Esmolol hydrochloride for Liver cirrhosis|Type 2 diabetes mellitus|Antineoplastic-induced cardiotoxicity

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years.\n- Absence of previous heart disease, defined as the absence of relevant 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.\n- Existence of at least an acceptable ultrasound window, allowing visualization of at least 14 of the 17 segments of the LV myocardium.\n- Sinus rhythm, with basal heart rate above 50 bpm."}

Exclusion criteria

• {"criterion_text":"- Contraindication for the administration of esmolol (according to technical data sheet): a. Hypersensitivity to esmolol hydrochloride. b. Severe sinus bradycardia (HR < 50 bpm). c. 2nd or 3rd degree atrioventricular block without pacemaker. d. Cardiogenic shock, severe hypotension, or decompensated heart failure. e. Untreated pheochromocytoma. f. Acute asthmatic crisis. g. Concomitant intravenous administration or in the first 48 hours after administration of verapamil.\n- Treatment with beta-blocking drugs (oral, topical or intravenous) in the last 7 days before the study.\n- History of ventricular or supraventricular arrhythmias that preclude safe withdrawal of antiarrhythmic or braking therapy prior to esmolol administration.\n- History of previous high-grade AV conduction disorder in patients without pacemakers.\n- Severe asthma with bronchial hyperresponsiveness.\n- Patients with acute infection.\n- Participants in other clinical trials in the 30 days prior to the start of the study.\n- Women who are pregnant, or plan to become pregnant, and women who are breastfeeding.\n- Patients with limitation to follow the protocol for any cause."}

Primary endpoints

• {"endpoint_text":"- To determine the reduction in variability in the measurement of LV systolic function obtained by the combination of acute adrenergic blockade. This reduction variability will be studied with reference to two conventional indices (EF and global longitudinal strain) and an alternative index (IVPD-IVUS).","definition_or_measurement_approach":"Reduction in measurement variability studied by comparing LV systolic function indices: ejection fraction (EF), global longitudinal strain, and alternative index IVPD-IVUS under acute adrenergic blockade (esmolol)."}
• {"endpoint_text":"- To establish patterns of normality and physiological changes in the measurement of myocardial function during a longitudinal period in patients and healthy subjects, obtained at baseline and after administration of esmolol.","definition_or_measurement_approach":"Longitudinal measurements of myocardial function at baseline and post-esmolol administration to establish normal and physiological change patterns."}
• {"endpoint_text":"- To compare the diagnostic accuracy (ROC curve analysis) of esmolol echocardiography with baseline echocardiography to identify patients with myocardial damage associated with DM2 (with and without ICFEN) and advanced cirrhosis.","definition_or_measurement_approach":"Diagnostic accuracy assessed by ROC curve analysis comparing esmolol echocardiography versus baseline echocardiography for detection of myocardial damage in specified patient groups."}
• {"endpoint_text":"- To compare the predictive ability of esmolol echocardiography with baseline echocardiography for the prediction of antineoplastic-induced cardiotoxicity.","definition_or_measurement_approach":"Comparative assessment of predictive performance of esmolol versus baseline echocardiography for later development of antineoplastic-induced cardiotoxicity (predictive ability metrics implied)."}
• {"endpoint_text":"- To study the incremental value of molecular biomarkers for characterization by smololol echocardiography and for establishing diagnostic and prognostic criteria in patients with DM2, cirrhosis and cancer.","definition_or_measurement_approach":"Evaluation of added value of molecular biomarkers alongside esmolol echocardiography for diagnostic/prognostic characterization in patient groups."}
• {"endpoint_text":"- To analyze whether the degree of neurohumoral activation, inflammation and myocardial damage characterized by blood biomarkers condition the response to esmolol and the characterization of systolic function in different groups of patients.","definition_or_measurement_approach":"Analysis of relationship between blood biomarker levels (neurohumoral activation, inflammation, myocardial damage) and response to esmolol in systolic function characterization."}
• {"endpoint_text":"- To evaluate the added value of the combination of systolic function parameters determined by imaging techniques and circulating biomarkers for the diagnosis of myocardial involvement and prediction of events in different patient groups.","definition_or_measurement_approach":"Assessment of combined imaging systolic parameters and circulating biomarkers for diagnosis of myocardial involvement and event prediction (incremental value analyses)."}

Secondary endpoints

• {"endpoint_text":"- The secondary prognostic endpoint is defined as the superiority of cardiac function measures obtained under esmolol infusion (IVPAD, EF and strain) over baseline measures in predicting the incidence of major cardiac events (cardiovascular death, development of HF) at 3 years of follow-up (prognostic efficacy).","definition_or_measurement_approach":"Prognostic efficacy assessed by comparing esmolol-derived measures (IVPAD, EF, strain) versus baseline measures for prediction of major cardiac events over 3 years (incidence of cardiovascular death and heart failure)."}
• {"endpoint_text":"- To analyze the prognostic implications of determining the degree of detectable sympathetic hyperactivity at the cardiac level by changes in systolic function obtained immediately pre- and post-smolol in patients with DM2, cirrhosis and cancer.","definition_or_measurement_approach":"Analysis of prognostic implications of cardiac sympathetic hyperactivity estimated via immediate pre- and post-esmolol systolic function changes."}
• {"endpoint_text":"- The use of multi-modality imaging and plasma biomarkers in combination for targets present at the primary endpoint, as well as sensitivity and mediation analysis to see the incremental value of each modality.","definition_or_measurement_approach":"Use of multi-modality imaging plus plasma biomarkers with sensitivity and mediation analyses to estimate incremental contribution of each modality to primary endpoint targets."}

Spain

Earliest CTIS Part Ii Submission Date

28-05-2024

Latest Decision Or Authorization Date

27-06-2024

Processing Time Days

30

Number Of Sites

7

Number Of Participants

1000

Primary sponsor

Full Name

Consorcio Centro De Investigacion Biomedica En Red

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain