Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Medical University of South Carolina
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eric M Graham, MD, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT01579513
First received: April 13, 2012
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Congenital Heart Disease
Disorder of Fetus or Newborn
Drug: Methylprednisolone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Incidence of a clinically derived composite morbidity-mortality outcome [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of mechanical ventilation post cardiac surgery. [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
    Amount of time on mechanical ventilation following cardiac surgery

  • Intensive care unit stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
    Amount of time in the intensive care unit following cardiac surgery

  • Hospital stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
    Total duration of hospital stay following cardiac surgery

  • Neurodevelopmental outcome [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Bayley Scale of Infant Development at 1 year


Estimated Enrollment: 190
Study Start Date: June 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intraoperative Methylprednisone
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
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.
Other Names:
  • Solulmedrol
  • Medrol
  • Corticosteroid
  • Steroid
  • Glucocorticoid
Placebo Comparator: Placebo
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
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.
Other Name: Normal Saline

Detailed 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

  Eligibility

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01579513

Contacts
Contact: Eric M Graham, MD 843-792-8704 grahamem@musc.edu
Contact: Patricia G Infinger 843-792-7857 infingep@musc.edu

Locations
United States, Georgia
Children's Healthcare of Atlanta/Emory University Recruiting
Atlanta, Georgia, United States, 30233
Contact: Bahaaldin Alsoufi, MD    404-785-1731    bahaaldin.alsoufi@emory.edu   
Contact: Janet Fernandez, BS    404-785-1731    janet.fernandez@choa.org   
Principal Investigator: Bahaaldin Alsoufi, MD         
United States, South Carolina
Medical University of South Carolina, Pediatric Cardiology Recruiting
Charleston, South Carolina, United States, 29425
Contact: Eric M Graham, MD    843-792-3287    grahamem@musc.edu   
Contact: Patricia G Infinger    843-792-7857    infingep@musc.edu   
Sub-Investigator: Scott M Bradley, MD         
Sub-Investigator: Andrew M Atz, MD         
Sub-Investigator: Minoo N Kavarana, MD         
Principal Investigator: Eric M Graham, MD         
Sub-Investigator: Renee H Martin, PhD         
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Principal Investigator: Eric M Graham, MD Medical University of South Carolina
  More Information

Publications:

Responsible Party: Eric M Graham, MD, Associate Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT01579513     History of Changes
Other Study ID Numbers: Pro16545, R01HL112968
Study First Received: April 13, 2012
Last Updated: February 3, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Medical University of South Carolina:
Cardiopulmonary Bypass (CPB)
Cardiac Surgical Procedures
Heart Disease
Heart Defects, Congenital
System Inflammatory Response
inflammation
Methylprednisolone
Neonates
Steroid
Children
Infants
Pediatrics
Glucocorticoid
Cardiovascular Diseases
Cardiovascular Abnormalities
Corticosteroid
methylprednisolone Hemisuccinate
Hormones
Physiological Effects of Drugs
Randomized Clinical Trial

Additional relevant MeSH terms:
Heart Diseases
Heart Defects, Congenital
Fetal Diseases
Pregnancy Complications
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Glucocorticoids
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Methylprednisolone acetate
Prednisolone acetate
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 14, 2014