Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Congenital Heart Disease Clinical Trial

Official title:

Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00934843
• Other study ID #: HR 17030
• Status: Completed
• Phase: N/A
• First received: July 6, 2009
• Last updated: November 7, 2011
• Start date: March 2007
• Est. completion date: September 2011

Study information

• Verified date: September 2011
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Randomized controlled trial of the use of glucocorticoids to improve the clinical course of neonates post-cardiopulmonary bypass (CPB).

Description:

This study proposes a randomized controlled trial of the use of glucocorticoids to improve the clinical course of neonates post-cardiopulmonary bypass (CPB). The study will focus on neonates for a few reasons. Although their post-CPB clinical course is typically more severe and intensive care unit (ICU) care more prolonged than older children, their modes of morbidity are also well characterized. Further, the 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. The well characterized scenario of low cardiac output syndrome (LCOS) will be used as the primary endpoint, while a variety of secondary endpoints will be related to the biochemical anti-inflammatory effects of therapy, ICU care and late neurological outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Days

Eligibility

Inclusion Criteria:

• Neonates Age </= 1 month

• Scheduled to undergo cardiac surgery involving Cardiopulmonary Bypass (CPB) (reparative or palliative procedures)

• Inpatient Status at MUSC a minimum of 8 hours prior to planned surgery

Exclusion Criteria:

• Prematurity: </= 36 weeks post gestational age at time of surgery

• Treatment with steroids, other than inhaled forms, in the two weeks 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 (e.g., gastrointestinal bleeding)

• Preoperative use of mechanical circulatory support or active resuscitation at the time of proposed randomization

• Inability to begin the pre-operative study drug at least 8 hours prior to surgery

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congenital Heart Disease
• Disorder of Fetus or Newborn
• Heart Defects, Congenital

Intervention

Drug:
• methylprednisolone (IVMP)
Neonates with congenital heart disease requiring surgery utilizing a cardiopulmonary bypass (CPB)machine in the first month of life that receive ONE doses intravenous methylprednisolone (IVMP) prior to heart surgery.Compare the effects and preoperative and intraoperative IVMP (2 dose steroid)to intraoperative IVMP alone (single dose steroid) on the inflammatory response to CPB cardiopulmonary bypass.
• methylprednisolone (two doses IVMP)
Neonates with congenital heart disease requiring surgery utilizing a cardiopulmonary bypass (CPB)machine in the first month of life that receive TWO doses intravenous methylprednisolone (IVMP) prior to heart surgery.Compare the effects and preoperative and intraoperative IVMP to intraoperative IVMP alone on the inflammatory response to CPB cardiopulmonary bypass. The hypothesis is that neonates treated with preoperative IVMP as well as the standard intraoperative IVMP will have decreased production of pro-inflammatory cytokines.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of South Carolina

Country where clinical trial is conducted

United States, 

References & Publications (21)

Bronicki RA, Backer CL, Baden HP, Mavroudis C, Crawford SE, Green TP. Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children. Ann Thorac Surg. 2000 May;69(5):1490-5. — View Citation

Chaney MA. Corticosteroids and cardiopulmonary bypass : a review of clinical investigations. Chest. 2002 Mar;121(3):921-31. Review. — View Citation

Checchia PA, Backer CL, Bronicki RA, Baden HP, Crawford SE, Green TP, Mavroudis C. Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Crit Care Med. 2003 Jun;31(6):1742-5. — View 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. — View Citation

Dickerson HA, Chang AC. Steroids and low cardiac output syndrome after cardiac surgery in children. Pediatr Crit Care Med. 2005 Jul;6(4):495-6. — View Citation

Frantz S, Bauersachs J, Kelly RA. Innate immunity and the heart. Curr Pharm Des. 2005;11(10):1279-90. Review. — View Citation

Friedman WF. Congenital heart disease in infancy and childhood. Heart Disease - A Textbook of Cardiovascular Medicine. 4th ed. Philadelphia, PA. W.B. Saunders Co.; 1992. p. 894.

