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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P120006 / PAS001 |
| Date Original Protocol Accepted |
10/05/2012
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| Date Current Protocol Accepted |
06/21/2013
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| Study Name |
Long Term Follow-up Study
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| Device Name |
OVATION ABDOMINAL STENT GRAFT SYSTEM
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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 |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
A prospective, consecutively enrolling, single-arm, non-randomized, multi-
center study
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| Study Population |
Patients with an abdominal aortic aneurysm with vascular morphology
suitable for endovascular repair with the Ovation/Ovation Prime Abdominal
Stent Graft System. Eligible patients must have met or must meet all of the inclusion criteria and none of the exclusion criteria.
Comparator: Performance Goal of 92%
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| Sample Size |
A total 320 subjects yielding at least 192 evaluable subjects at 5 years.
Comprises of 161 pivotal cohort subjects, all continued access subjects, all subjects from the HDE PAS and at least 59 de novo subjects enrolled from
a minimum of 15 U.S. sites.
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| Key Study Endpoints |
Primary Endpoint: Aneurysm-related mortality at 5 years
Secondary Endpoints:
¿ Serious Adverse Events (SAEs) assessed through 30 days, 12 months then annually until 5 years post initial implant.
¿ Mortality (AAA-related and all-cause)
¿ Device Patency
¿ Conversion to open surgical repair
¿ Endoleak
¿ AAA enlargement
¿ Stent Graft Migration
¿ Device integrity
¿ Secondary endovascular procedures
¿ Aneurysm rupture
All endpoints assessed at 30 days and 12 months, then annually thereafter
through 5 years post initial implant.
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| Follow-up Visits and Length of Follow-up |
5 years
30 days, 12 months and annually thereafter.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A total of 320 subjects were enrolled. This includes 161 Pivotal subjects; 77 Continued Access (CA) Subjects; 82 de novo subject.
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| Actual Number of Sites Enrolled |
49 sites (13 US de novo clinical sites, 36 worldwide clinical sites)
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| Patient Follow-up Rate |
The 5-year clinical follow-up rate for each cohort is as follows:
94% (87/93) of available subjects in the 5 year follow up interval for the Pivotal Cohort
95% (37/39) of available subjects at the 5-year follow-up interval for the Continued Access Cohort
100% (41/41) of available subjects at the 5-year follow-up interval for the de novo Cohort
The 5-year CT imaging compliance rate for each cohort is as follows:
90% (84/93) of available subjects in the 5 year follow up interva
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| Final Safety Findings |
Primary Endpoints
Aneurysm-Related Mortality:
Survival from aneurysm-related mortality by Kaplan Meier (KM) estimate at 5 years was 98.9% for all cohorts. Through 5 years there were three (3) aneurysm-related deaths all in the pivotal cohort. One subject had a death at day 17 from abdominal sepsis and disseminated intravascular coagulation (DIC). A death secondary to suprarenal aneurysm rupture at day 368 was also seen in a subject. An additional AAA-related death was reported for the pivotal cohort at day 1499 due to aneurysm rupture. There were no other aneurysm-related deaths in the other cohorts.
Secondary Endpoints:
All-Cause Mortality:
Through 5 years of follow-up, a total of 67 deaths (67/320, 20.9%) have been reported for the combined cohorts; 35 in the Pivotal cohort (35/161, 21.7%). 17 in the Continued Access cohort (17/77, 22.1%), and 15 in the de novo cohort (15/82, 18.3%). Individually, the all-cause mortality rates for the Pivotal, Continued Access, and de novo cohorts through 365 days is 2.5% (4/161), 5.2% (4/77), and 3.7% (3/82), respectively; the combined all-cause mortality for all cohorts at 365 days is 3.4% (11/320).
Surgical Conversion
One (1) surgical conversion was reported in the PAS, which was in the de novo cohort. The subject experienced with progressive enlargement due to Type II endoleak through 4-year follow-up and was converted to open repair. The surgical conversion rate at 5 years is 0.5% (1/206).
AAA Rupture
Two (2) AAA ruptures have been reported in the PAS; one (1) rupture in the Pivotal Cohort and one in the Continued Access cohort. The pivotal study subject died from rupture 1499 days post implant; the patient had Type IA, IB and II endoleaks (previously treated) that were persistent, and the patient refused further endoleak treatment. The continued access subject experienced a contained rupture at day 1486. The subject had a Type IA endoleak which was resolved after repeated coil embolization, yet likely contributed to the rupture. The combined AAA rupture rate at 5 years is 1.0% (2/206).
Polymer Leaks
There has been two incidence of polymer leaks in the study, occurring at the procedure timepoint in the pivotal cohort and continued access cohort (1 in each). The Ovation/Ovation Prime products were not included in the 2020 Class I Recall regarding the next generation Ovation iX device.
