LIFE-BTK Randomized Controlled Trial (LIFE-BTK)

LIFE-BTK (pivotaL Investigation of saFety and Efficacy of BRS Treatment-Below The Knee) Randomized Controlled Trial

The objective of this prospective, single-blinded, randomized controlled clinical investigation is to evaluate the safety and efficacy of the everolimus eluting Esprit BTK System for the planned treatment of narrowed infrapopliteal lesions. Approximately 225 subjects will be randomized in a 2:1 ratio. The clinical investigation will be conducted at approximately 65 clinical sites in the US, Asia, Australia, and New Zealand.

Study Overview

• Status: Active, not recruiting
• Conditions: Critical Limb Ischemia (CLI)
• Intervention / Treatment: Device: Esprit BTK Device; Device: Percutaneous Transluminal Angioplasty (PTA) Device

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Private Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• Singapore
  • Singapore, Singapore, 529889
    • Changi General Hospital
• Taiwan
  • Zhongzheng
    • Taipei City, Zhongzheng, Taiwan, 100
      • National Taiwan University Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85233
      • Comprehensive Integrated Care
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Heart Hospital
  • California
    • Deer Park, California, United States, 94574
      • St. Helena Hospital
    • Fremont, California, United States, 94538
      • Mission Cardiovascular Research Institute
    • Fresno, California, United States, 93701
      • UCSF Fresno
    • Orange, California, United States, 92868
      • St. Joseph Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Florida
    • Bradenton, Florida, United States, 34208
      • Manatee Memorial Hospital
    • Jacksonville, Florida, United States, 32218
      • First Coast Cardiovascular Institute
    • Miami Beach, Florida, United States, 33140
      • Palm Vascular Centers
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Via Christi Regional Medical Center - St. Francis Campus
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • Cardiovascular Institute of the South
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center
    • South Dartmouth, Massachusetts, United States, 02720
      • Charlton Memorial Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Jackson Heart Clinic
  • New Jersey
    • Browns Mills, New Jersey, United States, 08015
      • Deborah Heart & Lung Center
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Pomona, New Jersey, United States, 08240
      • Vascular Institute of Atlantic Medical Imaging
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • Bronx, New York, United States, 10468
      • James J. Peters VA Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10032
      • New York-Presbyterian/Columbia University Medical Center
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital/Cornell University
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • NC Heart & Vascular Research
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • The Lindner Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Oklahoma
    • Bartlesville, Oklahoma, United States, 74006
      • Ascension St. John Jane Phillips
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19096
      • Lankenau Institute for Medical Research
    • Erie, Pennsylvania, United States, 16502
      • Saint Vincent Consultants in Cardiovascular Diseases
    • Wormleysburg, Pennsylvania, United States, 17043
      • Pinnacle Health System
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont CVA Heart Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center at Dallas
    • Fort Worth, Texas, United States, 76104
      • Baylor All Saints Medical Center at Fort Worth
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center at Lubbock
    • San Antonio, Texas, United States, 78221
      • San Antonio Vascular and Endovascular Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

General Inclusion Criteria:

1. Subject must provide written informed consent prior to any clinical investigation related procedure.
2. Subject has symptomatic Critical Limb Ischemia (CLI), Rutherford Becker Clinical Category 4 or 5.
3. Subject requires primary treatment of up to two de novo or restenotic (treated with prior PTA) infrapopliteal lesions.
4. Subject must be at least 18 years of age.
5. Female subject of childbearing potential should not be pregnant and must be on birth control.

Note: Female subjects of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure per site standard test.

Anatomic Inclusion Criteria:

1. Up to two native infrapopliteal lesions, each lesion located in separate infrapopliteal vessel in the same limb. Restenotic (from prior PTA) lesions are allowed.

