Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 |
- 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.
- 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:
|
|
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 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 |
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| Contact: Eric M Graham, MD | 843-792-8704 | grahamem@musc.edu |
| Contact: Patricia G Infinger | 843-792-7857 | infingep@musc.edu |
| United States, South Carolina | |
| Medical University of South Carolina, Pediatric Cardiology | Recruiting |
| Charleston, South Carolina, United States, 29425 | |
| Contact: Eric M Graham, MD 843-792-8704 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 | |
| Sub-Investigator: Francis X McGowan, MD | |
| 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: | April 27, 2013 |
| 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:
|
Infants Cardiopulmonary Bypass (CPB) System Inflammatory Response inflammation Methylprednisolone Neonates Steroid Cardiac Surgical Procedures Children Pediatrics |
Glucocorticoid Heart Disease Heart Defects, Congenital Cardiovascular Diseases Cardiovascular Abnormalities Corticosteroid methylprednisolone Hemisuccinate Hormones Physiological Effects of Drugs Randomized Clinical Trial |
Additional relevant MeSH terms:
|
Heart Diseases Heart Defects, Congenital 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 May 16, 2013