L-citrulline for Prevention of Sequelae of Acute Lung Injury in Pediatrics Undergoing Cardiopulmonary Bypass for Heart Defects
Condition: Acute Lung Injury
MeSH terms: Lung Injury; Acute Lung Injury; Wounds and Injuries
Intervention: L-citrulline; Placebo
Intervention description: Bolus of 150 mg/kg at the initiation of cardiopulmonary bypass, but after removal of any crystalloid base;
Addition of study medication at a concentration of 200 μmol/L given as a bolus during bypass. This may be administered as a one-time bolus or multiple administrations to compensate for fluids containing L-citrulline that may be removed from the patient during the course of the operation and thus to maintain the concentration of 200 μmol/L;
Bolus of 20 mg/kg 30 minutes after decannulation from cardiopulmonary bypass;
9 mg/kg/hr continuous infusion for up to 48 hours.; Bolus of 150 mg/kg at the initiation of cardiopulmonary bypass;
Addition of placebo matched for volume given as a bolus during bypass. This may be administered as a one-time bolus or multiple administrations during bypass;
Bolus of 20 mg/kg 30 minutes after decannulation from cardiopulmonary bypass;
9 mg/kg/hr continuous infusion for up to 48 hours.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 189.0
Sex: All
Maximum age: 18 Years
Healthy volunteers: No
Keywords: L-citrulline; pediatric; Lung Injury; Bypass; Heart Defects; Clinical Sequelae

Summary:

      The purpose of this study is to determine whether L-citrulline is effective and safe in the
      prevention of clinical sequelae of Acute Lung Injury in pediatric subjects undergoing surgery
      for congenital heart defects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects, parents, or legal guardian of the subject who are willing and able to sign
             informed consent

          -  Male and female subjects aged ≤18 years of age

          -  Infants, children and adolescents undergoing cardiopulmonary bypass (CPB) for repair
             of a large unrestrictive VSD, an ostium primum ASD, or a partial or complete AVSD

          -  Pre-operative echocardiogram which confirms the cardiovascular anatomy and defect to
             be surgically repaired

        Exclusion Criteria:

          -  Evidence of pulmonary artery or vein abnormalities on the pre-operative echocardiogram
             that will not be addressed surgically. Specific abnormalities excluded include the
             following:

               -  Significant pulmonary artery narrowing not amenable to surgical correction

               -  Previous pulmonary artery stent placement

               -  Significant left sided AV valve regurgitation not amenable to surgical correction

               -  Pulmonary venous return abnormalities not amenable to surgical correction

               -  Pulmonary vein stenosis not amenable to surgical correction

          -  Preoperative requirement for mechanical ventilation or intravenous inotrope support

          -  Presence of fixed or idiopathic pulmonary hypertension (i.e. Eisenmenger's Syndrome)
             prior to surgical repair

          -  Pre-operative use of medications to treat pulmonary hypertension

          -  Pregnancy; Females of child-bearing potential must be willing to participate an
             acceptable method of birth control for the duration of study participation (e.g. oral
             contraceptive, hormonal implant, intra-uterine device)

          -  Any condition which, in the opinion of the investigator, might interfere with the
             study objectives

          -  Participation in another clinical trial within 30 days of Screening or while
             participating in the current study, including the 28 days of follow-up post study drug
             administration