Effect of Postop Steroids on Cardiovascular/Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jeffrey Alten, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01595386
First received: March 16, 2012
Last updated: January 3, 2014
Last verified: January 2014

March 16, 2012
January 3, 2014
April 2012
November 2013   (final data collection date for primary outcome measure)
Average Inotrope Score [ Time Frame: first 48 hours after CICU admission post-op ] [ Designated as safety issue: No ]
The primary endpoint in this study is average inotrope score over first 48 hours after Cardiac Intensive Care Unit admission
Average Inotrope Score [ Time Frame: first 48 hours after CICU admission post-op ] [ Designated as safety issue: No ]
The primary endpoint in this study is average inotrope score over first 48 hours after CICU admission
Complete list of historical versions of study NCT01595386 on ClinicalTrials.gov Archive Site
  • Inotrope Score [ Time Frame: 24 hours post-op ] [ Designated as safety issue: No ]
    Hemodynamic variables such as maximum inotrope score at 24 hours post-op will be used as a secondary outcome
  • Alive, ventilator free days [ Time Frame: 28 days post-op ] [ Designated as safety issue: No ]
    Respiratory variables include such as alive, ventilator free days at 28 days post-op will be used as secondary outcome
  • Hospital Length of stay [ Time Frame: Admit to CICU till hospital discharge, approximately 3 weeks ] [ Designated as safety issue: No ]
    The average length of hospital stay from the time the subject is admitted to the CICU post-op until they are discharged will be used as a secondary outcome.
  • Changes in baseline inflammatory mediators [ Time Frame: 0, 4, and 24 hours post bypass ] [ Designated as safety issue: No ]
    Changes in pre-op inflammatory mediators will be assessed at 0, 4, and 24 hours post bypass and used as a secondary outcome.
  • Low Cardiac Output Syndrome (LCOS) [ Time Frame: first 48 hours post-op ] [ Designated as safety issue: No ]
    Hemodynamic variables such as LCOS within the first 48 hours post-op will be used as a secondary outcome.
  • Total fluid bolus [ Time Frame: 1st 48 hours post-op ] [ Designated as safety issue: No ]
    Hemodynamic variable such as total fluid boluses administered within the first 48 hours post-op will be used as a secondary outcome.
  • Changes in baseline alveolar-arterial oxygen difference [ Time Frame: 24 and 48 hours post-op ] [ Designated as safety issue: No ]
    Respiratory values such as changes in baseline alveolar-arterial oxygen difference at 24 and 48 hours post-op will be used as a secondary outcome.
  • Changes in dynamic lung compliance [ Time Frame: 24 and 48 hours post-op ] [ Designated as safety issue: No ]
    Respiratory values such as changes in dynamic lung compliance at 24 and 48 hours post-op will be used as a secondary outcome.
  • Duration of oxygen therapy [ Time Frame: Until discharge from hospital, approximately 2 weeks ] [ Designated as safety issue: No ]
    Respiratory values such as duration of oxygen therapy will be used as a secondary outcome.
  • CICU length of stay [ Time Frame: approximately 1 week ] [ Designated as safety issue: No ]
    CICU length of stay will be calculated from the time the subject is admitted to the CICU post-op until they are discharged from the unit. This will be used as a secondary outcome.
  • Mortality [ Time Frame: Duration of CICU stay, approximately 1 week ] [ Designated as safety issue: No ]
    Subject mortality will in the CICU will be used as a secondary outcome.
  • ACTH Stimulation Test [ Time Frame: 24 hours prebypass and 0 hours post-bypass ] [ Designated as safety issue: No ]
    AdrenoCorticoTropic Hormone stimulation test will be performed at least 24 hours pre-bypass and immediately after successful discontinuation of bypass and compared. These outcomes will be used as a secondary outcome.
