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

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ClinicalTrials.gov Identifier: NCT01595386
Recruitment Status : Completed
First Posted : May 10, 2012
Results First Posted : November 10, 2015
Last Update Posted : November 10, 2015
Sponsor:
Information provided by (Responsible Party):
Jeffrey Alten, MD, University of Alabama at Birmingham

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Heart Disease Congenital Complex
Interventions Drug: Hydrocortisone
Drug: Normal Saline
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Normal Saline Hydrocortisone
Hide Arm/Group Description

The subjects will receive a bolus after successful completion of bypass and the post-pump adrenocorticotrophic 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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

Subjects enrolled in this arm of the study will receive a 50mg/m2 bolus of Hydrocortisone after successful completion of cardiopulmonary bypass (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.

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.

Period Title: Overall Study
Started 21 19
Completed 21 19
Not Completed 0 0
Arm/Group Title Normal Saline-Placebo Hydrocortisone Total
Hide Arm/Group Description

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 21 19 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Days
Number Analyzed 21 participants 19 participants 40 participants
6
(5 to 11)
5
(4 to 7)
6
(5 to 8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 19 participants 40 participants
Female
8
  38.1%
5
  26.3%
13
  32.5%
Male
13
  61.9%
14
  73.7%
27
  67.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 19 participants 40 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
  23.8%
3
  15.8%
8
  20.0%
White
16
  76.2%
16
  84.2%
32
  80.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 21 participants 19 participants 40 participants
21 19 40
Surgical Procedure  
Measure Type: Number
Unit of measure:  Number of patients
Number Analyzed 21 participants 19 participants 40 participants
Norwood 7 6 13
Arterial switch operation 6 6 12
Interrupted aortic arch repair 3 4 7
Aortic arch augmentation 1 1 2
Truncus arteriosus repair 3 0 3
other 1 2 3
1.Primary Outcome
Title Incidence of Low Cardiac Output Syndrome (LCOS)
Hide Description 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.
Time Frame first 48 hours after cardiac intensive care unit (CICU) admission post-op
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Measure Type: Number
Unit of Measure: percentage of patients
57 26
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Study sample size was powered to detect a 60% difference in LCOS between groups at α 0.05 and β 0.70, assuming the prevalence of LCOS after neonatal bypass of 65% (based on retrospective data of patients who died, required rescue steroids, ECMO, or epinephrine > 0.1 μg/kg/min).
Statistical Test of Hypothesis P-Value 0.049
Comments A p-value of <0.05 represents the threshold for statistical significance.
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Mean Number of Days Subjects Alive and Ventilator Free
Hide Description 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.
Time Frame up to 28 days post op
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: days
24
(17 to 26.5)
25
(23 to 26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
3.Secondary Outcome
Title Hospital Length of Stay
Hide Description 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.
Time Frame Admit to CICU till hospital discharge, approximately 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: days
13.5
(9 to 24)
19
(9 to 24)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Changes in Baseline Inflammatory Mediators
Hide Description 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.
Time Frame 0, 4,12, 24, and 48 hours post bypass
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
Pre-op Il-10
4
(2.9 to 5.4)
4.3
(3 to 6.7)
0 hr post bypass Il-10
225
(119 to 298)
164
(105.3 to 312)
4 hr post bypss Il-10
53.5
(31.4 to 84.9)
92.2
(54.5 to 141)
12 hr post bypass Il-10
17.5
(8.9 to 28)
20.1
(17.3 to 34.8)
24 hr post bypass Il-10
11.4
(7.9 to 21.7)
10.7
(7 to 16.4)
48 hr post bypass Il-10
7.9
(4.8 to 10.2)
9.4
(7 to 15.4)
Pre-op Il-1 beta
0.49
(0.28 to 0.87)
0.53
(0.29 to 0.78)
0 hr post bypass Il-1 beta
0.44
(0.28 to 1.15)
0.5
(0.28 to 0.63)
4 hr post bypass Il-1 beta
0.83
(0.55 to 1.24)
1.2
