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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P180011 / PAS002 |
| Date Original Protocol Accepted |
09/18/2018
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| Date Current Protocol Accepted |
09/21/2023
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| Study Name |
REGAL and EMINENT Long Term f/u studies
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| Device Name |
Eluvia Drug-Eluting Vascular Stent System
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| Clinical Trial Number(s) |
NCT02574481
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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 |
Transit.Adolescent A (distinctively):18 yrs<22 yrs,
Transit.Adolescent B(as adults): 18 yrs < 22 yrs,
Adult: At least 22 yrs
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| Detailed Study Protocol Parameters |
| Study Objectives |
To confirm the effectiveness of the ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions up to 210 mm in length when compared against bare metal stents, and collect additional data including health economics data. This is a European Study. A prospective, multi-center, randomized 2:1 (ELUVIA vs Self-Expanding Bare Nitinol Stents), controlled, single-blind, superiority trial (RCT). Randomization will be stratified to ensure equal distribution of ELUVIA and Self-Expanding Bare Nitinol Stents in different lesion length subsets.
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| Study Population |
All comers; Eluvia DES only
EMINENT: Subjects presenting with lesions 30-210 mm long located in the femoropopliteal arteries with symptoms classified as Rutherford categories 2-4. Eluvia DES vs Bare metal Nitinol treated groups
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| Sample Size |
500 patients
EMINENT: - Up to 75 study centers in up to 15 European countries may enroll subjects. 750 subjects including 500 ELUVIA subjects and 250 Control subjects treated with Self-Expanding Bare Nitinol Stents.
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| Key Study Endpoints |
Health economics, technical/procedural success, MAEs, primary patency, CD-TLR
EMINENT: Primary Effectiveness - Primary patency at 12 months post-procedure; defined as a binary endpoint and will be determined to be a success when the duplex ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) is = 2.4 at 12- months Secondary Endpoints: - Walking Improvement at 12 months assessed by change in Six Minute Hall Walk (6MHW) / treadmill test from baseline, or preceding any Target Vessel Revascularization -Quality of Life Improvement at 12 months assessed by change in EQ-5D-5L from baseline, or preceding any target vessel revascularization -Major Adverse Event (MAE) rate (and individual components) at each time point, defined as all causes of death, target limb major amputation and/or Target Lesion Revascularization (TLR) -Primary Patency and Assisted Primary Patency at 6 months, 12 months, 24 months and 36 months using different DUS PSVRs -Clinically-driven Target Lesion Revascularization (TLR) and clinically-driven Target Vessel Revascularization (TVR) Rate at each time point - Adverse Event Rates (unanticipated, major, serious, device/procedure-related) at each time point
- Number of Stent Fractures reported at 12 months and 24 months utilizing VIVA definitions
- Distribution of Rutherford Class during follow-up as compared to baseline at 1 month, 6 months, 12 months, 24 months and 36 months -Walking Improvement at 1 month, 6 months, 12 months, 24 months and 36 months assessed by change in Walking Impairment Questionnaire (WIQ) from baseline -Quality of Life Improvement at 1 month, 6 months, 24 months and 36 months assessed by change in EQ-5D-5L™ from baseline -Rate of Primary and Secondary Sustained Clinical Improvement as assessed by changes in Rutherford Classification from baseline at 1 month, 6 months, 24 months and 36 months -Rate of Hemodynamic Improvement as assessed by changes in Ankle-Brachial Index (ABI) from baseline at 1 month, 6 months, 24 months and 36 months
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| Follow-up Visits and Length of Follow-up |
24 months
EMINENT: 6-, 12-, 24-, 36 post index procedure. Subjects will be evaluated at 1 (30 days -7 days to + 14 days) month if visit is local standard of care or if an ELUVIA stent or Self Expanding Bare Nitinol stent was not successfully implanted during the Index Procedure.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
REGAL Study
A total of two hundred and ninety-one (291) patients were enrolled.
EMINENT Study
775 subjects were enrolled of which 765 received treatment with either investigational device or control device, Eluvia (N=508 subjects) and Control (N=267 subjects) i.e., 2:1 randomization.
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| Actual Number of Sites Enrolled |
REGAL Study
Twenty-three (23) sites were enrolled in 4 European countries.
EMINENT Study
68 sites were activated in Europe
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| Patient Follow-up Rate |
REGAL Study
82.7% (224/271) at 1 year and 80.2% (211/263) at 2 years
EMINENT Study
Of the 775 enrolled study subjects:
702 (96.8%) subjects completed the 12-month follow-up visit
649 (94.1%) subjects completed the 24-month follow-up visit
624 (96.6%) subjects completed the 36-month follow-up visit.
36- month duplex ultrasound follow-up compliance was 75.8% (547/722) overall, 73.8% (347/470) for Eluvia group and 79.4% (200/252) for Control group.
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| Final Safety Findings |
REGAL Study
Major adverse events (defined as all cause death, major amputation, and target lesion revascularization) rate at 12 months and 24 months post index procedure was 22.5% (63/280) and 27.0% (72/267), respectively.
Clinically driven target lesion revascularization (CD-TLR) rate at 12 months and 24 months post index procedure was 8.6% (24/280) and 10.9% (29/267) respectively.
Clinically driven target vessel revascularization (CD-TVR) rate at 12 months and 24 months post index procedure was 10.4% (29/280) and 13.1% (35/267) respectively.
Amputation rate at 12months and 24 months post index procedure was 8.6% (24/280) and 9.7% (26/267), respectively.
All deaths rate at 12 months and 24 months post index procedure was 8.2% (23/280) and 10.5% (28/267) respectively.
