Efficacy of Esmolol Hydrochloride in Diagnosing Cardiovascular Disorders Induced by Cirrhosis, Diabetes Mellitus, and Cardiotoxic Treatments

The primary objective of this study is to evaluate the **superiority** of esmolol echocardiography over conventional echocardiography in diagnosing subclinical myocardial involvement associated with type 2 diabetes mellitus, cirrhosis, and antineoplastic treatments. This is clinically relevant as early and accurate identification of myocardial involvement can significantly impact patient management and outcomes, potentially preventing the progression of cardiovascular disorders in these high-risk populations. The study is a Phase III, prospective, multicenter, open-label trial, involving a total of 1,000 patients divided into four cohorts. No secondary objectives are specified in the study details.

The clinical trial involves a total of **1,000 participants** who are divided into four cohorts. The study population includes both **male and female** subjects aged **18 years and older**. Participants are selected based on the absence of previous heart disease, ensuring no significant cardiac structural alterations such as moderate or severe hypertrophy, altered segmental contraction, moderate or severe valvular heart disease, intraventricular obstructive gradient, or old myocardial infarction. Additionally, participants must have an acceptable ultrasound window for visualization of the left ventricular myocardium and maintain a sinus rhythm with a basal heart rate above 50 bpm. The trial focuses on individuals with cardiovascular alterations induced by **cirrhosis**, **diabetes mellitus**, and cardiotoxic treatments. The sponsor has not provided specific information regarding the total number of participants currently enrolled. The trial does not include a vulnerable population, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase III**, prospective, multicenter, open-label study designed to evaluate the efficacy of **esmolol hydrochloride** in the early identification of cardiovascular disorders induced by cirrhosis, diabetes mellitus, and cardiotoxic treatments. The trial is non-randomized and controlled, with a blinded analysis to ensure unbiased results. The study aims to include a total of 1,000 patients, divided into four cohorts, and is expected to conclude by December 31, 2025. Participants will be involved in the study for a period that aligns with the trial's estimated end date, with the possibility of early termination if specific conditions arise, such as adverse reactions or non-compliance with study protocols.

The trial involves a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥18 years), absence of previous heart disease, and the presence of an acceptable ultrasound window. Follow-up visits will be scheduled to monitor the participants' response to the intervention and to collect data on primary and secondary endpoints. The primary endpoints focus on the reduction in variability of left ventricular systolic function measurements and the comparison of diagnostic accuracy between esmolol echocardiography and baseline echocardiography. Secondary endpoints include the prognostic efficacy of cardiac function measures under esmolol infusion and the analysis of sympathetic hyperactivity at the cardiac level.

The study will utilize **esmolol hydrochloride** administered parenterally as a solution for infusion, with a maximum daily dose of 500 µg/kg. The trial's design does not require a placebo group, as the analysis and measurement of imaging are performed blind to the presence or absence of the drug. Participants will be monitored throughout the study, with an end-of-study visit to evaluate the overall outcomes and gather final data. The trial's methodology adheres to guidelines set by regulatory agencies, ensuring the scientific rigor and reliability of the results.

The clinical trial involves the administration of **esmolol hydrochloride**, marketed under the name BREVIBLOC 10 mg/ml, as the experimental medication. This pharmaceutical product is presented as a **solution for infusion** and is intended for **parenteral** administration. The dosage is specified as 500 µg/kg, with a maximum daily dose and total dose amounting to 500 µg/kg. The treatment period is limited to a maximum of one day. The active substance, esmolol hydrochloride, is of chemical origin and is classified under the ATC code C07AB09, indicating its role as a beta-blocker. The product is manufactured by Baxter SAS and is not formulated for pediatric use.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is designed to evaluate the efficacy of esmolol in the early identification of cardiovascular disorders induced by cirrhosis, diabetes mellitus, and cardiotoxic treatments. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the specified administration protocol. The study is a Phase III, multicenter, open-label trial, with a total of 1,000 patients divided into four cohorts, aiming to demonstrate the superiority of esmolol echocardiography over conventional echocardiography in diagnosing subclinical myocardial involvement.

The efficacy of esmolol in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on evaluating the reduction in variability of left ventricular (LV) systolic function measurements, using indices such as ejection fraction (EF), global longitudinal strain, and an alternative index, IVPD-IVUS. These measurements will be compared to establish patterns of normality and physiological changes in myocardial function, both at baseline and after esmolol administration. Additionally, the diagnostic accuracy of esmolol echocardiography will be compared with baseline echocardiography to identify myocardial damage associated with type 2 diabetes mellitus (DM2) and advanced cirrhosis, as well as to predict antineoplastic-induced cardiotoxicity. The study will also analyze the incremental value of molecular biomarkers in characterizing myocardial function and establishing diagnostic and prognostic criteria.

Secondary endpoints include assessing the prognostic efficacy of cardiac function measures obtained under esmolol infusion, such as IVPAD, EF, and strain, in predicting major cardiac events over a three-year follow-up period. The trial will also explore the prognostic implications of sympathetic hyperactivity at the cardiac level by evaluating changes in systolic function pre- and post-esmolol administration. Multi-modality imaging and plasma biomarkers will be used in combination to assess their incremental value in achieving the primary endpoint targets. The trial is designed as a prospective, multicenter, non-randomized study, with blinded analysis to ensure unbiased results. All clinical, laboratory, and imaging data will be reviewed by an Independent Drug Safety and Efficacy Monitoring Board (IDSEMB) to ensure the integrity and reliability of the efficacy assessments.