Low dose colchicine in patients with peripheral artery disease to address residual vascular risk: a randomized trial (LEADER-PAD)
Peripheral artery disease
Eligible participants who consent to take part in the study will undergo a 2-3 week test period when they will take colchicine 0.5 mg daily. Participants who tolerate colchicine (are not sensitive to medication side effects) and have taken at least 11 tablets will then be randomised to either colchicine or a placebo tablet in a 1:1 ratio. Randomisation will be carried out using an online system. Group 1: Colchicine 0.5 mg daily Participants will take a colchicine tablet by mouth daily for the duration of study participation. Study medication will be dispensed every year. Group 2: Placebo Participants will take a placebo tablet by mouth daily for the duration of the study participation. Study medication will be dispensed every year. Colchicine drug and placebo are of the same appearance and are indistinguishable. All investigators, study personnel and participants will be blinded to drug treatment assignment. Participants in each group will be followed up every 6 months for evaluation of clinical outcomes, including major cardiovascular and limb adverse events or hospitalisation for vascular complications or revascularisation. Participants will be asked to complete quality-of-life questionnaires annually. In the first year, participants will be contacted at months 3 and 9 to discuss any challenges in taking study drugs, and as needed, they will be re-contacted to address adherence issues.
Patients need to meet the following criteria for inclusion: 1. Age > 18 years old 2. Symptomatic atherosclerotic LE PAD fulfilling at least one of the following: 2.1. Intermittent claudication with ankle/arm blood pressure ratio* (ABI ≤ 0.90) or artery stenosis ≥ 50% plus one of 2.1.1. >1 vascular bed affected by atherosclerosis. 2.1.2. Diabetes 2.1.3. Heart failure 2.1.4. Chronic kidney disease (eGFR < 60 mL/min/1.73 m2) 2.2. Rest pain (mostly in the foot) OR necrosis of limb OR gangrene of limb (corresponding to either Fontaine stages 3 or 4 OR Rutherford Classification categories 4 to 6). All must have an ankle/arm blood pressure ratio* (ABI ≤ 0.90) OR artery stenosis ≥ 50%. *In cases of incompressible ankle arteries, the presence of toe pressure ≤ 60 mm Hg or toe-brachial index ≤ 0.70 is acceptable 2.3. Revascularization, defined as limb bypass surgery or endovascular revascularization procedures (irrespective of the specific device used), including percutaneous transluminal angioplasty/stent of iliac or infra-inguinal arteries or extra-anatomical bypass surgery. 2.4. Leg or foot amputation for arterial vascular indications 3. Written or verbal informed consent from the patient
1. Contraindication to colchicine 2. Long-term requirement for colchicine for another clinical indication 3. Active diarrhoea 4. eGFR < 30 mL/min/1.73 m2 (based on the local method for estimating eGFR) 5. Cirrhosis or severe chronic liver disease 6. Woman who is pregnant, breast-feeding or of child-bearing potential not protected by reliable contraception or is planning conception during the study 7. Current or planned long-term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (except azithromycin). Added 31/03/2026: In the UK patients on current or planned long-term use of azithromycin are also excluded. 8. Patients who are deemed unlikely to return for follow-up 9. Patients with life expectancy < 1 year