Atrial Fibrillation
Conditions
Keywords
Non-valvular atrial fibrillation, Left atrial appendage, Ablation
Brief summary
The primary objective of this study is to determine if left atrial appendage closure with the WATCHMAN FLX Device is a reasonable alternative to oral anticoagulation following percutaneous catheter ablation for high risk patients with non-valvular atrial fibrillation.
Detailed description
This study is a prospective, randomized, multi-center, global investigation to determine if left atrial appendage closure with the WATCHMAN FLX Device is a reasonable alternative to oral anticoagulation in patients after AF ablation. A subject who signs informed consent is considered enrolled in the study. Subjects will be randomized to OAC or WATCHMAN FLX in equal fashion. Randomization will be stratified by sequential vs. concomitant planned ablation +/- WATCHMAN implantation, to help ensure balance of treatment assignments within the sequential and concomitant groups.
Interventions
DRUGMarket-approved OAC
Used per IFU for atrial fibrillation stroke prevention for the duration of the trial.
DEVICEWATCHMAN FLX Implant
Left atrial appendage closure with the WATCHMAN FLX device
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subject is of legal age to participate in the study per the laws of their respective geography. 2. Underwent a prior catheter ablation procedure for non-valvular AF between 90 and 180 days prior to randomization (sequential) or is planning to have clinically indicated catheter ablation within 10 days of randomization (concomitant). 3. The subject has a calculated CHA2DS2-VASc score of 2 or greater for males or 3 or greater for females. 4. The subject is deemed to be suitable for the defined protocol pharmacologic regimen. 5. The subject is able to undergo TEE examinations. 6. The subject or legal representative is able to understand and is willing to provide written informed consent to participate in the trial. 7. The subject is able and willing to return for required follow-up visits and examinations.
Exclusion criteria
1. The subject is currently enrolled in another investigational study that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments. Each instance must be brought to the attention of the sponsor to determine eligibility, regardless of type of co-enrollment being proposed. 2. The subject requires long-term anticoagulation therapy for reasons other than AF-related stroke risk reduction, for example due to an underlying hypercoagulable state (i.e., even if the device is implanted, the subjects would not be eligible to discontinue OAC due to other medical conditions requiring chronic OAC therapy). 3. The subject is deemed by the treating physician to be unsuitable for chronic anticoagulation and/or aspirin therapy due to bleeding risk, allergy, or other reasons. 4. The subject had or is planning to have any cardiac or major non-cardiac interventional or surgical procedure (excluding non-valvular AF ablation and cardioversion) within 30 days prior to or 60 days after randomization \[including, but not limited to: percutaneous coronary intervention (PCI), other cardiac ablation (VT ablation, etc.), etc.\]. 5. The subject had a stroke or transient ischemic attack (TIA) within the 60 days prior to randomization. 6. The subject had a prior major bleeding event per ISTH definition within the 14 days prior to randomization. Lack of resolution of related clinical sequelae, or planned and pending interventions to resolve bleeding/bleeding source, are a further exclusion regardless of timing of the bleeding event. 7. The subject has had a myocardial infarction (MI) documented in the clinical record as either a non-ST elevation MI (NSTEMI) or as an ST-elevation MI (STEMI), with or without intervention, within 90 days prior to randomization. 8. The subject has a history of atrial septal repair or has an ASD/PFO device. 9. The subject has an implanted mechanical valve prosthesis in any position. 10. The subject is of childbearing potential and is, or plans to become pregnant during the time of the study (method of assessment upon study physician's discretion) 11. The subject has a documented life expectancy of less than two years. 12. The subject has a cardiac tumor. 13. The subject has signs/symptoms of acute or chronic pericarditis. 14. There is evidence of tamponade physiology. 15. Contraindications (anatomical or medical) to percutaneous catheterization procedures. 16. The subject has documented NYHA Class IV heart failure. 17. The subject has documented surgical closure of the left atrial appendage. 18. The subject has an active infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Effectiveness Endpoint: Stroke, All Cause Death, and Systemic Embolism | From randomization to 1095 days post randomization | Occurrence of stroke (including ischemic and/or hemorrhagic), all cause death, and systemic embolism events adjudicated by an Independent Clinical Event Committee |
| Primary Safety Endpoint: Non-procedural Bleeding | Non-procedural events are those occurring after 3 days, calculated from implant or attempted implant date for Device patients and from date of randomization for Control patients | Occurrence of non-procedural bleeding (ISTH major bleeding and clinically relevant non-major bleeding) events adjudicated by an Independent Clinical Event Committee |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ISTH Major Bleeding | From randomization to 1095 days post randomization | Occurence of ISTH major bleeding (including procedural bleeding) events adjudicated by an Independent Clinical Event Committee |
