|
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P100018 / PAS001 |
| Date Original Protocol Accepted |
04/06/2011
|
| Date Current Protocol Accepted |
06/27/2011
|
| Study Name |
Continued Follow-up of Premarket Cohort
|
| Device Name |
PIPELINE EMBOLIZATION DEVICE
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Analytical
|
| Detailed Study Protocol Parameters |
| Study Objectives |
Single arm prospective cohort
|
| Study Population |
Pipeline Embolic Device pivotal study cohort and the (device and control continued access cohort follow up. These were patients group) with wide-necked intracranial aneurysms in the internal
carotid artery from the petrous to the superior hypophyseal segments.
|
| Sample Size |
(no. 134 subjects, 2-subgroup analyses by aneurysm location
study sites and and by hypertension status
patients)
|
| Key Study Endpoints |
Ipsilateral stroke or neurovascular death Secondary: complete occlusion of treated aneurysm,
stenosis of the parent artery in PED, and device-related adverse events.
|
| Follow-up Visits and Length of Follow-up |
5 years
|
| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
Out of 138 consented patients, 135 patients were enrolled in the PUFS-PAS (108 PUFS between November 2008 and July 2009 + 27 PUFS-CA between May 2010 and April 2011) of which 134 PUFS- PAS patients were treated with the PED and 1 PUFS patient was not treated with the PED.
|
| Actual Number of Sites Enrolled |
12 centers (10 US, 2 OUS (1 Hungary, 1 Turkey)).
|
| Patient Follow-up Rate |
3- year follow-up rate: 107 / 130 (82.3%) 5-year follow-up rate: 100/128 (78.1%)
Note: These are general follow-up rates. For specific endpoints (e.g. safety and effectiveness endpoints requiring the use of angiography), the follow-up rate may be less, potentially leading to selection bias, which may leads to an underestimate of rates for adverse events or complications.
|
| Final Safety Findings |
The primary endpoint (incidence of ipsilateral stroke or neurovascular death at 5-year follow-up) was 8.3% (11/134; 95% CI: 4.7%-14.4%), meeting the threshold of success of < 25%.
There was no significant difference according to aneurysm location (at or below cavernous segment vs. at or above ophthalmic segment) in incidence of ipsilateral stroke or neurovascular death at 5-year follow-up.
There was a significantly higher incidence of ipsilateral stroke or neurovascular death at 5- year follow-up (P=0.0067) among patients with a history of hypertension (10/70 (14.3%)) vs. patients without a history of hypertension (1/64 (1.6%)).
Seven device related adverse events were observed during the long-term follow-up period:
5-year follow-up: 7 / 106 (6.6%)
0- to 3-year follow-up: 5/106 (4.7%)
4- to 5-year follow-up: 2/99 (2.0%)
Parent artery stenosis:
3 years 5 years
0-25% 80% (80/100) 80% (64/80)
>25-50% 8.0% (8/100) 5.0% (4/80)
>50%-75% 0.0% (0/100) 1.3% (1/80)
>75% 3.0% (3/100) 2.5% (2/80)
Indeterminate 9.0% (9/100) 11.3% (9/80)
Note: A total of 100 out of 106 patients had available parent artery stenosis data at 3 years of follow- up and a total of 80 out of 99 patients had available parent artery stenosis data at 5 years of follow- up. Therefore, follow-up rate is less than the overall follow-up rate at 3 years and 5 years. The finding that parent artery stenosis is less problematic at 5 years of follow-up as compared to 3 years of follow-up may be explained by selection bias.
Opthalmic artery flow at 1-year follow-up was 49 / 65 or 75.4% of patients.
|
| Final Effect Findings |
Complete aneurysm occlusion at 3-year follow-up was 90 / 100 or 90.0%.
Complete aneurysm occlusion at 5-year follow-up was 75 / 80 or 93.8%.
|
| Study Strengths & Weaknesses |
Strengths:
The prospective cohort design may be less prone to bias. Long-term follow-up of patients until 5 years post-procedure.
Powered to meet objective performance criterion for primary endpoint.
Definitions of safety and effectiveness endpoints facilitate comparison with literature.
Pre-specified primary, secondary and descriptive safety and effectiveness endpoints as well as sub- group analyses.
Follow-up rates were acceptable, limiting selection bias.
Independent assessment of endpoints, limiting misclassification bias.
Sensitivity analyses were performed to account for losses to follow-up.
Weaknesses:
Primary endpoint is composite in nature and there is not enough power to evaluate components of this safety endpoint.
Findings from worst-case imputation were inconsistent with findings from optimistic, completers, Kaplan-Meier and predictive distribution, with regard to 5-year complete occlusion rate and 5-year parent artery stenosis of 0-25%.
The 3-year follow-up rate was 107 / 130 (82.3%) and the 5-year follow-up rate was 100/128 (78.1%). However, these are general follow-up rates. For specific endpoints (e.g. safety and effectiveness endpoints requiring the use of angiography), the follow-up rate may be less, potentially leading to selection bias.
|
| Recommendations for Labeling Changes |
A history of hypertension is associated with increased risk of ipsilateral stroke or neurovascular death following PED treatment.
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