SELUTION4BTK Trial

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 withRutherford classification category 4 or 5 and symptoms of > 2 weeks duration.

4. Subject is willing and able to provide written informed consent and comply withstudy procedures and required follow-up evaluations.

5. Female subjects of childbearing potential must be non-breastfeeding and have anegative 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 withinthe 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-peronealtrunk, peroneal artery, anterior tibial artery, and posterior tibial artery.

2. BTK Target lesions cannot be contiguous with inflow lesions and at least 3 cm ofnormal 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 014DEB 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 othernon-target BTK lesions in separate non-target vessels may be enrolled, provided thatthe non-target lesions have been successfully treated (residual stenosis ≤ 30% withno distal embolization or flow limiting ≥ Grade C dissection). NOTE: Any adjunctivetherapies are permitted for the treatment of non-target BTK lesions, but no DEB orDES may be used.

6. Any target lesion must be ≥ 30 mm in length and the total combined length of alltarget lesions must be ≤ 140 mm (total treatment length ≤ 150 mm allowing for 5 mmproximal and distal shoulder treatment). Note: All target lesions and all inflowlesions must be treatable by one or more SELUTION SLR 014/018 DEB(s) such that thetotal planned per-subject drug dose (calculated by summing the drug dose of allindividual planned balloon sizes) would be ≤ 7069 μg. Note: A total treated segmentlength of ≤ 150 mm for BTK and ≤ 200 mm for inflow segment is acceptableirrespective of DEB balloon diameter.

7. The tibial and pedal runoff distal to the target lesions must be patent OR thetarget vessel(s) must reconstitute above the ankle or display normal terminalbranching as follows:

8. If the target vessel is the P3 segment, any 1 of the 3 distal arteries mustshow a patent (≤ 50% stenosis by visual estimate) outflow.

9. If the target vessel is the peroneal artery, the artery must demonstrate normalterminal branching.

10. If the target vessel is the anterior tibial (AT) or posterior tibial (PT)artery, the artery must reconstitute ≥ 1 cm above the tibiotalar joint toprovide an intact runoff vessel (AT: dorsalis pedis; PT: plantar artery).

11. If the target vessel is the tibio-peroneal trunk, outflow for either theperoneal OR the posterior tibial artery must be patent (≤ 50% stenosis byvisual estimate).

12. Subjects is free of significant inflow vessel disease or any inflow disease has beensuccessfully treated (see angiographic inclusion # 9). Significant inflow disease isdefined as ≥ 50% stenosis by visual estimate. Inflow vessels include the ipsilateralcommon iliac, external iliac, common femoral, profunda femoris, superficial femoralor popliteal artery proximal (≥ 3 cm) to the tibial plateau. Note: If access sitedoesn'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 presenceof significant inflow disease. If non-invasive imaging is not possible, a DUS of theCFA with a multiphasic wave form excluding significant disease AND a palpableipsilateral femoral pulse must be documented.

13. Subjects with significant inflow disease (≥ 50% stenosis by visual estimate) musthave documented successful treatment before randomizing the subject. Successfultreatment of inflow disease is defined as ≤ 30% final residual stenosis and nodistal embolization or flow-limiting > Grade C dissection. Note: Treatment of thecommon femoral and profunda femoris is not permitted. Inflow vessel treatment can beperformed with any commercially available non-DCB or non-DES device; if DCBtreatment is required, SELUTION SLR 018 must be used.

14. The BTK target lesion preparation must be documented to be successful by angiography (≤ 30% residual stenosis and no distal embolization or flow-limiting ≥ Grade Cdissection) before randomization. Note: Lesion preparation can include atherectomy (rotational, orbital, directional or laser), cutting, scoring, contoured balloons orintravascular 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 transmetatarsal level, salvageable only with complex foot reconstruction ornon-traditional trans metatarsal amputations. This includes subjects with:

2. Osteomyelitis involving proximal to the metatarsal head(s)

3. Any heel wound or wound with calcaneal bone involvement d) Wounds that would require flap coverage or complex wound management for largesoft tissue defect e) Full-thickness wounds on the dorsum of the foot with exposedtendon or bone

4. Subject has chronic renal insufficiency (dialysis dependent, or glomerularfiltration rate [GFR] ≤ 30 ml/min/1.73 m2 within 30 days of index procedure) or hasundergone renal transplantation.

