Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Congenital Heart Disease Clinical Trial

Official title:

Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01579513
• Other study ID #: Pro16545
• Secondary ID: R01HL112968
• Status: Completed
• Phase: N/A
• Start date: June 2012
• Est. completion date: December 19, 2018

Study information

• Verified date: November 2019
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: December 19, 2018
• Est. primary completion date: May 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 30 Days

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Heart Disease
• Disorder of Fetus or Newborn
• Heart Diseases

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta/Emory University	Atlanta	Georgia
United States	Medical University of South Carolina, Pediatric Cardiology	Charleston	South Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of South Carolina	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. Review. Update in: Cochrane Database Syst Rev. 2015;10:CD005550. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a Clinically Derived Composite Morbidity-mortality Outcome	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	Duration of Mechanical Ventilation Post Cardiac Surgery.	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
Secondary	Intensive Care Unit Stay	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
Secondary	Hospital Stay	Total duration of hospital stay following cardiac surgery	Participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Secondary	Neurodevelopmental Outcome	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