Clinical trial NCT04939883: Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy
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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cancer
Keywords: Carvedilol
Anthracyclines
Cardiotoxicity
Chemotherapy
Lead sponsor: Hospital Sirio-Libanes
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
First posted: 2021-06-25
Enrollment: 1018
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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 symptoms (dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and pulmonary and systemic congestion) suggestive of or a previous diagnosis 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)
* Congenital heart disease with left ventricular function impared
* Contra-indication to the use of beta-blockers.
* Pregnant or Breast-feeding females or women of childbearing age who intend to became pregnant.
* 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

Primary outcomes:
measure: Drop in ejection fraction within 12 months of starting treatment.
timeFrame: 12 months
measure: Cardiac events within 12 months of starting treatment.
timeFrame: 12 months
Secondary outcomes:
measure: Drop in ejection fraction within 12 months.
timeFrame: 12 months
measure: Reduction in myocardial strain in 12 months from the start of treatment.
timeFrame: 12 months
measure: Diastolic dysfunction within 12 months
timeFrame: 12 months
measure: Elevation of biomarkers during chemotherapy and up to 12 months of follow-up
timeFrame: 12 months
measure: Quality of life (EuroQol-5D).
timeFrame: 12 months
measure: Cardiovascular complications in 12 months.
timeFrame: 12 months
Other outcomes:
measure: Diagnosis of neoplasia within 12 months.
timeFrame: 12 months
measure: Progression of oncological disease within 12 months.
timeFrame: 12 months
measure: Tumor recurrence within 12 months.
timeFrame: 12 months.
Locations:
city: São Paulo
country: Brazil
facility: Hospital Sirio Libanes
state: Sao Paulo
Study officials:
affiliation: Hospital Sírio-Libanês
name: Renato H D. lopes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: