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NCT Number: NCT00335244

Intravenous L-Citrulline to Treat Children Undergoing Heart Bypass Surgery

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.

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Key information

Conditions

Heart Defects, Congenital Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Heart Diseases Hypertension Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases Vascular Diseases

Age range

Up to 17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Undergoing cardiopulmonary bypass surgery with 1 of the following 5 procedures:
  • AVSD repair
  • VSD repair
  • Bidirectional Glenn
  • Modified Fontan
  • Arterial switch

Exclusion criteria

  • Pulmonary artery or vein abnormalities not being addressed surgically
  • Preoperative requirement for mechanical ventilation or intravenous inotrope support
  • Any condition that might interfere with study objectives, as determined by the investigator
  • Pregnant

Treatment and study plan

L-citrulline

Drug

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

Placebo of Intravenous L-Citrulline

Drug

Placebo of intravenous L-citrulline

Primary outcomes

  1. Duration of postoperative mechanical ventilation in hours compared between treatment groups.

    Time frame: Measured in hours from the end of surgery until extubation

Secondary outcomes

  1. Incidence of increased PVT (defined as a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours, measured during the first 48 hours

    Time frame: Measured in hours from the end of surgery until extubation

  2. Postoperative intravenous inotrope score

    Time frame: Measured at 48 hours

  3. Length and volume of chest tube drainage

    Time frame: Measured in hours from the end of surgery until removal of chest tubes

  4. Length of ICU stay

    Time frame: Measured in hours from the end of surgery to discharge from ICU

  5. Length of hospitalization

    Time frame: Measured from the day of surgery until discharge from hospital

  6. Survival

    Time frame: Measured at 30 days post surgical repair

Sponsors and collaborators

Lead sponsor

Asklepion Pharmaceuticals, LLC

Industry

Collaborators

  • Vanderbilt University

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2009
Study completion
2009
First posted
Jun 9, 2006
Registry last updated
Feb 2, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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