Study of Remodulin® in Pediatric Pulmonary Hypertension With Single Ventricular Physiology After Fontan Surgery

Study Overview
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Brief Summary
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The aim of this study is to determine the safety and efficiency of Remodulin®（Treprostinil Injection）to reduce the pulmonary arterial pressure and prevent pulmonary hypertension (PH) after Fontan operation with univentricular physiology.

Detailed Description
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PH is a significant contributor to the postoperative morbidity and mortality of congenital heart disease, especially after Fontan operation with univentricular physiology. Mild increase of pulmonary vascular resistance may lead to failure of Fontan circulation. Remodulin® has been approved for the treatment of adults with PH, but little is known about the effects in children with PH after Fontan operation. The study aim is to determine the safety and efficiency of Remodulin® to reduce the pulmonary arterial pressure and prevent PH in children after Fontan operation. Meanwhile pharmacokinetics of the drug were checked with or without the peritoneal dialysis.

Official Title
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Randomized Single-blind Study of Intravenous Maintenance of Remodulin® for the Treatment of Pulmonary Hypertension After Fontan Operation

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Remodulin
* Drug: distilled water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: After Fontan procedure, the criteria should be met mPAP greater than 15 mmHg TPG greater than 6 mmHg (exclude the obstruction of cavopulmonary anastomosis) Exclusion Criteria: After Fontan surgery : Severe arrhythmia led to low cardiac output Platelets smaller than 50,000*109/L and obvious bleeding

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remodulin Injection<br>Drug: Remodulin Injection Dosage:5 ng/kg/min-80ng/kg/min(0.15ml/hr-2.4ml/hr) Frequency: intravenous maintenance increase at a rate of 10ng/kg/min (0.3ml/hr)every 30 minutes Durations:48 hours | Drug: Remodulin<br>* After Fontan operation, the mean pulmonary arterial pressure (mPAP)evaluated by CVP or transpulmonary pressure gradient(TPG) evaluated by Echo will be measured firstly, if the data met the criteria, and the patients were enrolled in the experimental group, the patients would be administrated intravenously of Remodulin® with the beginning of 5ng/kg/min, with the rate of 10ng/kg/min every 30 minutes up to 80ng/kg/min.<br>* Other names: Treprostinil Injection;|
| Placebo Comparator: Distilled water group<br>Drug:distilled water Dosage:0.15ml/hr-2.4ml/hr Frequency:increase at a rate of 0.3ml/hr every 30 minutes Durations:48 hours | Drug: distilled water<br>* After Fontan operation, the mPAP (evaluated by CVP) or TPG (evaluated by Echo) will be measured firstly, if the data met the criteria, and the patients were enrolled in placebo group, then the patients would be administrated intravenously of distilled water with the beginning of 0.15ml/hr, with the rate of 0.3ml/hr every 30 minutes up to 2.45ml/hr.<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point is a composite variable | consisting of death, failing Fontan or failed Fontan according to high pulmonary vascular resistance | the first 48 hours after Remodulin used | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from base line of pulmonary hemodynamic measurements | Pp/Ps reduce >10% or TPG≤6mmHg. | baseline and 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remodulin®, pulmonary vascular resistance, univentricular physiology