(0.58 to 1.57)
12 hr post bypss Il-1 beta
0.49
(0.37 to 1.37)
0.33
(0.21 to 0.8)
24 hr post bypass Il-1 beta
1.71
(0.89 to 4.01)
0.77
(0.38 to 1.13)
48 hr post bypass Il-1 beta
0.76
(0.45 to 1.08)
0.29
(0.13 to 0.54)
Pre-op Il-6
3.6
(1.2 to 18.8)
5.8
(2.8 to 15.1)
0 hr post bypass IL-6
13.6
(9.2 to 20.6)
12.4
(9.7 to 19.8)
4 hr post bypsas Il-6
58
(44.8 to 83.4)
65.2
(40.3 to 89)
12 hr post bypass Il-6
93.7
(61.5 to 164)
50.4
(39.8 to 84.7)
24 hr post bypass Il-6
110
(59.2 to 199)
45.5
(33.4 to 91.6)
48 hr post bypass Il-6
40.1
(23.2 to 78.9)
15.3
(10.9 to 24.6)
Pre-op Il-8
27.1
(21.7 to 37.7)
23.5
(19.2 to 32.3)
0 hr post bypass Il-8
118
(88.7 to 255)
99.8
(71.4 to 188.5)
4 hr post bypss IL-8
212
(160 to 456)
261.5
(183.3 to 331.5)
12 hr post bypass IL-8
153
(105 to 223)
97
(62.9 to 139)
24 hr post bypass Il-8
129
(97.8 to 277)
103
(63.3 to 134.5)
48 hr post bypass Il-8
67.3
(43.3 to 127)
50.3
(37.4 to 59.1)
Pre-op tumor necrosis factor (TNF)-alpha
4.7
(3.4 to 5.4)
4.3
(2.9 to 5)
0 hr post bypass TNF-alpha
3.6
(2.5 to 5.4)
2.9
(2.2 to 4.1)
4 hr post bypass TNF-alpha
6.4
(4.5 to 8.7)
5.5
(4.9 to 6.9)
12 hr post bypss TNF-alpha
6.6
(4.5 to 8.7)
4.2
(3.2 to 4.8)
24 hr post bypass TNF-alpha
5.8
(4.5 to 8.7)
4.1
(3.2 to 5)
48 hr post bypass TNF-alpha
5.1
(4.5 to 8.7)
3
(2.3 to 4.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value <0.01
Comments interleukin-6 at 12, 24, and 48 hour. A p-value of <0.05 is the threshold for statistical significance.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value <0.01
Comments TNF-alpha at 12, 24, and 48 hours.A p-value of <0.05 is the threshold for statistical significance.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value <0.05
Comments Interleukin1-beta at 24 and 48 hours.A p-value of <0.05 is the threshold for statistical significance.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value <0.05
Comments Interleukin-8 at 24 and 48 hours.A p-value of <0.05 is the threshold for statistical significance.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value 0.03
Comments IL-10 at 4 hours.A p-value of <0.05 is the threshold for statistical significance.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Average Inotrope Score
Hide Description 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.
Time Frame first 48 hours post-op
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: Inotrope Score
Inotrope Score at 12 hours post bypass
5.3
(1.5 to 12.7)
4.7
(1.7 to 10.7)
Inotrope Score 24 hours post bypass
0
(0 to 7.7)
4
(0 to 7.3)
Inotrope Score 48 hours post bypass
0
(0 to 7.1)
0
(0 to 0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Fluid Balance
Hide Description 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.
Time Frame 1st 48 hours post-op
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: mL/kg
-64
(-107 to 12)
-114
(-148 to -60)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Changes in Baseline Arterial-venous Oxygen Saturation Difference
Hide Description 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.
Time Frame admit to the CICU
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: percentage of arterial-venous saturation
14
(10 to 24.2)
9.5
(7.7 to 13.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Time Until First Extubation
Hide Description Respiratory values such as duration of intubation will be used as a secondary outcome.
Time Frame Until discharge from hospital, approximately 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: hours
55
(21 to 195)
51
(34 to 83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value 0.7
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title CICU Length of Stay
Hide Description 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.
Time Frame approximately 1 week
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: hours
162
(137 to 389)
213
(118 to 501)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Mortality
Hide Description Subject mortality will in the CICU will be used as a secondary outcome.
Time Frame Duration of CICU stay, approximately 1 week
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Measure Type: Number
Unit of Measure: percentage of patients
14 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
11.Secondary Outcome
Title ACTH Stimulation Test
Hide Description 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.
Time Frame 24 hours prebypass and 0 hours post-bypass
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description:

