Clinical trial NCT04227899: LIFE-BTK Randomized Controlled Trial
Official title: LIFE-BTK (pivotaL Investigation of saFety and Efficacy of BRS Treatment-Below The Knee) Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Critical Limb Ischemia (CLI)
Keywords: Infrapopliteal lesions
Esprit BTK Everolimus Eluting Bioresorbable Scaffold System
Percutaneous transluminal angioplasty (PTA)
ABT-CIP-10293
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2020-01-14
Enrollment: 261
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Primary Efficacy Endpoint: Number of Participants With Composite of Limb Salvage and Primary Patency
timeFrame: At 1 year
measure: Primary Safety Endpoint: Freedom From Major Adverse Limb Event + Peri-Operative Death Rate (MALE + POD)
timeFrame: At 30 days (for POD) and 6 months (for MALE)
Secondary outcomes:
measure: First Powered Secondary Endpoint: Binary Restenosis of the Target Lesion
timeFrame: At 1 year
measure: Second Powered Secondary Endpoint: Freedom From Above Ankle Amputation in Index Limb, 100% Total Occlusion of the Target Vessel, and CD-TLR.
timeFrame: At 1 year
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Comprehensive Integrated Care
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: Deer Park
country: United States
facility: St. Helena Hospital
state: California
city: Fremont
country: United States
facility: Mission Cardiovascular Research Institute
state: California
city: Fresno
country: United States
facility: UCSF Fresno
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Bradenton
country: United States
facility: Manatee Memorial Hospital
state: Florida
city: Jacksonville
country: United States
facility: First Coast Cardiovascular Institute
state: Florida
city: Miami Beach
country: United States
facility: Palm Vascular Centers
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: West Des Moines
country: United States
facility: The Iowa Clinic
state: Iowa
city: Wichita
country: United States
facility: Via Christi Regional Medical Center - St. Francis Campus
state: Kansas
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: Boston
country: United States
facility: St. Elizabeth's Medical Center
state: Massachusetts
city: South Dartmouth
country: United States
facility: Charlton Memorial Hospital
state: Massachusetts
city: Jackson
country: United States
facility: Jackson Heart Clinic
state: Mississippi
city: Browns Mills
country: United States
facility: Deborah Heart & Lung Center
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Pomona
country: United States
facility: Vascular Institute of Atlantic Medical Imaging
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Bronx
country: United States
facility: James J. Peters VA Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: New York-Presbyterian/Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Cornell University
state: New York
city: Raleigh
country: United States
facility: NC Heart & Vascular Research
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Bartlesville
country: United States
facility: Ascension St. John Jane Phillips
state: Oklahoma
city: Bryn Mawr
country: United States
facility: Lankenau Institute for Medical Research
state: Pennsylvania
city: Erie
country: United States
facility: Saint Vincent Consultants in Cardiovascular Diseases
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health System
state: Pennsylvania
city: Anderson
country: United States
facility: Anmed Health
state: South Carolina
city: Kingsport
country: United States
facility: Wellmont CVA Heart Institute
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Fort Worth
country: United States
facility: Baylor All Saints Medical Center at Fort Worth
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center at Lubbock
state: Texas
city: San Antonio
country: United States
facility: San Antonio Vascular and Endovascular Clinic
state: Texas
city: Randwick
country: Australia
facility: Prince of Wales Private Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
state: Zhongzheng
Study officials:
affiliation: Prince of Wales Private Hospital, Randwick, NSW, Australia
name: Ramon L Varcoe, MBBS, MS, FRACS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York Presbyterian Hospital, New York, NY
name: Sahil Parikh, MD, FACC, FSCAI
role: PRINCIPAL_INVESTIGATOR
affiliation: NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY
name: Brian DeRubertis, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References: