Efficacy of Esmolol in the Identification of Cardiovascular Disorders by Cirrhosis, Diabetes Mellitus and Cardiotoxic Treatments

NCT05769868 | Recruiting Phase 3 DMC

• 2 other identifiers: ICI20/000112021-003889-12
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to assess the superiority of esmolol echocardiography over conventional echocardiography in the diagnosis of subclinical myocardial involvement associated with diabetes mellitus 2, cirrhosis and antineoplastic treatments.

Conditions

Cirrhosis; Diabetes Mellitus; Oncologic Disorders

Keywords

beta blockers; echocardiography; esmolol; systolic function; cardiovascular diagnosis; biomarkers; diagnostic techniques; medical imaging

Outcome Measures

Primary Outcomes (3)

• Left Ventricle (LV) ejection fraction

  Estimated with 3D echocardiography (Both: convectional and with esmolol administration)

  At Baseline (Day 1) until Month-24 according to cohort

• Peak measurement of global LV systolic longitudinal strain

  Estimated with 3D echocardiography (Both: convectional and with esmolol administration)

  At Baseline (Day 1) until Month-24 according to cohort

• Ejection Intraventricular Pressure Difference (EIVPD) measure

  Estimated with M-mode echocardiography (Both: convectional and with esmolol administration)

  At Baseline (Day 1) until Month-24 according to cohort

Secondary Outcomes (9)

• Ejection fraction

  At Baseline (Day 1) until Month-24 according to cohort

• Interleukin (IL)-1β

  At Baseline (Day 1) until Month-24 according to cohort

• High-sensitivity IL-6 (hsIL-6)

  At Baseline (Day 1) until Month-24 according to cohort

• Soluble Suppression of Tumorigenicity 2 (ST-2)

  At Baseline (Day 1) until Month-24 according to cohort

• N-terminal fragment of brain natriuretic peptide (NT-proBNP)

  At Baseline (Day 1) until Month-24 according to cohort

Study Arms (1)

Single Arm

EXPERIMENTAL

1 conventional echocardiography without esmolol administration followed by 1 echocardiography with esmolol administration at Baseline and other study visits.

Drug: Esmolol Injection [Brevibloc]

Interventions

Esmolol Injection [Brevibloc] DRUG

Brevibloc® will be administered intravenously by infusion pump following the administration schedule: Loading dose of 500 μg/kg for 1 minute, followed by a maintenance infusion of 50 μg/kg/minute over 5 minutes. If the target response is not obtained, the loading dose is repeated and the 50 dose is increased by 50 μg/kg/minute to a maximum of 200 μg/kg/minute. The objective response to esmolol beta-blockade is defined as a 15-20% reduction in heart rate, with lower limits of 55 bpm and a systolic blood pressure not less than 90 mmHg and diastolic blood pressure not less than 50 mmHg. The perfusion is kept active while the echocardiography image acquisition is completed (approx. 15-30 min).

Also known as: Anatomical Therapeutic Chemical (ATC) code: C07AB09, Esmolol Hydrochloride

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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 Human Epidermal growth factor Receptor 2 (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.

You may not qualify if:

• 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 atrioventricular (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 Diabetes Mellitus (DM) of any type other than type 2 \[type 1, Latent Autoimmune Diabetes in Adults (LADA), Maturity-Onset Diabetes of the Young (MODY), New Onset Diabetes After Transplant (NODAT), etc.\]
• Patients in New York Heart Association (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 Hepatitis B Virus (HBV) or Hepatitis B Virus (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.

Sponsors & Collaborators

• Consorcio Centro de Investigación Biomédica en Red (CIBER): lead
• Instituto de Salud Carlos III: collaborator

Study Sites (6)

Hospital Universitari Vall d&#39;Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Clínic de Barcelona

Barcelona, Barcelona, 08036, Spain

NOT YET RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Hospital Clínico Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, Valencia, 46026, Spain

NOT YET RECRUITING

Related Publications (3)

• Yotti R, Bermejo J, Benito Y, Sanz-Ruiz R, Ripoll C, Martinez-Legazpi P, del Villar CP, Elizaga J, Gonzalez-Mansilla A, Barrio A, Banares R, Fernandez-Aviles F. Validation of noninvasive indices of global systolic function in patients with normal and abnormal loading conditions: a simultaneous echocardiography pressure-volume catheterization study. Circ Cardiovasc Imaging. 2014 Jan;7(1):164-72. doi: 10.1161/CIRCIMAGING.113.000722. Epub 2013 Oct 30.

  PMID: 24173273 BACKGROUND

• Yotti R, Bermejo J, Desco MM, Antoranz JC, Rojo-Alvarez JL, Cortina C, Allue C, Rodriguez-Abella H, Moreno M, Garcia-Fernandez MA. Doppler-derived ejection intraventricular pressure gradients provide a reliable assessment of left ventricular systolic chamber function. Circulation. 2005 Sep 20;112(12):1771-9. doi: 10.1161/CIRCULATIONAHA.104.485128.

  PMID: 16172285 BACKGROUND

• Yotti R, Ripoll C, Benito Y, Catalina MV, Elizaga J, Rincon D, Fernandez-Aviles F, Bermejo J, Banares R. Left ventricular systolic function is associated with sympathetic nervous activity and markers of inflammation in cirrhosis. Hepatology. 2017 Jun;65(6):2019-2030. doi: 10.1002/hep.29104. Epub 2017 Apr 28.

  PMID: 28195341 BACKGROUND

MeSH Terms

Conditions

Fibrosis; Diabetes Mellitus

Interventions

esmolol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Javier Bermejo Thomas, MD, PhD

  Hospital Universitario Gregorio Marañón

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tania Luis García, BS

CONTACT

+34 917996034; tanialuisgarcia@cibercv.es

Projects Department (CIBER)

CONTACT

+34 918222874; proyectos@ciberisciii.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: March 15, 2023
• Study Start: April 18, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: October 1, 2024

Record last verified: 2024-09

Locations

ES (6)