Paroxysmal Atrial Fibrillation
Conditions
Brief summary
This is a prospective, adaptive, multi-center, randomized safety and effectiveness pivotal study comparing the FARAPULSE Pulsed Field Ablation System with standard of care ablation with force-sensing RF catheters and cryoballoon catheters indicated for the treatment of PAF.
Interventions
Ablation using the FARAPULSE Pulsed Field Ablation System
DEVICERadioFrequency and Cryoballoon Ablation
Contact Force Enabled RF and Cryoballoon ablation catheters indicated for Paroxysmal Atrial Fibrillation
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: Patients are required to meet all the following inclusion criteria to participate in this study: 1. Patients with drug-resistant symptomatic PAF meeting all the following criteria: a. Paroxysmal: AF that terminates spontaneously or with intervention within 7 days of onset. b. Frequency: i. Physician documentation of recurrent PAF (two or more episodes) within 6 months, AND ii. At least one (1) documented episode by a recording such as ECG, EM, Holter monitor or telemetry strip within 12 months of enrollment. c. Drug failed: Failed AAD treatment, meaning therapeutic failure of at least one (1) AAD (Class I to IV) for efficacy and / or intolerance. 2. Patients who are ≥ 18 and ≤ 75 years of age on the day of enrollment. 3. Patient who are willing and capable of: 1. Providing informed consent to undergo study procedures AND 2. Participating in all examinations and follow-up visits and tests associated with this clinical study. Key
Exclusion criteria
Patients will be excluded from participating in this study if they meet any one of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Safety Endpoint;Proportion of MITT Subjects With One or More of the Specified Device or Procedure Related SAEs | 7 days and 12 Months | Proportion of Intent to Treat subjects with one or more of the specified device or procedure related SAEs |
| Primary Effectiveness Endpoint | 12-Months | Treatment Success: The primary effectiveness endpoint is Treatment Success in MITT Subjects, defined as: 1. Acute Procedural Success AND 2. Chronic Success, defined as freedom from: 1. At the Index / Rescheduled Index Procedure: Use of a non-randomized treatment modality for PVI 2. After the Blanking Period: i. Occurrence of any Detectable AF, AFL or AT (excluding CTI-dependent flutter confirmed by EP study) ii. Any cardioversion for AF, AFL or AT (excluding for CTI-dependent flutter) iii. Use of any Type I or Type III antiarrhythmic medication for the treatment of AF, AFL or AT c. At any time: i. Re-ablation for AF, AFL or AT (other than for CTI-dependent flutter) ii. Use of amiodarone, except intra-procedurally to control an arrhythmia Endpoint status will be assessed through the Month 12 Assessment (Day 360 ± 30). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PV Cross-sectional Area | 3 months | Mean change in aggregate PV Cross-Sectional area (cm\^2) from baseline to Day 90 |
| Primary Effectiveness Treatment Success Tested for Superiority | 12 Months | The secondary effectiveness endpoint is the same as the primary effectiveness endpoint but will be tested for superiority rather than non-inferiority. The proportion of Pulsed Field Subjects with Treatment Success will be assessed for superiority to the proportion of Thermal Subjects with Treatment Success. |
Countries
United States
Participant flow
Pre-assignment details
There were 80 Roll-in subjects and 19 randomized subjects (ITT) that withdrew before the procedure.
