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Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure.

Publication ,  Journal Article
Armenian, SH; Hudson, MM; Chen, MH; Colan, SD; Lindenfeld, L; Mills, G; Siyahian, A; Gelehrter, S; Dang, H; Hein, W; Green, DM; Robison, LL ...
Published in: BMC Cardiovasc Disord
October 4, 2016

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 (diagnosed <21 years of age), 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.

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Published In

BMC Cardiovasc Disord

DOI

EISSN

1471-2261

Publication Date

October 4, 2016

Volume

16

Issue

1

Start / End Page

187

Location

England

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Ventricular Dysfunction, Left
  • Treatment Outcome
  • Time Factors
  • Risk Factors
  • Risk Assessment
  • Research Design
  • Propanolamines
  • Male
 

Citation

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Armenian, Saro H., Melissa M. Hudson, Ming Hui Chen, Steven D. Colan, Lanie Lindenfeld, George Mills, Aida Siyahian, et al. “Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure.BMC Cardiovasc Disord 16, no. 1 (October 4, 2016): 187. https://doi.org/10.1186/s12872-016-0364-6.
Armenian SH, Hudson MM, Chen MH, Colan SD, Lindenfeld L, Mills G, Siyahian A, Gelehrter S, Dang H, Hein W, Green DM, Robison LL, Wong FL, Douglas PS, Bhatia S. Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure. BMC Cardiovasc Disord. 2016 Oct 4;16(1):187.
Journal cover image

Published In

BMC Cardiovasc Disord

DOI

EISSN

1471-2261

Publication Date

October 4, 2016

Volume

16

Issue

1

Start / End Page

187

Location

England

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Ventricular Dysfunction, Left
  • Treatment Outcome
  • Time Factors
  • Risk Factors
  • Risk Assessment
  • Research Design
  • Propanolamines
  • Male