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Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

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ClinicalTrials.gov Identifier: NCT01579513
Recruitment Status : Completed
First Posted : April 18, 2012
Results First Posted : June 18, 2019
Last Update Posted : December 9, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Medical University of South Carolina

Tracking Information
First Submitted Date  ICMJE April 13, 2012
First Posted Date  ICMJE April 18, 2012
Results First Submitted Date  ICMJE May 7, 2019
Results First Posted Date  ICMJE June 18, 2019
Last Update Posted Date December 9, 2019
Study Start Date  ICMJE June 2012
Actual Primary Completion Date May 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
Number of Participants With 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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2012)
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 ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2019)
  • 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 ]
    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 ]
    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 ]
    Total duration of hospital stay following cardiac surgery
  • Neurodevelopmental Outcome [ Time Frame: 1 year ]
    Bayley Scales of Infant and Toddler Development version 3 at 1 year. Cognitive, language, and motor composite scores will be used. The general population has a mean of 100 with a standard deviation of 15 for each composite score. Higher scores are better. The minimum composite score is 46 and maximum 154.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2012)
  • 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 ]
    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 ]
    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 ]
    Total duration of hospital stay following cardiac surgery
  • Neurodevelopmental Outcome [ Time Frame: 1 year ]
    Bayley Scale of Infant Development at 1 year
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass
Official Title  ICMJE Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass
Brief Summary 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.
Detailed Description 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Congenital Heart Disease
  • Disorder of Fetus or Newborn
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2012)
190
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 19, 2018
Actual Primary Completion Date May 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 30 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01579513
Other Study ID Numbers  ICMJE Pro16545
R01HL112968 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Medical University of South Carolina
Study Sponsor  ICMJE Medical University of South Carolina
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Eric M Graham, MD Medical University of South Carolina
PRS Account Medical University of South Carolina
Verification Date November 2019

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