Participants by arm
| Arm | Count |
|---|---|
| FARAPULSE Pulsed Field Ablation System FARAPULSE Pulsed Field Ablation System: Ablation using the FARAPULSE Pulsed Field Ablation System | 305 |
| Force Sensing Radiofrequency Ablation and Cryoballoon Ablation Radiofrequency and Cryoballoon Ablation: Contact Force Enabled RF and Cryoballoon ablation catheters indicated for Paroxysmal Atrial Fibrillation | 302 |
| Total | 607 |
Baseline characteristics
| Characteristic | FARAPULSE Pulsed Field Ablation System | Force Sensing Radiofrequency Ablation and Cryoballoon Ablation | Total |
|---|---|---|---|
| Age, Continuous | 62.4 years | 62.5 years | 62.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 297 Participants | 299 Participants | 596 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 11 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 11 Participants | 19 Participants |
| Race (NIH/OMB) White | 286 Participants | 272 Participants | 558 Participants |
| Region of Enrollment United States | 305 Participants | 302 Participants | 607 Participants |
| Sex: Female, Male Female | 103 Participants | 107 Participants | 210 Participants |
| Sex: Female, Male Male | 202 Participants | 195 Participants | 397 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 305 | 1 / 302 |
| other Total, other adverse events | 88 / 305 | 103 / 302 |
| serious Total, serious adverse events | 37 / 305 | 34 / 302 |
Outcome results
Primary
Composite Safety Endpoint;Proportion of MITT Subjects With One or More of the Specified Device or Procedure Related SAEs
Proportion of Intent to Treat subjects with one or more of the specified device or procedure related SAEs
Time frame: 7 days and 12 Months
Population: MITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FARAPULSE Pulsed Field Ablation System | Composite Safety Endpoint;Proportion of MITT Subjects With One or More of the Specified Device or Procedure Related SAEs | 6 Participants |
| Force Sensing Radiofrequency Ablation and Cryoballoon Ablation | Composite Safety Endpoint;Proportion of MITT Subjects With One or More of the Specified Device or Procedure Related SAEs | 4 Participants |
Primary
Primary Effectiveness Endpoint
Treatment Success: The primary effectiveness endpoint is Treatment Success in MITT Subjects, defined as: 1. Acute Procedural Success AND 2. Chronic Success, defined as freedom from: 1. At the Index / Rescheduled Index Procedure: Use of a non-randomized treatment modality for PVI 2. After the Blanking Period: i. Occurrence of any Detectable AF, AFL or AT (excluding CTI-dependent flutter confirmed by EP study) ii. Any cardioversion for AF, AFL or AT (excluding for CTI-dependent flutter) iii. Use of any Type I or Type III antiarrhythmic medication for the treatment of AF, AFL or AT c. At any time: i. Re-ablation for AF, AFL or AT (other than for CTI-dependent flutter) ii. Use of amiodarone, except intra-procedurally to control an arrhythmia Endpoint status will be assessed through the Month 12 Assessment (Day 360 ± 30).
Time frame: 12-Months
Population: MITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FARAPULSE Pulsed Field Ablation System | Primary Effectiveness Endpoint | 204 Participants |
| Force Sensing Radiofrequency Ablation and Cryoballoon Ablation | Primary Effectiveness Endpoint | 194 Participants |
Comparison: The primary effectiveness endpoint for this study is Treatment Success, which will be analyzed as a test of non-inferiority of the event rate at 12 months using a noninferiority margin of 15%.~The null and alternative hypotheses are:~H0: PT ≤ PC - 0.15 versus HA: PT \> PC - 0.15 where PT is the Treatment Success rate at 12 months in the Pulsed Field Group and PC is the Treatment Success rate at 12 months in the Thermal (Control) Group.p-value: 0.05t-test, 1 sided
Secondary
Change in PV Cross-sectional Area
Mean change in aggregate PV Cross-Sectional area (cm\^2) from baseline to Day 90
Time frame: 3 months
Population: MITT
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FARAPULSE Pulsed Field Ablation System | Change in PV Cross-sectional Area | -0.18 cm^2. |
| Force Sensing Radiofrequency Ablation and Cryoballoon Ablation | Change in PV Cross-sectional Area | -1.18 cm^2. |
Secondary
Primary Effectiveness Treatment Success Tested for Superiority
The secondary effectiveness endpoint is the same as the primary effectiveness endpoint but will be tested for superiority rather than non-inferiority. The proportion of Pulsed Field Subjects with Treatment Success will be assessed for superiority to the proportion of Thermal Subjects with Treatment Success.
Time frame: 12 Months
Population: MITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FARAPULSE Pulsed Field Ablation System | Primary Effectiveness Treatment Success Tested for Superiority | 73.3 Treatment Success Rate |
| Force Sensing Radiofrequency Ablation and Cryoballoon Ablation | Primary Effectiveness Treatment Success Tested for Superiority | 71.3 Treatment Success Rate |
Comparison: The secondary effectiveness endpoint for the ADVENT Trial is Treatment Superiority uses the same definition as the primary effectiveness endpoint for Treatment Success, but the test is for superiority between MITT subjects in the PFA and Thermal Groups.p-value: 0.025t-test, 1 sided