Journal Article

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

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

2025

Overview

•The use of carvedilol is recommended by guidelines for the prevention of anthracycline-induced cardiotoxicity. However, the level of evidence behind this recommendation is weak.•CARDIOTOX is the largest clinical trial ever conducted to evaluate the potential role of carvedilol in preventing anthracycline-induced cardiotoxicity, including several types of cancer.•The monitoring of cardiotoxicity through systematic echocardiography with GLS and biomarkers (during chemotherapy and follow-up) might serve as a guidance for future strategies in managing these patients. 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. 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). 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. Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox). ClinicalTrials.gov ID NCT04939883. https://clinicaltrials.gov/study/NCT04939883

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adrenergic beta-Antagonists - administration & dosage / Adrenergic beta-Antagonists - therapeutic use / Adverse events / Angiotensin / Anthracycline / Anthracyclines - adverse effects / Arrhythmia / Beta blockers / Biomarkers / Bradycardia / Brazil / Breast cancer / Bronchospasm / Cancer / Cancer therapies / Cardiology / Cardiomyopathy / Cardiotoxicity / Cardiotoxicity - etiology / Cardiotoxicity - prevention & control / Carvedilol - administration & dosage / Carvedilol - therapeutic use / Chemotherapy / Clinical trials / Congestive heart failure / Disease prevention / Double-Blind Method / Echocardiography / Female / Health risks / Humans / Hypotension / Magnetic resonance imaging / Male / Meta-analysis / Middle Aged / Mortality / Multicenter Studies as Topic / Myocardial infarction / Neoplasms - drug therapy / Oncology / Patients / Placebos / Randomized Controlled Trials as Topic / Renin / Stroke Volume - drug effects / Syncope / Toxicity / Ultrasonic imaging