Evaluation of Cardiac and Endothelial Function in Children and Adolescents Treated With Anthracycline (CARDIO-PED)

Evaluation of Cardiac and Endothelial Function Measured by Laboratory Biomarkers and Echocardiographic and Endothelial Testing in Children and Adolescents Treated With Anthracyclines

In recent decades, the survival rate of children with cancer has increased significantly thanks to personalized treatments and the adoption of international therapeutic protocols. However, along with this increase in survival, side effects related to these treatments on various organs and systems have been observed.

Among the most widely used chemotherapeutic agents in pediatric age, anthracyclines play a crucial role in the treatment of various forms of neoplasms (both haematological such as acute lymphoblastic leukemia or lymphomas, and solid tumors such as sarcomas). However, in addition to their excellent antineoplastic effect, they are burdened by the potential for cardiotoxicity. This cardiotoxicity manifests clinically with left ventricular systolic dysfunction and arrhythmias.

At the moment, international guidelines recommend long-term cardiac follow-up evaluations for this group of patients, even after treatment has concluded.The methods used in the cardiac follow-up of patients undergoing anthracycline therapy include echocardiography, cardiac magnetic resonance imaging, tests to assess endothelial function, and measurements of the biomarkers troponin and atrial natriuretic peptide. These methods can assess anthracycline-induced cardiac and endothelial damage once it has already occurred, but they cannot predict its onset nor can they study its pathogenesis.

Furthermore, to date, no information is available regarding the possibility of using "endothelial-mesenchymal transition" biomarkers as predictors of the onset of anthracycline-induced cardiac damage.

This study analyzes these biomarkers as predictive tools for cardiac damage. Specifically, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will be measured in patients treated with anthracycline. The concentrations of these biomarkers will be compared with the results of the echocardiogram and with the treatments performed in order to identify any relationships. Furthermore, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will also be measured in a population of healthy subjects in order to obtain data on a possible relationship between the biomarkers and the anthracycline therapies performed.

Study Overview

• Status: Not yet recruiting
• Conditions: Chemotherapeutic Toxicity; Childhood Cancer Survivors; Anthracycline Related Cardiotoxicity in Childhood Cancers
• Intervention / Treatment: Diagnostic test: Biomarker detection; Diagnostic test: Biomarker detection

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Antonio Ruggiero, MD; Phone Number: +39 0630158305; Email: antonio.ruggiero@unicatt.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    • Contact: Antonio Ruggiero, MD; Phone Number: +39 0630158305; Email: antonio.ruggiero@policlinicogemelli.it
    • Principal Investigator: Antonio Ruggiero, MD
    • Sub-Investigator: Alberto Romano, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The patient group will be selected among patients who have undergone anthracycline therapy and are undergoing regular follow-up at the Pediatric Oncology Unit of the Fondazione Policlinico Universitario A. Gemelli in Rome. Information about the tumor, treatments, and cardiac monitoring (echocardiogram) must be available for all patients. The control group will be selected from patients who visit the Pediatric Oncology Unit for a hematological evaluation but who have never undergone anthracycline therapy and have no known cardiac problems. All subjects (patients and controls) will undergo a thorough medical history and a clinical assessment, including a physical examination and measurement of vital signs and anthropometric parameters. Furthermore, all enrolled subjects, both patients and controls, will be required to collect, at a routine blood sampling time, a 6 ml tube for the measurement of biomarkers of endothelial-mesenchymal transition and endothelial activation.

Description

Inclusion Criteria for the patient group:

• diagnosis of cancer during childhood (diagnosis made between 0 and 16 years of age);
• age at enrollment greater than or equal to 6 years;
• having received anthracycline chemotherapy;
• disease remission for at least 1 year;
• absence of known cardiac disease prior to anthracycline therapy;
• absence of congenital heart disease.

Exclusion Criteria for the patient group:

• disease remission for less than 1 year;
• age less than 6 years at the time of enrollment;
• presence of known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).

Inclusion Criteria for the control group:

• age at the time of enrollment: 6 years or older;
• good health.

Exclusion Criteria for the control group:

• having had oncological diseases;
• having undergone thoracic radiotherapy;
• having undergone anthracycline chemotherapy;
• being under 6 years of age at the time of enrollment;
• having known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with anthracyclines; Patients who recovered from cancers and who underwent treatment with anthracyclines (from January 2010 to November 2024) and are undergoing regular follow-up. Inclusion criteria for the patient group: diagnosis of hematologic oncology during childhood (diagnosis made between 0 and 16 years of age);; age at enrollment greater than or equal to 6 years;; having received anthracycline chemotherapy;; disease remission for at least 1 year;; absence of known cardiac disease prior to anthracycline therapy;; absence of congenital heart disease.	Diagnostic test: Biomarker detection; All patients will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin. In addition, the study will collect the following anamnestic data: patient demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data;; data relating to the neoplastic pathology and treatment performed; Diagnostic test: Biomarker detection; All controls will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin. In addition, the study will collect information on demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data.
Control group; Subjects never treated with anthracyclines and free of cancer. Inclusion criteria for the control group: Age at enrollment greater than or equal to 6 years;; Good health.	Diagnostic test: Biomarker detection; All patients will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin. In addition, the study will collect the following anamnestic data: patient demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data;; data relating to the neoplastic pathology and treatment performed; Diagnostic test: Biomarker detection; All controls will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin. In addition, the study will collect information on demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the possible presence of differences in the concentration of early biomarkers of "endothelial-mesenchymal transition" and endothelial damage between subjects treated with anthracycline therapy and healthy controls.	Measurement of the concentration of biomarkers of endothelial-mesenchymal transition and endothelial damage (Serpin 3, THBS1, TGF-beta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, endothelin) in patients who had recovered from cancer and underwent anthracycline therapy and compared with controls.	Biomarker assays will be performed only upon enrollment.
To evaluate possible associations between measured biomarkers and echocardiogram results and medical history in subjects treated with anthracycline therapy.	Measurement of the linear correlation between biomarkers and the results obtained in the echocardiographic examination and the treatments performed.	Biomarkers and medical history will be collected at the moment of enrollement in the study

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Antonio Ruggiero, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Childhood cancer survivors; Anthracycline related cardiotoxicity; Chemotherapy long term side effects; Cancer survivor follow up
• Other Study ID Numbers: 7304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No