Atrial Fibrillation, Ischemic Stroke, Peripheral Thromboembolism
Conditions
Keywords
ACP, Atrial Fibrillation, AF, A Fib, Stroke, Coumadin, Warfarin, Dabigatran, Pradaxa, Blood thinning medication, Left atrial appendage, LAA
Brief summary
The objective of this study is to evaluate the safety and effectiveness of the ACP in subjects with nonvalvular atrial fibrillation by demonstrating that the device is non-inferior to optimal medical therapy (OMT) with respect to the primary effectiveness endpoint and superior to OMT with respect to primary safety endpoint.
Interventions
DEVICEAMPLATZER Cardiac Plug
AMPLATZER Cardiac Plug is a percutaneous transcatheter device
Sponsors
Abbott Medical Devices
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
* Subject must have a documented history of paroxysmal, persistent or permanent nonvalvular atrial fibrillation * Subject must be ≥18 years of age * Subject must be on warfarin or dabigatran therapy * Subject must be eligible for long term warfarin or dabigatran therapy * Subject must have a CHADS(2) score of 2 or greater Summary of
Exclusion criteria
* Subject who requires warfarin or dabigatran for a condition other than AF * Subject who is on clopidogrel or another P2Y12 platelet inhibitor such as prasugrel or ticagrelor * Subject who has an absolute or relative contraindication to aspirin, or warfarin and dabigatran * Subject with a New York Heart Association (NYHA) classification equal to IV * Subject with an implanted or surgical repair atrial septal defect (ASD) device or patent foramen ovale (PFO) device * Subject with aortic or mitral valve regurgitation of grade 2+ or greater * Subject with left ventricular ejection fraction (LVEF) ≤30 * Subject with mitral or aortic prosthetic valve * Subject with a history of hemorrhagic or aneurysmal stroke * Subject with a history of previous radio frequency (RF) ablation for atrial fibrillation * Subject with a body mass index (BMI) ≥40 * Subject with a history of acute or recent MI, or unstable angina, or coronary artery bypass graft surgery (within 6 months) * Subject who is on aspirin dose therapy greater than 81mg/day at time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | From Randomization to Discharge Visit | An analysis comparing the rate of procedure related serious adverse events that occur in the device arm to a performance goal determined from literature reported rates for similar procedural techniques. The study as designed was intended to determine the difference in efficacy and safety between the device and control arm (subjects treated with OMT). However, due to early enrollment closure, the three primary endpoints were not analyzed as specified in the original trial protocol. As the Control arm subjects exited the study early, no sufficient data was available to summarize any endpoints. The three primary endpoints as mentioned in the Appendix D of the clinical investigational plan (Revision 06, dated September 2014) were summarized for the Device arm below. The secondary endpoint analysis requirement was removed from the protocol. |
| Long-term Safety - Device Arm Only | Randomization to 2 year follow-up | All-Cause Mortality and Major Bleeds Through 2 years in device arm subjects only. The study as designed was intended to determine the difference in efficacy and safety between the device and control arm (subjects treated with OMT). However, due to early enrollment closure, the three primary endpoints were not analyzed as specified in the original trial protocol. As the Control arm subjects exited the study early, no sufficient data was available to summarize any endpoints. The three primary endpoints as mentioned in the Appendix D of the clinical investigational plan (Revision 06, dated September 2014) were summarized for the Device arm. The secondary endpoint analysis requirement was removed from the protocol. |
| Effectiveness Endpoint - Device Arm Only | Randomization through 2 year follow up | Occurrence of ischemic stroke and peripheral thromboembolism in the device arm. The study as designed was intended to determine the difference in efficacy and safety between the device and control arm (subjects treated with OMT). However, due to early enrollment closure, the three primary endpoints were not analyzed as specified in the original trial protocol. As the Control arm subjects exited the study early, no sufficient data was available to summarize any endpoints. The three primary endpoints as mentioned in the Appendix D of the clinical investigational plan (Revision 06, dated September 2014) were summarized for the Device arm. The secondary endpoint analysis requirement was removed from the protocol. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Device AMPLATZER Cardiac Plug
AMPLATZER Cardiac Plug: AMPLATZER Cardiac Plug is a percutaneous transcatheter device | 68 |
| Optimal Medical Therapy (Control) Warfarin Dabigatran
AMPLATZER Cardiac Plug: AMPLATZER Cardiac Plug is a percutaneous transcatheter device | 29 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 5 |
| Overall Study | Enrollment Closure, Protocol Amendment | 6 | 15 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 8 |
Baseline characteristics
| Characteristic | Device | Optimal Medical Therapy (Control) | Total |
|---|---|---|---|
| Age, Continuous | 74.0 Years STANDARD_DEVIATION 8.5 | 73.4 Years STANDARD_DEVIATION 10 | 73.5 Years STANDARD_DEVIATION 8.9 |
| CHADS2 Score Chads2 Score 0 | 0 Participants | 0 Participants | 0 Participants |
| CHADS2 Score Chads2 Score 1 | 0 Participants | 0 Participants | 0 Participants |
| CHADS2 Score Chads2 Score 2 | 38 Participants | 17 Participants | 55 Participants |
| CHADS2 Score Chads2 Score 3 | 20 Participants | 7 Participants | 27 Participants |
| CHADS2 Score Chads2 Score 4 | 7 Participants | 4 Participants | 11 Participants |
| CHADS2 Score Chads2 Score 5 | 2 Participants | 1 Participants | 3 Participants |
