Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

November 25, 2019 updated by: Medical University of South Carolina
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.

Study Overview

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

Interventional

Enrollment (Actual)

190

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Georgia
      • Atlanta, Georgia, United States, 30233
        • Children's Healthcare of Atlanta/Emory University
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina, Pediatric Cardiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 weeks (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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:
  • Medrol
  • Steroid
  • Corticosteroid
  • Glucocorticoid
  • Solulmedrol
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.
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 Names:
  • Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
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
Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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
Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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
Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Eric M Graham, MD, Medical University of South Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

May 25, 2018

Study Completion (Actual)

December 19, 2018

Study Registration Dates

First Submitted

April 13, 2012

First Submitted That Met QC Criteria

April 16, 2012

First Posted (Estimate)

April 18, 2012

Study Record Updates

Last Update Posted (Actual)

December 9, 2019

Last Update Submitted That Met QC Criteria

November 25, 2019

Last Verified

November 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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