Countries
Australia, Belgium, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, United States
Participant flow
Recruitment details
1600 subjects were randomized from 11-Jun-2019 to 16-Jul-2021
Pre-assignment details
803 subjects were randomized to the WATCHMAN FLX DEVICE and 797 subjects were randomized to the OAC Control group (ITT analysis set)
Participants by arm
| Arm | Count |
|---|---|
| Oral Anticoagulant (Control) Catheter ablation for atrial ablation followed by market-approved OAC for the duration of the trial | 797 |
| WATCHMAN FLX DEVICE Catheter ablation for atrial fibrillation followed by WATCHMAN FLX Device implant with market-approved OAC and aspirin until the 3-month visit followed by aspirin until at least the 12-month visit | 803 |
| Total | 1,600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 34 | 29 |
| Overall Study | Death > 1095 day (not included in endpoint analyses) | 1 | 2 |
| Overall Study | Lost to Follow-up | 28 | 17 |
| Overall Study | Physician Decision | 5 | 4 |
| Overall Study | Reason not reported | 7 | 9 |
| Overall Study | Withdrawal by Subject | 43 | 28 |
Baseline characteristics
| Characteristic | Oral Anticoagulant (Control) | WATCHMAN FLX DEVICE | Total |
|---|---|---|---|
| Age, Continuous | 69.4 Years at time of Consent STANDARD_DEVIATION 7.9 | 69.7 Years at time of Consent STANDARD_DEVIATION 7.4 | 69.5 Years at time of Consent STANDARD_DEVIATION 7.6 |
| Race/Ethnicity, Customized American Indian or Alaska native | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Black, of African heritage | 11 Participants | 14 Participants | 25 Participants |
| Race/Ethnicity, Customized Caucasian | 686 Participants | 673 Participants | 1359 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 12 Participants | 13 Participants | 25 Participants |
| Race/Ethnicity, Customized Not disclosed | 83 Participants | 94 Participants | 177 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Australia | 12 Participants | 10 Participants | 22 Participants |
| Region of Enrollment Belgium | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment Denmark | 13 Participants | 12 Participants | 25 Participants |
| Region of Enrollment France | 61 Participants | 66 Participants | 127 Participants |
| Region of Enrollment Germany | 100 Participants | 104 Participants | 204 Participants |
| Region of Enrollment Italy | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Netherlands | 6 Participants | 6 Participants | 12 Participants |
| Region of Enrollment Poland | 9 Participants | 8 Participants | 17 Participants |
| Region of Enrollment Spain | 24 Participants | 27 Participants | 51 Participants |
| Region of Enrollment United States | 562 Participants | 560 Participants | 1122 Participants |
| Sex/Gender, Customized Female | 263 Participants | 283 Participants | 546 Participants |
| Sex/Gender, Customized Intersex | 1 Participants | 0 Participants | 1 Participants |
| Sex/Gender, Customized Male | 533 Participants | 520 Participants | 1053 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 797 | 31 / 803 |
| other Total, other adverse events | 248 / 797 | 254 / 803 |
| serious Total, serious adverse events | 797 / 797 | 803 / 803 |
Outcome results
Primary
Primary Effectiveness Endpoint: Stroke, All Cause Death, and Systemic Embolism
Occurrence of stroke (including ischemic and/or hemorrhagic), all cause death, and systemic embolism events adjudicated by an Independent Clinical Event Committee
Time frame: From randomization to 1095 days post randomization
Population: The primary analysis for the primary effectiveness endpoint was performed on an intent-to-treat basis, with all randomized subjects analyzed as part of their randomized group regardless of the actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Anticoagulant (Control) | Primary Effectiveness Endpoint: Stroke, All Cause Death, and Systemic Embolism | 44 Participants |
| WATCHMAN FLX DEVICE | Primary Effectiveness Endpoint: Stroke, All Cause Death, and Systemic Embolism | 41 Participants |
Primary
Primary Safety Endpoint: Non-procedural Bleeding
Occurrence of non-procedural bleeding (ISTH major bleeding and clinically relevant non-major bleeding) events adjudicated by an Independent Clinical Event Committee
Time frame: Non-procedural events are those occurring after 3 days, calculated from implant or attempted implant date for Device patients and from date of randomization for Control patients
Population: The primary analysis for the primary safety endpoint was performed on an intent-to-treat basis, with all randomized subjects analyzed as part of their randomized group regardless of the actual treatment received
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Anticoagulant (Control) | Primary Safety Endpoint: Non-procedural Bleeding | 137 Participants |
| WATCHMAN FLX DEVICE | Primary Safety Endpoint: Non-procedural Bleeding | 65 Participants |
Secondary
ISTH Major Bleeding
Occurence of ISTH major bleeding (including procedural bleeding) events adjudicated by an Independent Clinical Event Committee
Time frame: From randomization to 1095 days post randomization
Population: The primary analysis for the secondary endpoint was performed on an intent-to-treat basis, with all randomized subjects analyzed as part of their randomized group regardless of the actual treatment received
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Anticoagulant (Control) | ISTH Major Bleeding | 38 Participants |
| WATCHMAN FLX DEVICE | ISTH Major Bleeding | 30 Participants |