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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P100021 / PAS001 |
| Date Original Protocol Accepted |
05/09/2011
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| Date Current Protocol Accepted |
01/24/2014
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| Study Name |
ENGAGE
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| Device Name |
MEDTRONIC VASCULAR ENDURANT STENT GRAFT SYSTEM
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| General Study Protocol Parameters |
| Study Design |
Retrospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent & Historical Control
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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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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A total of 372 subjects were enrolled for the Engage PAS. The ENGAGE PAS cohort comprised of 328 subjects from the All Bifurcated arm and 44 subjects from the AUI IDE arm. The All Bifurcated arm included 178 de novo subjects and 150 Endurant IDE study subjects.
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| Actual Number of Sites Enrolled |
All Bifurcated arm: A total of 27 sites enrolled the Endurant IDE cohort subjects and 24 sites enrolled the de novo cohort.
Aorto-Uni-Iliac (AUI) IDE Arm: A total of 15 sites enrolled the (AUI) IDE arm.
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| Patient Follow-up Rate |
The clinical follow up rate at 5 years was 90% (99/110) for de novo cohort, 94% (95/101) for Endurant IDE cohort, and 93% (27/29) for AUI IDE cohort.
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| Final Safety Findings |
Aneurysm-related mortality (ARM)-All Bifurcated arm-The freedom from ARM at 5 years (Kaplan-Meier (KM) estimate) for all bifurcated arm subjects was 99% (95% CI: 97.9%, 100%). AUI IDE arm-The freedom from ARM at 5 yrs (KM estimate) for the AUI IDE subjects was 97.7% (95%CI: 93.3%, 100%).
The lower 95% confidence limit for the 5-yr survival estimate for both the Bifurcated & AUI IDE cohorts were greater than the pre-specified performance goal of 92%. All-Cause Mortality-All Bifurcated arm-The freedom from all-cause mortality (KM estimate) thru 5 yrs for the All Bifurcated subjects was 76.8% (95%CI: 72.0%, 81.6%). In total 74 deaths were reported for the All Bifurcated arm, 48 in the de novo cohort & 26 in the Endurant IDE cohort. Two deaths in de novo cohort were adjudicated by the clinical event committee (CEC) as aneurysm and procedure-related deaths and one death in Endurant IDE cohort was adjudicated by the CEC as device and aneurysm related death. The remaining deaths were adjudicated by the CEC as not aneurysm, device, or procedure related. AUI IDE arm-The freedom from all-cause mortality (KM estimate) thru 5 yrs in the Endurant AUI cohort was 67.6% (95% CI: 53.5%, 81.6%). There were 14 deaths in this cohort and the CEC adjudicated one death as related to the procedure. The remaining 13 deaths were adjudicated by the CEC as not related to aneurysm, device or procedure. Aneurysm Rupture (AR)-All Bifurcated arm-No AR (0%) was reported for the de novo subjects in this cohort. Two Endurant IDE subjects experienced AR. The AR rate at 1 and 4 yrs for the All Bifurcated arm subjects were 0.3% (1/314) and 0.4% (1/251) at 1 and 4 yrs respectively. There were no reports of AR (0.0%) at 2, 3 and 5 yrs.
AUI IDE arm-There were no AR thru 5 yrs (0%) in the AUI IDE cohort. Major Adverse Events (MAE)-All Bifurcated arm-The percentage of subjects in the All Bifurcated arm that experienced one or more MAE (including all-cause mortality, bowel ischemia, myocardial infarction, paraplegia, stroke, renal failure & respiratory failure) at 5 yrs follow-up was 8.8% (20/226). AUI IDE arm-The percentage of subjects in the AUI IDE arm that experienced one or more MAE at 5 yrs follow-up was 12.5% (4/32). Gender Analysis: A total of 45 females were enrolled in the All Bifurcated arm (32 in the de novo subjects and 13 Endurant IDE subjects), and 14 subjects enrolled in the AUI IDE arm. ARM-All bifurcated arm-Thru 5 yrs the freedom from ARM rate in both genders were similar. The freedom from ARM at 5 yrs (KM estimate) for female All Bifurcated subjects was 97.8% (95% CI: 93.5% to 100%), and for male All Bifurcated subjects was 99.2% (95% CI: 98.1% to 100%). AUI IDE arm-There was no ARM observed in female AUI IDE subjects. ARM occurred in only 1 male subject which resulted in freedom from ARM of 96.7% [95% CI: 90.2% to 100%] at 5 yrs.
All Cause-Mortality-The percentage of female subjects that experienced all-cause mortality in All Bifurcated arm at 5 yrs was 11.1 % (3/27) in the AUI IDE arm at 5 yrs was 0.0% (0/11).
MAE-The percentage of female subjects that experienced one or more MAEs in All Bifurcated arm at 5 yrs follow up was 14.8% (4/27), and 0% (0/11) in the AUI IDE Arm.
Race Analysis-A total of 11 (9 de novo subjects and 2 Endurant IDE subjects) non-white subjects were enrolled in the All Bifurcated cohort and 2 non-White subjects were enrolled in the AUI IDE cohort
ARM-The freedom from ARM at 5 yrs (KM estimate) for white subjects in All Bifurcated arm was 99% [95% CI: 97.8% to 100%] and in AUI IDE arm was 97.6% [95% CI: 93% to 100%]. There was no ARM reported for non-white subjects in All Bifurcated arm and AUI IDE arm. MAEs-All bifurcated arm-The percentage of non-white subjects in All Bifurcated arm that experienced one or more MAEs at 5 yrs follow up was 50.0% (2/4). AUI IDE arm-The percentage of non-white subjects in the AUI IDE arm that experienced one or more MAEs at 5 yrs follow -up was 0.0% (0/2).
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| Final Effect Findings |
Aneurysm Expansion greater 5mm: The percentage of subjects with aneurysm expansion greater than 5mm at 5 years for All Bifurcated cohort was 5.8% (10/173) [95% CI, 2.8%, 10.4%] and 4.2% (1/24) [95% CI, 0.1%, 21.1%] for the AUI IDE cohort.
Aneurysm Decrease greater 5 mm or stable: In both All Bifurcated cohort and AUI IDE cohorts, the majority of the subjects had aneurysm diameter decrease greater than 5mm or no change in size - All Bifurcated subjects 94.2%, and AUI IDE cohort 95.8%.
Conversion to Open Surgical Repair - There were no conversions to open repair (0.0%) through 5 years in the All Bifurcated subjects or the AUI IDE subjects.
Secondary Endovascular Procedure-The percentage of subjects that had secondary endovascular procedure at the 5-year time interval was 3.6% (8/220) for All Bifurcated cohort
and 3.2% (1/31) for the AUI IDE cohort.
Stent Graft Migration-Two (2) stent graft migrations greater than 10 mm occurred at days 1499 and 1479 (4 years) in two patients for de novo subjects. There was no stent graft migration greater than 10 mm in Endurant IDE subjects or in the AUI IDE subjects through 5 years.
Endoleaks-All Bifurcated arm-In total nine (9) Type I endoleaks were reported in All Bifurcated subjects. The Type I endoleak rates reported for the timepoints were 0.3% (1/311) at 1 month, 0.7% (2/279) at 1 year, 0.8% (2/266) at 2 years, 0.5% (1/208) at 3 years, 1.6% (3/189) at 4 years and 0.0% (0/166) at 5 years. The Type II endoleak rates reported for All Bifurcated subjects at the timepoints were 11.3% (35/311) at 1 month, 9.3% (26/279) at 1 year, 9.4% (25/266) at 2 years, 10.1% (21/208) at 3 years, 11.6% (22/189) at 4 years and 9.6% (16/166) at 5 years. There were no Type III, Type IV, or Type V endoleaks reported for All Bifurcated subjects.
AUI IDE arm-The type II endoleaks rate reported for AUI IDE subjects at the time points were 7.0% (3/43) at 1 month, 13.9% (5/36) at 1 year, 6.1% (2/33) at 2 years, 10.7% (3/28) at 3 years, 7.7% (2/26) at 4 years and 5.0% (1/20) at 5 years. There were no Type I, Type III, Type IV, or Type V endoleaks reported AUI IDE subjects.
Technical observations-There were no stent graft twisting, stent graft kinking, and stent graft stenosis reported at 5 years for All Bifurcated subjects and AUI IDE subjects.
Technical success-The technical success rate was 99.1% (325/328), 95% CI (97.4%, 99.8%) for All Bifurcated subjects and 97.7% (43/44), 95% CI (88.0%, 99.9%) for AUI IDE subjects indicating the successful delivery and deployment of the Endurant Stent Graft System in the planned location.
Subgroup Analysis: Gender Analysis: Stent Graft Occlusion/ Loss of Stent Graft Patency
There were no stent graft migration, no stent graft integrity, or no twisting reported in any of the female All Bifurcated subjects and AUI IDE arm at any time point.
Aneurysm Expansion greater 5mm-One (1) female subjects in All Bifurcated arm experienced aneurysm expansion greater than 5 mm at the 3, 4, and 5-year time point, as compared to 1 month. There was no aneurysm expansion greater than 5mm reported for female AUI IDE subjects.
Endoleaks-All bifurcated arm-Overall endoleaks were reported in 7 of 45 (15.6%) female All Bifurcated subjects. Type I endoleaks were reported in 2 of the 45 (4.4%) female All Bifurcated subjects. There were no Type III, Type IV, or Type V endoleaks reported at any time point.
AUI IDE arm-The Type II Endoleaks were reported in 2 of 14 (14.3%) female AUI IDE subjects. There were no Type I, Type III, Type IV, or Type V endoleaks reported for female AUI IDE subjects at any time point.
Race Analysis-There were no technical observations, aneurysm expansion >5mm, migration, stent graft integrity, kinking, twisting, occlusion, or stenosis reported in any of the non-white subjects for all bifurcated arm and AUI IDE arm.
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| Study Strengths & Weaknesses |
Strength: The ENGAGE PAS was a prospective, longer term, multicenter study. The study met the primary endpoint and provided long-term data. Weakness: The sample size for AUI arm cohort is too small to make any definitive conclusion of safety and effectiveness. There were too few non-whites in both all bifurcated cohort and AUI IDE cohort to draw meaningful conclusions about the relationship between race/ethnicity and the device performance.
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| Recommendations for Labeling Changes |
Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoint, follow-up visits etc.), final results, study strengths and limitations of the PAS.
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