Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

NCT01579513 | Completed Results DMC

• 2 other identifiers: Pro16545R01HL112968
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Duration of Mechanical Ventilation Post Cardiac Surgery.

  Participants will be followed for the duration of hospital stay, an expected average of 5 weeks

• Intensive Care Unit Stay

  Participants will be followed for the duration of hospital stay, an expected average of 5 weeks

• Hospital Stay

  Participants will be followed for the duration of hospital stay, an expected average of 5 weeks

• Neurodevelopmental Outcome

  1 year

Study Arms (2)

Intraoperative Methylprednisone

ACTIVE COMPARATOR

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.

Drug: Methylprednisolone

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Methylprednisolone 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.

Also known as: Solulmedrol, Medrol, Corticosteroid, Steroid, Glucocorticoid

Intraoperative Methylprednisone

Placebo 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.

Also known as: Normal Saline

Placebo

Eligibility Criteria

• Age: Up to 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age \< 1 month
• Male and female patients who are scheduled to undergo cardiac surgery involving CPB

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (2)

Children's Healthcare of Atlanta/Emory University

Atlanta, Georgia, 30233, United States

Location

Medical University of South Carolina, Pediatric Cardiology

Charleston, South Carolina, 29425, United States

Location

Related Publications (9)

• 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.

  PMID: 21600592 BACKGROUND

• 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.

  PMID: 12903869 BACKGROUND

• 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.

  PMID: 9551188 BACKGROUND

• 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.

  PMID: 15982431 BACKGROUND

• 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.

  PMID: 17943866 BACKGROUND

• 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.

  PMID: 21060075 BACKGROUND

• 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.

  PMID: 22271697 BACKGROUND

• 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.

  PMID: 21440149 BACKGROUND

• 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.

  PMID: 32374395 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital; Fetal Diseases; Inflammation; Heart Diseases; Cardiovascular Diseases; Cardiovascular Abnormalities

Interventions

Methylprednisolone; Adrenal Cortex Hormones; Steroids; Glucocorticoids; Saline Solution

Condition Hierarchy (Ancestors)

Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Nearly one third of the subjects received additional steroids in the early postoperative period, potentially diminishing the ability to detect both beneficial and adverse effects.

Results Point of Contact

• Title: Eric Graham, MD
• Organization: Medical University of South Carolina

grahamem@musc.edu

843-792-9570

Study Officials

• Eric M Graham, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2012
• First Posted: April 18, 2012
• Study Start: June 1, 2012
• Primary Completion: May 25, 2018
• Study Completion: December 19, 2018
• Last Updated: December 9, 2019
• Results First Posted: June 18, 2019

Record last verified: 2019-11

Locations

US (2)