Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

NCT00934843 | Completed Results

• 1 other identifier: HR 17030
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Congenital Heart Disease; Disorder of Fetus or Newborn

Keywords

Cardiopulmonary Bypass (CPB); System Inflammatory Response; Low Cardiac Output Syndrome (LCOS) in Neonates; Methylprednisolone; Cardiopulmonary Bypass (CPB) in Neonates; Glucocorticoid Use in Neonatal Cardiac Surgery; Steroid

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Inotropic Score

  over the first 36 hours after surgery

• Number of Participants Who Died Between 36 Hours and 30 Days Following Cardiac Surgery

  at 36 hours and 30 days

• Urine Output

  over 36 hours

• Total Intake/Output of Fluid

  over 36 hours

Study Arms (2)

Single dose steroid

EXPERIMENTAL

Neonates with congenital heart disease requiring surgery utilizing a cardiopulmonary bypass (CPB) machine in the first month of life that receive ONE dose intravenous methylprednisolone (IVMP) prior to heart surgery.

Drug: methylprednisolone (IVMP)

Two Dose steroid

EXPERIMENTAL

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.

Drug: methylprednisolone (two doses IVMP)

Interventions

methylprednisolone (IVMP) DRUG

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.

Also known as: Solumedrol, Steroid, glucocorticoid

Single dose steroid

methylprednisolone (two doses IVMP) DRUG

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.

Also known as: Solumedrol, Steroid, glucocorticoid

Two Dose steroid

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (24)

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• 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.

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• Frantz S, Bauersachs J, Kelly RA. Innate immunity and the heart. Curr Pharm Des. 2005;11(10):1279-90. doi: 10.2174/1381612053507512.

  PMID: 15853684 BACKGROUND

• Chaney MA. Corticosteroids and cardiopulmonary bypass : a review of clinical investigations. Chest. 2002 Mar;121(3):921-31. doi: 10.1378/chest.121.3.921.

  PMID: 11888978 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

• 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. doi: 10.1097/01.pcc.0000164640.09454.61. No abstract available.

  PMID: 16003215 BACKGROUND

• Mann DL. Targeted anticytokine therapy and the failing heart. Am J Cardiol. 2005 Jun 6;95(11A):9C-16C; discussion 38C-40C. doi: 10.1016/j.amjcard.2005.03.007.

  PMID: 15925559 BACKGROUND

• 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. doi: 10.1080/10408360590888983.

  PMID: 15697171 BACKGROUND

• 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. doi: 10.1097/01.CCM.0000063443.32874.60.

  PMID: 12794414 BACKGROUND

• 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. doi: 10.1161/01.CIR.0000070955.55636.25. Epub 2003 May 19.

  PMID: 12756159 BACKGROUND

• Varan B, Tokel K, Mercan S, Donmez 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. doi: 10.1007/s00246-002-0118-3.

  PMID: 12170362 BACKGROUND

• 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. doi: 10.1016/s0735-1097(01)01223-2.

  PMID: 11345387 BACKGROUND

• 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. doi: 10.1016/s0003-4975(00)01082-1.

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• Lindberg L, Forsell C, Jogi 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. doi: 10.1093/bja/aeg125.

  PMID: 12765886 BACKGROUND

• Ungerleider R. Practice patterns in neonatal cardiopulmonary bypass. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2004;7:172-9. doi: 10.1053/j.pcsu.2004.02.022.

  PMID: 15283366 BACKGROUND

• 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. doi: 10.1161/01.cir.51.5.867.

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• Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda 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. doi: 10.1161/01.cir.92.8.2226.

  PMID: 7554206 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 2023435 BACKGROUND

• 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.

  PMID: 8901721 BACKGROUND

• Schroeder LW, Buckley JR, Stroud RE, Martin RH, Nadeau EK, Barrs R, Graham EM. Plasma Neutrophil Gelatinase-Associated Lipocalin Is Associated With Acute Kidney Injury and Clinical Outcomes in Neonates Undergoing Cardiopulmonary Bypass. Pediatr Crit Care Med. 2019 Oct;20(10):957-962. doi: 10.1097/PCC.0000000000002035.

  PMID: 31206501 DERIVED

• Graham EM, Atz AM, McHugh KE, Butts RJ, Baker NL, Stroud RE, Reeves ST, Bradley SM, McGowan FX Jr, Spinale FG. Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: results from a randomized trial. J Thorac Cardiovasc Surg. 2014 Mar;147(3):902-8. doi: 10.1016/j.jtcvs.2013.06.010. Epub 2013 Jul 16.

  PMID: 23870160 DERIVED

• Butts RJ, Scheurer MA, Zyblewski SC, Wahlquist AE, Nietert PJ, Bradley SM, Atz AM, Graham EM. A composite outcome for neonatal cardiac surgery research. J Thorac Cardiovasc Surg. 2014 Jan;147(1):428-33. doi: 10.1016/j.jtcvs.2013.03.013. Epub 2013 Apr 12.

  PMID: 23587468 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital; Fetal Diseases; Cardiac Output, Low

Interventions

Methylprednisolone; Methylprednisolone Hemisuccinate; Steroids; Glucocorticoids

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Limitations and Caveats

Limitations of the current study include the lack of a true placebo group. Thus recommendations for or against intraoperative MP can not be made. The results of our trial do not preclude the efficacy of other glucocorticoid regimens.

Results Point of Contact

• Title: Dr. Eric Graham
• Organization: Medical University of South Carolina

grahamem@musc.edu

843-792-8704

Study Officials

• Eric M Graham, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 6, 2009
• First Posted: July 8, 2009
• Study Start: March 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: December 9, 2011
• Results First Posted: December 9, 2011

Record last verified: 2011-09

Locations

US (1)