Colchicine in Chronic Limb-Threatening Ischemia

Inclusion criteria

• Age ≥18 years.
• Documented chronic limb-threatening ischemia, meeting the following:

• 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 without prior revascularization; ABI ≤0.85 or TBI ≤0.65 for those with prior revascularization OR
• Ischemic rest pain alone (Rutherford class 4) defined as 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) defined as ankle systolic pressure <70 mmHg, toe pressure of <50 mmHg, transcutaneous PO2 of <30 mmHg, or flatline transtarsal pulse volume recording
• Recent successful revascularization:

• Underwent technically successful endovascular therapy (EVT) or surgical bypass within the last 7 days prior to randomization
• For individuals requiring multiple revascularization attempts on the same index leg, the procedure considered for eligibility (in other words, the qualifying or index procedure) must be the final planned or anticipated revascularization attempt
• There must be demonstrated graft or vascular patency after the qualifying revascularization procedure with one in-line blood flow to the foot, either by angiography, duplex ultrasound, CTA or MRA
• There must be no immediate plan for reintervention
• Informed Consent:

• Demonstrated ability and willingness to adhere to the study protocol, attend scheduled follow-up visits, complete all required assessments, and provide written informed consent

Exclusion criteria

• Age <18 years
• Asymptomatic or mild disease: Patients who underwent revascularization for disease graded Rutherford classes 0-3
• Patients with major tissue loss (Rutherford 6) in whom major amputation was planned at the time of screening
• Failure to establish at least one tibial artery outflow after revascularization
• Recent acute limb ischemia events within 2 weeks of screening
• Clinical signs of active, uncontrolled, severe limb infection or septicemia, such 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)
• Unstable hemodynamics after the index revascularization procedure
• Unable to tolerate any antiplatelet agent or with severe bleeding diathesis
• Acute coronary syndrome, acute stroke, or hospitalization for heart failure within 30 days of screening
• Any contraindication or known intolerance to colchicine
• Requirement for colchicine for another indication
• Need for use of medications known to have drug-drug interactions with colchicine, particularly drugs known to inhibit CYP3A4 or P-glycoprotein
• Active hepatitis or severe liver cirrhosis (Child Pugh C)
• Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception
• Previous (within 30 days) or concomitant participation in another clinical study with investigational medicinal product(s)
• Life expectancy <1 year