Cardiac Injury Due to Anthracycline in Paediatric Oncological Patients

May 6, 2025 updated by: IRCCS Burlo Garofolo

Prediction of Cardiac Injury Due to Anthracycline Chemotherapy in Paediatric Oncological Patients Using Advanced Echocardiography and Circulating Biomarkers.

The study investigates the role of echocardiography and of serum biomarkers (NT-proBNP, cardiac Troponin-I) in predicting cardiac injury in a cohort of paediatric oncological patients treated with Anthracycline chemotherapy.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Anthracycline chemotherapy (AC) can cause dose-related cardiomyocyte injury and death, possibly leading to left ventricular dysfunction. The most commonly accepted pathophysiological mechanism of anthracycline-induced cardiotoxicity is the oxidative stress hypothesis, which suggests that the generation of reactive oxygen species and lipid peroxidation of the cell membrane damage cardiomyocytes. However, there is considerable variability among patients in their susceptibility to anthracyclines: while many tolerate standard-dose anthracyclines without long-term complications, treatment-related cardiotoxicity may occur as early as after the first dose in other patients.

An increase in cancer survival, along with better awareness of the possible late effects of cardiotoxicity, has led to growing recognition of the need for surveillance of anthracycline-treated cancer survivors to prevent the development of heart failure.

Strategies for screening and detection of cardiotoxicity include cardiac imaging [echocardiography, nuclear imaging, cardiac magnetic resonance (CMR)] and biomarkers (troponin, natriuretic peptides).

The echocardiographic clinical standards for measuring left ventricular (LV) systolic function are LV ejection fraction (LVEF) and global longitudinal strain (GLS) with the latter as a more sensitive parameter to detect mild systolic dysfunction. There is abundant documentation that left ventricular ejection fraction (LVEF) is useful to guide clinical decisions, and emerging data show the clinical value of measuring global longitudinal strain (GLS). In the past, a study investigated the role of conventional- and speckle-tracking echocardiography in a cohort of asymptomatic children after anthracycline therapy, showing that impaired left ventricular myocardial deformation and mechanical dyssynchrony may exist after anthracycline therapy despite having normal left ventricular shortening fractions.

However, both left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) depend on left ventricular (LV) afterload and do not provide information regarding the ventricle's efficiency. Recently, the use of non-invasive myocardial work (MW) was proposed to measure left ventricular systolic function in a way that incorporates afterload and has the potential to quantify left ventricular (LV) energy waste.

Noninvasive myocardial work (MW) is a robust and reproducible index of left ventricular (LV) systolic performance. It correlates with myocardial metabolism and shows less afterload dependency than left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS).

Different studies have shown the potential role of myocardial work (MW) in predicting the response to cardiac resynchronisation therapy (CRT) in patients with heart failure and reduced ejection fraction (HFrEF). However, the role of myocardial work (MW) in cancer paediatric patients has not yet been fully investigated.

Study Type

Observational

Enrollment (Estimated)

22

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Paediatric oncological patients between 0 and 18 years with planned anthracycline therapy

Description

Inclusion Criteria:

  • Paediatric oncological patients 0-18 years
  • Planned start of anthracycline therapy
  • Normal left ventricular systolic function according to International Guidelines before the treatment with AC

Exclusion Criteria:

  • Previous anthracycline treatment, bone marrow transplantation or chest radiation
  • Pre-anthracycline treatment echocardiographic evidence of:
  • More than mild pericardial effusion
  • More than mild mitral regurgitation
  • Poor echocardiographic acoustic window

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Anthracycline therapy
Paediatric oncological patients receiving anthracycline chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity of change in myocardial work values 1 month after first Anthracycline chemotherapy treatment in predicting a decrease of the ejection fraction at 12 months
Time Frame: 12 months after first Anthracycline chemotherapy treatment
Patients will be evaluated with a complete echocardiogram, registering ejection fraction (EF) and myocardial work (MW) before the start of Anthracycline chemotherapy (AC) treatment and 1 and 12 months after first AC treatment. A Receiver operating characteristic (ROC) Curve will be constructed to evaluate the sensitivity of the myocardial work (MW) change in predicting a decrease in ejection fraction (EF). Youden index will be calculated to find the optimum value of the myocardial work (MW) discriminating the decrease or not of ejection fraction (EF).
12 months after first Anthracycline chemotherapy treatment
Sensitivity of change in myocardial work values 6 months after first Anthracycline chemotherapy treatment in predicting a decrease of the ejection fraction at 12 months
Time Frame: 12 months after first Anthracycline chemotherapy treatment
Patients will be evaluated with a complete echocardiogram, registering ejection fraction (EF) and myocardial work (MW) before the start of Anthracycline chemotherapy (AC) treatment and 6 and 12 months after first Anthracycline chemotherapy (AC) treatment. A Receiver operating characteristic (ROC) Curve will be constructed to evaluate the sensitivity of the myocardial work (MW) change in predicting a decrease in ejection fraction (EF). Youden index will be calculated to find the optimum value of the myocardial work (MW) discriminating the decrease or not of ejection fraction (EF).
12 months after first Anthracycline chemotherapy treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity of change in myocardial work values 1 month after first Anthracycline chemotherapy treatment combined with Troponin-I hs and NT-proBNP biomarkers in predicting a decrease of the ejection fraction at 12 months
Time Frame: 12 months after first Anthracycline chemotherapy treatment

Patients will be evaluated with a complete echocardiogram, registering ejection fraction (EF) and myocardial work (MW) before the start of Anthracycline chemotherapy (AC) treatment and 1 and 12 months after first Anthracycline chemotherapy (AC) treatment. Troponin-I hs and N-terminal pro b-type natriuretic peptide (NT-proBNP) will be evaluated in blood.

A Receiver operating characteristic (ROC) Curve will be constructed to evaluate the sensitivity of the myocardial work (MW) change combined with Troponin-I hs and NT-proBNP biomarkers in predicting a decrease in ejection fraction (EF).
12 months after first Anthracycline chemotherapy treatment
Sensitivity of change in myocardial work values 6 months after first Anthracycline chemotherapy treatment combined with Troponin-I hs and NT-proBNP biomarkers in predicting a decrease of the ejection fraction at 12 months
Time Frame: 12 months after first Anthracycline chemotherapy treatment

Patients will be evaluated with a complete echocardiogram, registering ejection fraction (EF) and myocardial work (MW) before the start of Anthracycline chemotherapy (AC) treatment and 1 and 12 months after first Anthracycline chemotherapy (AC) treatment. Troponin-I hs and N-terminal pro b-type natriuretic peptide (NT-proBNP) will be evaluated in blood.

A Receiver operating characteristic (ROC) Curve will be constructed to evaluate the sensitivity of the myocardial work (MW) change combined with Troponin-I hs and NT-proBNP biomarkers in predicting a decrease in ejection fraction (EF).
12 months after first Anthracycline chemotherapy treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Burlo Garofolo

Investigators

  • Principal Investigator: Thomas Caiffa, MD, IRCCS Burlo Garofolo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 21, 2023

Primary Completion (Estimated)

July 21, 2033

Study Completion (Estimated)

July 21, 2033

Study Registration Dates

First Submitted

March 20, 2025

First Submitted That Met QC Criteria

March 20, 2025

First Posted (Actual)

March 27, 2025

Study Record Updates

Last Update Posted (Actual)

May 9, 2025

Last Update Submitted That Met QC Criteria

May 6, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC 44/2023

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Injuries

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Qatar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe