Prospective, multicenter, open-label study to evaluate the efficacy of esmolol in the early identification of cardiovascular disorders induced by cirrhosis, diabetes mellitus, and cardiotoxic treatments.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 7
- 主要终点
- 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).
研究概览
简要总结
Phase III, publicly funded, prospective, multicenter, open to patients and operators, blinded at analysis, nonrandomized, controlled clinical trial to evaluate the superiority of esmolol echocardiography over conventional echocardiography in the diagnosis of subclinical myocardial involvement associated with DM2, cirrhosis, and antineoplastic treatments. The trial will include a total of n= 1,000 patients, divided into 4 cohorts.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •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.
- •Existence of at least an acceptable ultrasound window, allowing visualization of at least 14 of the 17 segments of the LV myocardium.
- •Sinus rhythm, with basal heart rate above 50 bpm.
排除标准
- •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.
- •Treatment with beta-blocking drugs (oral, topical or intravenous) in the last 7 days before the study.
- •History of ventricular or supraventricular arrhythmias that preclude safe withdrawal of antiarrhythmic or braking therapy prior to esmolol administration.
- •History of previous high-grade AV conduction disorder in patients without pacemakers.
- •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.
- •Women who are pregnant, or plan to become pregnant, and women who are breastfeeding.
- •Patients with limitation to follow the protocol for any cause.
结局指标
主要结局
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).
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).
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.
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.
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.
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.
To compare the predictive ability of esmolol echocardiography with baseline echocardiography for the prediction of antineoplastic-induced cardiotoxicity.
To compare the predictive ability of esmolol echocardiography with baseline echocardiography for the prediction of antineoplastic-induced cardiotoxicity.
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.
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.
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.
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.
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.
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.
次要结局
- 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).
- 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.
- 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.
研究者
Raquel Campo RESPONSABLE DEPARTAMENTO DE PROYECTOS
Scientific
Consorcio Centro De Investigacion Biomedica En Red