Clinical trial NCT02574481: ELUVIA™ Drug-eluting Stent Versus Zilver® PTX® Stent
Official title: A Randomized Trial Comparing the ELUVIA™ Drug-eluting Stent Versus Zilver® PTX® Stent for Treatment of Superficial Femoral and/or Proximal Popliteal Arteries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atherosclerosis of Native Arteries of the Extremities
Keywords: atherosclerosis
Superficial Femoral Artery (SFA)
Proximal Popliteal Artery (PPA)
lower extremities
stenting
paclitaxel
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2015-10-14
Enrollment: 524
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions up to 140 mm in length.

Long Lesion Substudy: to evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions \>140 mm and ≤ 190 mm in length.

Detailed description: Atherosclerosis is a systemic disease that has become increasingly recognized in the expanding elderly population as a significant cause of morbidity and mortality. Atherosclerosis in the vessels of the lower extremities can cause a variety of symptoms ranging from intermittent claudication to ischemic rest pain and critical ischemia with major tissue loss. Typically, femoropopliteal lesions have been difficult to successfully treat with endovascular therapy because the disease is often diffuse and located in an area of the body subject to significant mobility stresses such as extension, contraction, compression, elongation, flexion and torsion.

The IMPERIAL trial is a global, prospective, multi-center trial. Approximately 525-535 subjects will be enrolled at up to 75 study centers worldwide. Regions participating include the United States, Canada, European Union, Japan and New Zealand.

The trial consists of a prospective, multicenter, 2:1 randomized (ELUVIA vs Zilver PTX), controlled, single-blind, non-inferiority trial (RCT), a concurrent, non-blinded, non-randomized, single-arm, pharmacokinetic (PK) substudy and a concurrent, non-blinded, non-randomized, Long Lesion substudy.

Eligibility criteria: Inclusion Criteria:

1. Subjects age 18 and older.
2. Subject (or Legal Guardian if applicable) is willing and able to provide consent before any study-specific test or procedure is performed, signs the consent form, and agrees to attend all required follow-up visits. NOTE: For subjects less than 20 years of age enrolled at a Japanese center, the subject's legal representative, as well as the subject, must provide written informed consent.
3. Chronic, symptomatic lower limb ischemia defined as Rutherford categories 2, 3 or 4.
4. Stenotic, restenotic or occlusive lesion(s) located in the native SFA and/or PPA:

   * Degree of stenosis ≥ 70% by visual angiographic assessment
   * Vessel diameter ≥ 4 and ≤ 6 mm
   * Total lesion length (or series of lesions) ≥ 30 mm and ≤ 140 mm (Note: Lesion segment(s) must be fully covered with one ELUVIA stent or up to two Zilver PTX stents)
   * Long Lesion Substudy: Total lesion length (or series of lesions) \>140 mm and ≤ 190 mm (Note: Lesion segment(s) will require overlapping of two ELUVIA stents).
   * For occlusive lesions requiring use of re-entry device, lesion length ≤ 120 mm
   * Long Lesion Substudy: For occlusive lesions requiring use of re-entry device, lesion length \> 120 mm and ≤ 170 mm
   * Target lesion located at least three centimeters above the inferior edge of the femur
5. Patent infrapopliteal and popliteal artery, i.e., single vessel runoff or better with at least one of three vessels patent (\<50% stenosis) to the ankle or foot with no planned intervention.

Exclusion Criteria:

