Inclusion Criteria:

1. Age ≥18 years.

2. Documented chronic limb-threatening ischemia, meeting the following criteria according to guidelines(13):

   • Presence of ischemic symptoms compatible with CLTI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or rest pain consistent with Rutherford classes 4-5 AND
   • Imaging evidence within the past 12 months showing atherosclerotic PAD, including CTA, MRA, angiography or duplex ultrasound AND
   • Ankle-Brachial Index (ABI) ≤0.80 or Toe-Brachial Index (TBI) ≤0.60 for patients who never underwent revascularization; ABI ≤0.85 or TBI ≤0.65 for those with history of prior revascularization procedures OR
   • Ischemic rest pain alone (Rutherford class 4) with ankle systolic pressure <50 mmHg, toe pressure of <30 mmHg, transcutaneous PO2 of <30 mmHg, or flat-line transtarsal pulse volume recording OR
   • Tissue loss with or without ischemic rest pain (Rutherford class 5) with ankle systolic pressure <70 mmHg, toe pressure of <50 mmHg, transcutaneous PO2 of <30 mmHg, or flatline transtarsal pulse volume recording

3. Absence of occlusive upstream disease, defined by the following:

   • Demonstrated vascular patency from the aorta to the second segment of the popliteal artery (P2), either by angiography, duplex ultrasound, CTA or MRA within the last 7 days prior to randomization
   • In patients who underwent prior treatment for upstream disease, there are no restrictions in treatment modalities received as long as patency is demonstrated as previously defined
   • If upstream disease is planned to be treated in the same index procedure, technically successful treatment of the upstream vessels must be achieved before randomization, defined as less than 30% residual stenosis and no flow-limiting dissections

4. Informed Consent:

   • Demonstrated ability and willingness to adhere to the study protocol and provide written informed consent

Exclusion Criteria:

1. Age <18 years
2. Asymptomatic or mild disease: patients who underwent revascularization for disease graded Rutherford classes 0-3
3. Patients with major tissue loss (Rutherford 6) in whom major amputation was planned at the time of screening
4. Patient with a history of prior major (above-the-ankle) amputation of the study limb
5. Unable to tolerate any antiplatelet agent or with severe bleeding diathesis
6. Clinical signs of active, uncontrolled, severe limb infection or septicemia, defined as fever exceeding 38.5°C, a white blood cell count above 15,000 cells/µL, or hypotension, at the time of screening (this does not include osteomyelitis confined to the phalanges or metatarsal heads or foot cellulitis treatable with IV antibiotics at the time of revascularization)
7. Acute coronary syndrome or acute stroke within 30 days of screening
8. Active hepatitis or severe liver cirrhosis (Child Pugh C)
9. Advanced CKD (defined with eGFR<30 mL/min/1.73m2) or end-stage renal disease
10. Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception
11. Previous (within 30 days) or concomitant participation in another clinical study with investigational medicinal product(s) that has not yet reached its primary endpoint
12. Life expectancy <1 year