   1. Lesion must be located in the proximal 2/3 of native infrapopliteal vessels, with vessel diameter of ≥ 2.5 mm and ≤ 4.00 mm by investigator visual assessment.
   2. Total scaffold length to completely cover/treat a target lesion must not exceed 170 mm (total everolimus drug dose of 1790 µg).
   3. The total scaffold length among all target lesions must not exceed 170 mm.
   4. The target vessel cannot have any other angiographic significant lesions (≥50%).
   5. Tandem lesions are allowed if they are < 3 cm apart and the total scaffold length used to cover the entire diseased segment is ≤ 170 mm. Each tandem lesion is considered one lesion.
2. Target lesion(s) must have ≥ 70% stenosis, per visual assessment at the time of the procedure. If needed, quantitative imaging (angiography, IVUS, and/or OCT) can be used to aid accurate sizing of the vessels.
3. The distal margin of the target lesion must be located ≥ 10 cm proximal to the proximal margin of the ankle mortise. The vessel segment distal to the target lesion must be patent all the way to the ankle, with no significant lesion (≥ 50% stenosis).
4. Significant lesion (≥ 50% stenosis) in the inflow artery(ies) must be treated successfully (as per physician's assessment of the angiography) through standard of care prior to the treatment of the target lesion. Treatment can be done within the same trial procedure.
5. Non-target lesion(s) (if applicable) must be located in separate infrapopliteal vessel(s) from the target lesion, and suitable to be treated per institution standard of care.
6. Guidewire must cross the target lesion successfully. Crossing in an antegrade fashion is preferred, but retrograde crossing may be used. However, the treatment must be delivered antegrade.

Exclusion Criteria:

General Exclusion Criteria:

1. Subject is currently participating in another clinical investigation that has not yet completed its primary endpoint.
2. Pregnant or nursing subjects and those who plan pregnancy during the clinical investigation follow-up period.
3. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements.
4. Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, or individuals without legal authority, are excluded from the study population.
5. Subject has had any amputation to the ipsilateral extremity other than the toe or forefoot, or subject has had major amputation to the contralateral extremity < 1 year prior to index procedure and is not independently ambulating.
6. Subject has known hypersensitivity or contraindication to device material and its degradants (everolimus, poly (L-lactide), poly (DL-lactide), lactide, lactic acid) and cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoro polymers that cannot be adequately pre-medicated. Subject has a known contrast sensitivity that cannot be adequately pre-medicated.
7. Subject has known allergic reaction, hypersensitivity or contraindication to aspirin; or to ADP antagonists such clopidogrel, prasugrel or ticagrelor; or to anticoagulants such as heparin or bivalirudin, and therefore cannot be adequately treated with study medications. Subject with planned surgery or procedure necessitating discontinuation of antiplatelet medications, within 12 months after index procedure. Planned amputation that will necessitate discontinuation of antiplatelet medications is allowed.
8. Subject has life expectancy ≤ 1 year.
9. Subject has had a stroke within the previous 3 months with residual Rankin score of ≥ 2.
10. Subject has renal insufficiency as defined as an estimated GFR < 30 ml/min per 1.73m^2.
11. Subject is currently on dialysis.
12. Subject has platelet count < 100,000 cells/mm^3 or > 700,000 cells/mm^3, a WBC < 3,000 cells/mm^3, or hemoglobin < 9.0 g/dl.
13. Subject has known serious immunosuppressive disease (e.g., human immunodeficiency virus), or has severe autoimmune disease, that requires chronic immunosuppressive therapy (e.g., systemic lupus erythematosus, etc.), or subject is receiving immunosuppression therapy for other conditions. Subjects treated for HIV (Human Immunodeficiency Virus) and who have undetectable viral load, such that their immune system is not considered compromised, are eligible.
14. Subject has Body Mass Index (BMI) <18.
15. Subject is receiving or scheduled to receive anticancer therapy for malignancy within 6 months prior to index procedure or within 1 year after the procedure. Patients taking medications classified as chemotherapy but who have been in remission for at least 6 months are eligible.
16. Subject has coagulation disorder that increases the risk of arterial thrombosis. Subjects with deep vein thrombosis and disorders that increase the risk of deep vein thrombosis can be included in the study.
17. Subject who requires thrombolysis as a primary treatment modality or requires other treatment for acute limb ischemia of the target limb.
18. Subject has previously had, or requires surgical revascularization involving any vessel of the ipsilateral extremity. Prior femoropopliteal or aortobifemoral bypass is allowed. Any bypass to the tibial arteries is not allowed.
19. Subject has signs or symptoms of advanced limb infection or septicemia (fever > 38.5, WBC > 15,000 cells/microliter, hypotension) at the time of assessment. Osteomyelitis of the phalanges or metatarsal heads (as described in exclusion criteria #21a) or cellulitis of the foot amenable to treatment with IV antibiotics at the time of revascularization is acceptable.
20. Subject is bedridden or unable to walk (with assistance is acceptable). Subjects in wheelchair who are able to mobilize on their own can be enrolled.

