Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Study Overview
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Brief Summary
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Randomized controlled trial of the use of glucocorticoids to improve the clinical course of neonates post-cardiopulmonary bypass (CPB).

Detailed Description
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This study proposes a randomized controlled trial of the use of glucocorticoids to improve the clinical course of neonates post-cardiopulmonary bypass (CPB). The study will focus on neonates for a few reasons. Although their post-CPB clinical course is typically more severe and intensive care unit (ICU) care more prolonged than older children, their modes of morbidity are also well characterized. Further, the 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. The well characterized scenario of low cardiac output syndrome (LCOS) will be used as the primary endpoint, while a variety of secondary endpoints will be related to the biochemical anti-inflammatory effects of therapy, ICU care and late neurological outcome.

Official Title
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Preoperative 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 (IVMP)
* Drug: methylprednisolone (two doses IVMP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates Age </= 1 month Scheduled to undergo cardiac surgery involving Cardiopulmonary Bypass (CPB) (reparative or palliative procedures) Inpatient Status at MUSC a minimum of 8 hours prior to planned surgery Exclusion Criteria: Prematurity: </= 36 weeks post gestational age at time of surgery Treatment with steroids, other than inhaled forms, in the two weeks 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 (e.g., gastrointestinal bleeding) Preoperative use of mechanical circulatory support or active resuscitation at the time of proposed randomization Inability to begin the pre-operative study drug at least 8 hours prior to surgery

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose steroid<br>Neonates with congenital heart disease requiring surgery utilizing a cardiopulmonary bypass (CPB) machine in the first month of life that receive ONE dose intravenous methylprednisolone (IVMP) prior to heart surgery. | Drug: methylprednisolone (IVMP)<br>* Neonates with congenital heart disease requiring surgery utilizing a cardiopulmonary bypass (CPB)machine in the first month of life that receive ONE doses intravenous methylprednisolone (IVMP) prior to heart surgery.Compare the effects and preoperative and intraoperative IVMP (2 dose steroid)to intraoperative IVMP alone (single dose steroid) on the inflammatory response to CPB cardiopulmonary bypass.<br>* Other names: glucocorticoid;|
| Experimental: Two Dose steroid<br>Neonates with congenital heart disease requiring surgery utilizing a cardiopulmonary bypass (CPB) machine in the first month of life that receive TWO doses intravenous methylprednisolone (IVMP) prior to heart surgery.Compare the effects and preoperative and intraoperative IVMP to intraoperative IVMP alone on the inflammatory response to CPB cardiopulmonary bypass. The hypothesis is that neonates treated with preoperative IVMP as well as the standard intraoperative IVMP will have decreased production of pro-inflammatory cytokines. | Drug: methylprednisolone (two doses IVMP)<br>* Neonates with congenital heart disease requiring surgery utilizing a cardiopulmonary bypass (CPB)machine in the first month of life that receive TWO doses intravenous methylprednisolone (IVMP) prior to heart surgery.Compare the effects and preoperative and intraoperative IVMP to intraoperative IVMP alone on the inflammatory response to CPB cardiopulmonary bypass. The hypothesis is that neonates treated with preoperative IVMP as well as the standard intraoperative IVMP will have decreased production of pro-inflammatory cytokines.<br>* Other names: glucocorticoid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint: Number of Participants With Low Cardiac Output Syndrome (LCOS) or Death at 36 Hours From Admission to the Intensive Care Unit (ICU) After Surgery. | The presence of low cardiac output syndrome (LCOS) was defined by the same definition used in the PRIMACORP study (Hoffman TM.et.al. Circulation 2003 107:996-1002). Specifically, if there were clinical signs and symptoms of low cardiac output (e.g., tachycardia, oliguria, cold extremities, cardiac arrest, etc.) which required one or more of the following interventions: mechanical circulatory support, the escalation of existing pharmacological circulatory support to >100% over baseline, or the initiation of new pharmacological circulatory support. | 36 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inotropic Score | The inotropic score was calculated by the equation using drug dosages in micrograms/kg/min, (dopamine+dobutamine) + (milrinonex10) + (epinephrinex100) and recorded hourly upon arrival to the ICUthrough 36 hours postoperatively. The highest score during this timeframe was recorded. This score converts dosages of commonly used inotropic medications into a score. The higher the score the more inotropic medications required. The minimum score would be zero indicating no inotropic medications were used. There is no maximum score. | over the first 36 hours after surgery | 
| Number of Participants Who Died Between 36 Hours and 30 Days Following Cardiac Surgery | Number of participants who died of any cause between 36 hours and 30 days following cardiac surgery | at 36 hours and 30 days | 
| Urine Output | Total urine output in mL over the first 36 hours after cardiac surgery | over 36 hours | 
| Total Intake/Output of Fluid | Total amount of all fluids in and out during the first 36 hours postoperatively in mL. | over 36 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiopulmonary Bypass (CPB), System Inflammatory Response, Low Cardiac Output Syndrome (LCOS) in Neonates, Methylprednisolone, Cardiopulmonary Bypass (CPB) in Neonates, Glucocorticoid Use in Neonatal Cardiac Surgery, Steroid