Comparing a new drug-eluting balloon to standard balloon angioplasty for treating severe leg artery disease

Clinical Inclusion Criteria:

1. Subject age is ≥ 18 years or older depending on local regulations.
2. Subject life expectancy is ≥ 1 year.
3. Subject has documented chronic limb-threatening ischemia in the target limb with Rutherford classification category 4 or 5 and symptoms of \> 2 weeks duration.
4. Subject is willing and able to provide written informed consent and comply with study procedures and required follow-up evaluations.
5. Female subjects of childbearing potential must be non-breastfeeding and have a negative pregnancy test ≤ 7 days before the procedure.

Angiographic Inclusion Criteria:

Subjects must meet all the following criteria to be enrolled in the trial:

1. Target lesion(s) must be de novo or non-stented restenotic lesion(s) located within the BTK arteries distal to the tibial plateau and above the tibiotalar joint line. BTK arteries include the P3 segment of the popliteal artery, the tibio-peroneal trunk, peroneal artery, anterior tibial artery, and posterior tibial artery.
2. BTK Target lesions cannot be contiguous with inflow lesions and at least 3 cm of normal artery should extend beyond the tibial plateau to ensure there is no overlap.
3. Target lesions must have a diameter stenosis of ≥ 70% (including total occlusions) by visual estimate and must be indicated for PTA treatment.
4. Target vessel reference diameter(s) are ≥ 2mm and ≤ 4mm. Note: the SELUTION SLR 014 DEB and the control PTA balloon size cannot exceed 4.0 mm.
5. Target lesions must be confined to a single target vessel. NOTE: Subjects with other non-target BTK lesions in separate non-target vessels may be enrolled, provided that the non-target lesions have been successfully treated (residual stenosis ≤ 30% with no distal embolization or flow limiting ≥ Grade C dissection). NOTE: Any adjunctive therapies are permitted for the treatment of non-target BTK lesions, but no DEB or DES may be used.
6. Any target lesion must be ≥ 30 mm in length and the total combined length of all target lesions must be ≤ 140 mm (total treatment length ≤ 150 mm allowing for 5 mm proximal and distal shoulder treatment). Note: All target lesions and all inflow lesions must be treatable by one or more SELUTION SLR 014/018 DEB(s) such that the total planned per-subject drug dose (calculated by summing the drug dose of all individual planned balloon sizes) would be ≤ 7069 μg. Note: A total treated segment length of ≤ 150 mm for BTK and ≤ 200 mm for inflow segment is acceptable irrespective of DEB balloon diameter.
7. The tibial and pedal runoff distal to the target lesions must be patent OR the target vessel(s) must reconstitute above the ankle or display normal terminal branching as follows:

   1. If the target vessel is the P3 segment, any 1 of the 3 distal arteries must show a patent (≤ 50% stenosis by visual estimate) outflow.
   2. If the target vessel is the peroneal artery, the artery must demonstrate normal terminal branching.
   3. If the target vessel is the anterior tibial (AT) or posterior tibial (PT) artery, the artery must reconstitute ≥ 1 cm above the tibiotalar joint to provide an intact runoff vessel (AT: dorsalis pedis; PT: plantar artery).
   4. If the target vessel is the tibio-peroneal trunk, outflow for either the peroneal OR the posterior tibial artery must be patent (≤ 50% stenosis by visual estimate).
8. Subjects is free of significant inflow vessel disease or any inflow disease has been successfully treated (see angiographic inclusion # 9). Significant inflow disease is defined as ≥ 50% stenosis by visual estimate. Inflow vessels include the ipsilateral common iliac, external iliac, common femoral, profunda femoris, superficial femoral or popliteal artery proximal (≥ 3 cm) to the tibial plateau. Note: If access site doesn't permit angiographic imaging of the common iliac and common femoral artery (CFA), then non-invasive imaging (CTA or MRA) must be provided to exclude presence of significant inflow disease. If non-invasive imaging is not possible, a DUS of the CFA with a multiphasic wave form excluding significant disease AND a palpable ipsilateral femoral pulse must be documented.
9. Subjects with significant inflow disease (≥ 50% stenosis by visual estimate) must have documented successful treatment before randomizing the subject. Successful treatment of inflow disease is defined as ≤ 30% final residual stenosis and no distal embolization or flow-limiting \> Grade C dissection. Note: Treatment of the common femoral and profunda femoris is not permitted. Inflow vessel treatment can be performed with any commercially available non-DCB or non-DES device; if DCB treatment is required, SELUTION SLR 018 must be used.
10. The BTK target lesion preparation must be documented to be successful by angiography (≤ 30% residual stenosis and no distal embolization or flow-limiting ≥ Grade C dissection) before randomization. Note: Lesion preparation can include atherectomy (rotational, orbital, directional or laser), cutting, scoring, contoured balloons or intravascular lithotripsy and PTA only.

