Clinical Trial: Ambrisentan in Single Ventricle

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Safety, Pharmacokinetics (PK) and Hemodynamic Effects of Ambrisentan in Single Ventricle Pediatric Patients

Brief Summary:

Purpose: To evaluate the pharmacokinetics, bioavailability and hemodynamic efficacy of ambrisentan after Fontan surgical palliation of single ventricle heart defects.

Study activities and population group: Children undergoing Fontan surgical palliation for single ventricle defects will be eligible for the study. Up to 20 subjects will be enrolled (16 ambrisentan, 4 placebo) and will receive 3 days (3 doses) of ambrisentan starting on post-operative day #1 upon returning from the operating room. Ambrisentan plasma levels will be obtained at specified time points during treatment. Post-operative monitoring lines will be used to measure effects of ambrisentan on hemodynamics and pulmonary / systemic endothelial function.


Detailed Summary:

A. Purpose of the Study The purpose of the study is to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ambrisentan in children with single ventricle heart defects that are undergoing Fontan (stage III) surgical palliation. This is a double blind, placebo controlled study. The primary objective of this Phase I/II study is to assess the plasma PK, safety and PD of oral ambrisentan in children with surgically palliated single ventricle heart defects. A secondary objective will be to assess whether ambrisentan improves post-operative outcomes including amount and duration of chest tube drainage and hospital length of stay.

B. Background and Significance Complex congenital heart defects associated with underdevelopment of a ventricle account for ~8% of congenital heart disease with a birth incidence of 4-8/10000 live births. These single ventricle lesions are associated with high morbidity and 5 year mortality rates that approach 50%. Staged surgical palliation directs returning venous blood flow directly into the lungs so that pulmonary blood flow occurs without the aid of a pumping chamber. The final stage of surgery (stage III - the Fontan procedure) incorporates inferior caval blood flow directly into the pulmonary arteries. Consequently pulmonary blood flow and cardiac output are directly related to pulmonary vascular resistance and ventricular function. The limitations of single ventricle surgical palliation often result in a prolonged post-operative course with pleural effusions a particular concern. There is also continued long term attrition. Elevated pulmonary vascular resistance and impaired systemic ventricular function are important risk factors for early and late failure of single ventricle palliation.

Ambrisentan is an endothelin receptor antagonist that improves pulmonary and possibly sys
Sponsor: Kevin Hill

Current Primary Outcome: Plasma concentration of Ambrisentan [ Time Frame: Plasma samples collected at 0-1,1-6,18-30 and 40-60hrs after administration of the first ambrisentan dose. ]

Change Plasma concentration of ambrisentan


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Amount and duration of chest tube drainage post Fontan Operation [ Time Frame: Chest tube output will be measured daily for the duration of the post-operative hospitalization or for 30 days whichever is shorter. Chest tube duration will be calculated as the number of days from placement to removal. ]
    Collect these data to assess whether ambrisentan improves post-operative outcomes.
  • Change in hemodynamic parameters [ Time Frame: Hemodynamic evaluation performed prior to initiation of study drug and at 0-1,1-6,18-30 and 40-60hrs after administration of the first ambrisentan dose ]
    Hemodynamic data, including Fontan pressures and saturations, will be collected at the specified timepoints
  • Safety [ Time Frame: 30 days after last ambrisentan dose ]
    Adverse events will be collected during hospitalization and for 30 days after administration of the last ambrisentan dose


Original Secondary Outcome: Same as current

Information By: Duke University

Dates:
Date Received: February 21, 2014
Date Started: July 2015
Date Completion: July 2018
Last Updated: May 2, 2017
Last Verified: May 2017