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RecruitingNCT05769868CIBERbBECHOUpdated Oct 1, 2024

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

A Phase 3 interventional study of Esmolol Injection [Brevibloc] in Cirrhosis, Diabetes Mellitus and Oncologic Disorders, sponsored by Consorcio Centro de Investigación Biomédica en Red (CIBER). Recruiting at 6 sites in Spain. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-10-01.

Sponsored by Consorcio Centro de Investigación Biomédica en Red (CIBER) · Phase 3, Interventional, and Diagnostic

From the registry’s dates

  • Started Apr 2023; still recruiting 3 years 5 months later.
Phase
Phase 3
Study type
Interventional
Enrollment
1,000
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

After being informed about the study and potential risks, all patients giving written informed consent will undergo a 10 days screening period to determine eligibility for study entry. At Baseline, patients who meet the eligibility requirements will be allocate in one of the 4 cohorts according to their medical conditions.

Trial design consists in a Screening period, Baseline, and 6 additional visits until Month-36.

All patients will undergo to a conventional echocardiography and echocardiography with esmolol administration at Baseline. This procedure will be performed at the following visits according their cohort.

Other complementary procedures will be the collection of blood samples to determine biomarkers, as well as hematology and biochemistry, vital signs and another explorations.

02

Conditions studied

  • Cirrhosis
  • Diabetes Mellitus
  • Oncologic Disorders

Keywords

  • beta blockers
  • echocardiography
  • esmolol
  • systolic function
  • cardiovascular diagnosis
  • biomarkers
  • diagnostic techniques
  • medical imaging
03

In context

Liver Cirrhosis

1,642 studies on the registry are indexed under Liver Cirrhosis; 358 are open to participants now.

This study's planned enrollment of 1,000 is above the median of 72 across 995 interventional studies indexed under Liver Cirrhosis.

Browse Liver Cirrhosis studies →

Lead sponsor

Consorcio Centro de Investigación Biomédica en Red (CIBER) is the lead sponsor of 18 studies on the registry; 7 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  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, alteration of segmental contraction, Moderate or severe valvular disease, intraventricular obstructive gradient, or old myocardial infarction.
  3. Existence of an at least acceptable ultrasonic window, which allows the visualization of at least 14 of the 17 segments of the LV myocardium.
  4. Sinus rhythm, with a basal heart rate greater than 50 bpm.
  5. Diabetic patients with a diagnosis of Diabetes Mellitus 2 (DM2) with or without Heart Failure with Normal Ejection Fraction (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).
  6. 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).
  7. 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 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.
  8. Expected survival> 6 months, first-diagnosis of cancer, and receiving treatment with chemotherapy that includes any of the previous schemes.
  9. 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.

Exclusion criteria

Exclusion Criteria:

  1. 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.
  2. Treatment with beta-blocker drugs (oral, topical or intravenous) in the last 7 days before the study.
  3. History of ventricular or supraventricular arrhythmias that prevent the safe withdrawal of antiarrhythmic or braking treatment before the administration of esmolol.
  4. History of previous high-grade atrioventricular (AV) conduction disorder in non-pacemaker patients.
  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. Pregnant women, or who plan to be, and women during breastfeeding.
  9. Patients with limitation to follow the protocol for any reason.
  10. 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.]
  11. Patients in New York Heart Association (NYHA) functional class IV or with advanced heart failure.
  12. Treatment with an oral beta-blocker at the time of the examination that cannot be safely temporarily suspended 72 hours before the test.
  13. Active evidence of Hepatitis B Virus (HBV) or Hepatitis B Virus (HCV) infection.
  14. Personal history of previous cancer requiring systemic treatment (excludes skin or localized cancers treated locally surgically).
  15. Previous exposure to systemic antitumor treatment or radiotherapy on the thoracic region.
05

Study design

Phase
Phase 3
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
1,000 participants (estimated)

Study arms

  • Experimental
    Single Arm

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

    Drug: Esmolol Injection [Brevibloc]

Interventions

  • DrugEsmolol Injection [Brevibloc]

    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

06

What researchers measure

Primary outcomes

  1. Left Ventricle (LV) ejection fraction

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

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

  2. Peak measurement of global LV systolic longitudinal strain

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

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

  3. Ejection Intraventricular Pressure Difference (EIVPD) measure

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

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

Secondary outcomes

  1. Ejection fraction

    Obtained with 2D echocardiography (Simpson's biplane method)

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

  2. Interleukin (IL)-1β

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

  3. High-sensitivity IL-6 (hsIL-6)

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

  4. Soluble Suppression of Tumorigenicity 2 (ST-2)

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

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

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

  6. Ultrasensitive troponin I (hsTnI)

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

  7. Procollagen type I terminal propeptide (PICP)

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

  8. C-terminal telopeptide collagen type I (CITP)

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

  9. Matrix metalloproteinase-1 (MMP-1)

    Biochemical variables in blood in relation to the alteration of the different components of the myocardium

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

07

Study locations

4 of 6 sites recruiting
  • Hospital Universitari Vall d&#39;Hebron
    Barcelona, 08035, Spain
    Recruiting
  • Hospital Clínic de Barcelona
    Barcelona, 08036, Spain
    Not yet recruiting
  • Hospital General Universitario Gregorio Marañón
    Madrid, 28007, Spain
    Recruiting
  • Hospital Universitario La Paz
    Madrid, 28046, Spain
    Recruiting
  • Hospital Clínico Universitario de Salamanca
    Salamanca, 37007, Spain
    Recruiting
  • Hospital Universitari i Politècnic La Fe
    Valencia, 46026, Spain
    Not yet recruiting
08

References and documents

Publications

  • 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. PubMed 24173273 ↗
  • 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. PubMed 16172285 ↗
  • 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. PubMed 28195341 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 1, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05769868
Lead sponsor
Consorcio Centro de Investigación Biomédica en Red (CIBER)
Collaborators
Instituto de Salud Carlos III
Responsible party
Sponsor
First posted
Mar 15, 2023
Start date
Apr 18, 2023
Primary completion
Mar 2027 (estimated)
Completion
Sep 2027 (estimated)
Last update
Oct 1, 2024

Study contacts

Tania Luis García, BS
Contact
tanialuisgarcia@cibercv.es
+34 917996034 ext. 47304
Projects Department (CIBER)
Contact
proyectos@ciberisciii.es
+34 918222874
Javier Bermejo Thomas, MD, PhD
principal investigator · Hospital Universitario Gregorio Marañón

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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