Crossover Study on Coronary Risk Factor Control and Platelet Aggregation Using Ramipril, Acetylsalicylic Acid, and Atorvastatin Calcium Trihydrate in Patients

The primary objective of this study is to analyze the level of **systolic blood pressure** and **LDL-cholesterol** in the same patient during two different periods: one under treatment for 3 months with the Trinomia® polypill and another for 3 months with the components administered separately. This objective is clinically relevant as it aims to evaluate the efficacy of the polypill in managing coronary risk factors, potentially simplifying treatment regimens and improving patient adherence.

Secondary objectives include evaluating the following parameters: total cholesterol and **HDL** levels, diastolic blood pressure level, patient satisfaction level, degree of adherence to treatment, platelet aggregation degree using a thromboxane A2 kit, and the occurrence of adverse events. These secondary objectives provide a comprehensive assessment of the treatment's impact on cardiovascular health and patient experience.

The clinical trial involves **patients** with ischemic heart disease, focusing on the degree of control of coronary risk factors and platelet aggregation. The study population includes both male and female participants over the age of 18. Participants are required to be under treatment with the Trinomia® polypill for secondary prevention and must be able to attend six visits necessary to complete the study. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of the **Trinomia** polypill in managing coronary risk factors and platelet aggregation. This is a randomized, double-blind, controlled, cross-over study involving patients with ischemic heart disease. The trial aims to compare the effects of the polypill, which contains **ramipril**, **acetylsalicylic acid**, and **atorvastatin calcium trihydrate**, against the individual components administered separately. The primary endpoints are the levels of systolic blood pressure and LDL cholesterol, assessed over two distinct 3-month treatment periods. The trial is categorized as a Phase IV, low-intervention study, with an estimated duration from October 2022 to October 2025.

Participants will undergo a series of study visits, beginning with an inclusion visit to confirm eligibility based on criteria such as age over 18 years, a diagnosis of ischemic heart disease, and current treatment with the Trinomia polypill. Following the inclusion visit, participants will attend six scheduled visits throughout the study. These visits are structured to monitor the participants' health status, adherence to the treatment regimen, and to collect data on the primary endpoints. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the outcomes of the treatment periods.

The expected length of participant involvement is approximately six months, encompassing both treatment periods and all study visits. Conditions that may lead to early termination from the study include adverse reactions to the study medication, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of several **experimental medications** and **non-experimental treatments**. The primary experimental medication is Trinomia, which is available in various formulations, including 100 mg/20 mg/5 mg, 100 mg/40 mg/5 mg, 100 mg/20 mg/2.5 mg, 100 mg/20 mg/10 mg, 100 mg/40 mg/2.5 mg, and 100 mg/40 mg/10 mg. Each formulation is presented as a hard capsule containing a combination of **ramipril**, **acetylsalicylic acid**, and **atorvastatin calcium trihydrate**. The maximum daily dose varies depending on the formulation, ranging from 122.5 mg to 150 mg. The route of administration is oral, and the treatment period is set for a maximum of 3 months.

In addition to the experimental medications, the study includes non-experimental treatments that serve as comparator treatments. These include Adiro 100 mg gastro-resistant tablets, which contain **acetylsalicylic acid** as the active substance. The maximum daily dose for Adiro is 100 mg, administered orally for a period of up to 3 months. Another comparator is Cardyl, available in 20 mg and 40 mg film-coated tablets, containing **atorvastatin**. The maximum daily doses for Cardyl are 20 mg and 40 mg, respectively, with oral administration for up to 3 months.

Further comparator treatments include Acovil tablets, available in 2.5 mg, 5 mg, and 10 mg formulations, containing **ramipril**. The maximum daily doses for Acovil are 2.5 mg, 5 mg, and 10 mg, respectively, with oral administration for a maximum treatment period of 3 months. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in the clinical trial will be assessed by evaluating the primary endpoints, which include the levels of **systolic blood pressure** and **LDL cholesterol**. These parameters will be measured to determine the effectiveness of the Trinomia® polypill compared to its individual components. The trial is designed as a cross-over study, where each patient will undergo two different treatment periods of three months each. During one period, patients will receive the Trinomia® polypill, and during the other, they will receive the components separately.

The measurement of systolic blood pressure and LDL cholesterol will be conducted at specified intervals throughout the trial to ensure accurate and reliable data collection. The trial aims to analyze these parameters in the same patient across the two treatment periods, providing a direct comparison of the efficacy of the polypill versus the separate components. The data collected will be analyzed to determine any significant differences in the control of these risk factors, contributing to the overall assessment of the polypill's efficacy in managing ischemic heart disease.