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Transposition of Great VesselsPhase 2NCT00374088

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

A Phase 2 study testing N-acetylcysteine in people with Transposition of Great Vessels and Congenital Heart Disease, run by University of Michigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 3 months
What is being tested?
N-acetylcysteine
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
1 siteUnited States
Study dates
Feb 2005to Jun 2008
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 3 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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).

Who cannot join

  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Michigan

    Ann Arbor, Michigan, 48109-0204

Other trials in United States

About this study

Official title: Attenuation of Myocardial Dysfunction by N-Acetylcysteine in Infants Undergoing Arterial Switch Procedure

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.

Read the 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.

Being tested
N-acetylcysteine, Placebo
Keywords
N-acetylcysteine, Myocardial dysfunction, Transposition of the Great Arteries
Medical subject headings
Transposition of Great Vessels, Heart Defects, Congenital

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • N-acetylcysteineDrug

    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.

  • PlaceboDrug

    D5W bolus prior to surgery and D5W infusion after surgery in an equal volume to the drug arm.

Study groups in NCT00374088
Study groupRoleWhat they receive
PlaceboPlacebo comparatorThese patients receive a placebo infusion of D5W prior to and after surgery
Receives: Drug: Placebo
N-AcetylcysteineExperimentalThese patients receive a loading dose of N-Acetylcysteine 100 mg/kg in D5W IV 1 hour prior to surgery. They receive a maintenance infusion of N-Acetylcysteine 10 mg/kg/hr in D5W IV for 24 hours after surgery.
Receives: Drug: N-acetylcysteine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Decline in Measured Cardiac Output

    Serial cardiac output was measured by thermodilution. The outcome of maximum decline in indexed cardiac output from 1 hour postoperative to lowest output within 24 hours postoperative was then calculated and compared between NAC and placebo groups.

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2006 (estimated)
  2. Study startFeb 2005
  3. Primary completionJun 2008
  4. Study completionJun 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00374088
Sponsor's protocol ID
IRBMED No.: 2004-851
Status last verified
Dec 2011
First submitted
7 Sep 2006
Last updated
19 Jan 2012
Data monitoring committee
Yes

Publications

  • Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW, Wessel DL. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995 Oct 15;92(8):2226-35. doi: 10.1161/01.cir.92.8.2226.

    PubMed 7554206
  • Tossios P, Bloch W, Huebner A, Raji MR, Dodos F, Klass O, Suedkamp M, Kasper SM, Hellmich M, Mehlhorn U. N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double-blind, placebo-controlled clinical trial. J Thorac Cardiovasc Surg. 2003 Nov;126(5):1513-20. doi: 10.1016/s0022-5223(03)00968-1.

    PubMed 14666027
  • Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest. 1985 Nov;76(5):1713-9. doi: 10.1172/JCI112160. No abstract available.

    PubMed 4056048
  • Kofsky E, Julia P, Buckberg GD, Young H, Tixier D. Studies of myocardial protection in the immature heart. V. Safety of prolonged aortic clamping with hypocalcemic glutamate/aspartate blood cardioplegia. J Thorac Cardiovasc Surg. 1991 Jan;101(1):33-43.

    PubMed 1986168
  • Julia P, Kofsky ER, Buckberg GD, Young HH, Bugyi HI. Studies of myocardial protection in the immature heart. III. Models of ischemic and hypoxic/ischemic injury in the immature puppy heart. J Thorac Cardiovasc Surg. 1991 Jan;101(1):14-22.

    PubMed 1986156
  • Itoi T, Lopaschuk GD. Calcium improves mechanical function and carbohydrate metabolism following ischemia in isolated Bi-ventricular working hearts from immature rabbits. J Mol Cell Cardiol. 1996 Jul;28(7):1501-14. doi: 10.1006/jmcc.1996.0140.

    PubMed 8841937
  • Matherne GP, Berr SS, Headrick JP. Integration of vascular, contractile and metabolic responses to hypoxia: effects of maturation and adenosine. Am J Physiol. 1996 Apr;270(4 Pt 2):R895-905. doi: 10.1152/ajpregu.1996.270.4.R895.

    PubMed 8967420
  • Carr LJ, VanderWerf QM, Anderson SE, Kost GJ. Age-related response of rabbit heart to normothermic ischemia: a 31P-MRS study. Am J Physiol. 1992 Feb;262(2 Pt 2):H391-8. doi: 10.1152/ajpheart.1992.262.2.H391.

    PubMed 1539698
  • Young JN, Choy IO, Silva NK, Obayashi DY, Barkan HE. Antegrade cold blood cardioplegia is not demonstrably advantageous over cold crystalloid cardioplegia in surgery for congenital heart disease. J Thorac Cardiovasc Surg. 1997 Dec;114(6):1002-8; discussion 1008-9. doi: 10.1016/S0022-5223(97)70014-X.

    PubMed 9434695
  • Najm HK, Wallen WJ, Belanger MP, Williams WG, Coles JG, Van Arsdell GS, Black MD, Boutin C, Wittnich C. Does the degree of cyanosis affect myocardial adenosine triphosphate levels and function in children undergoing surgical procedures for congenital heart disease? J Thorac Cardiovasc Surg. 2000 Mar;119(3):515-24. doi: 10.1016/s0022-5223(00)70131-0.

    PubMed 10694612
  • Nagashima M, Nollert G, Stock U, Sperling J, Hatsuoka S, Shum-Tim D, Takeuchi K, Nedder A, Mayer JE Jr. Cardiac performance after deep hypothermic circulatory arrest in chronically cyanotic neonatal lambs. J Thorac Cardiovasc Surg. 2000 Aug;120(2):238-46. doi: 10.1067/mtc.2000.106984.

    PubMed 10917937
  • Ahola T, Fellman V, Laaksonen R, Laitila J, Lapatto R, Neuvonen PJ, Raivio KO. Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants. Eur J Clin Pharmacol. 1999 Nov;55(9):645-50. doi: 10.1007/s002280050687.

    PubMed 10638393
  • Perry HE, Shannon MW. Efficacy of oral versus intravenous N-acetylcysteine in acetaminophen overdose: results of an open-label, clinical trial. J Pediatr. 1998 Jan;132(1):149-52. doi: 10.1016/s0022-3476(98)70501-3.

    PubMed 9470017
  • Andersen LW, Thiis J, Kharazmi A, Rygg I. The role of N-acetylcystein administration on the oxidative response of neutrophils during cardiopulmonary bypass. Perfusion. 1995;10(1):21-6. doi: 10.1177/026765919501000105.

    PubMed 7795309
  • Arstall MA, Yang J, Stafford I, Betts WH, Horowitz JD. N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. Circulation. 1995 Nov 15;92(10):2855-62. doi: 10.1161/01.cir.92.10.2855.

    PubMed 7586252

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing N-acetylcysteine in people with Transposition of Great Vessels and Congenital Heart Disease, run by University of Michigan at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jan 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Decline in Measured Cardiac Output (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00374088, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2012.

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