Overview

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

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 length of target lesion (including significant stenosis 70~99% or occlusion) ≤ 190mm;
  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 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.