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: microg/dL
Pre-op ACTH
24.5
(10 to 33)
31
(16.5 to 54)
Pre-op Pre-stimulation cortisol
18.2
(7.5 to 26)
23.3
(11.4 to 30.4)
Pre-op Post-stimulation cortisol
43.6
(34.6 to 51)
47.1
(35 to 53.3)
Post-op ACTH
10.5
(6.5 to 14)
7.5
(6.4 to 9.6)
Post-op Pre-Stimulation cortisol
89.4
(40.5 to 130.8)
87.2
(58.1 to 131)
Post-op Post-stimulation cortisol
112.3
(66.6 to 145.9)
118.8
(72.9 to 143.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculations were not performed on this statistical calculation.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value <0.001
Comments post-operative cortisol.A p-value of <0.05 is the threshold for statistical significance.
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value 0.004
Comments Adrenal Insufficiency after bypass.A p-value of <0.05 is the threshold for statistical significance.
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Normal Saline-Placebo, Hydrocortisone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments There was not a power calculation for this statistic
Statistical Test of Hypothesis P-Value 0.02
Comments Development of Low cardiac output syndrome in subjects with Adrenal Insufficiency.A p-value of <0.05 is the threshold for statistical significance.
Method Fisher Exact
Comments [Not Specified]
Time Frame Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Normal Saline-Placebo Hydrocortisone
Hide Arm/Group Description

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.

Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

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.

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.

All-Cause Mortality
Normal Saline-Placebo Hydrocortisone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Normal Saline-Placebo Hydrocortisone
Affected / at Risk (%) Affected / at Risk (%)
Total   3/21 (14.29%)   1/19 (5.26%) 
Cardiac disorders     
Extracorporeal Membrane Oxygenation  [1]  2/21 (9.52%)  1/19 (5.26%) 
Surgical and medical procedures     
Death   3/21 (14.29%)  0/19 (0.00%) 
Indicates events were collected by systematic assessment
[1]
Subject's requiring extracorporeal membrane oxygenation support post-cardiopulmonary bypass
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Normal Saline-Placebo Hydrocortisone
Affected / at Risk (%) Affected / at Risk (%)
Total   19/21 (90.48%)   17/19 (89.47%) 
Endocrine disorders     
Hyperglycemia  [1]  15/21 (71.43%)  10/19 (52.63%) 
Infections and infestations     
Antibiotics for suspected infection   8/21 (38.10%)  7/19 (36.84%) 
Renal and urinary disorders     
Acute Kidney injury   7/21 (33.33%)  7/19 (36.84%) 
Indicates events were collected by systematic assessment
[1]
Subjects whose blood glucose level was >180 mg/dL
small, single-center trial; included subjects from more than one surgeon; all patients received preoperative and rescue steroids; definition of low cardiac output syndrome although appropriate must ultimately be arbitrary.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jeffrey Alten, M.D., Director of Clinical and Translational Research Department
Organization: University of Alabama at Birmingham, Pediatric Cardiac Critical Care
Phone: 205-975-3123
EMail: jalten@peds.uab.edu
Layout table for additonal information
Responsible Party: Jeffrey Alten, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01595386    
Other Study ID Numbers: Postop Steroids after CPB
First Submitted: March 16, 2012
First Posted: May 10, 2012
Results First Submitted: January 28, 2015
Results First Posted: November 10, 2015
Last Update Posted: November 10, 2015