Project Details

Early Career

Status: Funded - Open

Evaluation of endothelial function in single ventricle patients receiving Ambrisentan after surgery

Elliot Pearson, M.D.


BACKGROUND:  Children with single ventricle heart defects have high mortality and morbidity, and these outcomes are a direct result of pulmonary and systemic endothelial dysfunction.
A critical obstacle to use of endothelial modulators in children is the need for invasive measurements (e.g. cardiac catheterization) to assess drug response.  Less invasive methods, including biomarkers and functional testing, have been studied in adults but there is little experience in children and no experience in the single ventricle population.

GAP:  We will use a combination of invasive measures performed as part of routine clinical care, and non-invasive tests to: a) evaluate the utility of non-invasive methods to quantify endothelial dysfunction; and b) assess the pharmacodynamic response to ambrisentan in children with single ventricle heart defects.

HYPOTHESIS:  Hypothesis 1: Pulmonary and systemic endothelin-1 levels and brachial artery flow-mediated vasodilation will reliably correlate with invasively measured pulmonary and systemic vascular resistance.    Hypothesis 2: Ambrisentan-mediated endothelin receptor antagonism will increase peak percent change in brachial artery flow mediated diameter and response will correlate with systemic endothelin-1 levels.

METHODS:  Prospective study of 25 children post stage III single-ventricle surgical palliation (Fontan procedure), who are enrolled in a trial to evaluate the pharmacokinetics of ambrisentan.

RESULTS:  Pending

IMPACT:  Results of this early phase trial will establish dosing, feasibility and acute hemodynamic effect of ambrisentan in children with single ventricle heart defects and these results will be used to justify a future multicenter efficacy and safety trial.

Supervising Institution:
Duke University

Jennifer Li

Project Location:
North Carolina

Award Amount: