A Prospective Multi-Center Randomized Study to Evaluate the Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,018
- 试验地点
- 1
- 主要终点
- Drop in ejection fraction within 12 months of starting treatment.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years of age at the time of screening
- •Cancer patients that will receive chemotherapy with anthracyclines.
排除标准
- •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
研究组 & 干预措施
Intervention Group
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.
干预措施: Carvedilol (Drug)
Control Group
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Drop in ejection fraction within 12 months of starting treatment.
时间窗: 12 months
Drop in ejection fraction\> 10% to values less than 50% of the left ventricle
Cardiac events within 12 months of starting treatment.
时间窗: 12 months
Cardiac events such as death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias
次要结局
- Drop in ejection fraction within 12 months.(12 months)
- Diastolic dysfunction within 12 months(12 months)
- Reduction in myocardial strain in 12 months from the start of treatment.(12 months)
- Elevation of biomarkers during chemotherapy and up to 12 months of follow-up(12 months)
- Quality of life (EuroQol-5D).(12 months)
- Cardiovascular complications in 12 months.(12 months)