Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Study Overview
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Brief Summary
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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
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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

Official Title
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Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Conditions
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Congenital Heart Disease, Disorder of Fetus or Newborn

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 30 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intraoperative Methylprednisone<br>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. | Drug: Methylprednisolone<br>* 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.<br>* Other names: Glucocorticoid;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* 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.<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinically Derived Composite Morbidity-mortality Outcome | 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. | Participants will be followed for the duration of hospital stay, an expected average of 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Mechanical Ventilation Post Cardiac Surgery. | Amount of time on mechanical ventilation following cardiac surgery | Participants will be followed for the duration of hospital stay, an expected average of 5 weeks | 
| Intensive Care Unit Stay | Amount of time in the intensive care unit following cardiac surgery | Participants will be followed for the duration of hospital stay, an expected average of 5 weeks | 
| Hospital Stay | Total duration of hospital stay following cardiac surgery | Participants will be followed for the duration of hospital stay, an expected average of 5 weeks | 
| Neurodevelopmental Outcome | 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. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steroid, Cardiopulmonary Bypass (CPB), System Inflammatory Response, inflammation, Methylprednisolone, Neonates, Cardiac Surgical Procedures, Children, Infants, Pediatrics, Glucocorticoid, Heart Disease, Heart Defects, Congenital, Cardiovascular Diseases, Cardiovascular Abnormalities, Corticosteroid, methylprednisolone Hemisuccinate, Hormones, Physiological Effects of Drugs, Randomized Clinical Trial