Cryptogenic Stroke
Conditions
Keywords
Cryptogenic, Stroke, PFO, Patent foramen ovale, AMPLATZER, Occluder
Brief summary
The purpose of this study is to investigate whether percutaneous Patent Foramen Ovale (PFO) closure, using the AMPLATZER PFO Occluder, is superior to current standard of care medical treatment in the prevention of recurrent embolic stroke.
Detailed description
The AMPLATZER PFO Occluder is a percutaneous, transcatheter occlusion device intended for the non-surgical closure of patent foramen ovale in subjects who have had a cryptogenic stroke due to presumed paradoxical embolism within the last 270 days.
Interventions
DEVICEAMPLATZER PFO Occluder
patent foramen ovale closure device
OTHERStandard of Care - Medical Management
Medical management - aspirin alone, Coumadin alone, Clopidogrel alone, aspirin combined with dipyridamole
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
AMPLATZER PFO Occluder
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who have had a cryptogenic stroke within the last 270 days * Subjects who have been diagnosed with a Patent Foramen Ovale (PFO) * Subjects willing to participate in follow-up visits
Exclusion criteria
* Subjects with intracardiac thrombus or tumor * Subjects who have an acute or recent (within 6 months) myocardial infarction or unstable angina * Subjects with left ventricular aneurysm or akinesis * Subjects with atrial fibrillation/atrial flutter (chronic or intermittent) * Subjects with another source of right to left shunt identified at baseline, including an atrial septal defect and/or fenestrated septum * Subjects with contraindication to aspirin or Clopidogrel therapy * Pregnant or desire to become pregnant within the next year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Recurrent Nonfatal Ischemic Stroke, Fatal Ischemic Stroke, or Early Death After Randomization | Trial enrollment was stopped once 25 unique subjects were mutually adjudicated by the CEC and DSMB as having experienced a primary endpoint event. This occurred on December 20, 2011. The mean follow-up time was 2.6 years. | Nonfatal stroke is defined as: focal neurological deficit presumed to be due to focal ischemia, and either 1) symptoms persisting 24 hours or greater, or 2) symptoms persisting less than 24 hours but associated with MR or CT imaging findings of a new, neuroanatomically relevent, cergral infarct. Post-randomization death is defined as: in the MM group as all-cause mortality within 45 days after randomization, and in the device group as all-cause mortality 30 days after implant or 45 days after randomizaiton, whichever occurs last. |
Secondary
| Measure | Time frame |
|---|---|
| Rate of Complete PFO Closure (Assessed by TEE Bubble Study) at the 6-month Follow-up in the Device Group | 6 months |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Device AMPLATZER PFO Occluder: patent foramen ovale closure device | 499 |
| Medical Management Aspirin alone, Coumadin alone, Clopidogrel alone, or Aspirin combined with dipyridamole | 481 |
| Total | 980 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 11 |
| Overall Study | Investigator request | 3 | 4 |
| Overall Study | Lost to Follow-up | 60 | 67 |
| Overall Study | Withdrawal by Subject | 34 | 78 |
Baseline characteristics
| Characteristic | Device | Medical Management | Total |
|---|---|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 9.7 | 46.2 years STANDARD_DEVIATION 10 | 45.9 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 231 Participants | 213 Participants | 444 Participants |
| Sex: Female, Male Male | 268 Participants | 268 Participants | 536 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 499 | 11 / 481 |
| other Total, other adverse events | 285 / 499 | 70 / 481 |
| serious Total, serious adverse events | 201 / 499 | 173 / 481 |
Outcome results
Primary
Composite of Recurrent Nonfatal Ischemic Stroke, Fatal Ischemic Stroke, or Early Death After Randomization
Nonfatal stroke is defined as: focal neurological deficit presumed to be due to focal ischemia, and either 1) symptoms persisting 24 hours or greater, or 2) symptoms persisting less than 24 hours but associated with MR or CT imaging findings of a new, neuroanatomically relevent, cergral infarct. Post-randomization death is defined as: in the MM group as all-cause mortality within 45 days after randomization, and in the device group as all-cause mortality 30 days after implant or 45 days after randomizaiton, whichever occurs last.
Time frame: Trial enrollment was stopped once 25 unique subjects were mutually adjudicated by the CEC and DSMB as having experienced a primary endpoint event. This occurred on December 20, 2011. The mean follow-up time was 2.6 years.
Population: All primary endpoints that occurred in the trial were recurrent non-fatal ischemic strokes.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Device | Composite of Recurrent Nonfatal Ischemic Stroke, Fatal Ischemic Stroke, or Early Death After Randomization | 9 Participants |
| Medical Management | Composite of Recurrent Nonfatal Ischemic Stroke, Fatal Ischemic Stroke, or Early Death After Randomization | 16 Participants |
p-value: 0.0895% CI: [0.22, 1.11]Log Rank
Secondary
Rate of Complete PFO Closure (Assessed by TEE Bubble Study) at the 6-month Follow-up in the Device Group
Time frame: 6 months
Population: Only subjects with complete PFO closure data at 6-months were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Device | Rate of Complete PFO Closure (Assessed by TEE Bubble Study) at the 6-month Follow-up in the Device Group | 249 Participants |
Post Hoc
Rate of Recurrent Nonfatal Stroke, Post-randomization Death, and Fatal Ischemic Stroke Through Long Term Follow-up
Time frame: Long Term Follow-up, median of 5.9 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Device | Rate of Recurrent Nonfatal Stroke, Post-randomization Death, and Fatal Ischemic Stroke Through Long Term Follow-up | 18 Participants |
| Medical Management | Rate of Recurrent Nonfatal Stroke, Post-randomization Death, and Fatal Ischemic Stroke Through Long Term Follow-up | 28 Participants |
p-value: 0.04695% CI: [0.31, 0.999]Log Rank