Stent thrombosis rate at 12 months and 24 months post index procedure was 7.1% (20/280) and
9.7% (26/267) respectively.
EMINENT Study
CEC adjudicated events through 36 months are as following:
TLR rate in Eluvia subjects was 22.1% (100/452) and 20.7% (53/256) in Control subjects, p=0.6590.
TVR rate in Eluvia subjects was 23.7% (107/452) and 21.9% (56/256) in Control group, p=0.5851.
Amputation rate in Eluvia subjects was 1.1% (5/452) and 0.8% (2/256) in control subjects, p=1.0000
Stent thrombosis rate in Eluvia subjects was 11.9% (54/452) and 6.3% (16/256) in Control subjects, p=0.0147.
Major Adverse Events
Major Adverse Events (All cause death, Target limb major amputation, and TLR) through 36-month: MAE rate at 36-months for Eluvia subjects was 30.2% (136/451)] and control subjects was 26.3% (67/255), p=0.2738.
All-cause death rate at 36 months for Eluvia subjects was 8.4% (38/451) and Control subjects was 5.9% (15/255), p=0.2180.
A total of 73 deaths were reported. Of the 73 deaths, forty-two (42; 57.5%) were adjudicated as non-cardiovascular, twenty-six (26; 35.6%) events were adjudicated as cardiac, and five (5; 6.8%) events were adjudicated as vascular.
Stent Fractures
In total 13 stents were examined for Eluvia subjects and 7 stents were examined for control subjects. One (1) stent fracture was identified for Eluvia subjects and 2 stent fractures were identified for control subjects as assessed by the independent core laboratory.
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| Final Effect Findings |
REGAL Study
Primary Patency rate at 12 months and 24 months post index procedure was 79.2% (114/144) and
65.5% (72/110) respectively.
Assisted Primary Patency rate at 12 months and 24 months post index procedure was 92.8% (116/125) and 88.2% (75/85) respectively.
Primary Sustained Clinical Improvement rate at 12 months and 24 months post index procedure as assessed by changes in Rutherford Classification from baseline was 83.5% (187/224) and 81.7% (165/202) respectively
Secondary Clinical Improvement rate at 12 months and 24 months post index procedure as assessed by changes in Rutherford Classification from baseline was 90.6% (203/224) and respectively 91.6% (185/202) respectively.
At 12 months and 24 months post index procedure, 80.9% (182/225) and 83.3% (169/203) of patients were asymptomatic or had mild claudication, respectively.
Hemodynamic Improvement at 12 months and 24 months post index procedure as assessed by changes in Ankle-Brachial Index (ABI) from baseline without the need for TLR was 80.1% (137/171) and
76.1% (102/134) respectively.
Hemodynamic Improvement at 12 months and 24 months post index procedure as assessed by changes in Ankle-Brachial Index (ABI) from baseline including TLR was 85.4% (146/171) and 85.1% (114/134) respectively.
Significantly positive results were observed at the time points 1 month through 24 months in each of the three components (p-value<0.0001) of the Walking Impairment Questionnaire (distance, speed and stair climbing).
EMINENT Study
Primary and Assisted Primary Patency
Primary patency rate at 12 months post index procedure was 83.2% in the treatment group (Eluvia) and 74.3% in the control group (BMS), binary rate difference of 8.9%, superiority p-value = 0.0077.
Primary patency rate at 24 months post index procedure was 73.4% in the treatment group (Eluvia) and 71.8% in the control group (BMS).
Primary patency rate at 36 months post index procedure was 62.7.% in the treatment group (Eluvia) and 66.7% in the control group (BMS).
Assisted primary patency at 36-months is 87.7% in the treatment group (Eluvia) and 89.8% in the control group (BMS).
Quality of Life Questionnaire: Walking Impairment Questionnaire (WIQ)
The WIQ was administered to enrolled subjects at baseline and at 1-month, 6-month, 12-month, 24-month, and 36-month follow-up visits post index procedure.
Walking impairment improved significantly as assessed with WIQ through 36 months for both Eluvia and control subjects when compared to baseline measurements, p<0.0001 at each time point.
Quality of Life Questionnaire: EQ-5D
The EQ-5D Questionnaire was administered to enrolled subjects at baseline and at the 1-month, 6-month, 12-month, 24-month, and 36-month follow-up visits post index procedure.
The EQ-5D Index Value increased from 0.7 at baseline to 0.8 at 36-months in the treatment group (Eluvia). The EQ VAS score changed from 64.5 at baseline to 71.5 at 36-months in Eluvia subjects.
In the control subjects (BMS) the EQ-5D Index Value increased from 0.7 at baseline to 0.8 at 36-months. The EQ VAS score increased from 66.2 at baseline to 71.4 at 36-months in control subjects.
Quality-of-Life improvement: there were no statistically significant differences between Eluvia and control subjects in quality-of-life improvement over 36 months.
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| Study Strengths & Weaknesses |
REGAL Study
This was an all-comer, multicenter study in which patients were followed according to standard of care practice. The sample size was not hypothesis driven and study endpoint results were not evaluated by formal hypothesis testing. The study faced enrollment challenges and patient enrollment had to be terminated earlier than planned while all enrolled patients continued through 2 years of follow-up.
EMINENT Study
This was a randomized, multicenter study that met the primary endpoint of primary patency a 12- months post index procedure.
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| Recommendations for Labeling Changes |
REGAL Study
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 study objective, design, patient population, data source, sample size including number of sites, endpoints, length of follow-up and frequency of follow-up, final results (final endpoint results, follow-up rate etc.), strengths and limitations of the surveillance project.
EMINENT Study
Labeling updates is recommended with the final study results to include:
Long-term patency including K-M curves; and
MAEs and their components including K-M curves.
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