Clinical trial NCT06330493: AcoArt Litos PCB Below-the-knee Global Trial
Official title: Prospective Multi-Center Randomized Controlled Trial to Evaluate the Safety and Efficacy of AcoArt Litos Paclitaxel Coated Percutaneous Transluminal Angioplasty (PTA) Balloon Versus Non-Coated Standard Balloon Angioplasty for the Treatment of Infrapopliteal Obstructions in Patients With Chronic Limb-Threatening Ischemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Limb-Threatening Ischemia
Lead sponsor: Acotec Scientific Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-03-26
Enrollment: 288
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 study is to assess whether efficacy of the AcoArt Litos PCB is superior and whether safety of AcoArt Litos PCB is noninferior to the control device (FDA cleared PTA Balloon Catheter) regarding treatment of obstructions in the infrapopliteal arteries (located distal to the P3 segment of the popliteal artery and extending to the tibiotalar joint) in patients presenting with chronic limb-threatening ischemia (CLTI)(Rutherford 4-5)


Eligibility criteria: Inclusion Criteria:

- General Inclusion Criteria

1. Age ≥ 18 years at the time of consent;
2. Subjects has been informed of the nature of the study, is willing to comply with all required follow-up evaluations within the defined follow-up visit windows and has signed an Institutional Review Board(IRB)/Ethics Commitee(EC) approved consent form;
3. Female subjects of childbearing potential have a negative pregnancy test ≤ 7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation. Female subjects will be exempted from this requirement in case they are sterile, infertile, or have been post-menopausal for at least 12 months (no menses);
4. Life expectancy \> 1 year in the Investigator's opinion;
5. Subject presenting with documented chronic limb-threatening ischemia(CLTI) in the target limb defined as Rutherford category 4 or 5;
6. In case of Rutherford category 5: Subjects with documented wound score 0-1, infection grade 0-2 and ischemia grade 2-3 according to the wound ischemia foot infection (WIfI) classification;
7. No other prior surgical or vascular interventions within 2 weeks before and/or planned 30 days after the protocol treatment.

   * Angiographic Inclusion Criteria
8. Reference Vessel Diameter(RVD) ≥2.0 and ≤ 4.0mm and able to be treated with available device size matrix;
9. Total occlusion within the target veseel and cumulative lesion length ≤ 140mm;
10. The lesion must be located in the infrapopliteal arteries and above the ankle joint. Lesions may not extend proximal to the P3 segment of the popliteal artery indicated by the tibial plateau or below the tibiotalar joint(arteries of the foot). The treatment(investigational device or PTA, including pre-dilatation) may not extend beyond these indicated regions for more than 1cm;
11. Presence of documented run-off to the foot(clearly visible at least one of the following run-off vessels; dorsalis pedis or pedal arch or plantar arteries by angiography). The target vessels should give direct or indirect run-off to the foot;
12. Absence of flow-limiting(≥ 50% stenosis) in-flow lesions confirmed by angiography. Patients with flow-limiting inflow lesions can be included if the lesion(s) have been treated successfully before enrollment, with a maximum residual restenosis of ≤30% per visual assessment. If an inflow lesion must be treated within or proximal to the P3 segment of the popliteal artery, there must be a minimum of 3 cm healthy vascular segment between this(treated) lesion and the infrapopliteal target lesion;
13. Successful pre-dilatation of the(entire) target lesion. Success being documented by angiographic visual estimate of ≤ 50% residual diameter stenosis of the target lesion and no flow limiting dissection(\< Grade D dissection). Target lesion is not considered non-dilatable by the operator due to concentric, circumferential calcium and target lesion can be treated successfully by balloon angioplasty without the need for bail-out stenting.

Exclusion Criteria:

- General Exclusion Criteria

1. Planned index limb amputation above the metatarsal level, or any other planned major surgery within 30 days pre- or post-procedure. A planed amputation including and below the metatarsal level(1 or multiple rays) is accepted.
2. Recent MI or stroke \< 30 days prior to the index procedure;
3. Known or suspected active infection at the time of the index procedure(abnormal white blood cell count, fever, sepsis, or positive blood culture), with the exception of a localized, controlled infection of a lower extremity wound on the target limb(only WIfI infection grade 0-2 allowed);
4. Subjects with infection grade 3 and ischemia grade 0 and 1 according to WIfI classification;
5. Subjects not independently ambulating.
6. Subjects with neurotrophic ulcers, heel pressure ulcers or calcaneal ulcers with a risk for major amputation; Subjects with uncomplicated ulcers can be included;
7. Subjects with documented active osteomyelitis, excluding the phalanges, that is beyond cortical involvement of the bone per clinical judgement;
8. Subjects with vasculitis, systemic Lupus Erythematosus or polymyalgia rheumatica on active treatment;
9. Subjects with impaired renal function defined as eGFR \<30 ml/min or on dialysis;
10. Patient receiving systemic corticosyeroid therapy(expected dosage exceeding 5 mg of prednisolone or equivalent, per day, during the initial 9 months after procedure);
11. Known allergies or sensitivities to heparin, aspirin(ASA), other anticoagulant/anti-platelet therapies which could not be substitued, and/or paclitaxel or an allergy to contrast media that cannot be adequately pre-treated prior to the index procedure;
12. Subjects currently enrolled in another investigational device, drug, or biological trial;
13. Femal subjects who are breast feeding at the time of enrollment;
14. Significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy;
15. Any severe medical comorbidities(e.g., untreated CAD/CHF, NYHA class IV heart failure, Left Ventricular ejection fraction(LVEF) \</= 30%(obtained within 1 month of index procedure), severe COPD, metastatic malignacy, etc.) that would preclude compliance with the study protocol or currently receiving immune-suppressive, chemotherapeutic, or radiation therapy;

