Heart Disease Congenital ComplexNCT01595386
Effect of Postop Steroids on Cardiovascular/Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass
A study testing Hydrocortisone and Normal Saline in people with Heart Disease Congenital Complex, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 day to 28 days
- Conditions the study is for
- Heart Disease Congenital Complex
- What is being tested?
- Hydrocortisone and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Nov 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
- Successfully weaned off cardiopulmonary bypass after cardiac surgery
Who cannot join
- requirement for extracorporeal membrane oxygenation (ECMO) in the operating room
- Known immune deficiency
- Having previously received systemic steroids (except for two routine preoperative doses)
- A current signed Do not resuscitate (DNR) or limitation of care order
- Current enrollment in another interventional clinical study
- Refusal of parental consent
- Previous diagnosis of adrenal insufficiency
- > 28 days old at time of surgery whose repair dose not require CPB
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35233
About this study
Official title: 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.
Read the 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.
- Conditions
- Heart Disease Congenital Complex
- Being tested
- Hydrocortisone, Normal Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Also called Solu Cortef
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.
Normal SalineDrug
Also called 0.9% Sodium Chloride
This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.
| Study group | Role | What they receive |
|---|---|---|
| Normal Saline | Placebo comparator | The subjects will receive a bolus after successful completion of bypass and the post-pump adrenal corticotrophin hormone (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. Receives: Drug: Normal Saline |
| Hydrocortisone | Experimental | 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. Receives: Drug: Hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Low Cardiac Output Syndrome (LCOS)
Low Cardiac Output Syndrome (LCOS) within the first 48 hours after post-operative admission to the Pediatric Cardiac Intensive Care Unit was used as the primary outcome. This was defined as a double in inotropic support from post-operative admit, requiring Extracorporeal Membrane Oxygenation (ECMO) support, receiving Cardiopulmonary Resuscitation, or death.
Measured: first 48 hours after cardiac intensive care unit (CICU) admission post-op
Secondary outcomes (10)
Mean Number of Days Subjects Alive and Ventilator Free
Respiratory variables include such as alive, ventilator free days at 28 days post-op will be used as secondary outcome. The mean number of days subjects were live and ventilator free up to the 28 days after surgery.
Measured: up to 28 days post op
Hospital Length of Stay
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.
Measured: Admit to CICU till hospital discharge, approximately 3 weeks
Changes in Baseline Inflammatory Mediators
Changes in pre-op inflammatory mediators will be assessed at 0, 4, 12, 24 and 48 hours post bypass and used as a secondary outcome.
Measured: 0, 4,12, 24, and 48 hours post bypass
Average Inotrope Score
Average inotrope score over first 48 hours after Cardiac Intensive Care Unit admission was used as a secondary outcome. Inotrope Score is calculated based on the dose of inotropes currently infusing at a given time points. The formula for calculation is as follows: Epinephrine/Norepinephrine (mcg/kg/min) dose x100, plus Dopamine/Dobutamine (mcg/kg/min) dose x 1, plus Neosynephrine (mcg/kg/min) dose x10, plus Vasopressin (units/kg/hr) [(dose x60)/10,000] = Inotrope Score. Our institution does not include Milrinone in our inotrope score calculation because every patient receives a continuous infusion in the immediate post-operative period. The higher the inotrope score the more cardiac support the patient is requiring or the worse their cardiac function is becoming.
Measured: first 48 hours post-op
Fluid Balance
Hemodynamic variable such as total fluid balance within the first 48 hours post-op will be used as a secondary outcome. Fluid balance is a calculation of the overall fluid status for a given time period. The total input (fluid, medications, etc) that are given to a patient during a given time frame (24 hours) minus the total output (urine, stool, drainage, etc. ) that comes out of a patient during a given time frame.
Measured: 1st 48 hours post-op
Changes in Baseline Arterial-venous Oxygen Saturation Difference
Respiratory values such as changes in baseline arterial-venous oxygen saturation difference at admission to the pediatric cardiac intensive care unit will be used as a secondary outcome.
