Document Type

Article

Publication Date

10-4-2016

Identifier

PMCID: PMC5050602 DOI: 10.1186/s12872-016-0364-6

Abstract

Background: Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy in pediatric and adult non-oncology populations, yet remains unstudied in the pediatric oncology population.

Methods/design: The primary objective of the trial is to determine impact of the intervention on echocardiographic markers of cardiac remodeling and HF risk, including: LV wall thickness/ dimension ratio (LVWT/D; primary endpoint), as well as LV ejection fraction, volume, and blood biomarkers (natriuretic peptides, galectin-3) associated with HF risk. Secondary objectives are to establish safety and tolerability of the 2-year course of carvedilol using: 1) objective measures: hepatic and cardiovascular toxicity, treatment adherence, and 2) subjective measures: participant self-reported outcomes. Two hundred and fifty survivors of childhood cancer (diagnosedage), and previously treated with high-dose (≥300 mg/m2) anthracyclines will be enrolled in a randomized, double-blind, placebo controlled trial. After baseline assessments, participants will be randomized in a 1:1 ratio to low-dose carvedilol (maximum dose: 12.5 mg/day) or placebo. Carvedilol or placebo is up-titrated (starting dose: 3.125 mg/day) according to tolerability.

Discussion: When completed, this study will provide much-needed information regarding a physiologically plausible pharmacological risk-reduction strategy for childhood cancer survivors at high risk for developing anthracycline-related HF.

Trial registration: ClinicalTrials.gov; NCT02717507.

Journal Title

BMC cardiovascular disorders [electronic resource]

Volume

16

Issue

1

First Page

187

Last Page

187

MeSH Keywords

Adrenergic beta-Antagonists; Age Factors; Anthracyclines; Antibiotics, Antineoplastic; Carbazoles; Cardiotoxicity; Carvedilol; Clinical Protocols; Double-Blind Method; Female; Heart Failure; Humans; Hypertrophy, Left Ventricular; Male; Propanolamines; Research Design; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Keywords

Anthracyclines; Cardiomyopathy; Carvedilol; Childhood cancer; Heart failure; Risk reduction; Survivors

Comments

Secondary source ID

Grant support

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Publisher's Link: https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-016-0364-6

Download

Share

COinS