Evaluation of Oral Colchicine for Prevention of Restenosis in Superficial Femoral Artery in Patients with Lower Extremity Artery Disease

The primary objective of the study is to evaluate the **effectiveness** of oral colchicine in preventing restenosis in the superficial femoral artery in patients with lower extremity artery disease (LEAD) who are treated with an uncoated vascular stent. This is compared to the local release of paclitaxel by drug-eluting stents. Additionally, the study aims to assess the tolerance and safety of oral colchicine in the treatment of restenosis in these patients. The clinical relevance of this objective lies in its potential to improve outcomes for patients with LEAD by reducing the incidence of restenosis, which is a common complication following stent placement.

Secondary objectives include: - Evaluation of the effectiveness of oral colchicine in the secondary prevention of major adverse cardiovascular events (MACE) in patients with LEAD treated with an uncoated vascular stent, compared to the local release of paclitaxel by drug-eluting stents. - Identifying genetic changes that modify the therapeutic effect of colchicine and biomarkers for monitoring therapy.

The clinical trial focuses on patients with **lower extremity artery disease** (LEAD) and aims to evaluate the effectiveness and safety of oral colchicine in preventing restenosis in the superficial femoral artery. The study population includes both male and female participants, aged over 30 years, who are experiencing chronic lower limb ischemia as classified by the Rutherford classification (grade 3-5). Participants must have an arteriographically diagnosed lesion in the superficial femoral artery, classified as TASC A or TASC B, with occlusion or de novo lesion and/or restenosis of the superficial femoral artery ≥50% and an ankle-brachial index (ABI) <0.90. The trial includes a vulnerable population, and participants are required to sign informed consent for both participation in the trial and genetic testing. The sponsor has not provided the total number of participants. Lifestyle considerations include postmenopausal or surgically sterile women and men who must agree to abstain from heterosexual sexual intercourse or use contraceptive methods. The trial population was selected based on specific medical and anatomical criteria, ensuring the target lesion is appropriately located and the reference diameter of the target vessel is between 4.0 mm and 7.0 mm. The study does not provide further details on the general health status or lifestyle habits of the participants.

The clinical trial is designed to evaluate the effectiveness and safety of **colchicine** in preventing restenosis in the superficial femoral artery in patients with lower extremity artery disease (LEAD) who have been treated with an uncoated vascular stent. This study is a randomized, double-blind, controlled trial, with an estimated duration extending until December 31, 2027. The trial will commence recruitment on June 1, 2024, and will involve a series of structured study visits to monitor patient progress and gather data.

Participants will first attend an inclusion visit, which serves as a screening to ensure they meet the principal inclusion criteria, such as being over 30 years of age, having chronic lower limb ischemia, and providing informed consent for genetic testing and trial participation. Following successful screening, participants will be randomized to receive either the investigational product or a control. The trial will include regular follow-up visits to assess the primary endpoint, which is the patency of the superficial femoral artery 24 months post-implantation, as well as secondary endpoints like target vessel revascularization and late lumen loss.

The expected length of participant involvement is 24 months, during which time they will be monitored for adverse events and overall treatment efficacy. Conditions that may lead to early termination from the study include the occurrence of major adverse cardiovascular events or any serious adverse events that compromise patient safety. The end-of-study visit will conclude the trial for each participant, where final assessments will be conducted to evaluate the long-term outcomes of the treatment. Throughout the trial, data will be collected and analyzed to determine the potential benefits and risks associated with the use of colchicine in this patient population.

The clinical trial involves the administration of **colchicine** as the experimental medication. The product used is "COLCHICAN, 0.5 mg, film-coated tablets," manufactured by POLFARMEX S.A. The pharmaceutical form is a film-coated tablet, and the active substance is colchicine, a chemical compound. The medication is administered orally. The maximum daily dose is 1 mg, with a total maximum dose of 228 mg over the course of the study. The treatment period is limited to a maximum of 12 weeks. The trial aims to evaluate the effectiveness of oral colchicine in preventing restenosis in the superficial femoral artery in patients with lower extremity artery disease (LEAD) treated with an uncoated vascular stent.

In addition to the experimental treatment, the study involves a comparator treatment, which is the local release of paclitaxel by drug-eluting stents. This comparator is used to assess the effectiveness and safety of colchicine in relation to the standard treatment for restenosis. The study does not involve the use of a placebo or any other non-experimental treatments. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

The efficacy of oral colchicine in preventing restenosis in the superficial femoral artery will be assessed through a series of primary and secondary endpoints over a 24-month period. The primary endpoints include the **patency** of the superficial femoral artery, evaluated by Doppler ultrasound to confirm three-phase and fast-flow blood circulation, and the overall risk assessment of the procedure, determined by the number of subjects experiencing adverse events. Secondary endpoints encompass a range of measures, such as Target Vessel Revascularization (TVR), Late Lumen Loss (LLL), and percentage narrowing of the vessel diameter in the stent. These will be measured at various intervals, including 6 months and 24 months post-stent implantation.

Additional secondary endpoints include improvements in the ankle-brachial index (ABI) and the Rutherford ischemia classification, occurrence of major amputation, major adverse cardiovascular events (MACE), and death from cardiovascular causes. The study will also track the number of hospitalization days for any cause and those specifically related to lower extremity artery disease (LEAD) in the stented leg. Patient-reported outcomes will be assessed using the NRS scale for ischemic pain intensity and the VascuQol protocol for quality of life, with improvements measured over the 24-month period. These efficacy parameters will be collected and analyzed to determine the effectiveness of colchicine in the specified patient population.