Cardiovascular disorders induced by cirrhosis, diabetes mellitus and cardiotoxic treatments.
Conditions
Interventions
Trade Name: Brevibloc
Product Name: esmolol hydrochloride
Product Code: 670502
Pharmaceutical Form: Solution for injection
Sponsors
Consorcio Centro de Investigacion Biomedica en Red, M.P. (CIBER)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years. - Absence of previous heart disease, defined as the absence of relevant cardiac structural alterations such as moderate or severe hypertrophy, alteration of segmental contraction, Moderate or severe valvular disease, intraventricular obstructive gradient, or old myocardial infarction. - Existence of an at least acceptable ultrasonic window, which allows the visualization of at least 14 of the 17 segments of the LV myocardium. - Sinus rhythm, with a basal heart rate greater than 50 bpm. - Diabetic patients with a diagnosis of DM2 with or without HFNEF (n = 300) will be included. Previous diagnosis of HFNEF with clinical stability at the time of inclusion (n = 200). No previous diagnosis of HFNEF (n = 100). - 200 patients with cirrhosis stratified by the following additional criteria will be included: Child-Pugh A class (n = 25); Child-Pugh B class (n = 75); Child-Pugh C class (with and without ascites n = 50 and n = 50, respectively). - 300 cancer patients will be included, divided into 3 therapeutic groups: 125 patients diagnosed with Lymphoma or Sarcoma receiving chemotherapy based on anthracyclines at high doses (= 240 mg / m2); 125 patients with HER2 positive breast cancer receiving chemotherapy regimen that includes trastuzumab without anthracyclines; 50 patients with hepatocarcinoma receiving treatment with Sorafenib. - Expected survival> 6 months, first-diagnosis of cancer, and receiving treatment with chemotherapy that includes any of the previous schemes. - A control group (n = 200) without heart disease and without any of the study conditions will be included: diabetes from any cause, cancer or active cancer treatment or some degree of liver disease. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: - Contraindication for the administration of esmolol (according to technical data sheet): Hypersensitivity to esmolol hydrochloride; Severe sinus bradycardia (HR <50 bpm); 2nd or 3rd degree atrioventricular block without pacemaker; Cardiogenic shock, severe hypotension, or decompensated heart failure; Untreated pheochromocytoma; Acute asthmatic attack; Concomitant intravenous administration or within the first 48 hours after verapamil. - Treatment with beta-blocker drugs (oral, topical or intravenous) in the last 7 days before the study. - History of ventricular or supraventricular arrhythmias that prevent the safe withdrawal of antiarrhythmic or braking treatment before the administration of esmolol. - History of previous high-grade AV conduction disorder in non-pacemaker patients. - Severe asthma with bronchial hyperresponsiveness. - Patients with acute infection. - Participants in other clinical trials in the 30 days prior to the start of the study. - Pregnant women, or who plan to be, and women during breastfeeding. - Patients with limitation to follow the protocol for any reason. - Diagnosis of DM of any type other than type 2 (type 1, LADA, MODY, NODAT, etc.). - Patients in NYHA functional class IV or with advanced heart failure. - Treatment with an oral beta-blocker at the time of the examination that cannot be safely temporarily suspended 72 hours before the test. - Active evidence of HBV or HCV infection. - Personal history of previous cancer requiring systemic treatment (excludes skin or localized cancers treated locally surgically). - Previous exposure to systemic antitumor treatment or radiotherapy on the thoracic region.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Improve one of the still unresolved aspects of cardiovascular diagnosis. By combining a simple pharmacological intervention with a safe, ultra-short-acting drug, a fundamental parameter can be obtained to guide therapeutic decision-making in patients with a large number of cardiac and extra-cardiac diseases.;Timepoint(s) of evaluation of this end point: Patients with DM2 and cirrhosis: ECHO with esmolol at Day 1. ECHO without esmolol at Day 1 and month 12. Cancer patients: ECHO with esmolol at Day 1, Month 1, Month 3, Month 6. ECHO without esmolol at Day 1, Month 1, Month 3, Month 6, Month 12, Month 24. NMR at Day 1, Month 12. Control Group: ECHO with esmolol at Day 1, Month 3, Month 6. ECHO without esmolol at Day 1, Month 3, Month 6, Month 12.;Main Objective: To evaluate the efficacy of esmolol in the early identification of cardiovascular disorders induced by cirrhosis, diabetes mellitus and cardiotoxic treatments.;Secondary Objective: 1. To determine the reduction of variability in the measurement of LV systolic function that is obtained by the combination of acute adrenergic blockade. This reduction in variability will be studied with reference to two conventional indices (EF and global longitudinal strain) and an alternative index (IVPD). 2. Establish the normality patterns and physiological changes in the measurement of myocardial function during a longitudinal period in healthy patients , obtained at baseline and after the administration of esmolol. 3. 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 HFNEF) and advanced cirrhosis. 4. To compare the anticipation capacity of esmolol echocardiography with baseline echocardiography for the prediction of antineoplastic-induced cardiotoxicity. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To study the incremental value that molecular biomarkers contribute to characterization by echocardiography with esmolol and to establish diagnostic and prognostic criteria in patients with DM2, cirrhosis and cancer. 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 the different groups of patients.;Timepoint(s) of evaluation of this end point: Patients with DM2 and cirrhosis: Biomarkers at Day 1 and Month 12. Cancer patients: Biomarkers at Day 1, Month 1, Month 3, Month 6, Month 12, Month 24. Control Group: Biomarkers at Day 1, Month 3, Month 6, Month 12. | — |
Countries
Spain
Contacts
Public ContactRebeca
Consorcio Centro de Investigacion Biomedica en Red, M.P. (CIBER)
Outcome results
None listed