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| Final Effect Findings |
AAA Enlargement:
Through 5 years, the total number of patients that experienced aneurysm size enlargement (>5mm) was 24/226 (10.6%) for pivotal and CA combined; 11.5% in the pivotal study cohort (18/156) and 8.6% CA (6/70). In the de novo cohort, 10/67 (14.9%) patients experienced AAA size enlargement, but this was not confirmed by a corelab.
Through 5 years, the total number of patients that experienced aneurysm size decrease (>5mm) was 106/226 (46.9%) for the pivotal and CA cohorts; 42.3% in the pivotal cohort (66/156), 57.1% CA (40/70). In the de novo cohort, 32/67 (47.8%) patients experienced aneurysm size decrease. Through 5 years, the total number of patients that experienced no change in aneurysm size was 96/226 (42.5%) for the pivotal and CA cohorts; 46.1 % in the pivotal study cohort (72/156), 34.3% CA (24/70). In the de novo cohort, 25/67 (37.3%) patients experienced no change in aneurysm size.
Endoleaks
No Type I, III, or IV endoleaks were identified by the imaging Core Laboratory through 5 year follow up in the Pivotal and CA cohorts. In the de novo cohort, 1 Type IIIA endoleak was identified at 5 years (1/82, 1.2%), and 2 type I endoleaks were identified in the same 2 patients at 30-days and persistent through 5-year (2/82, 2.4%). In total, the rate of type I and type III endoleaks through 5-years is 0.6% (2/320) and 0.3% (1/320), respectively, for all cohorts combined
In total, 113/232 (48.7%) patients were reported to have Type II endoleaks by the Core Lab in the combined cohorts (pivotal and CA); 49.0% in the pivotal study cohort (77/157) and 48.0% CA (36/75). Twenty-nine patients (29/77, 46.0%) were identified in the de novo cohort with Type II endoleaks but were not confirmed by the corelab.
In total, 5/238 (2.1%) patients were reported to have indeterminate endoleaks by the Core Lab in the pivotal and CA cohorts; 1.2% in the pivotal study cohort (2/161), and 0% CA (0/77). Three patients (3/82; 3.7%) were identified in the de novo cohort but were not confirmed by the corelab.
Loss of Device Integrity
Stent fractures were identified by the imaging Core Laboratory through 12 months post-treatment in 1.9% (6 of 315) of all subjects treated in the Pivotal, CA, and de novo cohorts.
Stent fractures were identified by the imaging Core Laboratory through 5-years post-treatment in 17/238 (7.1%) of all subjects treated in the Pivotal and CA cohorts, combined. Of the 11 Pivotal subjects with reported stent fractures through 5 years, six patients had 1 reported stent fracture, four had 2 reported stent fractures, and one had >2 reported stent fractures. In the patients with more than 1 stent fracture, the stent fractures initially occurred in the same axial region of the proximal stent. There were 6 subjects having stent fractures in the CA cohort. There were no stent graft fractures for the de novo cohort.
The stent fractures were not associated with clinical sequelae or associated with intervention.
There were no reports of loss of integrity (e.g., holes, tears) of the PTFE graft material.
Secondary Interventions
The freedom from secondary interventions through 5 years [Kaplan-Meier (KM) estimate] for all cohorts was 87.1%; 89.7% for pivotal, 82.5% for CA, and 85.4% for the de novo. Reinterventions occurred over all follow-up time periods. The primary reason for reinterventions were Type II Endoleaks treated with embolization.
Stent Graft Migration
There have been no device migrations (defined as evidence of proximal or distal movement of the stent graft >10mm relative to fixed anatomic landmarks) reported in any cohort.
Loss of Device Patency
Loss of device patency is defined as complete occlusion of the treated vessel. The freedom from occlusion through 5 years [KM estimate] for the combined cohorts was 96.1%; 96.3% for the pivotal cohort, 93.4% for the CA cohort, and 98.8% for the de novo cohort.
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| Study Strengths & Weaknesses |
Study Strengths: This study is a multicenter study involving 49 investigational sites, 13 sites in the US and 36 sites outside of the US.
Study Weaknesses: Due to loss to subject during follow-up and withdrawal, Endologix did not meet the pre-determined goal of 192 evaluable subjects at the 5-year follow-up visit, which was the original post-market target set to perform the primary endpoint analysis of freedom from aneurysm related mortality. However, Endologix performed a tipping point analysis, in which it was concluded that given that it took 10.5% of “missing” subjects (12/114) to fail the endpoint, and that this is substantially higher than the 1.1% 5-year rate provided by the Kaplan-Meier estimate, the analysis supports that the conclusions of the primary endpoint analysis remain valid.
It is also important to note that the Core Lab did not evaluate the de novo cohort.
Although we have presented KM estimates and cumulative rates above, there was not adequate follow-up at all timepoints for all patients to assess each of the endpoints. Therefore, the rates provided may be an underestimate of the actual rates of events.
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| Recommendations for Labeling Changes |
Not Recommended, as the Ovation/Ovation Prime devices are no longer marketed.
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