Prevention of Chemotherapy Induced Cardiotoxicity in Children With Bone Tumors and Acute Myeloid Leukemia

NCT03389724 | Completed Phase 3

• 1 other identifier: CCHE -AML0001
• Study Type: interventional
• Target: 245
• Locations: 1 country
• Sites: 1

Brief Summary

Prevention and early detection of chemotherapy-induced cardiotoxicity in children with bone tumors and Acute Myeloid Leukemia by giving capoten

Conditions

Cardiotoxicity; Acute Myeloid Leukemia in Children; Bone Tumor

Outcome Measures

Primary Outcomes (3)

• To determine the effect of ACE-I in preventing chemotherapy-related cardiotoxicity using both investigation techniques: Troponin I level and cardiac imaging ( TTE, TDI, STE).

  ALL patients will be subjected to the following cardiac imaging ( TTE, TDI, STE) at the each time intervals of the study. Plasma troponin I (TnI) concentration will be measured for all the patients at the each time intervals of the study.

  3 years

• To determine the role of Troponin I (TnI) as an early marker of cardiac toxicity

  Troponin I (TnI) concentration is to be determined by a fluorometric enzyme immunoassay analyzer (Stratus CS, Dade Behring, Miami, Fla) with a functional sensitivity of 0.03 g/L; the cutoff level was 0.08 ng/mL. Plasma troponin I (TnI) concentration will be measured in both groupsas follows : * Early TnI: TnI concentration will be measured before and soon after each cycle of HDC. Determination of early TnI consists of a curve of assays (2ml blood sample): baseline initially, before \& after immediately, and 12 and 24 hours after the end of Anthracycline chemotherapy infusion.This sequence will be repeated with each cycle of therapy containing Anthracycline. For each patient, the highest TnI value will be considered for each chemotherapy cycle. * Late TnI: TnI value also is to be determined at the end of treatment and 2, 3, 6, and 12 months after end of treatment in both groups.

  3 years

• To measure the accuracy of other radiological techniques for early detection of cardiotoxicity like Tissue Doppler Imaging (TDI) and Speckle-tracking Echo (STE).

  Patients will be evaluated Clinically for cardiac functions using ECG , conventional echo, Tissue Doppler Imaging (TDI) and SpeckelTracking Echocardiography STE , before each chemotherapy cycle maximum one week given

  3 years

Study Arms (2)

Group capoten (Intervention arm)

EXPERIMENTAL

Patients will receive prophylactic ACE-I(Capoten®) at day 1 of initiation of chemotherapy and is to be continued for 1 year after the end of treatment. Patients will remain on this arm until they experience any of the study primary or secondary end-point where they will be off-study and will receive cardiotoxicity treatment independently.

Drug: Capoten®

Group standard treatment (Control arm)

NO INTERVENTION

Patients will not receive ACE-I as prophylaxis, and will be monitored and evaluated for first signs of cardiotoxicity based on the above mentioned end-points.

Interventions

Capoten® DRUG

ACE-I (Capoten®) will be given to patients in the Intervention arm with the start of chemotherapy, twice daily at a dose of 0.5 mg/kg/day (divided over 2 doses)

Also known as: Captopril

Group capoten (Intervention arm)

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All Acute Myeloid Leukemia and Bone Tumors patients (Osteosarcoma and Ewing's Sarcoma) who didn't receive chemotherapy will be included in the study.
• Written Informed Consent from parents/guardian

You may not qualify if:

• Patients who received chemotherapy before starting of the study
• Patients with history of cardiac impairment, (existing or congenital heart disease).
• Patients who show intolerance or contra-indications to ACE-I.
• Patients developing acute (\< 2 weeks) cardiotoxicity after the first high-dose chemotherapy (HDC) course.

Sponsors & Collaborators

• Children's Cancer Hospital Egypt 57357: lead

Study Sites (1)

Children's Cancer Hospital Egypt 57357 Cairo, Egypt

Cairo, Egypt

Location

MeSH Terms

Conditions

Cardiotoxicity; Bone Neoplasms

Interventions

Captopril

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms by Site; Neoplasms; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Zeniab salah, MD

  Children's Cancer Hospital Egypt 57357 Cairo, Egypt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective randomized study where all patients presenting to the CCHE with de novo diagnosis of Bone tumor (ES and OS) and AML will be randomized to receive (Intervention arm) or not to receive (Control arm) prophylactic ACE-I with the start of chemotherapy.

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: January 4, 2018
• Study Start: November 14, 2017
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: November 8, 2022

Record last verified: 2022-11

Locations

EG (1)