Measured: admit to the CICU
Time Until First Extubation
Respiratory values such as duration of intubation will be used as a secondary outcome.
Measured: Until discharge from hospital, approximately 2 weeks
CICU Length of Stay
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.
Measured: approximately 1 week
Mortality
Subject mortality will in the CICU will be used as a secondary outcome.
Measured: Duration of CICU stay, approximately 1 week
ACTH Stimulation Test
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.
Measured: 24 hours prebypass and 0 hours post-bypass
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2012 (estimated)
- Study startApr 2012
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart Disease Congenital ComplexStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffrey Alten, MD, University of Alabama at Birmingham
- Investigators
- Jeffrey Alten, MD, Principal investigator, UAB Pediatric Critical Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01595386
- Sponsor's protocol ID
- Postop Steroids after CPB
- Status last verified
- Oct 2015
- First submitted
- 16 Mar 2012
- Last updated
- 10 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Postoperative Hydrocortisone on Cardiovascular and Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT01595386
- Acronym / sponsor ID
- Postop Steroids after CPB
- Conditions
- Heart Disease Congenital Complex
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 10 May 2012 (estimated)
- Results
- Posted 10 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal Saline | Placebo comparator | Drug: Normal SalineThe subjects will receive a bolus after successful completion of bypass and the post-pump adrenal corticotrophin hormone (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. |
| Hydrocortisone | Experimental | Drug: HydrocortisoneSubjects 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. |
Who may qualify
- Ages
- 1 day to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
- Successfully weaned off cardiopulmonary bypass after cardiac surgery
Key exclusion criteria (8 listed)
- requirement for extracorporeal membrane oxygenation (ECMO) in the operating room
- Known immune deficiency
- Having previously received systemic steroids (except for two routine preoperative doses)
- A current signed Do not resuscitate (DNR) or limitation of care order
- Current enrollment in another interventional clinical study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocortisoneAlso: Solu CortefThe 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. | Drug | Hydrocortisone |
| Normal SalineAlso: 0.9% Sodium ChlorideThis will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm. | Drug | Normal Saline |
Primary outcome
Incidence of Low Cardiac Output Syndrome (LCOS)
Time frame: first 48 hours after cardiac intensive care unit (CICU) admission post-op
Low Cardiac Output Syndrome (LCOS) within the first 48 hours after post-operative admission to the Pediatric Cardiac Intensive Care Unit was used as the primary outcome. This was defined as a double in inotropic support from post-operative admit, requiring Extracorporeal Membrane Oxygenation (ECMO) support, receiving Cardiopulmonary Resuscitation, or death.
10 secondary outcomes
Mean Number of Days Subjects Alive and Ventilator Free
Time frame: up to 28 days post op
Hospital Length of Stay
Time frame: Admit to CICU till hospital discharge, approximately 3 weeks
Changes in Baseline Inflammatory Mediators
Time frame: 0, 4,12, 24, and 48 hours post bypass
Average Inotrope Score
Time frame: first 48 hours post-op
Fluid Balance
Time frame: 1st 48 hours post-op
Changes in Baseline Arterial-venous Oxygen Saturation Difference
Time frame: admit to the CICU
Time Until First Extubation
Time frame: Until discharge from hospital, approximately 2 weeks
CICU Length of Stay
Time frame: approximately 1 week
Mortality
Time frame: Duration of CICU stay, approximately 1 week
ACTH Stimulation Test
Time frame: 24 hours prebypass and 0 hours post-bypass
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Alten, MD principal investigator
UAB Pediatric Critical Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydrocortisone and Normal Saline in people with Heart Disease Congenital Complex, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Low Cardiac Output Syndrome (LCOS) (time frame: first 48 hours after cardiac intensive care unit (CICU) admission post-op). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2015.