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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P100018 S015/ PAS001 |
| Date Original Protocol Accepted |
12/14/2018
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| Date Current Protocol Accepted |
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| Study Name |
PREMIER Post-Approval Study
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| Device Name |
Pipeline Flex Embolization Device
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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 |
Historical Control
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| Analysis Type |
Descriptive
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| Detailed Study Protocol Parameters |
| Study Objectives |
The “Prospective Study on Embolization of Intracranial Aneurysms with the Pipeline™ Device” (PREMIER) study is a prospective, multi-center non-randomized clinical study evaluating safety and effectiveness outcomes in patients with small or medium wide-necked intracranial aneurysms measuring less than or equal to 12 mm who are treated with the Pipeline™ device. The study includes continued follow-up of the premarket cohort for up to three (3) years post-procedure.
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| Study Population |
The study enrolled patients with small or medium wide-necked intracranial aneurysms measuring =12 mm who were treated with the Pipeline™ device.
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| Sample Size |
Out of 197 consented patients, 141 patients were implanted with the Pipeline device.
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| Key Study Endpoints |
The primary safety endpoint is the rate of major or disabling strokes or neurological deaths.
The primary effectiveness endpoint is the rate of patients who have complete (100%) Raymond-Roy Class I intracranial aneurysm occlusion without clinically significant parent artery stenosis or retreatment of the target aneurysm.
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| Follow-up Visits and Length of Follow-up |
Three years
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
Consented 197 subjects to meet the 141 evaluable (ITT) subjects.
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| Actual Number of Sites Enrolled |
23 sites with 22 US sites and 1 Canadian site
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| Patient Follow-up Rate |
The follow-up rates for ITT population at 1-yr, 2-yr, and 3-yr follow-up visits are 98.6%, 95%, and 90.8%, respectively.
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| Final Safety Findings |
Incidence of major stroke: Major strokes in the territory supplied by the treated artery or Neurological Death at long-term (2-year and 3-year follow-up) occurred in 2.8% (4/141) of subjects. The incidence rate of major stroke at long-term is comparable with the rate at 1-year follow-up (2.4%). Specifically, only 1 additional subject (Subject: 109-022) experienced a Major Stroke between 1- and 2-year follow-up; none of the subjects had neurological death in this period. No additional Major Stroke in the territory supplied by the treated artery or Neurological Death occurred between 2- and 3-year follow up.
Delayed ICH: The rate of delayed ICH at long-term (1.4%) is comparable with the rate at 1-year follow-up (0.73%). Specifically, only one subject (Subject: 109-022) had a delayed ICH between 1- and 2-year follow-up. No additional delayed intracerebral hemorrhage occurred between the 2- and 3-year follow up.
Device-Related Neurological Adverse Event Rate: Fifteen of the 141 subjects (10.6%, 15/141) experienced device-related neurological AE’s through 3-years post-procedure. The rate of device-related neurological AE is comparable to that at 1-year follow-up (7.8%). Specifically, 4 new subjects reported device-related neurological events between 1- and 2- year follow-up. No additional device-related neurological AE’s occurred between 2- and 3-year follow-up 10.6% (15/141) of subjects.
Cerebrovascular Events: The incidence rates for intracranial hemorrhage (ICH) at 1-yr, 2-yr, and 3-yr follow-up are 0.7%, 0.7%, and 0% respectively. Similarly, the incidence rates for ischaemic stroke at 1-yr, 2-yr, and 3-yr follow-up are 0.7%, 0%, and 0% respectively. There is no increase in the annual incidence rates of hemorrhagic and ischaemic cerebrovascular events over time.
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| Final Effect Findings |
Complete aneurysm occlusion rate without significant parent artery stenosis (= 50%) or retreatment of the target aneurysm at 1-year follow up is 78.98% (LCL: 72.05%) with 1-sided 97.5% exact binomial lower bound of 72.05%. Similarly the Complete aneurysm occlusion rates Using LOCF (last observation carry forward) approach at 2-year follow-up and 3-year follow-up are 78.8% (LCL: 70.8%) and 80.3% (LCL: 72.5%), respectively.
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| Study Strengths & Weaknesses |
Strength: A prospective and long-term study with follow-up rate for ITT population above 90%.
Weaknesses: Single arm study not controlling for confounding factors. Gender distribution is skewed. The majority of study subjects were female (87.9%) and male subjects were under presented, which leads to a limitation in the generalizability of the study results. Understanding of device performance in subjects vertebral aneurysms is limited due to small sample size (N=7).
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| Recommendations for Labeling Changes |
Yes
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