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| General |
| Study Status |
Progress Adequate |
Application Number /
Requirement Number |
P120021 / PAS001 |
| Date Original Protocol Accepted |
09/22/2017
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| Date Current Protocol Accepted |
05/23/2019
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| Study Name |
Amplatzer PFO Occluder New Enrollment PAS
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| Device Name |
AMPLATZER PFO OCCLUDER
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
This is a single arm, multi-center, prospective, new enrollment study.
The objectives of this study are the following:
(1) To demonstrate safety of the AMPLATZER PFO Occluder by assessing the short-term (30-day) rate of device- or procedure-related serious adverse
events (including those that led to death)
(2) To demonstrate that the AMPLATZER PFO Occluder is effective by assessing the rate of recurrent ischemic stroke through 5 years
(3) To demonstrate effectiveness of the training program for new operators
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| Study Population |
Patients over the age of 18 years and less than 60 years who have experienced a cryptogenic stroke diagnosed by a neurologist in the 547 days prior to consent and have a patent foramen ovale diagnosed by transesophageal echocardiogram.
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| Sample Size |
The overall sample size for this trial is 1214 subjects, which is driven by the primary effectiveness endpoint. The overall sample size accounts for 25% attrition over 5 years. To ensure that enrollment is balanced across sites, no investigational site will be allowed to enroll more than 20% of the maximum sample size (242 subjects).
The sample size is estimated to have adequate power to test the primary effectiveness endpoint. The assumed primary effectiveness endpoint event rate is 2.2% and the performance goal is 3.9%. Using a one-sided 2.5% significance level, 910 subjects are required to have 80% power to reject the null hypothesis with the exact binomial method. Assuming 25% attrition over 5 years, a total of 1214 subjects is required.
The sample size is estimated to have adequate power to test the primary safety endpoint. The assumed primary safety endpoint event rate is 2.07% and the performance goal is 4.14%. Using a one- sided 2.5% significance level, 653 subjects are required to obtain 80% power to reject the null hypothesis with the exact binomial method. Due to the acute nature of this endpoint, no attrition is assumed.
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| Key Study Endpoints |
Primary Safety: Device- or procedure-related serious adverse events (as adjudicated by a Clinical Events Committee) through 30 days, including:
Atrial Fibrillation
Pulmonary Embolism
Deep Vein Thrombosis
Device Thrombus
Device Erosion
Device Embolization
Ischemic stroke if subject was not successfully implanted with a device
Hemorrhagic Stroke
Major Bleeding requiring transfusion, or surgical or endovascular intervention
Vascular Access Site Complication requiring surgical intervention
Device- or Procedure-Related Serious Adverse Event leading to death
Primary Effectiveness: 5-year rate of recurrent ischemic stroke
Ischemic stroke is defined as acute 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 findings of a new, neuroanatomically relevant, cerebral infarct.
Descriptive Endpoints:
Rate of stroke of unknown cause (determined by ASCOD adjudication) through each annual follow-up
Rate of Transient Ischemic Attack (TIA)1 through each annual follow-up
Rate of atrial fibrillation through each annual follow-up
Rate of pulmonary embolism through each annual follow-up – the rate will be descriptively compared to the rates observed in the randomized groups in the RESPECT investigational device exemption (IDE) trial
Rate of deep vein thrombosis through each annual follow-up – the rate will be descriptively compared to the rate observed in the randomized groups in the RESPECT IDE trial
Rate of venous thromboembolism events (DVT or PE) through each annual follow-up – the rate will be descriptively compared to the rate observed in the randomized groups in the RESPECT IDE trial
Rate of device thrombus through each annual follow-up
Rate of device erosion through each annual follow-up
Rate of device embolization through each annual follow-up
Rate of ischemic stroke through each annual follow-up
Rate of hemorrhagic stroke through each annual follow-up
Rate of atrial flutter through each annual follow-up
Rate of paroxysmal supraventricular tachycardia requiring treatment through each annual follow-up
Antithrombotic medication (single antiplatelet, dual antiplatelet, warfarin, novel oral anticoagulant, other) use at each follow-up
SF-12 quality of life physical and mental component score at baseline, 1 month, 6 months and 1 year
Health state utility values from EQ-5D at baseline, 1 month, 6 months and 1 year
Effective closure – Grade 0 or 1 maximal shunt through the PFO at rest and/or Valsalva as assessed by transthoracic echocardiogram (TTE) or transesophageal echocardiogram (TEE) at 1 year
Complete closure – Grade 0 maximal shunt through the PFO at rest and/or Valsalva as assessed by TTE or TEE at 1 year
Technical success – Successful delivery and release of the AMPLATZER PFO Occluder for subjects in whom the delivery system entered the body
Procedural success – Successful implantation of the AMPLATZER PFO Occluder with no reported in-hospital serious adverse events (SAEs) for subjects in whom the delivery system entered the body
Training effectiveness - will be summarized by reporting the procedure-related SAE rate for new operators
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| Follow-up Visits and Length of Follow-up |
Subjects will be followed for 5 years post implant.
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| Interim or Final Data Summary |
| Interim Results |
Primary Safety Endpoint: The Safety hypothesis will be assessed once all eligible subjects have met 30-day follow-up. As of this report, 18 subjects have had a Serious Adverse Event (atrial fibrillation) that counts towards the primary safety endpoint.
Primary Effectiveness Endpoint: The Effectiveness hypothesis will be assessed once all eligible subjects have completed 5-year follow-up. As of this report, four subjects had an event that was adjudicated as an Ischemic Stroke. These events will count towards the primary effectiveness endpoint.
Serious Adverse Events: 105 events have been adjudicated as Serious Adverse Events, 39 of these were adjudicated as device related. The device-related events were arrhythmia (n=2), atrial fibrillation (n=17), atrial flutter (n=3), chest pain – non cardiac (n=1), chest pain/discomfort (n=1), device embolization (n=1), ischemic stroke (n=2), migraine (n=1), paroxysmal supraventricular tachycardia (n=1), pulmonary embolism (n=4), Reintervention for Residual Shunt/device Removal (n=2), thrombus on device (n=2), and transient ischemic attack (n=2)
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| Actual Number of Patients Enrolled |
Subject enrollment is ongoing. 728 Subjects are enrolled. Subject enrollment is approximately 60% (728/1214) complete.
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| Actual Number of Sites Enrolled |
Site enrollment is complete. 81 Sites have IRB approval and are activated, and 71 Sites are enrolling subjects.
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| Patient Follow-up Rate |
Subject follow-up is ongoing. The reported follow-up rate is currently 96% at the 1-month study visit, 87% at the 6-month study visit, 82% at the 12-month study visit, 77% at the 24-month visit, 64% at the 36-month visit, and 13% at the 48-month visit. Approximately 28% of currently enrolled subjects have met the 3-year visit time point, but few have reached the 4-year visit time-point.
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| Study Strengths & Weaknesses |
Not yet applicable
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