic data (\>=30 seconds on an ECG, CEM, or Holter device) during the effectiveness evaluation period (Day 91-365 post catheter insertion) and freedom from the following failure modes: acute procedural failure, repeat ablation failure, non-study catheter failure, AAD failure, continuous AF/AT/AFL of unknown origin on ECG, any DCCV procedure were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pivotal Main Phase PP Analysis Set: Change From Baseline in Overall Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT) Total Score | Baseline, and 12 months post catheter insertion on Day 0 | Change from baseline in overall AFEQT total score were reported. Change in the AFEQT score included 20 questions on a 7-point Likert scale. Questions 1-18 evaluated Health Related Quality of Life (HRQoL) and questions 19-20 were related to the patient's satisfaction with treatment. The first 18 questions were used to calculate the overall AFEQT score. The total AFEQT scores was calculated as 100 minus (\[Sum of severity for all questions answered minus number of questions answered) divided by total number of questions answered\*6\])\*100. The overall AFEQT scores ranged from 0 (complete disability) to 100 (no disability). Therefore, a positive change in score corresponded to improvement in QoL. |
| Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Change From Baseline in Overall Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT) Total Score | Baseline, and 12 months post catheter insertion on Day 0 | Change from baseline in overall AFEQT total score were reported. Change in the AFEQT score included 20 questions on a 7-point Likert scale. Questions 1-18 evaluated HRQoL and questions 19-20 were related to the patient's satisfaction with treatment. The first 18 questions were used to calculate the overall AFEQT score. The total AFEQT scores was calculated as 100 minus (\[Sum of severity for all questions answered minus number of questions answered) divided by total number of questions answered\*6\])\*100. The overall AFEQT scores ranged from 0 (complete disability) to 100 (no disability). Therefore, a positive change in score corresponded to improvement in QoL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pilot Safety Analysis Set Participants enrolled in the pilot phase with symptomatic paroxysmal atrial fibrillation (PAF) and had an insertion of the Biosense Incorporated Webster (BWI) Irreversible Electroporation (IRE) Ablation System (with or without delivery of PFA), underwent electrophysiology mapping and pulsed field ablation (PFA) for treatment of Antiarrhythmic Drug (AAD) refractory symptomatic PAF. | 21 |
| Pivotal Roll-In Analysis Set Participants enrolled in the pivotal roll-In phase with symptomatic paroxysmal atrial fibrillation (PAF) had an insertion of the BWI IRE Ablation System and PFA delivery, underwent electrophysiology mapping and PFA for treatment of AAD refractory symptomatic PAF. | 64 |
| Pivotal Main Safety Analysis Set Participants enrolled in the in pivotal main phase with symptomatic PAF had an insertion of the BWI IRE Ablation System (with or without delivery of PFA), underwent electrophysiology mapping and PFA for treatment of AAD refractory symptomatic PAF. | 277 |
| Total | 362 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 5 |
| Overall Study | Other | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Pilot Safety Analysis Set | Pivotal Roll-In Analysis Set | Pivotal Main Safety Analysis Set | Total |
|---|---|---|---|---|
| Age, Continuous Age (Year) | 62.1 Years STANDARD_DEVIATION 10.2 | 61.2 Years STANDARD_DEVIATION 8.97 | 61.5 Years STANDARD_DEVIATION 10.3 | 61.5 Years STANDARD_DEVIATION 10.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 7 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 57 Participants | 215 Participants | 292 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 55 Participants | 62 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 12 Participants | 15 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 3 Participants | 25 Participants | 28 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 54 Participants | 228 Participants | 302 Participants |
| Sex: Female, Male Female | 9 Participants | 26 Participants | 99 Participants | 134 Participants |
| Sex: Female, Male Male | 12 Participants | 38 Participants | 178 Participants | 228 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 1 / 64 | 0 / 277 |
| other Total, other adverse events | 12 / 21 | 23 / 64 | 109 / 277 |
| serious Total, serious adverse events | 2 / 21 | 7 / 64 | 31 / 277 |
Outcome results
Primary
Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Freedom of Documented Atrial Tachyarrhythmia
Number of Participants With freedom from documented (symptomatic and asymptomatic) atrial tachyarrhythmia (AF, AT, or AFL of unknown origin positive) episodes based on electrocardiographic data (\>=30 seconds on an ECG, CEM, or Holter device) during the effectiveness evaluation period (Day 91-365 post catheter insertion) and freedom from the following failure modes: acute procedural failure, repeat ablation failure, non-study catheter failure, AAD failure, continuous AF/AT/AFL of unknown origin on ECG, any DCCV procedure were reported.
Time frame: Day 91 to Day 365 post catheter insertion on Day 0
Population: Pilot phase used the safety analysis set, included participants enrolled in the Pilot phase and had insertion of the study catheter (with or without delivery of PFA). Pivotal roll-In phase analysis set included all participants enrolled and had insertion of the study catheter and undergone PFA delivery with the IRE ablation system. Here N (Overall number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Main Phase mITT Analysis Set | Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Freedom of Documented Atrial Tachyarrhythmia | 16 Participants |
| Pivotal Roll-In Analysis Set | Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Freedom of Documented Atrial Tachyarrhythmia | 43 Participants |
Primary
Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Primary Adverse Events (PAEs)
An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. PAEs included the following AEs: Phrenic Nerve Paralysis (permanent), Stroke/CVA, Major Vascular Access Complication/Bleeding, Thromboembolism, Myocardial Infarction, Transient Ischemic Attack (TIA), Pericarditis, Pulmonary Edema (Respiratory Insufficiency), Heart Block, and Vagal Nerve Injury/ Gastroparesis.