1. Previously stented target lesion/vessel.
2. Target lesion/vessel previously treated with drug-coated balloon \<12 months prior to randomization/enrollment.
3. Subjects who have undergone prior surgery of the SFA/PPA in the target limb to treat atherosclerotic disease.
4. Use of atherectomy, laser or other debulking devices in the target limb SFA/PPA during the index procedure.
5. History of major amputation in the target limb.
6. Documented life expectancy less than 24 months due to other medical co-morbid condition(s) that could limit the subject's ability to participate in the clinical trial, limit the subject's compliance with the follow-up requirements, or impact the scientific integrity of the clinical trial.
7. Known hypersensitivity or contraindication to contrast dye that, in the opinion of the investigator, cannot be adequately pre-medicated.
8. Known hypersensitivity/allergy to the investigational stent system or protocol related therapies (e.g., nitinol, paclitaxel, or structurally related compounds, polymer or individual components, and antiplatelet, anticoagulant, thrombolytic medications).
9. Platelet count \<80,000 mm3 or \>600,000 mm3 or history of bleeding diathesis.
10. Concomitant renal failure with a serum creatinine \>2.0 mg/dL.
11. Receiving dialysis or immunosuppressant therapy.
12. History of myocardial infarction (MI) or stroke/cerebrovascular accident (CVA) within 6 months prior to randomization/enrollment.
13. Unstable angina pectoris at the time of randomization/enrollment.
14. Pregnant, breast feeding, or plan to become pregnant in the next 5 years.
15. Current participation in another investigational drug or device clinical study that has not completed the primary endpoint at the time of randomization/enrollment or that clinically interferes with the current study endpoints (Note: studies requiring extended follow-up for products that were investigational, but have become commercially available since then are not considered investigational studies).
16. Septicemia at the time of randomization/enrollment.
17. Presence of other hemodynamically significant outflow lesions in the target limb requiring intervention within 30 days of randomization/enrollment.
18. Presence of aneurysm in the target vessel.
19. Acute ischemia and/or acute thrombosis of the SFA/PPA prior to randomization/enrollment.
20. Perforated vessel as evidenced by extravasation of contrast media prior to randomization/enrollment.
21. Heavily calcified lesions.