5. Subject has acute renal insufficiency confirmed by 50% increase of serum creatininewithin 48 hours before procedure and/or decrease in urine output.

6. Subject has acute limb ischemia with onset of index limb symptoms less than 2 weeksprior to index procedure.

7. Subjects has wounds that are deemed to be neuropathic or non-ischemic in nature orany venous or mixed wounds.

8. Subject has had prior major amputation of the ipsilateral extremity or planned majoramputation of either leg.

9. Target limb iliac or common femoral artery bypass within 6 weeks of index procedure.

10. Prior (within 14 days) or planned (within 30 days) surgical or endovascularprocedures. The following procedures are permitted:

11. Target limb inflow treatment at the index procedure, provided it meets thecriteria in Angiographic Inclusion Criteria #12

12. Contralateral limb iliac artery treatment

13. Diagnostic angiography

14. Foot wound debridement

15. Planned minor amputation of digit(s) at the phalangeal level

16. Target lesion has undergone prior DCB within 1 year, or ANY prior DES or bare metalstent (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 ANDthere is ≤ 30% in-stent diameter stenosis.

17. 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, orintravascular lithotripsy.

18. Target lesion requires treatment via pedal access or upper extremity access.

19. Subject has undergone non-coronary artery treatment with any limus-based drug coatedballoon (DCB) or DES or other device within 3 months prior to index procedure.

20. Subject has known hypersensitivity or allergy to Sirolimus or other pharmacologicagents required for the procedure (such as contrast agent, heparin, bivalirudin)that cannot be adequately pre-treated.

21. Subject has contraindication to antiplatelet therapy.

22. Subject has experienced disabling stroke or ST-segment elevation myocardialinfarction (STEMI) within 3 months of index procedure.

23. Subject has acute coronary syndrome. Stabilized Acute Coronary Syndrome (ACS) ispermitted.

24. Subject has non-atherosclerotic disease of the target vessel (including aneurysmaldisease and vasculitis) or Buerger's disease.

25. Subject has hypercoagulable state or disorder, or coagulopathy, including plateletcount ≤ 100,000 per microliter.

26. Subject has systemic infection (White Blood Count [WBC] > 12,000 and febrile). [Note: Enrollment permitted after successful treatment of infection with resolutionof leukocytosis and/or febrile state].

27. Subject is known to be immune compromised (e.g., Human Immunodeficiency virus [HIV],Systemic Lupus Erythematosus [SLE]) or is receiving treatment with immunesuppressive medications (NOTE: topical corticosteroids are permitted)

28. Subject is receiving (or is scheduled to receive) cancer treatment with surgery orchemotherapy or radiation therapy or has metastatic malignancy. Note: localapplication of chemotherapeutic creams is allowed.

29. Subject has New York Heart Association (NYHA) class IV congestive heart failure.

30. Subject is bedridden.

31. Subject has a body mass index (BMI) < 18.

32. Subject is currently participating in another investigational drug or device studythat has not completed primary endpoint follow-up.

33. Subject has other anatomic, medical, social, or psychological conditions that in theinvestigator's opinion could limit the patient's ability to participate in theclinical 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 targetlesion is located ≥ 30 mm from the stent AND there is ≤ 30% in-stent diameterstenosis.

2. There is significant (> 50% diameter stenosis) inflow disease in the common femoraland profunda femoris arteries (inflow treatment of the common femoral and profundafemoris 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 notedon initial diagnostic angiography or following treatment of inflow disease orpre-treatment of target lesion.

5. Subject requires treatment of the tibial arteries distal to the tibiotalar jointline, or treatment of the pedal arteries. Angioplasty at or below the tibiotalarjoint is not permitted.