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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P180011 / PAS001 |
| Date Original Protocol Accepted |
09/18/2018
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| Date Current Protocol Accepted |
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| Study Name |
IMPERIAL Continued f/u study
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| Device Name |
Eluvia Drug-Eluting Vascular Stent System
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| General Study Protocol Parameters |
| Study Design |
Randomized Clinical Trial
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent Control
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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 |
Continued follow-up of premarket cohort; RCT
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| Study Population |
Test: Eluvia DES
Control: Zilver PTX DES
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| Sample Size |
485
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| Key Study Endpoints |
Premarket:
The primary safety hypothesis to be tested is that the 12-month MAE-free rate in subjects treated with ELUVIA is non-inferior to subjects treated with Zilver PTX by a margin of -10% (negative value) at one-sided significance level of 5%.
The primary effectiveness hypothesis to be tested is that the 12-month primary patency in subjects treated with ELUVIA is non-inferior to subjects treated with Zilver PTX by a margin of -10% (negative value) at one-sided significance level of 5%.
PAS:
Above endpoints at 24 months (descriptively).
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| Follow-up Visits and Length of Follow-up |
5 years
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A total of 524 subjects were enrolled in the trial including 465 subjects in the RCT (Eluvia subjects, N=309 and Zilver PTX subjects N=156 subjects), 50 subjects in the Long Lesion substudy (LL) and 13 subjects in the Pharmacokinetic (PK) substudy. Four (4) subjects enrolled in the PK and LL substudies.
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| Actual Number of Sites Enrolled |
Seventy -three (73) sites worldwide including the United States, Canada, Europe Japan and New Zealand
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| Patient Follow-up Rate |
Overall compliance at 60 months: 75.7%, 296/391 for the RCT (74.3% for Eluvia and 78.5% for Zilver), 65.8%, 25/38 for the LL substudy and 88.9% (8/9) for PK substudy.
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| Final Safety Findings |
Major Adverse Event (MAE) free rate at 60 months for RCT Eluvia subjects was 67.2% (156/232) versus 64.9% (74/114) for RCT Zilver PTX (control subjects), 95% confidence interval (CI) for the difference, 2.3% [-8.3%, 13.0%], p= 0.6662.
MAE free rate for LL sub-study was 54.3% (19/35) with 95%CI: 36.6%, 71.2%.
Target limb major amputation rate for RCT Eluvia subjects was 3.4% (8/232) versus 2.6% (3/114) for Zilver PTX control subjects, 95% CI for the difference, 0.8% [-2.9%, 4.6%], p=1.000
There were no amputations in the LL sub-study subjects 0.0% (0/35) through 60 months.
Target lesion revascularization (TLR) rate for RCT Eluvia subjects was 30.6% (71/232) versus 35.1% (40/114) for Zilver PTX control subjects, 95%CI for the difference, 95% CI for the difference -4.5% [-15.1%, 6.1%], p 0.4000.
Target lesion revascularization rate for LL sub-study subjects was 45.7% (16/35) with 95% CI
28.8%, 63.4%.
At 60 months tent thrombosis rate in the RCT Eluvia treatment subjects was 7.3% (20/273) versus 6.5% (9/139) in Zilver PTX control subjects with 95% confidence interval for the difference
0.9% [-4.3%, 6.0%], p = 0.7495.
Stent thrombosis rate in LL subjects at 60 months was 2.2% (1/46) with 95% CI: 0.1%, 11.5%.
A total of 9 stent fractures were reported for the RCT Eluvia subjects, 4 fractures for the LL subjects and 1 fracture for PK subjects. One fracture was reported for Zilver PTX subjects of the RCT substudy.
A total of 172 RCT subjects had evaluable diagnostic 60-month imaging with 59 subject imaging studies presenting with a halo. Of these, 40 subjects in the treatment group (Eluvia) and 19 in the control group (Zilver PTX) had a halo present, with no statistically significant differences between the groups (p-value =0.3264.
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| Final Effect Findings |
The primary patency rate at 60 months was 53.6% (98/183) in the Eluvia treatment group and 57.7% (60/104) in the Zilver PTX control group. Assisted primary patency showed a 60-month patency rate of 91.2% (125/137) in the Eluvia treatment group and 94.1% (80/85) in the Zilver PTX control group, p=0.4333.
The primary patency and primary assisted patency rate at 60 months in the LL substudy were 35.5% (11/31) and 73.7% (14/19), respectively.
At the 60-month, 79.7% (145/182) RCT Eluvia subjects and 83.9% (78/93) of Zilver PTX subjects presented with Rutherford Category 0 or I (asymptomatic or had very mild symptoms).
At 60 months primary sustained clinical improvement was achieved in 66.5% (121/182) and 65.6% (61/93) in RCT Eluvia and Zilver PTX subjects, respectively with no statistically significant difference between the two subgroups, p=0.8824. Secondary sustained clinical improvement was achieved in 87.4% (159/182) and 93.5% (87/93) in RCT Eluvia and Zilver PTX subjects, respectively, p= 0.1114.
At the 60-month, 77.3% (17/22) of LL subjects presented with Rutherford Category 0 or I (asymptomatic or had very mild symptoms).
At 60 months primary sustained clinical improvement was achieved in 59.1% (13/22) of LL subjects. When considering subjects with repeat TLR, secondary sustained clinical improvement was achieved by 77.3% (17/22) of subjects.
For ankle brachial index (ABI) assessment at 60 months, hemodynamics improvement was achieved by
52.6% (100/190) of RCT Eluvia subjects and 46.6% (48/103) of Zilver PTX subjects, p= 0.3243.
For ABI assessment at 60 months, hemodynamic improvement was achieved by 37.5% (12/32) of LL subjects.
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| Study Strengths & Weaknesses |
The Imperial trial included a randomized control substudy that compared performance of the Eluvia drug eluting stent system with the Zilver PTX stent system and therefore had inherent properties of an RCT. However, the continued follow-up results were not evaluated with formal hypothesis testing.
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| Recommendations for Labeling Changes |
Labeling change is recommended to reflect the long-term results of the continued 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.
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