Time frame: From Day 0 to Day 7 post catheter insertion on Day 0
Population: Pilot phase used the safety analysis set, included participants enrolled in the Pilot phase and had insertion of the study catheter (with or without delivery of PFA). Pivotal roll-In phase analysis set included all participants enrolled and had insertion of the study catheter and undergone PFA delivery with the IRE ablation system. Here, N (Overall number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Main Phase mITT Analysis Set | Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Primary Adverse Events (PAEs) | 0 Participants |
| Pivotal Roll-In Analysis Set | Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Number of Participants With Primary Adverse Events (PAEs) | 0 Participants |
Primary
Pivotal Main Phase Modified Intent-To-Treat (mITT) Analysis Set: Number of Participants With Primary Adverse Events (PAEs)
An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. PAEs included the following AEs: Phrenic Nerve Paralysis (permanent), Stroke/Cerebrovascular accident (CVA), Major Vascular Access Complication/Bleeding, Thromboembolism, Myocardial Infarction, Transient Ischemic Attack (TIA), Pericarditis, Pulmonary Edema (Respiratory Insufficiency), Heart Block, and Vagal Nerve Injury/ Gastroparesis.
Time frame: From Day 0 to Day 7 post catheter insertion on Day 0
Population: mITT analysis set included all participants enrolled in the pivotal main phase who met eligibility criteria and had insertion of the study catheter. Here, N (Overall number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Main Phase mITT Analysis Set | Pivotal Main Phase Modified Intent-To-Treat (mITT) Analysis Set: Number of Participants With Primary Adverse Events (PAEs) | 8 Participants |
Primary
Pivotal Main Phase Per-Protocol (PP) Analysis Set: Number of Participants With Freedom of Documented Atrial Tachyarrhythmia
Number of Participants With freedom from documented (symptomatic and asymptomatic) atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial tachycardia \[AT\], or atrial flutter \[AFL\] of unknown origin positive) episodes based on electrocardiographic data (greater than or equal to \[\>=\] 30 seconds on an electrocardiogram \[ECG\], sponsor-provided cardiac event monitor \[CEM\], or Holter device) during the effectiveness evaluation period (Day 91-365 post catheter insertion procedure) and freedom from the following failure modes: acute procedural failure, repeat ablation failure, non-study catheter failure, AAD failure, continuous AF/AT/AFL of unknown origin on ECG, any Direct Current Cardioversion (DCCV) procedure were reported.
Time frame: Day 91 to Day 365 post catheter insertion on Day 0
Population: PP analysis set included all participants enrolled in the pivotal main phase who were treated for the study-related arrhythmia with the study catheter and without protocol deviations that would affect the scientific integrity of the study. Here N (Overall number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Main Phase mITT Analysis Set | Pivotal Main Phase Per-Protocol (PP) Analysis Set: Number of Participants With Freedom of Documented Atrial Tachyarrhythmia | 183 Participants |
Secondary
Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Change From Baseline in Overall Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT) Total Score
Change from baseline in overall AFEQT total score were reported. Change in the AFEQT score included 20 questions on a 7-point Likert scale. Questions 1-18 evaluated HRQoL and questions 19-20 were related to the patient's satisfaction with treatment. The first 18 questions were used to calculate the overall AFEQT score. The total AFEQT scores was calculated as 100 minus (\[Sum of severity for all questions answered minus number of questions answered) divided by total number of questions answered\*6\])\*100. The overall AFEQT scores ranged from 0 (complete disability) to 100 (no disability). Therefore, a positive change in score corresponded to improvement in QoL.
Time frame: Baseline, and 12 months post catheter insertion on Day 0
Population: Pilot phase used the safety analysis set, included participants enrolled in the Pilot phase and had insertion of the study catheter (with or without delivery of PFA). Pivotal roll-In phase analysis set included all participants enrolled and had insertion of the study catheter and undergone PFA delivery with the IRE ablation system. Here N (Overall number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pivotal Main Phase mITT Analysis Set | Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Change From Baseline in Overall Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT) Total Score | 31.13 score on a scale | Standard Deviation 27.15 |
| Pivotal Roll-In Analysis Set | Pilot Safety Analysis Set and Pivotal Roll-In Analysis Set: Change From Baseline in Overall Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT) Total Score | 34.98 score on a scale | Standard Deviation 24.553 |
Secondary
Pivotal Main Phase PP Analysis Set: Change From Baseline in Overall Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT) Total Score
Change from baseline in overall AFEQT total score were reported. Change in the AFEQT score included 20 questions on a 7-point Likert scale. Questions 1-18 evaluated Health Related Quality of Life (HRQoL) and questions 19-20 were related to the patient's satisfaction with treatment. The first 18 questions were used to calculate the overall AFEQT score. The total AFEQT scores was calculated as 100 minus (\[Sum of severity for all questions answered minus number of questions answered) divided by total number of questions answered\*6\])\*100. The overall AFEQT scores ranged from 0 (complete disability) to 100 (no disability). Therefore, a positive change in score corresponded to improvement in QoL.
Time frame: Baseline, and 12 months post catheter insertion on Day 0
Population: PP analysis aet included all participants enrolled in the pivotal main phase who were treated for the study-related arrhythmia with the study catheter and without protocol deviations that would affect the scientific integrity of the study. Here N (Overall number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pivotal Main Phase mITT Analysis Set | Pivotal Main Phase PP Analysis Set: Change From Baseline in Overall Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT) Total Score | 32.03 score on a scale | Standard Deviation 23.075 |