| CHADS2 Score Chads2 Score 6 | 1 Participants | 0 Participants | 1 Participants |
| History of Atrial Fibrillation Paroxysmal | 32 Participants | 19 Participants | 51 Participants |
| History of Atrial Fibrillation Permanent | 15 Participants | 3 Participants | 18 Participants |
| History of Atrial Fibrillation Persistent | 21 Participants | 7 Participants | 28 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Rhythm Status at Baseline Atrial Fibrillation | 29 Participants | 5 Participants | 34 Participants |
| Rhythm Status at Baseline Other Arrhythmias or Conduction Disturbance | 2 Participants | 2 Participants | 4 Participants |
| Rhythm Status at Baseline Paced Rhythm | 17 Participants | 15 Participants | 32 Participants |
| Rhythm Status at Baseline Sinus Rhythm | 19 Participants | 7 Participants | 26 Participants |
| Sex: Female, Male Female | 23 Participants | 11 Participants | 34 Participants |
| Sex: Female, Male Male | 45 Participants | 18 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 68 | 5 / 29 |
| other Total, other adverse events | 61 / 68 | 15 / 29 |
| serious Total, serious adverse events | 52 / 68 | 15 / 29 |
Outcome results
Primary
Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only
An analysis comparing the rate of procedure related serious adverse events that occur in the device arm to a performance goal determined from literature reported rates for similar procedural techniques. The study as designed was intended to determine the difference in efficacy and safety between the device and control arm (subjects treated with OMT). However, due to early enrollment closure, the three primary endpoints were not analyzed as specified in the original trial protocol. As the Control arm subjects exited the study early, no sufficient data was available to summarize any endpoints. The three primary endpoints as mentioned in the Appendix D of the clinical investigational plan (Revision 06, dated September 2014) were summarized for the Device arm below. The secondary endpoint analysis requirement was removed from the protocol.
Time frame: From Randomization to Discharge Visit
Population: No data were collected for the Control Arm/Group due to early enrollment closure and the pre-specified analysis was revised accordingly to report data for only the Device Arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Pericardial Tamponade | 3 events |
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Cardiac Perforation* | 1 events |
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Pericardial Effusion | 1 events |
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Cardiogenic Shock* | 1 events |
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Pericarditis* | 1 events |
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Device Embolization | 3 events |
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Pleural Effusion | 1 events |
| Device Arm | Acute Safety - Procedure Related SAEs From Randomization Through Discharge For Device Arm Only | Hematoma | 1 events |
Primary
Effectiveness Endpoint - Device Arm Only
Occurrence of ischemic stroke and peripheral thromboembolism in the device arm. The study as designed was intended to determine the difference in efficacy and safety between the device and control arm (subjects treated with OMT). However, due to early enrollment closure, the three primary endpoints were not analyzed as specified in the original trial protocol. As the Control arm subjects exited the study early, no sufficient data was available to summarize any endpoints. The three primary endpoints as mentioned in the Appendix D of the clinical investigational plan (Revision 06, dated September 2014) were summarized for the Device arm. The secondary endpoint analysis requirement was removed from the protocol.
Time frame: Randomization through 2 year follow up
Population: No data were collected for the Control Arm/Group due to early enrollment closure and the pre-specified analysis was revised accordingly to report data for only the Device Arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Device Arm | Effectiveness Endpoint - Device Arm Only | Ischemic Stroke | 2 events |
| Device Arm | Effectiveness Endpoint - Device Arm Only | Peripheral Thromboembolism | 0 events |
Primary
Long-term Safety - Device Arm Only
All-Cause Mortality and Major Bleeds Through 2 years in device arm subjects only. The study as designed was intended to determine the difference in efficacy and safety between the device and control arm (subjects treated with OMT). However, due to early enrollment closure, the three primary endpoints were not analyzed as specified in the original trial protocol. As the Control arm subjects exited the study early, no sufficient data was available to summarize any endpoints. The three primary endpoints as mentioned in the Appendix D of the clinical investigational plan (Revision 06, dated September 2014) were summarized for the Device arm. The secondary endpoint analysis requirement was removed from the protocol.
Time frame: Randomization to 2 year follow-up
Population: No data were collected for the Control Arm/Group due to early enrollment closure and the pre-specified analysis was revised accordingly to report data for only the Device Arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Device Arm | Long-term Safety - Device Arm Only | Empyema (Major Bleeding) | 1 Events |
| Device Arm | Long-term Safety - Device Arm Only | Hemothorax (Major Bleeding) | 1 Events |
| Device Arm | Long-term Safety - Device Arm Only | Hematoma (Major Bleeidng) | 1 Events |
| Device Arm | Long-term Safety - Device Arm Only | Bleeding (Major Bleeding) | 1 Events |
| Device Arm | Long-term Safety - Device Arm Only | Respiratory Failure (Death) | 2 Events |
| Device Arm | Long-term Safety - Device Arm Only | Congestive Heart Failure (Death) | 1 Events |
| Device Arm | Long-term Safety - Device Arm Only | Device Embolization (Death) | 1 Events |