Greeley WJ, Kern FH, Ungerleider RM, Boyd JL 3rd, Quill T, Smith LR, Baldwin B, Reves JG. The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children. J Thorac Cardiovasc Surg. 1991 May;101(5):783-94. — View Citation

Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, Bailey JM, Akbary A, Kocsis JF, Kaczmarek R, Spray TL, Wessel DL. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation. 2003 Feb 25;107(7):996-1002. — View Citation

Kulik TJ, Moler FW, Palmisano JM, Custer JR, Mosca RS, Bove EL, Bartlett RH. Outcome-associated factors in pediatric patients treated with extracorporeal membrane oxygenator after cardiac surgery. Circulation. 1996 Nov 1;94(9 Suppl):II63-8. — View Citation

Lindberg L, Forsell C, Jögi P, Olsson AK. Effects of dexamethasone on clinical course, C-reactive protein, S100B protein and von Willebrand factor antigen after paediatric cardiac surgery. Br J Anaesth. 2003 Jun;90(6):728-32. — View Citation

Mann DL. Targeted anticytokine therapy and the failing heart. Am J Cardiol. 2005 Jun 6;95(11A):9C-16C; discussion 38C-40C. Review. — View Citation

Mott AR, Fraser CD Jr, Kusnoor AV, Giesecke NM, Reul GJ Jr, Drescher KL, Watrin CH, Smith EO, Feltes TF. The effect of short-term prophylactic methylprednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary bypass. J Am Coll Cardiol. 2001 May;37(6):1700-6. — View Citation

Parr GV, Blackstone EH, Kirklin JW. Cardiac performance and mortality early after intracardiac surgery in infants and young children. Circulation. 1975 May;51(5):867-74. — View Citation

Schroeder VA, Pearl JM, Schwartz SM, Shanley TP, Manning PB, Nelson DP. Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation. 2003 Jun 10;107(22):2823-8. Epub 2003 May 19. — View Citation

Thompson LD, McElhinney DB, Findlay P, Miller-Hance W, Chen MJ, Minami M, Petrossian E, Parry AJ, Reddy VM, Hanley FL. A prospective randomized study comparing volume-standardized modified and conventional ultrafiltration in pediatric cardiac surgery. J Thorac Cardiovasc Surg. 2001 Aug;122(2):220-8. — View Citation

Tuckermann JP, Kleiman A, McPherson KG, Reichardt HM. Molecular mechanisms of glucocorticoids in the control of inflammation and lymphocyte apoptosis. Crit Rev Clin Lab Sci. 2005;42(1):71-104. Review. — View Citation

Turley K, Mavroudis C, Ebert PA. Repair of congenital cardiac lesions during the first week of life. Circulation. 1982 Aug;66(2 Pt 2):I214-9. — View Citation

Ungerleider R. Practice patterns in neonatal cardiopulmonary bypass. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2004;7:172-9. — View Citation

Varan B, Tokel K, Mercan S, Dönmez A, Aslamaci S. Systemic inflammatory response related to cardiopulmonary bypass and its modification by methyl prednisolone: high dose versus low dose. Pediatr Cardiol. 2002 Jul-Aug;23(4):437-41. — View Citation

Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castañeda AR, Newburger JW, Wessel DL. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995 Oct 15;92(8):2226-35. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Endpoint: Number of Participants With Low Cardiac Output Syndrome (LCOS) or Death at 36 Hours From Admission to the Intensive Care Unit (ICU) After Surgery.	The presence of low cardiac output syndrome (LCOS) was defined by the same definition used in the PRIMACORP study (Hoffman TM.et.al. Circulation 2003 107:996-1002). Specifically, if there were clinical signs and symptoms of low cardiac output (e.g., tachycardia, oliguria, cold extremities, cardiac arrest, etc.) which required one or more of the following interventions: mechanical circulatory support, the escalation of existing pharmacological circulatory support to >100% over baseline, or the initiation of new pharmacological circulatory support.	36 hours	No
Secondary	Inotropic Score	The inotropic score was calculated by the equation using drug dosages in micrograms/kg/min, (dopamine+dobutamine) + (milrinonex10) + (epinephrinex100) and recorded hourly upon arrival to the ICUthrough 36 hours postoperatively. The highest score during this timeframe was recorded. This score converts dosages of commonly used inotropic medications into a score. The higher the score the more inotropic medications required. The minimum score would be zero indicating no inotropic medications were used. There is no maximum score.	over the first 36 hours after surgery	No
Secondary	Number of Participants Who Died Between 36 Hours and 30 Days Following Cardiac Surgery	Number of participants who died of any cause between 36 hours and 30 days following cardiac surgery	at 36 hours and 30 days	No
Secondary	Urine Output	Total urine output in mL over the first 36 hours after cardiac surgery	over 36 hours	No
Secondary	Total Intake/Output of Fluid	Total amount of all fluids in and out during the first 36 hours postoperatively in mL.	over 36 hours	No