Evaluation of Genotype-Guided Antithrombotic Therapy with Carbasalate Calcium, Telmisartan, and Rivaroxaban in Peripheral Arterial Disease Patients

The primary objective of the study titled "Genotype-guided strategy for antithrombotic treatment versus conventional clopidogrel therapy in **Peripheral Arterial Disease** (GENPAD)" is to evaluate the efficacy of a genotype-guided antithrombotic treatment in reducing adverse clinical events associated with arterial thrombosis in patients with Peripheral Arterial Disease (PAD). The adverse clinical events of interest include major adverse cardiovascular events such as myocardial infarction, stroke, and transient ischemic attack, as well as major adverse limb events including acute or chronic limb ischemia, peripheral vascular intervention, and amputation, in addition to mortality. This objective is clinically relevant as it aims to improve patient outcomes by potentially offering a more personalized treatment approach that could reduce the incidence of these serious events.

The clinical trial involves participants diagnosed with **Peripheral Arterial Disease** (PAD). The study population includes both male and female subjects, with an age range starting from 16 years and above. The total number of participants is not provided by the sponsor. Participants were selected based on specific criteria, including an indication for monotherapy with clopidogrel 75mg once daily, an ankle-brachial index of less than 0.9 and/or a toe brachial index of less than 0.5, and current or previous symptoms due to insufficient vascularization of one or two lower extremities, such as intermittent claudication, pain at rest, and/or gangrene, classified under Rutherford category 1-6. Additionally, participants must be consulting a vascular surgeon for the diagnosis, treatment, and/or follow-up of PAD. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed to evaluate the efficacy of a **genotype-guided** antithrombotic treatment strategy compared to conventional clopidogrel therapy in patients with **peripheral arterial disease**. This study is a randomized, double-blind, controlled trial with an estimated duration of 36 months. The primary objective is to assess the reduction in adverse clinical events related to arterial thrombosis, including major adverse cardiovascular events, major adverse limb events, and death, over a 24-month period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 16 years, indication for clopidogrel monotherapy, and specific vascular indices. Following the screening, participants will be randomly assigned to either the genotype-guided treatment group or the conventional therapy group. The trial includes regular follow-up visits to monitor the participants' health status and adherence to the treatment protocol. The end-of-study visit will occur at the conclusion of the 24-month treatment period, where final assessments will be conducted to evaluate the primary and any secondary endpoints.

The expected length of participant involvement is up to 36 months, including the treatment and follow-up phases. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that necessitate discontinuation of the study medication. The trial aims to provide valuable insights into the potential benefits of personalized medicine approaches in the management of peripheral arterial disease.

The clinical trial involves the administration of **carbasalate calcium**, a chemical compound known for its antithrombotic properties. The pharmaceutical form of carbasalate calcium is an enteric-coated tablet, containing 100 mg of **acetylsalicylic acid**. The medication is administered orally, with a maximum daily dose of 100 mg. The treatment period extends up to 36 months, ensuring sustained therapeutic effects. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

Another treatment in the trial is **clopidogrel**, a P2Y12 inhibitor that irreversibly inhibits platelet aggregation. Clopidogrel is provided in a pharmaceutical form identified as PHF00245MIG and is administered orally. The maximum daily dose is 75 mg, with a treatment duration of up to 36 months. The trial protocol includes measures to monitor participant compliance and ensure the correct administration of the medication.

The trial also includes **rivaroxaban**, an antithrombotic agent that directly inhibits factor Xa. Rivaroxaban is administered in a pharmaceutical form designated as PHF00082MIG, with a maximum daily dose of 5 mg. The route of administration is oral, and the treatment period is set for up to 36 months. Compliance monitoring is an integral part of the study to ensure participants adhere to the prescribed dosing regimen.

Throughout the trial, the administration of these medications is carefully monitored to evaluate their efficacy in reducing adverse clinical events related to arterial thrombosis in patients with peripheral arterial disease. The study aims to compare the outcomes of genotype-guided antithrombotic treatment against conventional clopidogrel therapy, with a focus on major adverse cardiovascular and limb events, as well as mortality.

Efficacy in the clinical trial titled "Genotype-guided strategy for antithrombotic treatment versus conventional clopidogrel therapy in peripheral arterial disease (GENPAD)" will be assessed primarily through the occurrence of adverse clinical events related to arterial thrombosis at 24 months. These events include death from any cause, major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, and transient ischemic attack, as well as major adverse limb events (MALE) like acute or chronic limb ischemia and peripheral vascular intervention, including amputation. The primary endpoint is designed to evaluate the ability of genotype-guided antithrombotic treatment to reduce these adverse clinical events in patients with peripheral arterial disease (PAD).