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Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox)

Primary Purpose

Cancer

Status
Recruiting
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Carvedilol
Placebo
Sponsored by
Hospital Sirio-Libanes
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cancer focused on measuring Carvedilol, Anthracyclines, Cardiotoxicity, Chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • ≥18 years of age at the time of screening
  • Cancer patients that will receive chemotherapy with anthracyclines.

Exclusion Criteria:

  • Inability to adequate asses left ventricular function
  • Previous history of heart failure
  • Previous history of any cardiomyopathy (eg.: valve disease, Chagas' disease, infiltrative cardiomyopathy)
  • LVEF < 50%
  • Previous history of myocardial revascularization
  • Permanent tachyarrhythmia (flutter, atrial fibrillation, atrial tachycardia)
  • Contra-indication to the use of beta-blockers.
  • Trastuzumab indication
  • Pregnant or Breast-feeding females.
  • On kidney replacement therapy
  • ECOG >= 4 or Karnofsky <=30
  • Advanced hepatic failure (C score Child-Pugh and MELD > 15);
  • Previous use of anthracycline
  • Have any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study
  • Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Sites / Locations

  • Hospital Sirio LibanesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention Group

Control Group

Arm Description

Patients allocated to the intervention group will receive carvedilol 6.25 mg twice daily, then increased to 12.5 mg twice daily, until maximum dose of 25 mg twice daily according to the patients' tolerance; The dosis increments will occur every 5 days. If after the increment the patient develops bradycardia or hypotension, the dose will be reduced to the maximum tolerated dose. Carvedilol will ideally be maintained for up to 30 days after the end of chemotherapy.

Patients allocated to this group will receive placebo in a presumably staggered and progressive manner similar to the group intervention. The placebo will ideally be maintained for up to 30 days after the end of chemotherapy.

Outcomes

Primary Outcome Measures

Drop in ejection fraction within 12 months of starting treatment.
Drop in ejection fraction> 10% to values less than 50% of the left ventricle
Cardiac events within 12 months of starting treatment.
Cardiac events such as death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias

Secondary Outcome Measures

Drop in ejection fraction within 24 months.
Drop in ejection fraction greater than 10% and values less than 55%
Reduction in myocardial strain in 24 months from the start of treatment.
Relative reduction of more than 15% in myocardial strain
Diastolic dysfunction within 24 months
Development of diastolic dysfunction within 24 months
Elevation of biomarkers during chemotherapy and up to 24 months of follow-up
Elevation of biomarkers (NT-pro BNP and troponin) during chemotherapy and up to 24 months of follow-up
Quality of life (EuroQol-5D).
Quality of life measured by questionnaire in up to 24 months.
Cardiovascular complications in 24 months.
Cardiovascular complications (death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias) in 24 months.

Full Information

First Posted
June 17, 2021
Last Updated
October 6, 2023
Sponsor
Hospital Sirio-Libanes
Collaborators
Ministry of Health, Brazil
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1. Study Identification

Unique Protocol Identification Number
NCT04939883
Brief Title
Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy
Acronym
CardioTox
Official Title
A Prospective Multi-Center Randomized Study to Evaluate the Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2021 (Actual)
Primary Completion Date
December 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Sirio-Libanes
Collaborators
Ministry of Health, Brazil

