Prediction of Delayed Toxic Cardiomyopathy in Children (SpeckleAnthra2)

Longitudinal Analysis of Myocardial Function by Speckle Tracking Echocardiography and Prediction of Delayed Toxic Cardiomyopathy Associated With Anthracycline Therapy in Children

Longitudinal analysis of myocardial function using "Speckle Tracking Echocardiography" STE analysis and prediction of delayed toxic induced cardiomyopathy in young patients who received anthracycline therapy in childhood.

Study Overview

• Status: Terminated
• Conditions: Childhood Cancer; Cardiotoxicity
• Intervention / Treatment: Diagnostic test: cardiac ultrasound with speckle tracking analysis

Detailed Description

Anthracycline therapy may have short-, medium- or long-term cardiac toxicity that impacts patient's life. The main recognized risk factors for delayed cardiotoxicity are cumulative anthracycline dose, female gender, association with mediastinal radiotherapy and young age at administration. Prediction of delayed cardiotoxicity in children population is still challenging.

The "Speckle Tracking Echocardiography" (STE) method, an innovative echocardiographic technique, analyses the myocardial displacement of natural acoustic markers via a software. The objective of the study is to analyze, in young patients who received anthracycline therapy in childhood, 5-years after their inclusion in the "Speckle Anthra" study and first STE results, the evolution of myocardial function using STE method.

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Pediatric and Congenital Cardiology and Pulmonology Department, Arnaud De Villeneuve University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 27 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

ANTHRA GROUP

Inclusion Criteria:

• Patients who were treated with anthracyclines for malignant disease between the ages of 0 and 18
• Patient aged 11 to 27 years
• Included in the "SpeckleAnthra" Study (NCT02893787)
• Discontinued chemotherapy for more than 6 years
• Patient in remission of malignant disease
• Enrolled in a social security plan
• Written informed consent from at least one legal representative for the minor patient/ Written informed consent for patients of legal age

Exclusion Criteria:

• Onset of active malignancy or recurrence of malignancy after the "Speckle Anthra" study that required resumption of chemotherapy or mediastinal radiotherapy.
• Chronic cardiac, pulmonary or muscular pathology of etiology other than secondary to anthracycline therapy
• For adult patients: subject under guardianship or curators

CONTROL GROUP

Inclusion Criteria:

• Control patient included in the "Speckle Control" study (NCT02056925)
• Had a cardiological consultation with echocardiography performed for a banal reason (heart murmur test, cardiological symptoms) and whose result was normal
• No chronic disease or long-term drug treatment

Exclusion Criteria:

• Refusal to participate in the study by the patient and/or parents or legal guardian after receipt of the study's information and non-objection note.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Cardiac ultrasound analysis with speckle tracking of age- and sex-matched healthy patients in the Anthra2 group	Diagnostic test: cardiac ultrasound with speckle tracking analysis; Experimental group: cardiac ultrasound with speckle tracking analysis done during a regular cardiac visit planned after receiving cardiotoxic chemotherapy in childhood. Control group: cardiac ultrasound with speckle tracking analysis done during a cardiac visit for minor symptoms (murmur, physical aptitude). Advocated Tomtec software will be used to make post-processing speckle tracking analysis based on 2D ultrasound cineloop acquired during a standard echocardiography.
Experimental: Anthra2; Patient will have an echocardiography with speckle tracking analysis 5 years after the end of their participation to "SpeckleAnthra" study (NCT02893787)	Diagnostic test: cardiac ultrasound with speckle tracking analysis; Experimental group: cardiac ultrasound with speckle tracking analysis done during a regular cardiac visit planned after receiving cardiotoxic chemotherapy in childhood. Control group: cardiac ultrasound with speckle tracking analysis done during a cardiac visit for minor symptoms (murmur, physical aptitude). Advocated Tomtec software will be used to make post-processing speckle tracking analysis based on 2D ultrasound cineloop acquired during a standard echocardiography.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricle Global Longitudinal 2D strain (LVGLS) expressed in percentage and obtained from cardiac ultrasound cineloop of 2D 4,3 and 2 apical views analyzed by the Tomtec STE Software.	To compare the evolution at 5 years ("Anthra2" study timeframe) of LVGLS obtained by STE analysis on patients treated with anthracyclines in childhood and previously included in first "Speckle Anthra" study, with the normal evolution of this parameter with age in healthy matched volunteers.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death secondary to toxic cardiomyopathy	Correlation between the rate of patients died with a toxic cardiomyopathy and the left global longitudinal 2D strain expressed in percentage and measured during the previous SpeckleAnthra study	5 years
Left Ventricle Ejection fraction (LVEF) by Simpson method (%)	Compare the standard ultrasound parameter LVEF and the LVGLS obtained in "Speckle Anthra 2" on patients treated with anthracyclines in childhood and in the group of healthy volunteers.	The day of inclusion
Left ventricular myocardial dysfunction defined by LVEF < 55%	Correlation between the left ventricular myocardial dysfunction is defined by FeVG < 55% and the left global longitudinal 2D strain expressed in percentage and measured during the previous SpeckleAnthra study	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Troponin T on the experimental group	Troponin T is a biological markers of cardiotoxicity obtained in a standard blood test analysis and expressed in ng/ml. normal troponin value is between 0 and 0.04 ng/mL	The day of inclusion
Known risk factors for cardiotoxicity	To assess the effect of known risk factors for anthracycline cardiotoxicity, the anthracycline cumulative dose will be collected	the day of inclusion
NT-pro-BNP on the experimental group	NT-pro-BNP (N terminal-pro-brain natriuretic peptides) is a biological markers of cardiotoxicity obtained in a standard blood test analysis and expressed in pg/ml. Normal NT-proBNP value is < 400pg/ml	The day of inclusion
Known risk factors for cardiotoxicity	To assess the effect of known risk factors for anthracycline cardiotoxicity, young age at administration will be collected	the day of inclusion
Known risk factors for cardiotoxicity	To assess the effect of known risk factors for anthracycline cardiotoxicity, female gender, will be collected	the day of inclusion
Known risk factors for cardiotoxicity	To assess the effect of known risk factors for anthracycline cardiotoxicity, association with mediastinal radiotherapy will be collected	The day of inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: VINCENTI Marie, PH, University Hospital, Montpellier

Publications and helpful links

General Publications

• Amedro P, Vincenti M, Abassi H, Lanot N, De La Villeon G, Guillaumont S, Gamon L, Mura T, Lopez-Perrin K, Haouy S, Sirvent A, Cazorla O, Vergely L, Lacampagne A, Avesani M, Sirvent N, Saumet L. Use of speckle tracking echocardiography to detect late anthracycline-induced cardiotoxicity in childhood cancer: A prospective controlled cross-sectional study. Int J Cardiol. 2022 May 1;354:75-83. doi: 10.1016/j.ijcard.2022.02.012. Epub 2022 Feb 12.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2023
• Primary Completion (Actual): January 7, 2025
• Study Completion (Actual): January 7, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Echocardiography; Stroke Volume; Ventricular function
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Heart Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cardiomyopathies; Cardiotoxicity
• Other Study ID Numbers: RECHMPL22_0513

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: sharing of results after obtaining
• IPD Sharing Time Frame: 5years
• IPD Sharing Access Criteria: Clinical trials
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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