  • Post-op Cortisol [ Time Frame: 2 and 24 hours after bypass ] [ Designated as safety issue: No ]
    Cortisol levels will be checked at 2 and 24 hours after bypass. The results will be used as a secondary outcome.
  • Post-op ACTH [ Time Frame: 2 and 24 hour post-bypass ] [ Designated as safety issue: No ]
    Serum ACTH will be checked at 2 and 24 hours after bypass. The results of these will be compared and used as a secondary outcome.
  • Inotrope Score [ Time Frame: 24 hours post-op ] [ Designated as safety issue: No ]
    Hemodynamic variables such as maximum inotrope score at 24 hours post-op will be used as a secondary outcome
  • Alive, ventilator free days [ Time Frame: 28 days post-op ] [ Designated as safety issue: No ]
    Respiratory variables include such as alive, ventilator free days at 28 days post-op will be used as secondary outcome
  • Hospital Length of stay [ Time Frame: Admit to CICU till hospital discharge, approximately 3 weeks ] [ Designated as safety issue: No ]
    The average length of hospital stay from the time the subject is admitted to the CICU post-op until they are discharged will be used as a secondary outcome.
  • Changes in baseline inflammatory mediators [ Time Frame: 0, 4, and 24 hours post bypass ] [ Designated as safety issue: No ]
    Changes in pre-op inflammatory mediators will be assessed at 0, 4, and 24 hours post bypass and used as a secondary outcome.
  • Low Cardiac Output Syndrome (LCOS) [ Time Frame: first 48 hours post-op ] [ Designated as safety issue: No ]
    Hemodynamic variables such as LCOS within the first 48 hours post-op will be used as a secondary outcome.
  • Total fluid bolus [ Time Frame: 1st 48 hours post-op ] [ Designated as safety issue: No ]
    Hemodynamic variable such as total fluid boluses administered within the first 48 hours post-op will be used as a secondary outcome.
  • Changes in baseline alveolar-arterial oxygen difference [ Time Frame: 24 and 48 hours post-op ] [ Designated as safety issue: No ]
    Respiratory values such as changes in baseline alveolar-arterial oxygen difference at 24 and 48 hours post-op will be used as a secondary outcome.
  • Changes in dynamic lung compliance [ Time Frame: 24 and 48 hours post-op ] [ Designated as safety issue: No ]
    Respiratory values such as changes in dynamic lung compliance at 24 and 48 hours post-op will be used as a secondary outcome.
  • Duration of oxygen therapy [ Time Frame: Until discharge from hospital, approximately 2 weeks ] [ Designated as safety issue: No ]
    Respiratory values such as duration of oxygen therapy will be used as a secondary outcome.
  • CICU length of stay [ Time Frame: approximately 1 week ] [ Designated as safety issue: No ]
    CICU length of stay will be calculated from the time the subject is admitted to the CICU post-op until they are discharged from the unit. This will be used as a secondary outcome.
  • Mortality [ Time Frame: Duration of CICU stay, approximately 1 week ] [ Designated as safety issue: No ]
    Subject mortality will in the CICU will be used as a secondary outcome.
  • ACTH Stimulation Test [ Time Frame: 24 hours prebypass and 0 hours post-bypass ] [ Designated as safety issue: No ]
    ACTH stimulation test will be performed at least 24 hours pre-bypass and immediately after successful discontinuation of bypass and compared. These outcomes will be used as a secondary outcome.
  • Post-op Cortisol [ Time Frame: 2 and 24 hours after bypass ] [ Designated as safety issue: No ]
    Cortisol levels will be checked at 2 and 24 hours after bypass. The results will be used as a secondary outcome.
  • Post-op ACTH [ Time Frame: 2 and 24 hour post-bypass ] [ Designated as safety issue: No ]
    Serum ACTH will be checked at 2 and 24 hours after bypass. The results of these will be compared and used as a secondary outcome.
Not Provided
Not Provided
 
Effect of Postop Steroids on Cardiovascular/Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass
Effect of Postoperative Hydrocortisone on Cardiovascular and Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass

This protocol is designed to offer insight into critical illness related corticosteroid insufficiency and steroid supplementation in neonates undergoing cardiac surgery with cardiopulmonary bypass by administering exogenous steroids in the immediate post-operative period.

Open-heart surgery with cardiopulmonary bypass (CPB) induces an acute systemic inflammatory response (SIRS) via synthesis and release of inflammatory mediators. These inflammatory cascades may result in the development of capillary leak and generalized tissue edema, which are associated with multiorgan dysfunction involving the myocardium, lungs, kidneys, pancreas, and central nervous system. Neonates are especially susceptible to the injurious effects of SIRS. In attempt to blunt post-bypass SIRS, most neonatal heart programs have protocols in which patients receive preoperative and/or intraoperative steroids. Despite this widespread use, studies have not demonstrated consistent benefit in this therapy, and neonates often continue to suffer the deleterious effects of SIRS postoperatively. Only one study was designed to evaluate the impact of prophylactic postoperative steroid administration on outcomes after neonatal CPB. The early postoperative periods is a crucial time during which attenuation of CPB-induced SIRS by exogenous steroids may lead to improved clinical outcomes.

Adrenal insufficiency in neonates post-CPB may accentuate the harmful effects of SIRS by diminishing the anti-inflammatory and hemodynamic stabilization benefits of endogenous cortisol. Evidence suggests that neonates may suffer from inadequate cortisol activity relative to the severity of illness post-CPB, in part related to immaturity of their hypothalamic-pituitary-adrenal (HPA) axis. This so-called critical illness-related corticosteroids insufficiency (CIRCI) may contribute to low cardiac output syndrome (LCOS), respiratory dysfunction, and capillary leak in the postoperative period.

Much of the support for CIRCI as a contributor to LCOS after CPB originates from small clinical studies that demonstrate benefit of exogenous steroid supplementation on various short term clinical outcomes in patients with shock. Yet it is not clear if benefit from exogenous steroids suggests by dysregulation of the HPA axis or whether these are merely alternative effects of steroids. Investigators have recently begun to describe the cortisol response in neonates post-CPB, but there is no consensus regarding the incidence of clinically important adrenal insufficiency, its identification, or who should receive exogenous steroids.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Heart Disease Congenital Complex
  • Drug: Hydrocortisone
    The drug will be bolused at 50mg/m2 followed by a continuous infusion that will start at 50mg/m2 for the first 48 hours and then be tapered as follows: 40mg/m2/day over 24 hours, 30mg/m2/day over 12 hours, 20 mg/m2/day over 12 hours, 10mg/m2/day over 24 hours, then off.
    Other Name: Solu Cortef
  • Drug: Normal Saline
    This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.
    Other Name: 0.9% Sodium Chloride
  • Placebo Comparator: Normal Saline
    The subjects will receive a bolus after successful completion of bypass and the post-pump ACTH stim test equal to a 50mg/m2 dose of Hydrocortisone. This will be followed by a continuous infusion comparable to the rates a Hydrocortisone drip would run at. This infusion will be tapered down over the next 120 hours.
    Intervention: Drug: Normal Saline
  • Experimental: Hydrocortisone
    Subjects enrolled in this arm of the study will receive a 50mg/m2 bolus of Hydrocortisone after successful completion of CPB and the post-pump ACTH stim test has been performed. This will be followed by a continuous infusion of Hydrocortisone that will be tapered over the next 120 hours.
    Intervention: Drug: Hydrocortisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
November 2013
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Neonate (< 28 days old) undergoing correct cardiac surgery, or infants undergoing the following surgery procedures: Norwood, Arterial Switch, Total Anomalous Pulmonary Venous Return Repair, Interrupted Aortic Arch Repair, Truncus Arteriosus Repair
  2. Successfully weaned off cardiopulmonary bypass after cardiac surgery

Exclusion Criteria:

  1. requirement for extracorporeal membrane oxygenation (ECMO) in the operating room
  2. Known immune deficiency
  3. Having previously received systemic steroids (except for two routine preoperative doses)
  4. A current signed Do not resuscitate (DNR) or limitation of care order
  5. Current enrollment in another interventional clinical study
  6. Refusal of parental consent
  7. Previous diagnosis of adrenal insufficiency
  8. > 28 days old at time of surgery whose repair dose not require CPB
Both
up to 2 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01595386
Postop Steroids after CPB
Yes
Jeffrey Alten, MD, University of Alabama at Birmingham
University of Alabama at Birmingham
Not Provided
Principal Investigator: Jeffrey Alten, MD UAB Pediatric Critical Care
University of Alabama at Birmingham
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP