ALTE1621 Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Heart Failure (PREVENT-HF): A Phase 2b Randomized Placebo-Controlled (Carvedilol) Trial (CTMS# 16-0090)
1.1 Primary Aim To determine the impact of a two-year course of low-dose carvedilol on surrogate echocardiographic indices of heart failure (HF) risk, including Left Ventricular (LV) Posterior Wall Thickness-Dimension Ratio (LV T-D) a well-established index of early myocardial remodeling and subsequent HF risk (primary endpoint). LV systolic and diastolic function and afterload established echocardiographic indices associated with HF risk. Natriuretic peptides, troponins, and Galectin-3 - circulating biomarkers associated with myocardial injury, and HF risk. 1.2 Secondary Aims 1.2.1 To establish safety and tolerability of this two-year course of low-dose carvedilol, assessing both objective measures (hepatic function) and patient reported outcomes. 1.2.2 To examine the modifying effect of demographic, clinical, and molecular characteristics on the risk: benefit ratio from this two-year carvedilol intervention. 1.3 Exploratory Aim To evaluate the long-term efficacy of carvedilol in preventing cardiomyopathy and/or heart failure in high-risk childhood cancer survivors.