N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
Condition: Transposition of Great Vessels; Congenital Heart Disease
MeSH terms: Heart Diseases; Heart Defects, Congenital; Transposition of Great Vessels
Intervention: N-acetylcysteine; Placebo
Intervention description: Loading dose: Subjects randomized to IV NAC will receive a total loading dose of 100 mg/kg of 10% (100 mg/mL) solution. Acetadote is supplied as a 20% solution (200 mg/mL) and will be diluted 1:1 with an equal volume of D5W. The volume of the loading dose will be 1 mL/kg, anticipated to be 2.5-5 mL in our patient population. The loading dose will be administered over 1 hr beginning 1 hr prior to the patient's OR time. Subjects in the placebo group will receive 1 mL/kg of D5W over 1 hr.
Maintenance infusion: Subjects randomized to IV NAC will receive an infusion of 10 mg/kg/hr of 10% (100 mg/mL) solution for 24 hrs, starting in the OR after weaning from CPB. Acetadote is supplied as a 20% solution (200 mg/mL) and will be diluted 1:1 with an equal volume of D5W. The volume of the maintenance infusion will be 0.1 mL/kg/hr, anticipated to be 0.25-0.5 mL/hr in our patient population. Subjects in the placebo group will receive 0.1 mL/kg/hr of D5W for 24 hrs.; D5W bolus prior to surgery and D5W infusion after surgery in an equal volume to the drug arm.
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 21.0
Sex: All
Maximum age: 3 Months
Healthy volunteers: No
Keywords: N-acetylcysteine; Myocardial dysfunction; Transposition of the Great Arteries

Summary:

      The purpose of this study is to determine whether intravenous N-acetylcysteine (also known as
      Acetadote), an antioxidant medication that has been used for years to treat Tylenol overdose,
      helps prevent heart dysfunction in the early postoperative period following congenital heart
      surgery. Children undergoing major heart surgery, such as the arterial switch operation,
      routinely develop temporary heart dysfunction in the first 12-24 hours after surgery. This
      heart dysfunction may be severe and contributes to an increased risk for death or prolonged
      hospitalization. Current standard treatments include intravenous medications such as
      dopamine, epinephrine, and vasopressin that support your child's blood pressure and heart
      function. Unfortunately, high doses of these medications have the potential to cause severe
      side effects including loss of fingers and toes, liver and kidney dysfunction, and heart
      rhythm abnormalities. Our goal is to find a way to reduce heart dysfunction after major heart
      surgery in order to promote a smoother postoperative period, and reduce the risks associated
      with heart operations in children.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients transferred to or born at C.S. Mott Children's Hospital between 0 and
             3-months-old undergoing ASO for d-TGA or anatomic variants (including double-outlet
             right ventricle with transposition physiology).

        Exclusion Criteria:

          -  Less than 36-weeks post-conceptional age at the time of enrollment

          -  Birth weight less than 1800 grams;

          -  Evidence of significant renal, hepatic, or neurological dysfunction

          -  Additional significant cardiac lesions other than patent ductus arteriosus, isolated
             ventricular septal defect, simple coarctation, and/or atrial septal defect

          -  Preoperative extracorporeal membrane oxygenation (ECMO).