Efficacy and Safety of Low-Dose Colchicine in Reducing Cardiovascular Events in Patients with Peripheral Arterial Disease: A Randomized Controlled Trial

The primary objective of the study is to evaluate the **efficacy** and **safety** of low-dose **colchicine** (0.5 mg daily) in patients with **peripheral arterial disease** (PAD). The study aims to determine whether colchicine can reduce the incidence of significant cardiovascular events, including cardiovascular death, myocardial infarction, stroke, or severe limb ischemia that necessitates intervention, such as major vascular amputation. This is clinically relevant as PAD patients are at high risk for these adverse events, and effective management could significantly improve patient outcomes.

The clinical trial involves a total of **5852 participants** diagnosed with **peripheral arterial disease** (PAD). The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants were selected based on specific criteria, including symptomatic atherosclerotic lower extremity PAD, with conditions such as intermittent claudication, rest pain, or necrosis of the limb. The trial does not specify particular lifestyle considerations such as diet or physical activity. The selection process required participants to provide written informed consent, ensuring that they meet the necessary health status and medical condition requirements for inclusion in the study.

The clinical trial is designed to evaluate the **efficacy** and safety of **colchicine** 0.5 mg daily in patients with **peripheral arterial disease** (PAD). This is a randomized, double-blind, placebo-controlled trial, which aims to assess the reduction in the incidence of major adverse cardiovascular and limb events (MACE or MALE). The trial is expected to commence recruitment on November 30, 2024, and conclude by November 30, 2029. Participants will be randomly assigned to receive either the active treatment, Colchicine Tiofarma 500 microgram tablets, or a matching placebo. The trial will involve multiple study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18 years, symptomatic atherosclerotic lower extremity PAD, and written informed consent.

Following the screening, participants will undergo regular follow-up visits to monitor their health status and adherence to the treatment regimen. These visits will include assessments of cardiovascular health, limb ischemia, and any adverse events. The primary endpoint is the rate of MACE or MALE, which includes cardiovascular deaths, myocardial infarction, stroke, and severe limb ischemia requiring intervention. Secondary endpoints encompass extended MALE, cardiovascular death, myocardial infarction, stroke, hospitalization, and overall mortality, among others. The trial will conclude with an end-of-study visit to evaluate the overall outcomes and collect final data.

Participant involvement is expected to last for the duration of the trial, with a maximum treatment period of 60 days for the active medication. Conditions that may lead to early termination from the study include withdrawal of consent, non-compliance with the study protocol, or the occurrence of significant adverse events. The trial is categorized as a Phase III study, focusing on the efficacy and safety of the intervention in reducing cardiovascular and limb-related events in PAD patients.

The clinical trial involves the administration of **Colchicine Tiofarma 500 microgram Tablets** as the experimental medication. This pharmaceutical product is formulated as a **tablet** and contains the active substance **colchicine**, which is of chemical origin. The medication is administered orally at a dosage of 0.5 mg per day. The maximum treatment period for participants is 60 days. The primary objective of this trial is to evaluate the efficacy and safety of colchicine in reducing the incidence of cardiovascular events in patients with peripheral artery disease (PAD). Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.

In addition to the experimental medication, a **placebo** is used as a comparator treatment in this study. The placebo is designed to match the Tiofarma colchicine 500 mcg tablets in appearance but does not contain any active substance. The placebo is administered in the same manner as the experimental medication, ensuring that the study remains double-blind. This allows for an accurate assessment of the colchicine's effects by comparing outcomes between the treatment and placebo groups. Participant compliance with the placebo administration will also be monitored to maintain the integrity of the trial data.

The efficacy of the clinical trial titled "Low dose ColchicinE in pAtients with peripheral artery DiseasE to address residual vascular Risk: A randomized trial- LEADER PAD" will be assessed through a series of primary and secondary endpoints. The primary endpoint is the rate of major adverse cardiovascular and limb events (MACE or MALE), which is a composite outcome consisting of cardiovascular deaths, myocardial infarction, stroke, and severe limb ischemia requiring vascular intervention or major vascular amputation. Secondary endpoints include extended MALE, cardiovascular death, myocardial infarction, stroke, hospitalization, acute or chronic limb-threatening ischemia, all revascularization, total vascular amputation, overall mortality, any thrombosis or thromboembolism, Fontaine Stage, Standard Assessment of Global Everyday Activities (SAGEA), Vascular Quality of Life Questionnaire-6 (VascQOL-6), and EuroQol 5 Dimension 5 Level (EQ-5D-5L).

The trial will evaluate the efficacy of **colchicine** 0.5 mg daily in reducing the incidence of these events in patients with peripheral artery disease (PAD). The assessment of these endpoints will involve the collection and analysis of data related to cardiovascular and limb events, as well as patient-reported outcomes using validated questionnaires. The trial is designed as a Phase III study, with an estimated end date of November 30, 2029, and a recruitment start date of November 30, 2024. The maximum treatment period for participants is 60 days. The trial aims to provide comprehensive data on the efficacy and safety of colchicine in this patient population.