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

NCT ID: NCT05769868

Last Updated: 2024-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-18

Study Completion Date

2027-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cirrhosis Diabetes Mellitus Oncologic Disorders

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Single Arm

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

Group Type EXPERIMENTAL

Esmolol Injection [Brevibloc]

Intervention Type 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).

Interventions

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Esmolol 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).

Intervention Type DRUG

Other Intervention Names

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Anatomical Therapeutic Chemical (ATC) code: C07AB09 Esmolol Hydrochloride

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role collaborator

Consorcio Centro de Investigación Biomédica en Red (CIBER)

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Javier Bermejo Thomas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Gregorio Marañón

Locations

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Hospital Universitari Vall d&#39;Hebron

Barcelona, Barcelona, Spain

Site Status RECRUITING

Hospital Clínic de Barcelona

Barcelona, Barcelona, Spain

Site Status NOT_YET_RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Clínico Universitario de Salamanca

Salamanca, Salamanca, Spain

Site Status RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, Valencia, Spain

Site Status NOT_YET_RECRUITING

Countries

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Spain

Central Contacts

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Tania Luis García, BS

Role: CONTACT

+34 917996034 ext. 47304

Projects Department (CIBER)

Role: CONTACT

+34 918222874

Facility Contacts

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José F Rodríguez Palomares, MD, PhD

Role: primary

+34 932746134

Marta Sitges Carreño, MD, PhD

Role: primary

+34 932275722

Javier Bermejo Thomas, MD, PhD

Role: primary

+34 915868279

Esther Pérez David, MD, PhD

Role: primary

+34 639607988

Candelas Pérez del Villar Moro, MD

Role: primary

+34 620778540

Jaume Agüero Ramón-Llin, MD, PhD

Role: primary

+34 629378483

References

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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.

Reference Type BACKGROUND
PMID: 24173273 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16172285 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28195341 (View on PubMed)

Other Identifiers

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2021-003889-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ICI20/00011

Identifier Type: -

Identifier Source: org_study_id

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