    * Angiographic Exclusion Criteria
16. Occlusions located or extending into the popliteal artery or distal to the ankle joint space;
17. Untreated (≥50% measured by angiography) inflow lesion or occlusion in the ipsilateral iliac, SFA nad popliteal arteries;
18. Failure to obtain a ≤30% residual stenosis in pre-existing, hemodynamically significant(≥50% measured by angiography) in flow lesions in the ipsilateral iliac, SFA and popliteal artery. Inflow lesions should be treated per standard of care;
19. Prior stent(s) or bypass surgery within the target vessel(s) (including stents placed within target vessels during the index procedure prior to randomization);
20. Previous procedure with drug-coated balloons in the target vessels within 6 months prior to index procedure.
21. Aneurysm in the target vessel;
22. Angiographic evidence of thrombus within target limb;
23. Pre-dilatation resulted in a major(≥ Grade D) flow-limiting dissection(observed on 2 orthogonal views) or residual stenosis \>50%;
24. Use of alternative therapy, e.g. atherectomy, scoring balloon, laser, radiation therapy, stents as part of target vessel treatment.

Primary outcomes:
measure: Primary Efficacy Endpoint: Composite of freedom from major amputation and primary patency
timeFrame: 6 months
measure: Primary Safety Endpoint: Composite of MALE and POD (Major Adverse Limb Event + Peri-Operative Death)
timeFrame: 30 days
Secondary outcomes:
measure: Powered Secondary Endpoint: Freedom from clinically driven TLR (CD-TLR) at 12 months
timeFrame: 1, 3, 12, 24 and 36 months
measure: Patency rate
timeFrame: 1, 3, 6, 12, 24, 36 months
measure: Freedom from CD-TLR
timeFrame: 1, 3, 6, 12, 24, 36 months
measure: Re-occlusion rate of target lesion
timeFrame: 1, 3, 6, 12, 24, 36 months
measure: Rate of Major adverse events(MAE)
timeFrame: 1, 3, 6, 12, 24, 36 months
measure: Rate of target limb major amputation
timeFrame: 1, 3, 6, 12, 24, 36, 48, 60 months
measure: Rate of all-cause death
timeFrame: 1, 3, 6, 12, 24, 36, 48, 60 months
measure: Amputation free survival rate
timeFrame: 1, 3, 6, 12, 24, 36, 48, 60 months
measure: Change in ankle-brachial index(ABI)
timeFrame: 1, 3, 6, 12, 24, 36 months
measure: Change in toe-brachial index(TBI)
timeFrame: 1, 3, 6, 12, 24 months
measure: Change in Rutherford category
timeFrame: 1, 3, 6, 12, 24 and 36 months
measure: Change in EQ-5D
timeFrame: 1, 3, 6, 12, 24 and 36 months
measure: Change in VascuQol
timeFrame: 1, 3, 6, 12, 24 and 36 months
measure: Primary sustained clinical improvement
timeFrame: 1 year
measure: Secondary sustained clinical improvement
timeFrame: 1 year
measure: Wound healing
timeFrame: 1, 3, 6, 12, 24 and 36 months
measure: Rate of Device Success
timeFrame: During the procedure(After using the PCB catheter)
measure: Rate of Technical Success
timeFrame: During the procedure(After using the PCB catheter)
measure: Rate of Procedure Success
timeFrame: within 72 hours of the index procedure
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Miami Vascular Center
state: Florida
city: Jacksonville
country: United States
facility: First Coast Cardiovascular Institute
state: Florida
city: Davenport
country: United States
facility: Midwest Cardiovascular Research Foundation
state: Iowa
city: New York
country: United States
facility: Columbia University/NYPH
state: New York
city: Charlotte
country: United States
facility: South Charlotte General & Vascular Surgery
state: North Carolina
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Clements University Hospital (UTSW)
state: Texas
city: Danville
country: United States
facility: Sunrise Vascular
state: Virginia
city: Graz
country: Austria
facility: Medical University Graz
city: Dendermonde
country: Belgium
facility: AZ Sint Blasius Hospital
Study officials:
affiliation: University of California, San Francisco
name: Peter Schneider, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Sahil Parikh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Herzzentrum Freiburg
name: Thomas Zeller, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: