N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)

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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