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Citrulline for Children Undergoing Cardiopulmonary Bypass Surgery

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rick Barr, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00201214
First received: September 16, 2005
Last updated: September 10, 2013
Last verified: September 2013

September 16, 2005
September 10, 2013
December 2003
January 2006   (final data collection date for primary outcome measure)
  • Oxygen index (OI) data to assess increased PVT [ Time Frame: Measured through the use of continuous mean arterial pressure monitoring ] [ Designated as safety issue: No ]
  • Qp:Qs ratios to assess increased PVT [ Time Frame: Measured by blood gases collected 48 hours post-operative ] [ Designated as safety issue: No ]
  • Increased PVT as measured by a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours during the first 24 hours postoperatively [ Time Frame: Measured through the use of continuous mean arterial pressure monitoring 48 hours post-operative ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00201214 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Citrulline for Children Undergoing Cardiopulmonary Bypass Surgery
Phase I/II Clinical Trial to Determine the Pharmacokinetics and Safety Profile of Citrulline in Children Undergoing Cardiopulmonary Bypass

This study will determine the pharmacokinetics and safety of intravenous citrulline given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.

BACKGROUND:

Increased pulmonary vascular tone (PVT) can complicate the postoperative course of the following six 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) Norwood I procedure; 5) bidirectional Glenn shunt procedure; and 6) Fontan procedure for single ventricle lesions. PVT is partially controlled by nitric oxide (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 the six previous surgical procedures. It was found that urea cycle function and plasma arginine levels were significantly decreased in all patients. Furthermore, patients with increased PVT had significantly lower arginine levels compared to patients 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.

DESIGN NARRATIVE:

This phase I/II study will determine the pharmacokinetics and safety of three doses of intravenous citrulline that will be given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cardiovascular Diseases
  • Heart Diseases
  • Heart Defects, Congenital
Drug: Citrulline
Phase I - 150mg/kg IV bolus after initiation of cardiopulmonary bypass with dosage escalation study 50mg/kg, 100mg/kg, 150mg/kg IV at 6, 12, 24, 48 hours post operative. Phase II - 150mg/kg IV bolus after initiation of cardiopulmonary bypass with 9mg/kg/hr continuous IV starting 4 hours post bolus and infusing for 48 hours or discharge from PCCU.
Not Provided
Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
26
December 2009
January 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Undergoing cardiopulmonary bypass via one of the following surgical procedures:

    1. AVSD repair
    2. VSD repair
    3. Bidirectional Glenn
    4. Modified Fontan
    5. Arterial Switch
  • Parents willing and able to sign consent

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
Both
up to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00201214
281, R01HL073317, R01 HL73317
Yes
Rick Barr, Vanderbilt University
Vanderbilt University
National Heart, Lung, and Blood Institute (NHLBI)
Study Chair: Frederick E. Barr, MD, MSCI Vanderbilt University
Vanderbilt University
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP