Clinical trial NCT01579513: Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass
Official title: Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Heart Disease
Disorder of Fetus or Newborn
Keywords: 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
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Institutes of Health (NIH)
First posted: 2012-04-18
Enrollment: 190
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With a Clinically Derived Composite Morbidity-mortality Outcome
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Secondary outcomes:
measure: Duration of Mechanical Ventilation Post Cardiac Surgery.
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Intensive Care Unit Stay
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Hospital Stay
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Neurodevelopmental Outcome
timeFrame: 1 year
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta/Emory University
state: Georgia
city: Charleston
country: United States
facility: Medical University of South Carolina, Pediatric Cardiology
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Eric M Graham, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.