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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05769868




Registration number
NCT05769868
Ethics application status
Date submitted
15/02/2023
Date registered
15/03/2023
Date last updated
1/10/2024

Titles & IDs
Public title
Efficacy of Esmolol in the Identification of Cardiovascular Disorders by Cirrhosis, Diabetes Mellitus and Cardiotoxic Treatments
Scientific title
Prospective, Multicenter and Open Study to Evaluate the Efficacy of Esmolol in the Early Identification of Cardiovascular Disorders Induced by Cirrhosis, Diabetes Mellitus and Cardiotoxic Treatments
Secondary ID [1] 0 0
2021-003889-12
Secondary ID [2] 0 0
ICI20/00011
Universal Trial Number (UTN)
Trial acronym
CIBERbBECHO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cirrhosis 0 0
Diabetes Mellitus 0 0
Oncologic Disorders 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Diabetes
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Esmolol Injection [Brevibloc]

Experimental: Single Arm - 1 conventional echocardiography without esmolol administration followed by 1 echocardiography with esmolol administration at Baseline and other study visits.


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Left Ventricle (LV) ejection fraction
Timepoint [1] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Primary outcome [2] 0 0
Peak measurement of global LV systolic longitudinal strain
Timepoint [2] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Primary outcome [3] 0 0
Ejection Intraventricular Pressure Difference (EIVPD) measure
Timepoint [3] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [1] 0 0
Ejection fraction
Timepoint [1] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [2] 0 0
Interleukin (IL)-1ß
Timepoint [2] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [3] 0 0
High-sensitivity IL-6 (hsIL-6)
Timepoint [3] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [4] 0 0
Soluble Suppression of Tumorigenicity 2 (ST-2)
Timepoint [4] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [5] 0 0
N-terminal fragment of brain natriuretic peptide (NT-proBNP)
Timepoint [5] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [6] 0 0
Ultrasensitive troponin I (hsTnI)
Timepoint [6] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [7] 0 0
Procollagen type I terminal propeptide (PICP)
Timepoint [7] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [8] 0 0
C-terminal telopeptide collagen type I (CITP)
Timepoint [8] 0 0
At Baseline (Day 1) until Month-24 according to cohort
Secondary outcome [9] 0 0
Matrix metalloproteinase-1 (MMP-1)
Timepoint [9] 0 0
At Baseline (Day 1) until Month-24 according to cohort

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/04/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2027
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Spain
State/province [1] 0 0
Barcelona
Country [2] 0 0
Spain
State/province [2] 0 0
Madrid
Country [3] 0 0
Spain
State/province [3] 0 0
Salamanca
Country [4] 0 0
Spain
State/province [4] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Government body
Name
Consorcio Centro de Investigación Biomédica en Red (CIBER)
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Instituto de Salud Carlos III
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05769868
Trial related presentations / 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.
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.
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.
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Javier Bermejo Thomas, MD, PhD
Address 0 0
Hospital Universitario Gregorio Marañón
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tania Luis García, BS
Address 0 0
Country 0 0
Phone 0 0
+34 917996034
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05769868