Effect of spironolactone in the prevention of anthracycline-induced cardiotoxicity: a randomized clinical trial (SPIROTOX trial)

• Grant number: 22/13135-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2023
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ludhmila Abrahão Hajjar
• Grantee: Lucas Tokio Kawahara
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The use of mineralocorticoid receptor antagonists for the prevention of anthracycline-induced cardiotoxicity is controversial and lacks evidence. The aim of this study is to evaluate the effect of spironolactone in the primary prevention of cardiotoxicity in cancer patients undergoing chemotherapy with anthracycline within 12 months. Methods: Randomized, double-blind, single-center, placebo-controlled clinical trial. Patients with cancer, age > 18 years, indicated to start treatment with anthracycline will be included. Exclusion criteria are: previous use of anthracycline, hypersensitivity to any mineralocorticoid receptor antagonist, symptoms of heart failure, left ventricular ejection fraction (LVEF) < 45%, previous diagnosis of cardiomyopathy, coronary artery disease, or moderate to severe mitral or aortic disease, renal failure, hyperkalemia, chronic liver disease, or current participation in another study. The inclusion of 264 patients is estimated. Enrolled patients will be randomized in a 1:1 ratio to receive spironolactone or placebo for 1 year. The primary endpoint will be the 12-month incidence of cardiotoxicity, defined as a decrease in LVEF e 10% to values less than 50% or a relative reduction in global longitudinal strain > 15% from baseline or a new increase in cardiac biomarkers (troponin T > 99th percentile and/or NT-proBNP > 125 pg/mL). (AU)