|
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P020018 S040/ PAS001 |
| Date Original Protocol Accepted |
04/04/2012
|
| Date Current Protocol Accepted |
12/12/2012
|
| Study Name |
Long Term F/U Study
|
| Device Name |
ZENITH FENESTRATED AAA ENDOVASCULAR GRAFT
|
| General Study Protocol Parameters |
| Study Design |
Prospective & Retrospective Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
Objective Performance Criterion
|
| Analysis Type |
Analytical
|
| Study Population |
Transit. Adolescent A (distinctively) : 18-21 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
Observational, single-arm, multi-center, prospective cohort study
|
| Study Population |
Subjects from the pivotal trial plus at least 20 new subjects
|
| Sample Size |
88
|
| Key Study Endpoints |
Primary endpoint: 5-year aneurysm-related mortality rate;
Secondary endpoints: Aneurysm rupture, conversion to open surgery, device integrity, device patency, change in aneurysm size, endoleak, device migration, secondary interventions, and morbidity index, defined as the percent of patients who have one or more specified adverse events.
|
| Follow-up Visits and Length of Follow-up |
5 years
30 days, 1 year, and annually thereafter for 5 years.
|
| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A total on 88 patients (67 pre-approval patients and 21 post approval patients
|
| Actual Number of Sites Enrolled |
A total 21 sites were enrolled (15 pre-approval sites and 6 post-approval sites)
|
| Patient Follow-up Rate |
94.4% (51/54) and 88.9% (48/54) of patients completed clinical and CT follow -up at 5 years respectively; 63.0% (34/54) of patients had KUB X-ray imaging at 5 years.
|
| Final Safety Findings |
Aneurysm related mortality rate based on the numerate (n=2 deaths) and a denominator that included patients that had 5-year follow-up visit or death (per approved protocol) is 3.08% (2/65) [Upper confidence limit of 10.68%] compared to PG of 18% (P-value < 0.01).
Kaplan Meier estimates for freedom from aneurysm related mortality using a z statistics was 97.5% [95% CI: 94.0%, 100%] versus PG of 82%. Thus the study met the performance goal.
Tipping Point Analysis
A total of 23 patients had missing 5-year vital status data for the primary endpoint analysis.
Per the sponsor’s tipping point analysis, in addition to the 2 deaths already counted as AAA-related, it would require at least 22% (n=5) of the 23 cases with missing vital status data to also experience AAA-related death for the primary endpoint to fail the hypothesis. This is unlikely given that only 1 treated patient showed aneurysm growth due to Type II endoleak (> 5 mm increase in diameter) at last follow-up which resolved with reintervention while all remaining patients had favorable outcomes i.e., a stable or shrinking aneurysm at last follow-up (1 patient did not receive the study device).
|
| Final Effect Findings |
The percentage of patients with patency loss based on Core Lab analysis or as reported by site was 0% (0/66) at 2 years, 1.8% (1/56) at 3 years, 0% (0/49) at 4 years and 0% (0/44) at 5 years.
No conversions to open repair were reported through 5 years.
There were 30 secondary interventions in 25 unique patients.
One (1) patient experienced component separation and aneurysm rupture at 5-year time point.
One patient (2.1%, 1/48) experienced Type I distal endoleak at 3 years and one patient (3.0%, 1/33) experienced Type III at 5 years. Type II endoleak rate at 5 years was 9.1% (3/33).
Ten patients experienced aneurysm growth at one or more follow-up time points. At 5 years
72.7% (32/44) of patients had aneurysm shrinkage, 15.9% (7/44) had no change in aneurysm size and 11.4% (5/44) had aneurysm expansion.
Two cases of stent migration involving caudal movement of proximal components occurred in two patients, one at 2 years and the other at 5 years.
Stent graft barb separation and component separation were the most frequently reported device integrity problems 2.2% (1/46) each at 5 years. For fenestration stent, fracture rate and separation rate was 0% (0/44) each at 5 years.
|
| Study Strengths & Weaknesses |
The study primary endpoint met the performance goal with aneurysm related mortality rate of 2.27% (2/88) compared to PG of 18% (p<0.0001) at 5 years. The impact of missing data on the primary endpoint result was evaluated.
The absolute numbers for patients completing clinical follow-up and imaging assessment at 5 years were low: clinical follow-up (51), CT follow -up (48) and KUB X-ray (34).
|
| Recommendations for Labeling Changes |
Labeling change is recommended to reflect the long-term results of the post approval study. The labeling change should include a new section in the label showing a summary of the post- approval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
|
