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Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Primary Purpose

Congenital Heart Disease, Disorder of Fetus or Newborn

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

methylprednisolone (IVMP)

methylprednisolone (two doses IVMP)

About this trial

This is an interventional treatment trial for Congenital Heart Disease focused on measuring 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

Eligibility Criteria

undefined - 30 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Single dose steroid

Two Dose steroid

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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

Urine Output

Total urine output in mL over the first 36 hours after cardiac surgery

Total Intake/Output of Fluid

Total amount of all fluids in and out during the first 36 hours postoperatively in mL.

Full Information

NCT ID

NCT00934843

First Posted

July 6, 2009

Last Updated

November 7, 2011

Sponsor

Medical University of South Carolina

1. Study Identification

Unique Protocol Identification Number

NCT00934843

Brief Title

Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Official Title

Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Study Type

Interventional

2. Study Status

Record Verification Date

September 2011

Overall Recruitment Status

Completed

Study Start Date

March 2007 (undefined)

Primary Completion Date

September 2011 (Actual)

Study Completion Date

September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Medical University of South Carolina

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderOutcomes Assessor

Allocation

Randomized

Enrollment

77 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single dose steroid

Arm Type

Experimental

Arm Description

Arm Title

Two Dose steroid

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

methylprednisolone (IVMP)

Other Intervention Name(s)

Solumedrol, Steroid, glucocorticoid

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

methylprednisolone (two doses IVMP)

Other Intervention Name(s)

Solumedrol, Steroid, glucocorticoid

Intervention Description

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.

Primary Outcome Measure Information:

Title

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.

Description

Time Frame

36 hours

Secondary Outcome Measure Information:

Title

Inotropic Score

Description

Time Frame

over the first 36 hours after surgery

Title

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

Description

Number of participants who died of any cause between 36 hours and 30 days following cardiac surgery

Time Frame

at 36 hours and 30 days

Title

Urine Output

Description

Total urine output in mL over the first 36 hours after cardiac surgery

Time Frame

over 36 hours

Title

Total Intake/Output of Fluid

Description

Total amount of all fluids in and out during the first 36 hours postoperatively in mL.

Time Frame

over 36 hours

10. Eligibility

Sex

All

Maximum Age & Unit of Time

30 Days

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eric M Graham, MD

Organizational Affiliation

Medical University of South Carolina

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

12600913

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. doi: 10.1161/01.cir.0000051365.81920.28.

Results Reference

background

PubMed Identifier

11479493

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. doi: 10.1067/mtc.2001.114937.

Results Reference

background

PubMed Identifier

7083544

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.

Results Reference

background

PubMed Identifier

15853684

Citation

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

Results Reference

background

PubMed Identifier

11888978

Citation

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.

Results Reference

background

PubMed Identifier

15982431

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.

Results Reference

background

PubMed Identifier

16003215

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

Results Reference

background

PubMed Identifier

15925559

Citation

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.

Results Reference

background

PubMed Identifier

15697171

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. doi: 10.1080/10408360590888983.

Results Reference

background

PubMed Identifier

12794414

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. doi: 10.1097/01.CCM.0000063443.32874.60.

Results Reference

background

PubMed Identifier

12756159

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

Results Reference

background

PubMed Identifier

12170362

Citation

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.

Results Reference

background

PubMed Identifier

11345387

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

Results Reference

background

PubMed Identifier

10881828

Citation

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.

Results Reference

background

PubMed Identifier

12765886

Citation

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.

Results Reference

background

PubMed Identifier

15283366

Citation

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.

Results Reference

background

PubMed Identifier

235375

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. doi: 10.1161/01.cir.51.5.867.

Results Reference

background

PubMed Identifier

7554206

Citation

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.

Results Reference

background

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.

Results Reference

background

PubMed Identifier

2023435

Citation

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.

Results Reference

background

PubMed Identifier

8901721

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.

Results Reference

background

PubMed Identifier

31206501

Citation

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.

Results Reference

derived

PubMed Identifier

23870160

Citation

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.

Results Reference

derived

PubMed Identifier

23587468

Citation

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.

Results Reference

derived

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Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

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