Effects of carvedilol on the prevention of cardiotoxicity induced by anthracyclines: Design and rationale of the CARDIOTOX trial

IF 3.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

American heart journal Pub Date : 2025-02-22 DOI:10.1016/j.ahj.2025.02.014

Isabela Bispo Santos da Silva Costa MD, PhD , Remo H.M. Furtado MD, PhD , Luciano F. Drager MD, PhD , Pedro Gabriel Melo de Barros e Silva MD, PhD , Marcelo Dantas Tavares de Melo MD, PHD , Paula Araruna MD , Bruno C. Bacchiega MD , Sanderson Cauduro MD , Edilson Walter MD , Guilherme Loureiro Fialho MD, PhD , Odilson Silvestre MD, PhD, MPH , Lucas P. Damiani PhD , Lilian M. Barbosa MSc, MBA , Mariane Nascimento Luz Bsc , Ana Cecilia Alcantara Silva Bsc , Renata Rodrigues de Mattos MBA , Roberta Saretta MD , Marilia Harumi H.S. Rehder MD, PhD , Ludhmila Abrahao Hajjar MD, PhD , Teresa Lopes-Fernandez MD , Roberto Kalil Filho MD, PhD

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引用次数: 0

Abstract

Background

Patients with cancer undergoing chemotherapy with an anthracycline-based regimen are at increased risk of cardiotoxicity, predisposing to heart failure, arrhythmias and death. Whether carvedilol may confer benefit to prevent anthracycline-induced cardiotoxicity remains to be determined.

Design

CARDIOTOX is a double-blind, placebo controlled randomized clinical trial that plan to enroll 1,018 patients across 25 study sites in Brazil. Patients with active cancer scheduled to undergo an anthracycline-based chemotherapy regimen are eligible. Patients with prior HF or cardiomyopathy are excluded. Patients are randomized in 1:1 ratio to carvedilol (starting dose 6.25mg BID up titrated to 25mg BID or maximum tolerated dose) or placebo, stratified by site and use of renin-angiotensin blockers at baseline. Study drug is administered through the duration of chemotherapy and up to 30 days after the last dose of anthracycline. Patients are scheduled to undergo echocardiographic evaluations at baseline and at 3, 6, and 12 months. The study primary endpoint is the composite of new left ventricle ejection fraction (LVEF) reduction by at least 10% leading to an LVEF <50%, cardiovascular death, myocardial infarction, urgent care visit or hospitalization for heart failure, or clinically significant arrhythmias at 12 months. Echocardiographic images will be analyzed by a central core lab, clinical outcomes will be adjudicated, and safety endpoints include serious adverse events and adverse events of special interest (symptomatic bradycardia, hypotension, syncope and bronchospasm).

Summary

The CARDIOTOX trial is the largest trial to date analyzing the potential role of beta-blockers as prophylactic therapy to prevent cardiotoxicity induced by anthracyclines.

Trial Registration

Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox). ClinicalTrials.gov ID NCT04939883. https://clinicaltrials.gov/study/NCT04939883

查看原文本刊更多论文

卡维地洛预防蒽环类药物引起的心脏毒性的作用：CARDIOTOX试验的设计和基本原理。

背景：接受蒽环类化疗方案的癌症患者发生心脏毒性、心衰、心律失常和死亡的风险增加。卡维地洛是否有益于预防蒽环类药物引起的心脏毒性仍有待确定。设计：CARDIOTOX是一项双盲、安慰剂对照的随机临床试验，计划在巴西25个研究地点招募1018名患者。计划接受蒽环类药物化疗方案的活动性癌症患者符合条件。既往有心衰或心肌病的患者排除在外。患者按1:1的比例随机分配到卡维地洛（起始剂量为6.25mg BID，逐渐增加到25mg BID或最大耐受剂量）或安慰剂，根据部位和基线时肾素-血管紧张素阻滞剂的使用进行分层。研究药物在化疗期间和最后一次蒽环类药物后最多30天内施用。患者计划在基线和3,6和12个月时接受超声心动图评估。研究的主要终点是新左心室射血分数（LVEF）降低至少10%导致LVEF的复合。摘要：CARDIOTOX试验是迄今为止最大的试验，分析了β受体阻滞剂作为辅助治疗预防蒽环类药物引起的心脏毒性的潜在作用。试验注册：卡维地洛对接受蒽环类药物治疗（CardioTox）的癌症患者心脏毒性的影响。临床试验：政府编号NCT04939883。https://clinicaltrials.gov/study/NCT04939883。

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来源期刊

American heart journal 医学-心血管系统

CiteScore

8.20

自引率

2.10%

发文量

214

审稿时长

38 days

期刊介绍： The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.