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Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

NCT ID: NCT01579513

Last Updated: 2019-12-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

190 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2018-12-19

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

Conditions

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Congenital Heart Disease Disorder of Fetus or Newborn

Keywords

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Cardiopulmonary Bypass (CPB) System Inflammatory Response inflammation Methylprednisolone Neonates Steroid 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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type DRUG

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.

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Solulmedrol Medrol Corticosteroid Steroid Glucocorticoid Normal Saline

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.
Maximum Eligible Age

30 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eric M Graham, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

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Children's Healthcare of Atlanta/Emory University

Atlanta, Georgia, United States

Site Status

Medical University of South Carolina, Pediatric Cardiology

Charleston, South Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21600592 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12903869 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9551188 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15982431 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17943866 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21060075 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22271697 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21440149 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32374395 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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R01HL112968

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro16545

Identifier Type: -

Identifier Source: org_study_id