NCT00335244

Intravenous L-Citrulline to Treat Children Undergoing Heart Bypass Surgery

A Phase III Single-Blind, Randomized, Placebo Controlled, Clinical Trial to Determine the Safety and Efficacy of Intravenous L-Citrulline Versus Placebo in Children Undergoing Cardiopulmonary Bypass

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 77 (actual)
• Sponsor: Asklepion Pharmaceuticals, LLC · Industry
• Sex: All
• Age: 17 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial will determine the safety and effectiveness of intravenous L-citrulline in children undergoing cardiopulmonary bypass during heart surgery. Participants will be randomly assigned to either L-citrulline or a placebo (a substance that has no medicine in it). Citrulline is a protein building block in the body that can convert into another substance, nitric oxide (NO), which controls blood pressure in the lungs. Increased blood pressure in the lungs can be an important surgical problem; it may also lead to problems following surgery, such as severe high blood pressure in the lungs (pulmonary hypertension), increased time spent on a breathing machine, and a longer stay in the intensive care unit (ICU). The hypothesis of this study is that perioperative supplementation with intravenous citrulline will increase plasma citrulline, arginine and NO metabolites and prevent elevations in the postoperative PVT leading to a decrease in the duration of postoperative invasive mechanical ventilation.

Detailed description

Increased pulmonary vascular tone (PVT) can complicate the postoperative course of the following five surgical procedures for congenital heart defects: 1) unrestrictive ventricular septal defect (VSD) repair; 2) atrioventricular septal (AVSD) repair; 3) arterial switch procedure for transposition of the great arteries (TGA); 4) bidirectional Glenn shunt procedure; and 5) Fontan procedure for single ventricle lesions. PVT is partially controlled by NO. Arginine, the precursor to NO, is a product of the urea cycle. Preliminary data have been presented regarding 169 infants and children who have undergone one of six previous surgical procedures. It was found that urea cycle function and plasma arginine levels were significantly decreased in all participants. Furthermore, participants with increased PVT had significantly lower arginine levels compared to participants with normal PVT. Finally, a genetic single nucleotide polymorphism (SNP) in the rate limiting urea cycle enzyme (carbamyl phosphate synthetase I \[CPSl T1405N\]) appeared to affect postoperative plasma arginine levels and PVT. The hypothesis is that genetic polymorphisms in the rate limiting urea cycle enzyme CPSl, and other important enzymes in the urea cycle, influence the availability of NO precursors. It is further hypothesized that perioperative enhancement of urea cycle function with the key urea cycle intermediate (citrulline) will increase plasma arginine and NO metabolites and prevent elevations in PVT.

Conditions

• Heart Defects, Congenital
• Hypertension, Pulmonary

Interventions

Type	Name	Description
DRUG	L-citrulline	150mg bolus X 1 after initiation of cardiopulmonary bypass followed by continuous infusion of 9mg/kg/hr IV, starting 4 hours post bolus administration and ending at 48 hours continuous infusion or discharge from the PCCU
DRUG	Placebo of intravenous L-citrulline	Placebo of intravenous L-citrulline

Timeline

• Start date: 2006-05-01
• Primary completion: 2009-12-01
• Completion: 2009-12-01
• First posted: 2006-06-09
• Last updated: 2015-02-02

Locations

1 site across 1 country: United States