Evaluation of Ischemic and Bleeding Outcomes with Angiolite Stent and Abbreviated Dual Antiplatelet Therapy in Coronary Artery Disease Patients

The primary objectives of this study are twofold: First, to evaluate the **rate of target lesion failure** at one year between the Angiolite stent and the Xience stent family, assessing for non-inferiority in both the standard of care dual antiplatelet therapy (DAPT) regimen and the abbreviated antiplatelet therapy group. This is clinically relevant as it addresses the efficacy of different stent types in preventing lesion failure, which is critical for patient outcomes in coronary artery disease. Second, to determine the rate of clinically relevant **bleeding events** (Bleeding Academic Research Consortium 2, 3, or 5) at one year between an abbreviated dual antiplatelet therapy regimen and the standard of care DAPT, tested for superiority of the experimental arm. This is significant as it evaluates the safety profile of the therapy regimens, aiming to reduce bleeding risks while maintaining therapeutic efficacy.

Secondary objectives include: - Determining the rate of adverse **ischemic events** between an abbreviated dual antiplatelet therapy regimen and the standard of care DAPT, tested for non-inferiority. This is important for understanding the balance between reducing ischemic risks and minimizing bleeding complications. - Evaluating the rate of target lesion failure at one year between the Angiolite stent and the Xience stent family (Skypoint or Sierra), tested for non-inferiority in the standard of care subgroup. This further investigates the comparative effectiveness of stent types in a specific patient population.

The clinical trial involves participants diagnosed with **Coronary Artery Disease**. The study population includes both male and female subjects, aged between 18 and 94 years. Participants are required to have one or more coronary artery stenosis of 50% or more, suitable for coronary stent implantation, with a reference vessel diameter of at least 2.00 mm. The trial does not include a vulnerable population. Participants must be able to provide informed consent and be willing to participate in the trial. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that individuals with the specified medical condition and age range are included, while lifestyle factors such as diet and physical activity are not specified as part of the selection process.

The clinical trial is designed to evaluate the efficacy and safety of an abbreviated dual **antiplatelet** therapy regimen compared to the standard of care in patients with **coronary artery disease**. This is a randomized, controlled, double-blind trial with a 2x2 factorial design. The trial aims to assess the rate of target lesion failure and clinically relevant bleeding events over a 12-month period. Participants will be randomly assigned to receive either the angiolite stent or the Xience stent, along with either the standard or abbreviated antiplatelet therapy. The trial is expected to conclude by February 28, 2031, with recruitment starting on October 13, 2023.

Study visits are structured to ensure comprehensive data collection and participant safety. The initial inclusion visit involves screening participants based on criteria such as age (18-94 years) and the presence of significant coronary artery stenosis. Participants must provide informed consent to be eligible. Follow-up visits will occur at regular intervals to monitor the primary endpoints, including target lesion failure and adverse ischemic events. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.

Participant involvement is expected to last for the entire 12-month duration of the trial. However, conditions such as withdrawal of consent, adverse events, or protocol violations may lead to early termination from the study. The trial's primary endpoints include cardiovascular death, target-vessel myocardial infarction, and target lesion revascularization, while secondary endpoints focus on ischemic events like all-cause death, non-fatal myocardial infarction, or stroke. The trial's methodology and design ensure rigorous evaluation of the therapeutic interventions, contributing valuable insights into the management of coronary artery disease.

The clinical trial involves the administration of several **antiplatelet** medications, each with specific roles and characteristics. **Clopidogrel** is utilized in two forms: as a combination with **acetylsalicylic acid** and as a standalone treatment. The combination is administered orally in a pharmaceutical form identified as PHF00082MIG, with a maximum daily dose of 75 mg and a total dose of up to 600 mg over a 12-month period. The standalone **clopidogrel** is provided as a film-coated tablet, also administered orally, with the same dosing parameters. Both forms are used as part of the experimental treatment regimen.

**Acetylsalicylic acid**, commonly known as aspirin, is administered in two forms: as a standalone treatment and in combination with **clopidogrel**. The standalone form is provided as a gastro-resistant tablet, with a maximum daily dose of 200 mg and a total dose of up to 300 mg over 12 months. This formulation is used as a comparator in the trial. The combination with **clopidogrel** follows the same dosing schedule as described previously.

**Ticagrelor** is another experimental medication used in the trial, administered orally as a film-coated tablet. The maximum daily dose is 180 mg, with a total dose of 180 mg over the treatment period. This medication is part of the experimental arm of the study, aiming to evaluate its efficacy in comparison to standard treatments.

**Prasugrel** is also included in the trial, provided as a film-coated tablet for oral administration. The maximum daily dose is 10 mg, with a total dose of up to 60 mg over the 12-month period. This medication serves as a comparator in the study, allowing for the assessment of its effectiveness relative to other treatments.

All medications are administered orally, and participant compliance is monitored throughout the trial to ensure adherence to the dosing schedules. The trial aims to evaluate the efficacy and safety of these treatments in managing ischemic and bleeding outcomes following stent implantation, with a focus on comparing standard and abbreviated dual antiplatelet therapy regimens.

The efficacy of the clinical trial will be assessed through the evaluation of two co-primary endpoints. The first co-primary endpoint is the rate of target lesion failure at 1-year, which includes cardiovascular death, target-vessel myocardial infarction, and target lesion revascularization. This will be measured to determine non-inferiority between the angiolite stent and the Xience stent family in both the standard of care dual antiplatelet therapy (DAPT) regimen and the abbreviated antiplatelet therapy group. The second co-primary endpoint is the rate of clinically relevant bleeding events, classified according to the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5, at 1 year. This endpoint will be used to test the superiority of the experimental arm with an abbreviated dual antiplatelet therapy regimen compared to the standard of care DAPT.

Secondary endpoints include the occurrence of ischemic events, such as all-cause death, non-fatal myocardial infarction, or stroke. The trial will utilize a 2x2 factorial design and will be conducted in a multicenter, randomized controlled setting. Efficacy parameters will be collected and analyzed at the 1-year follow-up to ensure comprehensive assessment of the trial objectives. The trial is designed to meet the requirements of the Haute Autorité de santé (HAS) and is categorized as a Phase III clinical trial.