Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

This study is currently recruiting participants.
Verified February 2014 by Medical University of South Carolina
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eric M Graham, MD, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT01579513
First received: April 13, 2012
Last updated: February 3, 2014
Last verified: February 2014

April 13, 2012
February 3, 2014
June 2012
June 2017   (final data collection date for primary outcome measure)
Incidence of a clinically derived composite morbidity-mortality outcome [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
The composite morbidity-mortality outcome will be met if any of the following occur after surgery but before hospital discharge: death, cardiac arrest, extracorporeal membrane oxygenation, renal insufficiency (creatinine more than two times normal), hepatic insufficiency (aspartate aminotransferase or alanine aminotransferase more than two times normal), or rising lactic acidosis (>5mmol/L). This outcome was choosen because death rarely occurs in this population. We have found this endpoint to be highly associated with other important clinical outcomes in this population.
Incidence of a clinically derived composite morbidity-mortality outcome [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
The composite morbidity-mortality outcome will be met if any of the following occur after surgery but before hospital discharge: death, cardiac arrest, extracorporeal membrane oxygenation, renal insufficiency (creatinine more than two times normal), hepatic insufficiency (aspartate aminotransferase or alanine aminotransferase more than two times normal), or lactic acidosis (>5mmol/L). This outcome was choosen because death rarely occurs in this population. We have found this endpoint to be highly associated with other important clinical outcomes in this population.
Complete list of historical versions of study NCT01579513 on ClinicalTrials.gov Archive Site
  • Duration of mechanical ventilation post cardiac surgery. [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
    Amount of time on mechanical ventilation following cardiac surgery
  • Intensive care unit stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
    Amount of time in the intensive care unit following cardiac surgery
  • Hospital stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
    Total duration of hospital stay following cardiac surgery
  • Neurodevelopmental outcome [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Bayley Scale of Infant Development at 1 year
Same as current
Not Provided
Not Provided
 
Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass
Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Although cardiopulmonary bypass (heart-lung machine) is a necessary component of heart surgery, it is not without consequences. Cardiopulmonary bypass initiates a potent inflammatory response secondary to the body's recognition of the abnormal environment of the heart-lung machine. This inflammatory response may lead to poor heart, lung and kidney function after the heart surgery. This is turn can lead to longer times on the ventilator (breathing machine), the need for higher doses of heart medications, a longer stay in the intensive care unit and even death. This is particularly true in infants less than one month of age due to their size and the immaturity of their organs. The appreciation of the post-cardiopulmonary bypass inflammatory response has resulted in a number of interventions directed at its reduction. No therapy has been recognized as the standard of care; however steroid therapy has been applied most often despite unclear evidence of a benefit. This study aims to determine if steroids improve the outcomes of babies undergoing heart surgery.

This study is a multi-institutional randomized double-blind placebo controlled trial of the use of glucocorticoids to improve the clinical course of neonates following cardiac surgery. Cardiopulmonary bypass (CPB) is critical to cardiac surgery, but the pathophysiologic processes engendered by CPB play an important role in post-operative recovery. The use, doses and schedule of glucocortiocoid administration to ameliorate these CPB induced processes is highly variable and without clear data to provide direction. The Primary Aim of this study is to compare the effects of intraoperative methylprednisolone to placebo on a composite morbidity-mortality outcome following neonatal CPB. Secondary Endpoints include: inotropic requirements, incidence of low cardiac output syndrome, fluid balance, ICU stay parameters, levels of inflammatory molecules, neuro-developmental outcomes, and safety parameters. The study will focus on neonates because their post-CPB clinical course is typically more severe, and that high level of severity itself provides a substrate for identifying the positive effects of a particular therapy. Finally, a therapy identified as beneficial has the greatest potential for benefit in this vulnerable population

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Congenital Heart Disease
  • Disorder of Fetus or Newborn
  • Drug: Methylprednisolone
    Methylprednisolone at a dose of 30 mg/kg body weight and a concentration of 62.5 mg/cc. The study drug will be delivered in a blinded fashion to the anesthesiologist and will be administered intravenously with the induction of anesthesia.
    Other Names:
    • Solulmedrol
    • Medrol
    • Corticosteroid
    • Steroid
    • Glucocorticoid
  • Drug: Placebo
    Normal saline will be drawn up in an identical volume to that needed for active study drug. The study drug will be delivered in a blinded fashion to the anesthesiologist and will be administered intravenously with the induction of anesthesia.
    Other Name: Normal Saline
  • Active Comparator: Intraoperative Methylprednisone
    Neonates with congenital heart disease requiring surgery utilizing cardiopulmonary bypass(CPB) in the first month of life that receive one dose of intravenous methylprednisolone (30 mg/kg) during anesthetic induction.
    Intervention: Drug: Methylprednisolone
  • Placebo Comparator: Placebo
    Neonates with congenital heart disease requiring surgery utilizing cardiopulmonary bypass (CPB) in the first month of life that receive one dose of placebo (normal saline) during anesthetic induction.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
190
June 2017
June 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age < 1 month
  • Male and female patients who are scheduled to undergo cardiac surgery involving CPB

Exclusion Criteria:

  • Prematurity: < 37 weeks post gestational age at time of surgery
  • Treatment with intravenous steroids within the two days prior to scheduled surgery.
  • Participation in research studies involving the evaluation of investigational drugs within 30 days of randomization.
  • Suspected infection that would contraindicate steroid use (eg - Herpes)
  • Known hypersensitivity to IVMP or one of its components or other contraindication to steroid therapy (eg - gastrointestinal bleeding).
  • Preoperative use of mechanical circulatory support or active resuscitation at the time of proposed randomization.
Both
up to 30 Days
No
Contact: Eric M Graham, MD 843-792-8704 grahamem@musc.edu
Contact: Patricia G Infinger 843-792-7857 infingep@musc.edu
United States
 
NCT01579513
Pro16545, R01HL112968
Yes
Eric M Graham, MD, Medical University of South Carolina
Medical University of South Carolina
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Institutes of Health (NIH)
Principal Investigator: Eric M Graham, MD Medical University of South Carolina
Medical University of South Carolina
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP