- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01579513
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
Status
Completed
Intervention / Treatment
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
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Georgia
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Atlanta, Georgia, United States, 30233
- Children's Healthcare of Atlanta/Emory University
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina, Pediatric Cardiology
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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 |
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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.
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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:
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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.
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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:
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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
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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.
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Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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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
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Amount of time on mechanical ventilation following cardiac surgery
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Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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Intensive Care Unit Stay
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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Amount of time in the intensive care unit following cardiac surgery
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Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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Hospital Stay
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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Total duration of hospital stay following cardiac surgery
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Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
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Neurodevelopmental Outcome
Time Frame: 1 year
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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.
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1 year
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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
- Pasquali SK, Hall M, Li JS, Peterson ED, Jaggers J, Lodge AJ, Marino BS, Goodman DM, Shah SS. Corticosteroids and outcome in children undergoing congenital heart surgery: analysis of the Pediatric Health Information Systems database. Circulation. 2010 Nov 23;122(21):2123-30. doi: 10.1161/CIRCULATIONAHA.110.948737. Epub 2010 Nov 8.
- Robertson-Malt S, Afrane B, El Barbary M. Prophylactic steroids for pediatric open heart surgery. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005550. doi: 10.1002/14651858.CD005550.pub2.
- Graham EM, Atz AM, Butts RJ, Baker NL, Zyblewski SC, Deardorff RL, DeSantis SM, Reeves ST, Bradley SM, Spinale FG. Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery: results from a randomized trial. J Thorac Cardiovasc Surg. 2011 Dec;142(6):1523-9. doi: 10.1016/j.jtcvs.2011.04.019. Epub 2011 May 20.
- Clarizia NA, Manlhiot C, Schwartz SM, Sivarajan VB, Maratta R, Holtby HM, Gruenwald CE, Caldarone CA, Van Arsdell GS, McCrindle BW. Improved outcomes associated with intraoperative steroid use in high-risk pediatric cardiac surgery. Ann Thorac Surg. 2011 Apr;91(4):1222-7. doi: 10.1016/j.athoracsur.2010.11.005.
- Checchia PA, Bronicki RA, Costello JM, Nelson DP. Steroid use before pediatric cardiac operations using cardiopulmonary bypass: an international survey of 36 centers. Pediatr Crit Care Med. 2005 Jul;6(4):441-4. doi: 10.1097/01.PCC.0000163678.20704.C5.
- Pasquali SK, Li JS, He X, Jacobs ML, O'Brien SM, Hall M, Jaquiss RD, Welke KF, Peterson ED, Shah SS, Gaynor JW, Jacobs JP. Perioperative methylprednisolone and outcome in neonates undergoing heart surgery. Pediatrics. 2012 Feb;129(2):e385-91. doi: 10.1542/peds.2011-2034. Epub 2012 Jan 23.
- Seghaye MC. The clinical implications of the systemic inflammatory reaction related to cardiac operations in children. Cardiol Young. 2003 Jun;13(3):228-39. doi: 10.1017/s1047951103000465. No abstract available.
- Seghaye MC, Heyl W, Grabitz RG, Schumacher K, von Bernuth G, Rath W, Duchateau J. The production of pro- and anti-inflammatory cytokines in neonates assessed by stimulated whole cord blood culture and by plasma levels at birth. Biol Neonate. 1998;73(4):220-7. doi: 10.1159/000013980.
- Everett AD, Buckley JP, Ellis G, Yang J, Graham D, Griffiths M, Bembea M, Graham EM. Association of Neurodevelopmental Outcomes With Environmental Exposure to Cyclohexanone During Neonatal Congenital Cardiac Operations: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2020 May 1;3(5):e204070. doi: 10.1001/jamanetworkopen.2020.4070.
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
Terms related to this study
Keywords
- Cardiovascular Diseases
- Children
- Pediatrics
- Heart Defects, Congenital
- Cardiovascular Abnormalities
- inflammation
- Corticosteroid
- Steroid
- Infants
- Heart Disease
- Methylprednisolone
- Physiological Effects of Drugs
- Neonates
- Randomized Clinical Trial
- Hormones
- Glucocorticoid
- Cardiac Surgical Procedures
- Cardiopulmonary Bypass (CPB)
- System Inflammatory Response
- methylprednisolone Hemisuccinate
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Congenital Abnormalities
- Pregnancy Complications
- Cardiovascular Abnormalities
- Heart Diseases
- Heart Defects, Congenital
- Fetal Diseases
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
- Glucocorticoids
Other Study ID Numbers
- Pro16545
- R01HL112968 (U.S. NIH Grant/Contract)
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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