Clinical Exclusion Criteria:

Subjects will be excluded if any of the following criteria apply:

1. Subject has extensive tissue loss (Rutherford category 6) extending above the trans metatarsal level, salvageable only with complex foot reconstruction or non-traditional trans metatarsal amputations. This includes subjects with:

   1. Osteomyelitis involving proximal to the metatarsal head(s)
   2. Any heel wound or wound with calcaneal bone involvement

   d) Wounds that would require flap coverage or complex wound management for large soft tissue defect e) Full-thickness wounds on the dorsum of the foot with exposed tendon or bone
2. Subject has chronic renal insufficiency (dialysis dependent, or glomerular filtration rate \[GFR\] ≤ 30 ml/min/1.73 m2 within 30 days of index procedure) or has undergone renal transplantation.
3. Subject has acute renal insufficiency confirmed by 50% increase of serum creatinine within 48 hours before procedure and/or decrease in urine output.
4. Subject has acute limb ischemia with onset of index limb symptoms less than 2 weeks prior to index procedure.
5. Subjects has wounds that are deemed to be neuropathic or non-ischemic in nature or any venous or mixed wounds.
6. Subject has had prior major amputation of the ipsilateral extremity or planned major amputation of either leg.
7. Target limb iliac or common femoral artery bypass within 6 weeks of index procedure.
8. Prior (within 14 days) or planned (within 30 days) surgical or endovascular procedures. The following procedures are permitted:

   1. Target limb inflow treatment at the index procedure, provided it meets the criteria in Angiographic Inclusion Criteria #12
   2. Contralateral limb iliac artery treatment
   3. Diagnostic angiography
   4. Foot wound debridement
   5. Planned minor amputation of digit(s) at the phalangeal level
9. Target lesion has undergone prior DCB within 1 year, or ANY prior DES or bare metal stent (BMS) treatment (no in-stent restenosis \[ISR\] treatment is permitted). Note: Prior stent is permitted if the target lesion is located ≥ 30 mm from the stent AND there is ≤ 30% in-stent diameter stenosis.
10. Target lesion(s) requires treatment with alternative therapies such as thrombolysis, thrombus aspiration, stenting, cryoplasty, brachytherapy, or re-entry device. Note: The following adjunctive lesion preparation therapies are permitted: Atherectomy (rotational, orbital, directional or laser), cutting/scoring/contoured balloon, or intravascular lithotripsy.
11. Target lesion requires treatment via pedal access or upper extremity access.
12. Subject has undergone non-coronary artery treatment with any limus-based drug coated balloon (DCB) or DES or other device within 3 months prior to index procedure.
13. Subject has known hypersensitivity or allergy to Sirolimus or other pharmacologic agents required for the procedure (such as contrast agent, heparin, bivalirudin) that cannot be adequately pre-treated.
14. Subject has contraindication to antiplatelet therapy.
15. Subject has experienced disabling stroke or ST-segment elevation myocardial infarction (STEMI) within 3 months of index procedure.
16. Subject has acute coronary syndrome. Stabilized Acute Coronary Syndrome (ACS) is permitted.
17. Subject has non-atherosclerotic disease of the target vessel (including aneurysmal disease and vasculitis) or Buerger's disease.
18. Subject has hypercoagulable state or disorder, or coagulopathy, including platelet count ≤ 100,000 per microliter.
19. Subject has systemic infection (White Blood Count \[WBC\] \> 12,000 and febrile). \[Note: Enrollment permitted after successful treatment of infection with resolution of leukocytosis and/or febrile state\].
20. Subject is known to be immune compromised (e.g., Human Immunodeficiency virus \[HIV\], Systemic Lupus Erythematosus \[SLE\]) or is receiving treatment with immune suppressive medications (NOTE: topical corticosteroids are permitted)
21. Subject is receiving (or is scheduled to receive) cancer treatment with surgery or chemotherapy or radiation therapy or has metastatic malignancy. Note: local application of chemotherapeutic creams is allowed.
22. Subject has New York Heart Association (NYHA) class IV congestive heart failure.
23. Subject is bedridden.
24. Subject has a body mass index (BMI) \< 18.
25. Subject is currently participating in another investigational drug or device study that has not completed primary endpoint follow-up.
26. Subject has other anatomic, medical, social, or psychological conditions that in the investigator's opinion could limit the patient's ability to participate in the clinical study and/or comply with the follow-up requirements.

Angiographic Exclusion Criteria:

Subjects will be excluded if any of the following criteria apply:

1. Presence of a previously placed stent in the target vessel(s), UNLESS the target lesion is located ≥ 30 mm from the stent AND there is ≤ 30% in-stent diameter stenosis.
2. There is significant (\> 50% diameter stenosis) inflow disease in the common femoral and profunda femoris arteries (inflow treatment of the common femoral and profunda femoris is not permitted).
3. The target lesion could not be successfully pre-dilated (residual stenosis \> 30%, distal embolization, or flow-limiting ≥ Grade C dissection after pre-dilatation).
4. Intra-arterial thrombus, thromboembolism or atheroembolism in the index limb noted on initial diagnostic angiography or following treatment of inflow disease or pre-treatment of target lesion.
5. Subject requires treatment of the tibial arteries distal to the tibiotalar joint line, or treatment of the pedal arteries. Angioplasty at or below the tibiotalar joint is not permitted.