Effect of Postop Steroids on Cardiovascular/Respiratory F... | NCT01595386

Effect of Postop Steroids on Cardiovascular/Respiratory F... | NCT01595386 | Trialant

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	Drug: Hydrocortisone

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Hydrocortisone	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	first 48 hours after cardiac intensive care unit (CICU) admission post-op

Secondary Outcomes

Measure	Description	Time Frame
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.	up to 28 days post op
Hospital Length of Stay

Contacts/Locations Module

Name	Affiliation	Role
Jeffrey Alten, MD	UAB Pediatric Critical Care	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States

Arm/Group Information

ID	Title	Description
FG000	Normal Saline	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.
FG001	Hydrocortisone	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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00119 subjects
COMPLETED		FG00021 subjects FG00119 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Normal Saline-Placebo	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Number

percentage of patients

first 48 hours after cardiac intensive care unit (CICU) admission post-op

ID	Title	Description
OG000	Normal Saline-Placebo	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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Normal Saline-Placebo	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Extracorporeal Membrane Oxygenation	Cardiac disorders		Systematic Assessment	Subject's requiring extracorporeal membrane oxygenation support post-cardiopulmonary bypass

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Acute Kidney injury	Renal and urinary disorders		Systematic Assessment

More Info Module

Certain Agreements

Point of Contact

Title	Organization	Phone	Extension	Email
Jeffrey Alten, M.D., Director of Clinical and Translational Research Department	University of Alabama at Birmingham, Pediatric Cardiac Critical Care	205-975-3123		jalten@peds.uab.edu

Intervention Browse Module

ID	Term
D006854	Hydrocortisone
D000077330	Saline Solution
D012965	Sodium Chloride

ID	Term
D011282	Pregnenediones
D011283	Pregnenes
D011278	Pregnanes
D013256	Steroids
D000072473

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020
Asian	BG0000 BG0010 BG0020
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020
Black or African American	BG0005 BG0013 BG0028
White	BG00016 BG00116 BG00232
More than one race	BG0000 BG0010 BG0020
Unknown or Not Reported	BG0000 BG0010 BG0020

Surgical Procedure

Number

number of patients

Title

Denominators

Categories

Norwood

Title	Measurements
	BG0007 BG0016 BG00213

Arterial switch operation

Title	Measurements
	BG0006 BG0016 BG00212

Interrupted aortic arch repair

Title	Measurements
	BG0003 BG0014 BG0027

Aortic arch augmentation

Title	Measurements
	BG0001 BG0011 BG0022

Truncus arteriosus repair

Title	Measurements
	BG0003 BG0010 BG0023

other

Title	Measurements
	BG0001 BG0012 BG0023

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.049	A p-value of <0.05 represents the threshold for statistical significance.					2-Sided							Yes	Non-Inferiority or Equivalence	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).

Secondary

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.

Posted

Median

Inter-Quartile Range

days

up to 28 days post op

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Title	Measurements
	OG00024(17 to 26.5) OG00125(23 to 26)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Chi-squared		0.44						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

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.

Posted

Median

Inter-Quartile Range

days

Admit to CICU till hospital discharge, approximately 3 weeks

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Title	Measurements
	OG00013.5(9 to 24) OG00119(9 to 24)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.62						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

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.

Posted

Median

Inter-Quartile Range

pg/mL

0, 4,12, 24, and 48 hours post bypass

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Pre-op Il-10

Title	Measurements
	OG0004(2.9 to 5.4) OG0014.3(3 to 6.7)

0 hr post bypass Il-10

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		<0.05						2-Sided	95						Yes	Non-Inferiority or Equivalence	There was not a power calculation for this statistic
OG000 OG001		Wilcoxon (Mann-Whitney)

Secondary

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.

Posted

Median

Inter-Quartile Range

Inotrope Score

first 48 hours post-op

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Inotrope Score at 12 hours post bypass

Title	Measurements
	OG0005.3(1.5 to 12.7) OG0014.7(1.7 to 10.7)

Inotrope Score 24 hours post bypass

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		<0.05						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

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.

Posted

Median

Inter-Quartile Range

mL/kg

1st 48 hours post-op

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Title	Measurements
	OG000-64(-107 to 12) OG001-114(-148 to -60)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.04						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

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.

Posted

Median

Inter-Quartile Range

percentage of arterial-venous saturation

admit to the CICU

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Title	Measurements
	OG00014(10 to 24.2) OG0019.5(7.7 to 13.5)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.03						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

Time Until First Extubation

Respiratory values such as duration of intubation will be used as a secondary outcome.

Posted

Median

Inter-Quartile Range

hours

Until discharge from hospital, approximately 2 weeks

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Title	Measurements
	OG00055(21 to 195) OG00151(34 to 83)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.7						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

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.

Posted

Median

Inter-Quartile Range

hours

approximately 1 week

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Title	Measurements
	OG000162(137 to 389) OG001213(118 to 501)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.76						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

Mortality

Subject mortality will in the CICU will be used as a secondary outcome.

Posted

Number

percentage of patients

Duration of CICU stay, approximately 1 week

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Title	Measurements
	OG00014 OG0010

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		0.23						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.

Secondary

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.

Posted

Median

Inter-Quartile Range

microg/dL

24 hours prebypass and 0 hours post-bypass

ID	Title	Description
OG000	Normal Saline-Placebo	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.
OG001	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. 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.

Units	Counts
Participants	OG00021 OG00119

Title

Denominators

Categories

Pre-op ACTH

Title	Measurements
	OG00024.5(10 to 33) OG00131(16.5 to 54)

Pre-op Pre-stimulation cortisol

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		<0.05						2-Sided	95						Yes	Non-Inferiority or Equivalence	Power calculations were not performed on this statistical calculation.
OG000 OG001		Fisher Exact