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Neoplasia is the main cause of general death in the Brazilian population. In 2016, they were responsible for approximately 211,343 (16%) deaths, followed by cardiovascular diseases (12.6%). Despite the high mortality rate of neoplasia, oncological treatment have advanced substantially in recent decades improving the prognosis of patients. However, growing evidence suggest that some oncological agents may induce significant toxicity that may play a major role in the quality of life, morbidity and mortality. The cardiovascular system is often negatively affected with cancer therapy, predisposing several patients to stop appropriate treatments or to have cardiovascular events related to the cardiotoxicity. The most typical manifestation of cardiotoxicity and related consequences (heart failure) are related to the use of anthracyclines. Anthracyclines are part of the chemotherapy regimen for solid tumors and hematological neoplasms in children and adults, and are associated with an increase in life expectancy. Carvedilol is an α and β-blocker that also has antioxidant properties. Preliminary studies have shown that carvedilol and its metabolites prevent lipid peroxidation, inhibit the formation and inactivate free radicals, in addition to preventing the depletion of endogenous antioxidants, such as vitamin E. These effects would potentially prevent anthracycline injury but definitive evidence is still needed. This is a multi-center, double-blind, randomized, placebo-controlled study that aims to establish the efficacy of carvedilol for the primary prevention of left ventricular systolic dysfunction in cancer patients obtained with anthracycline chemotherapy, in different schedules and doses.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
Keywords
Carvedilol, Anthracyclines, Cardiotoxicity, Chemotherapy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Randomization will be in the proportion of 1: 1 (carvedilol x placebo). Both randomization and allocation of patients will be chosen in a veiled manner to patients and to assess. Data on randomization and allocation will be under custody of the Data analysis and safety committee.
Allocation
Randomized
Enrollment
1018 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention Group
Arm Type
Experimental
Arm Description
Patients allocated to the intervention group will receive carvedilol 6.25 mg twice daily, then increased to 12.5 mg twice daily, until maximum dose of 25 mg twice daily according to the patients' tolerance; The dosis increments will occur every 5 days. If after the increment the patient develops bradycardia or hypotension, the dose will be reduced to the maximum tolerated dose. Carvedilol will ideally be maintained for up to 30 days after the end of chemotherapy.
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Patients allocated to this group will receive placebo in a presumably staggered and progressive manner similar to the group intervention. The placebo will ideally be maintained for up to 30 days after the end of chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Description
Carvedilol will be dispensed in a staggered and progressive manner, initially from 6.25 mg twice daily, then increased to 12.5 mg twice daily, until maximum dose of 25 mg twice daily or development of contraindications
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients will receive placebo in a presumed staggered and progressive manner similar to the intervention group. The placebo will ideally be maintained for up to 30 days after the end of chemotherapy.
Primary Outcome Measure Information:
Title
Drop in ejection fraction within 12 months of starting treatment.
Description
Drop in ejection fraction> 10% to values less than 50% of the left ventricle
Time Frame
12 months
Title
Cardiac events within 12 months of starting treatment.
Description
Cardiac events such as death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Drop in ejection fraction within 24 months.
Description
Drop in ejection fraction greater than 10% and values less than 55%
Time Frame
24 months
Title
Reduction in myocardial strain in 24 months from the start of treatment.
Description
Relative reduction of more than 15% in myocardial strain
Time Frame
24 months
Title
Diastolic dysfunction within 24 months
Description
Development of diastolic dysfunction within 24 months
Time Frame
24 months
Title
Elevation of biomarkers during chemotherapy and up to 24 months of follow-up
Description
Elevation of biomarkers (NT-pro BNP and troponin) during chemotherapy and up to 24 months of follow-up
Time Frame
24 months
Title
Quality of life (EuroQol-5D).
Description
Quality of life measured by questionnaire in up to 24 months.
Time Frame
24 months
Title
Cardiovascular complications in 24 months.
Description
Cardiovascular complications (death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias) in 24 months.
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
Diagnosis of neoplasia within 24 months.
Description
Diagnosis of another neoplasia
Time Frame
24 months
Title
Progression of oncological disease within 24 months.
Description
Progression of oncological disease
Time Frame
24 months
Title
Tumor recurrence within 24 months.
Description
Tumor recurrence
Time Frame
24 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥18 years of age at the time of screening Cancer patients that will receive chemotherapy with anthracyclines. Exclusion Criteria: Inability to adequate asses left ventricular function Previous history of heart failure Previous history of any cardiomyopathy (eg.: valve disease, Chagas' disease, infiltrative cardiomyopathy) LVEF < 50% Previous history of myocardial revascularization Permanent tachyarrhythmia (flutter, atrial fibrillation, atrial tachycardia) Contra-indication to the use of beta-blockers. Trastuzumab indication Pregnant or Breast-feeding females. On kidney replacement therapy ECOG >= 4 or Karnofsky <=30 Advanced hepatic failure (C score Child-Pugh and MELD > 15); Previous use of anthracycline Have any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ana Cecilia A Silva, MD, PhD
Phone
+551133944094
Email
ana.ceasilva@hsl.org.br
First Name & Middle Initial & Last Name or Official Title & Degree
Isabela B dos Santos da Silva, MD, PhD
Phone
+551133944094
Email
isabela.bsscosta@hsl.org.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renato H D. lopes, MD, PhD
Organizational Affiliation
Hospital Sírio-Libanês
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Sirio Libanes
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
01308-050
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Renato D Lopes, MD, PhD
Email
renato.lopes@duke.edu
First Name & Middle Initial & Last Name & Degree
Renato D Lopes, MD, PhD
First Name & Middle Initial & Last Name & Degree
Isabela B Costa, MD, PhD
First Name & Middle Initial & Last Name & Degree
Luciano Drager, MD, PhD
First Name & Middle Initial & Last Name & Degree
Roberto K Filho, MD,PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy

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