Primary outcomes:
measure: Percentage of Participants With Major Adverse Events (MAEs)
timeFrame: 12 Months
measure: Number of Participants Reaching Primary Patency
timeFrame: 12 Months
Secondary outcomes:
measure: Number of CEC-adjudicated Events Through 12 Months
timeFrame: 12 Months
measure: Count of Participants Meeting Primary Sustained Clinical Improvement
timeFrame: 12 Months
measure: Number of Participants With Hemodynamic Improvement
timeFrame: 12 Months
measure: Walking Impairment Questionnaire (WIQ) Scores
timeFrame: Baseline to 12 Months
measure: 6-Minute Walk Test - Distance Walked
timeFrame: Change in baseline to 12-Months
measure: 6-Minute Walk Test - Speed
timeFrame: Baseline to 12 months
Other outcomes:
measure: Freedom From Major Adverse Events
timeFrame: Through 60 Months
measure: Clinical Events Committee Adjudicated Clinically-Driven Target Lesion Revascularization Rate
timeFrame: Through 60 Months
measure: Percentage of Participants With Target Limb Major Amputation
timeFrame: Through 60 Months
Locations:
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Gainesville
country: United States
facility: Florida Research Network, LLC
state: Florida
city: Jacksonville
country: United States
facility: First Coast Cardiovascular Institute
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: Baptist Cardiac and Vascular Institute
state: Florida
city: Ocala
country: United States
facility: MediQuest Research at Munroe Regional Medical Center
state: Florida
city: Pensacola
country: United States
facility: Baptist Hospital
state: Florida
city: Augusta
country: United States
facility: University Hospital
state: Georgia
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Peoria
country: United States
facility: St. Francis Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: St. Joseph Hospital
state: Indiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Steward St. Elizabeth's Medical Center of Boston, Inc.
state: Massachusetts
city: Petoskey
country: United States
facility: Northern Michigan Hospital
state: Michigan
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Foundation
state: Minnesota
city: Omaha
country: United States
facility: Alegent Creighton Health Bergan Mercy Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Heart Institute, PA
state: New Mexico
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital-Columbia University Medical Center
state: New York
city: Concord
country: United States
facility: Carolinas HealthCare System NorthEast
state: North Carolina
city: Raleigh
country: United States
facility: Rex Hospital
state: North Carolina
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Willoughby
country: United States
facility: LakeWest Hospital/Northeast Ohio Vascular Associates, Inc.
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincents Medical Center
state: Oregon
city: Bryn Mawr
country: United States
facility: Lankenau Institute for Medical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health Cardiovascular Institute
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Heart Hospital of South Dakota
state: South Dakota
city: Chattanooga
country: United States
facility: University Surgical Associates
state: Tennessee
city: Jackson
country: United States
facility: Jackson-Madison County General Hospital
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas Research Institute, LLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Health Presbyterian Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Wausau
country: United States
facility: Aspirus Heart and Vascular Institute - Research and Education
state: Wisconsin
city: Graz
country: Austria
facility: Medical University Graz, Department of Radiology
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus AKH
city: Vienna
country: Austria
facility: Hanusch Hospital
city: Genk
country: Belgium
facility: Ziekenhuis oost Limburg
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Tienen
country: Belgium
facility: Regionaal Ziekenhuis Heilig Hart Tienen
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Sherbrooke
country: Canada
facility: Fleurimont Hospital
state: Quebec
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Bad Krozingen
city: Berlin
country: Germany
facility: Center for Diagnostic Radiology and Minimally Invasive Therapy at The Jewish Hospital Berlin
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln
city: Flensburg
country: Germany
facility: Ev. Luth. Diakonissenanstalt Flensburg
city: Leipzig
country: Germany
facility: Universität Leipzig
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Amagasaki
country: Japan
facility: Kansai Rosai Hospital
state: Hyogo
city: Kawasaki
country: Japan
facility: Takatsu General Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Saiseikai Yokohama-City Eastern Hospital
state: Kanagawa
city: Kashihara-shi
country: Japan
facility: Nara Medical University Hospital
state: Nara
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Meguro
country: Japan
facility: Toho University Ohashi Medical Center
state: Tokyo
city: Minato
country: Japan
facility: The Jikei University Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Fukuoka Sanno Hospital
city: Osaka
country: Japan
facility: Morinomiya Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Hamilton
country: New Zealand
facility: Clinical Trials NZ
Study officials:
affiliation: Main Line Health
name: William Gray, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ev. Luth. Diakonissenanstalt Flensburg
name: Stefan Müller-Hülsbeck, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iida O, Fujihara M, Kawasaki D, Mori S, Yokoi H, Miyamoto A, Kichikawa K, Nakamura M, Ohki T, Diaz-Cartelle J, Muller-Hulsbeck S, Gray WA, Soga Y. 24-Month Efficacy and Safety Results from Japanese Patients in the IMPERIAL Randomized Study of the Eluvia Drug-Eluting Stent and the Zilver PTX Drug-Coated Stent. Cardiovasc Intervent Radiol. 2021 Sep;44(9):1367-1374. doi: 10.1007/s00270-021-02901-6. Epub 2021 Jul 7.
citation: Muller-Hulsbeck S, Benko A, Soga Y, Fujihara M, Iida O, Babaev A, O'Connor D, Zeller T, Dulas DD, Diaz-Cartelle J, Gray WA. Two-Year Efficacy and Safety Results from the IMPERIAL Randomized Study of the Eluvia Polymer-Coated Drug-Eluting Stent and the Zilver PTX Polymer-free Drug-Coated Stent. Cardiovasc Intervent Radiol. 2021 Mar;44(3):368-375. doi: 10.1007/s00270-020-02693-1. Epub 2020 Nov 22.
citation: Golzar J, Soga Y, Babaev A, Iida O, Kawasaki D, Bachinsky W, Park J, Prem JT, Vermassen F, Diaz-Cartelle J, Muller-Hulsbeck S, Gray WA. Effectiveness and Safety of a Paclitaxel-Eluting Stent for Superficial Femoral Artery Lesions up to 190 mm: One-Year Outcomes of the Single-Arm IMPERIAL Long Lesion Substudy of the Eluvia Drug-Eluting Stent. J Endovasc Ther. 2020 Apr;27(2):296-303. doi: 10.1177/1526602820901723. Epub 2020 Jan 28.
citation: Soga Y, Fujihara M, Iida O, Kawasaki D, Hirano K, Yokoi H, Miyamoto A, Kichikawa K, Nakamura M, Ohki T, Diaz-Cartelle J, Gray WA, Muller-Hulsbeck S. Japanese Patients Treated in the IMPERIAL Randomized Trial Comparing Eluvia and Zilver PTX Stents. Cardiovasc Intervent Radiol. 2020 Feb;43(2):215-222. doi: 10.1007/s00270-019-02355-x. Epub 2019 Nov 5.
citation: Gray WA, Keirse K, Soga Y, Benko A, Babaev A, Yokoi Y, Schroeder H, Prem JT, Holden A, Popma J, Jaff MR, Diaz-Cartelle J, Muller-Hulsbeck S; IMPERIAL investigators. A polymer-coated, paclitaxel-eluting stent (Eluvia) versus a polymer-free, paclitaxel-coated stent (Zilver PTX) for endovascular femoropopliteal intervention (IMPERIAL): a randomised, non-inferiority trial. Lancet. 2018 Oct 27;392(10157):1541-1551. doi: 10.1016/S0140-6736(18)32262-1. Epub 2018 Sep 24.