Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Trial
I. To determine the impact of a two-year course of low-dose carvedilol on surrogate
echocardiographic indices of CHF risk, including: left ventricular (LV) posterior wall
thickness-dimension ratio (LV T-D); LV systolic and diastolic function, and afterload;
natriuretic peptides, troponins, and galactin-3.
II. To establish safety and tolerability of this two-year course of low-dose carvedilol,
assessing both objective measures (hepatic function) and patients reported outcomes.
III. To examine the modifying effect of demographic, clinical, and molecular characteristics
on the risk: benefit ratio from this two-year carvedilol intervention.
IV. As an exploratory goal, to examine the relationship between carvedilol and clinical
measures of efficacy such as prevention of CHF.
OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive low-dose carvedilol orally (PO) once (QD) or twice daily (BID) for
ARM II: Patients receive placebo PO QD or BID for 24 months.
After completion of study treatment, patients are followed up annually.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
LV thickness-dimension ration (LV T-D), reported in terms of LV posterior wall dimension in systole and LV dimension based on the internal diameter in diastole
Z-scores appropriately transformed to normality as necessary. The analysis will be conducted using the linear mixed-effects model approach for normally distributed data, to account for correlation among repeated measurements within individuals. This may be done using the generalized estimating equation (GEE) approach without the random effects or by the restricted maximum likelihood estimation (REML) approach with random effects. Various covariance structures will be assumed, including the unstructured, compound symmetry, and autoregressive lag-1 correlation. Implemented using GENMOD & MIXED.
Up to 24 months
Saro Armenian, DO, MPH
City of Hope Medical Center
United States: Federal Government
|City of Hope Medical Center||Duarte, California 91010|
|St. Jude Childrens Research Hospital||Memphis, Tennessee 38105|
|University of Michigan, C.S. Mott Children's Hospital||Ann Arbor, Michigan 48109|