Brief Title
N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
Official Title
Attenuation of Myocardial Dysfunction by N-Acetylcysteine in Infants Undergoing Arterial Switch Procedure
Brief 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.
Detailed Description
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Maximum Decline in Measured Cardiac Output
Condition
Transposition of Great Vessels
Intervention
N-acetylcysteine
Study Arms / Comparison Groups
Placebo
Description: These patients receive a placebo infusion of D5W prior to and after surgery
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
21
Start Date
February 2005
Completion Date
June 2008
Primary Completion Date
June 2008
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).
Gender
All
Ages
N/A - 3 Months
Accepts Healthy Volunteers
No
Contacts
Ranjit M Aiyagari, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00374088
Organization ID
IRBMED No.: 2004-851
Responsible Party
Principal Investigator
Study Sponsor
University of Michigan
Study Sponsor
Ranjit M Aiyagari, MD, Principal Investigator, University of Michigan
Verification Date
December 2011