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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
1,018
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
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.
Hospital Sirio Libanes
São Paulo, São Paulo, Brazil
RECRUITINGDrop in ejection fraction within 12 months of starting treatment.
Drop in ejection fraction\> 10% to values less than 50% of the left ventricle
Time frame: 12 months
Cardiac events within 12 months of starting treatment.
Cardiac events such as death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias
Time frame: 12 months
Drop in ejection fraction within 12 months.
Drop in ejection fraction greater than 10% and values less than 55%
Time frame: 12 months
Reduction in myocardial strain in 12 months from the start of treatment.
Relative reduction of more than 15% in myocardial strain
Time frame: 12 months
Diastolic dysfunction within 12 months
Development of diastolic dysfunction within 12 months
Time frame: 12 months
Elevation of biomarkers during chemotherapy and up to 12 months of follow-up
Elevation of biomarkers (NT-pro BNP and troponin) during chemotherapy and up to 24 months of follow-up
Time frame: 12 months
Quality of life (EuroQol-5D).
Quality of life measured by questionnaire in up to 12 months.
Time frame: 12 months
Cardiovascular complications in 12 months.
Cardiovascular complications (death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias) in 24 months.
Time frame: 12 months
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