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Sponsored by: |
University of Michigan |
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Information provided by: | University of Michigan |
ClinicalTrials.gov Identifier: | NCT00374088 |
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.
Condition | Intervention | Phase |
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Transposition of Great Vessels Congenital Heart Disease |
Drug: N-acetylcysteine |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Attenuation of Myocardial Dysfunction by N-Acetylcysteine in Infants Undergoing Arterial Switch Procedure |
Enrollment: | 20 |
Study Start Date: | February 2005 |
Study Completion Date: | June 2008 |
Primary Completion Date: | June 2008 (Final data collection date for primary outcome measure) |
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.
This is a randomized, placebo-controlled, blinded study of intravenous N-acetylcysteine (NAC) for the prevention of postoperative myocardial dysfunction and apoptosis in infants undergoing arterial switch for D-transposition of the great arteries. Subjects will be age 0-3 months, and no distinctions will be made based on gender or race. Infants operated before 36 weeks post-conceptional age or with birth weight less than 1.8 kilograms will be excluded. Informed consent will be obtained from the patient's parent by one of the investigators in the hospital before the infants undergo surgery.
Subjects will be randomized based on a block randomization scheme to receive placebo or NAC infusion, starting with a loading dose 1 hour prior to surgery. If there is any concern by the ICU physician that the patient is developing toxicity to the medicine, the study drug will be discontinued and the patient removed from the study. Patients will have a thermodilution catheter placed during surgery for postoperative direct measurement of cardiac output. Endomyocardial biopsy will be performed by the surgeon pre- and post-bypass for measurement of markers of apoptosis. Postoperatively, patients will continue to receive an infusion of IV NAC for 24 hours. Blood draws will be through existing arterial and central venous catheters. Serum labs collected will include serial lactate values (already collected routinely), liver and renal function tests, CK-MB and troponin-I levels as a marker of myocardial injury, and S100b level as a marker of brain injury. Total additional blood removed for research purposes will be less than 15 mL. Cardiac output will be measured serially by thermodilution. Serial transthoracic echocardiography will be used to determine left ventricular function. Inotropic score, duration of mechanical ventilation, length of ICU stay, and length of hospitalization will be recorded.
Ages Eligible for Study: | up to 3 Months |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Michigan | |
University of Michigan | |
Ann Arbor, Michigan, United States, 48109-0204 |
Principal Investigator: | Ranjit M Aiyagari, MD | University of Michigan |
Responsible Party: | University of Michigan ( Ranjit Aiyagari, MD ) |
Study ID Numbers: | IRBMED No.: 2004-851 |
Study First Received: | September 7, 2006 |
Last Updated: | June 5, 2008 |
ClinicalTrials.gov Identifier: | NCT00374088 |
Health Authority: | United States: Food and Drug Administration |
N-acetylcysteine Myocardial dysfunction Transposition of the Great Arteries |
Transposition of great arteries Heart Diseases Cardiovascular Abnormalities Transposition of Great Vessels Great vessels transposition |
Acetylcysteine Congenital Abnormalities Heart Defects, Congenital N-monoacetylcystine |
Respiratory System Agents Anti-Infective Agents Antioxidants Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Antiviral Agents Protective Agents |
Pharmacologic Actions Expectorants Therapeutic Uses Free Radical Scavengers Cardiovascular Diseases Antidotes |