Using esmolol to improve heart disease diagnosis in patients with cirrhosis and diabetes

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

This study is testing if a special heart test using esmolol can help doctors find hidden heart problems in people with diabetes and liver disease.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1000 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER) (Government)
• Drugs / interventions: trastuzumab, chemotherapy
• Locations: 6 sites (Barcelona, Barcelona and 5 other locations)
• Trial ID: NCT05769868 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of esmolol-enhanced echocardiography compared to standard echocardiography in diagnosing subclinical heart issues in patients with diabetes mellitus type 2, cirrhosis, and those undergoing cancer treatments. Participants will undergo a screening period followed by baseline assessments and multiple follow-up visits over three years. The study will include blood sample collection and various health assessments to monitor cardiovascular function and biomarkers. Patients will be grouped based on their specific medical conditions for tailored evaluations.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with diabetes mellitus type 2 or cirrhosis, who have no prior heart disease.

Not a fit: Patients with significant pre-existing heart conditions or those unable to undergo echocardiography will likely not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to earlier and more accurate diagnosis of cardiovascular disorders in patients with complex medical conditions.

How similar studies have performed: Previous studies have shown promise in using beta-blockers like esmolol for cardiovascular assessments, but this specific application is relatively novel.

Eligibility criteria

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.

Where this trial is running

Barcelona, Barcelona and 5 other locations

• Hospital Universitari Vall d'Hebron — Barcelona, Barcelona, Spain (Recruiting)
• Hospital Clínic de Barcelona — Barcelona, Barcelona, Spain (Not_yet_recruiting)
• Hospital General Universitario Gregorio Marañón — Madrid, Madrid, Spain (Recruiting)
• Hospital Universitario La Paz — Madrid, Madrid, Spain (Recruiting)
• Hospital Clínico Universitario de Salamanca — Salamanca, Salamanca, Spain (Recruiting)
• Hospital Universitari i Politècnic La Fe — Valencia, Valencia, Spain (Not_yet_recruiting)

Study contacts

• Principal investigator: Javier Bermejo Thomas, MD, PhD — Hospital Universitario Gregorio Marañón
• Study coordinator: Tania Luis García, BS

Conditions Cirrhosis; Diabetes Mellitus; Oncologic Disorders; beta blockers; echocardiography; esmolol; systolic function; cardiovascular diagnosis