21. Subject with extensive tissue loss salvageable only with complex foot reconstruction or non-traditional transmetatarsal amputations. This includes subjects with:

    1. Osteomyelitis that extends proximal to the metatarsal heads. Osteomyelitis limited to the phalanges or metatarsal heads is acceptable for enrollment.
    2. Gangrene involving the plantar skin of the forefoot, midfoot, or heel.
    3. Deep ulcer or large shallow ulcer (> 3 cm) involving the plantar skin of the forefoot, midfoot, or heel.
    4. Full thickness heel ulcer with/without calcaneal involvement.
    5. Any wound with calcaneal bone involvement.
    6. Wounds that are deemed to be neuropathic or non-ischemic in nature.
    7. Wounds that would require flap coverage or complex wound management for large soft tissue defect.
    8. Full thickness wounds on the dorsum of the foot with exposed tendon or bone.
22. Subject is unable or unwilling to provide written consent prior to enrollment.
23. Subject has active symptoms and/or a positive test result of COVID-19 or other rapidly spreading novel infectious agent within the prior 2 months.

Anatomic Exclusion Criteria:

1. Lesions with severe calcification, in which there is a high likelihood that successful pre-dilatation cannot be achieved.
2. Lesion that has prior metallic stent implant.
3. Significant (≥ 50% stenosis) lesion in a distal outflow artery that would be perfused by the target vessel and that requires treatment at the time of the index procedure.
4. Subject has had or will require treatment in any vessel with an everolimus drug-coated or drug-eluting device < 30 days pre-study procedure, or during the index procedure, such that the cumulative (Esprit BTK plus everolimus-eluting device) everolimus drug dose exceeds 1790 μg.
5. Target or (if applicable) non-target vessel contains visible thrombus as indicated in the angiographic images.
6. Subject has angiographic evidence of thromboembolism or atheroembolism in the ipsilateral extremity. (Pre- and post-angiographic imaging must confirm the absence of emboli in the distal anatomy).
7. Unsuccessfully treated proximal inflow limiting arterial stenosis or inflow-limiting arterial lesions left untreated.
8. No angiographic evidence of a patent pedal artery.
9. Target or (if applicable) non-target lesion location requiring bifurcation treatment method that requires scaffolding of both branches (provisional treatment, without intention of scaffolding both branches is acceptable).
10. Aneurysm in the iliac, common femoral, superficial femoral, popliteal or target artery of the ipsilateral extremity.
11. Visual assessment of the target lesion suggests that the investigator is unable to pre-dilate the lesion according to the vessel diameter.
12. Target lesion has a high probability that atherectomy will be required at the time of index procedure for treatment of the target vessel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esprit BTK; Participants who receives Esprit BTK device will be included in this arm	Device: Esprit BTK Device; Participants will receive Esprit BTK Device
Active Comparator: Percutaneous Transluminal Angioplasty (PTA); Participants who receives PTA treatment will be included in this arm	Device: Percutaneous Transluminal Angioplasty (PTA) Device; Participants will receive PTA treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Endpoint: Composite of Limb Salvage and Primary Patency	Composite of Limb Salvage and Primary Patency includes freedom from: above ankle amputation in index limb, 100% total occlusion of target vessel, binary restenosis of target lesion and clinically-driven target lesion revascularization (CD-TLR).	At 1 year
Primary Safety Endpoint: Freedom from MALE+POD (Major Adverse Limb Event + Peri-Operative Death)	MALE includes above ankle amputation in index limb, major re-intervention on index limb at 6 months and POD includes perioperative (30-day) mortality.	At 30 days (for POD) and 6 months (for MALE)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Powered Secondary Endpoint: Binary restenosis of the target lesion	Includes better evaluation of the device as binary restenosis can be used as a marker for disease progression over time.	At 1 year
Powered Secondary Endpoint: Composite endpoint	Includes freedom from: above ankle amputation in index limb, 100% total occlusion of target vessel and clinically-driven target lesion revascularization (CD-TLR) at 1 year.	At 1 year

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Investigators: Principal Investigator: Ramon L Varcoe, MBBS, MS, FRACS, PhD, Prince of Wales Private Hospital, Randwick, NSW, Australia; Principal Investigator: Sahil Parikh, MD, FACC, FSCAI, New York Presbyterian Hospital, New York, NY; Principal Investigator: Brian DeRubertis, MD, FACS, NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): August 17, 2023
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Infrapopliteal lesions; Esprit BTK Everolimus Eluting Bioresorbable Scaffold System; Percutaneous transluminal angioplasty (PTA); ABT-CIP-10293
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Atherosclerosis; Peripheral Vascular Diseases; Chronic Disease; Peripheral Arterial Disease; Ischemia; Chronic Limb-Threatening Ischemia
• Other Study ID Numbers: ABT-CIP-10293

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes