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
  Purpose

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.


Condition Intervention
Heart Disease Congenital Complex
Drug: Hydrocortisone
Drug: Normal Saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Postoperative Hydrocortisone on Cardiovascular and Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 40
Study Start Date: April 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01595386

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Jeffrey Alten, MD UAB Pediatric Critical Care
  More Information

No publications provided

Responsible Party: Jeffrey Alten, MD, Principal Investigator, Associate Professor of Pediatrics, Medical Director of the UAB Pediatric Cardiac Intensive Care Unit, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01595386     History of Changes
Other Study ID Numbers: Postop Steroids after CPB
Study First Received: March 16, 2012
Last Updated: January 3, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on April 22, 2014