Perioperative Treprostinil in Pediatric Patients Undergoing the Fontan Operation

The purpose of this study is to test the efficacy of treprostinil (TRE) in the perioperative non-fenestrated, extracardiac Fontan patients in order to reduce duration of chest tube drainage (in days).

The Fontan operation is performed for patients with single ventricle physiology as the final palliation to create a series circulation, with passive systemic venous return to the pulmonary arteries and the single ventricle solely providing systemic output.

Patients undergoing extracardiac Fontan tend to have elevation of Fontan pressures immediately following the operation with inflammation from surgery requiring additional fluid administration to maintain blood pressure. Increased Fontan pressures and fluid overload lead to prolonged chest tube drainage.

The hypothesis is that treprostinil, a prostacyclin drug that dilates the pulmonary arteries, will improve immediate postoperative Fontan pressures. Treprostinil is not FDA approved for this use. Anecdotally and in a small case series, prostacyclin therapy has been shown to assist in transitioning patients off nitric oxide. The investigators believe that this improvement in hemodynamics will decrease duration of chest tube drainage resulting in a shorter length of hospital stay.

Study Overview

• Status: Terminated
• Conditions: Single Ventricle
• Intervention / Treatment: Drug: Treprostinil

Detailed Description

In order to understand the effect of treprostinil on Fontan patients, this study has two parts:

1. reactivity testing with inhaled treprostinil in the cardiac catheterization lab for pre-Fontan patients undergoing routine catheterization in anticipation of the Fontan operation;
2. perioperative use of subcutaneous treprostinil starting immediately pre-op until postoperative day #7 to improve immediate postoperative hemodynamics and ultimately reduce overall length of hospital stay.

The investigators hope to learn how pulmonary vasodilator therapy affects and/or improves post- operative hemodynamics following the Fontan operation. This knowledge would be very important in the care of single ventricle patients following the Fontan operation if there is improvement of immediate outcomes and reduction of hospital length of stay. On a broader scale, if the use of treprostinil in perioperative Fontan patients can achieve the same results other centers achieve with the use of a fenestration this may have wide scale implications in the nationwide treatment of Fontan patients.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital, Stanford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patient undergoing Fontan operation and/or pre-Fontan cardiac catheterization at Lucile Packard Children's Hospital (LPCH)

Exclusion Criteria:

• Platelet count < 50K (treprostinil can act as a platelet inhibitor and this may place patient at additional risk of bleeding if already thrombocytopenic)
• Dermatologic condition that renders the patient unable to tolerate a subcutaneous infusion (can still take part in inhaled vasodilator testing during cardiac catheterization)
• Currently receiving any vasodilator therapy specifically for the purpose of pulmonary vasodilation (phosphodiesterase type 5 inhibitor, endothelia receptor antagonist and/or prostacyclin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treprostinil; The subcutaneous continuous treprostinil infusion will start at a dose of 2 ng/kg/min. The dose will be increased over the first 24 hours to goal 10 ng/kg/min through day five. On postoperative day six, the dose will be decreased by 2 ng/kg/min every 8 hours with plans for discontinuation on postoperative day seven.	Drug: Treprostinil; Administration of drug (treprostinil) vs placebo (saline) in the post-operative period; Other Names: Remodulin
PLACEBO_COMPARATOR: Saline; Saline administration via subcutaneous infusion	Drug: Treprostinil; Administration of drug (treprostinil) vs placebo (saline) in the post-operative period; Other Names: Remodulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest Tube Duration	This outcome measures the number of days that chest tubes were in place postoperatively.	2-3 wks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	This outcome measures the hospital length of stays in days.	2-3 wks
Postoperative Fontan Pressure	Patient hemodynamics as measured by invasive postoperative lines were recorded and compared between groups	postoperative hour 0, 12 and 24
Postoperative Atrial Pressure	Patient hemodynamics as measured by invasive postoperative lines were recorded and compared between groups	postoperative hour 0, 12 and 24
Postoperative Transpulmonary Gradient	Patient hemodynamics as measured by invasive postoperative lines were recorded and compared between groups. Transpulmonary pressure gradient is defined as the difference between mean pulmonary artery pressure and left atrial pressure (commonly estimated by a pulmonary artery wedge pressure).	postoperative hour 0, 12 and 24

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Jeffrey Feinstein, Stanford University

Publications and helpful links

General Publications

• Handler SS, Ogawa MT, Hopper RK, Sakarovitch C, Feinstein JA. Subcutaneous treprostinil in pediatric patients with failing single-ventricle physiology. J Heart Lung Transplant. 2017 Sep 14:S1053-2498(17)31993-9. doi: 10.1016/j.healun.2017.09.008. Online ahead of print. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): December 1, 2020
• Study Completion (ACTUAL): December 1, 2020

Study Registration Dates

• First Submitted: July 13, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (ESTIMATE): July 15, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Fontan; Treprostinil; Single ventricle; Remodulin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Univentricular Heart; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: 33852

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO