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 (CIBER-bB-ECHO).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorcio Centro De Investigacion Biomedica En Red

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

27 Jun 2024 → ongoing

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514880-25-00

EudraCT number

2021-003889-12

ClinicalTrials.gov

NCT05769868

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Efficacy

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.

Conditions and MedDRA coding

Patients with cardiovascular alterations induced by cirrhosis, diabetes mellitus and cardiotoxic treatments.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥ 18 years.
2. 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.
3. Existence of at least an acceptable ultrasound window, allowing visualization of at least 14 of the 17 segments of the LV myocardium.
4. Sinus rhythm, with basal heart rate above 50 bpm.

Exclusion criteria 9

1. 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.
2. Treatment with beta-blocking drugs (oral, topical or intravenous) in the last 7 days before the study.
3. History of ventricular or supraventricular arrhythmias that preclude safe withdrawal of antiarrhythmic or braking therapy prior to esmolol administration.
4. History of previous high-grade AV conduction disorder in patients without pacemakers.
5. Severe asthma with bronchial hyperresponsiveness.
6. Patients with acute infection.
7. Participants in other clinical trials in the 30 days prior to the start of the study.
8. Women who are pregnant, or plan to become pregnant, and women who are breastfeeding.
9. Patients with limitation to follow the protocol for any cause.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. 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).
2. 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.
3. 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.
4. To compare the predictive ability of esmolol echocardiography with baseline echocardiography for the prediction of antineoplastic-induced cardiotoxicity.
5. 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.
6. 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.
7. 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.

Secondary endpoints 3

1. 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).
2. 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.
3. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorcio Centro De Investigacion Biomedica En Red

Sponsor organisation

Consorcio Centro De Investigacion Biomedica En Red

Address

Pab 11, Avenida De Monforte De Lemos 3-5 Avenida De Monforte De Lemos 3-5

City

Madrid

Postcode

28029

Country

Spain

Scientific contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Raquel Campo RESPONSABLE DEPARTAMENTO DE PROYECTOS

Public contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Raquel Campo RESPONSABLE DEPARTAMENTO DE PROYECTOS

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications