Post-bypass Prophylactic IVIG in Infants and Neonates

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Completed

CT.gov ID

NCT02043379

Collaborator

Grifols Biologicals, LLC (Industry)

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study protocol is to determine if administering Intravenous Immunoglobulin (IVIG) for treatment of cardiopulmonary bypass (CPB) induced hypogammaglobulinemia in the early post-operative period can impact post-surgical outcomes (i.e., infection, fluid overload, and associated morbidities).

Condition or Disease	Intervention/Treatment	Phase
Hypogammaglobulinemia Congenital Heart Disease	Drug: IVIG Other: Placebo	N/A

Detailed Description

The intense post-CPB systemic inflammatory response syndrome (SIRS) is well described in neonates and infants. Increased production and release of pro-inflammatory cytokines, including Tumor Necrosis Factor, Interleukin1-B, and Interleukin-6 may suppress myocardial contractility, induce capillary leak, and activate complement and the clotting cascade - together leading to potential organ injury and death. SIRS is also frequently accompanied by impairment of the humoral immune response. One potential reason for this acquired immunodeficiency after cardiac surgery is the removal of immunoglobulins (Ig)s from the vascular space into other compartments where they are either sequestered or lost from the body altogether. We recently demonstrated that such Ig depletion from the intravascular compartment occurs in neonates following cardiac surgery. In a retrospective study of 53 children <3 months of age, we showed that plasma Immunoglobulin G (IgG) concentration drops precipitously after cardiac surgery and does not return to preoperative levels by 7 days; 51% of patients had hypogammaglobulinemia.

An important question is whether post-CPB low IgG has clinical consequence. IgG plays an essential role in the humoral immune system, activating complement and inducing the phagocytic system to neutralize pathogens. IgG deficiency is a known risk factor for infections in other pediatric populations. We were the first to demonstrate that post-CPB hypogammaglobulinemia is associated with worse clinical outcomes, including increased secondary infections (37% vs.12% in those without low IgG, p<0.05). These novel findings are paramount in that they identify a potential modifiable risk factor to improve outcomes after pediatric cardiac surgery with CPB. Additionally, low IgG is accompanied by fluid overload and prolonged mechanical ventilation. Igs constitute an important component of plasma oncotic pressure, so hypogammaglobulinemia may exacerbate anasarca, prolonging postoperative convalescence and increasing the morbidities associated with increased ICU length of stay.9

Igs have an increasingly recognized role in modulating the innate immune response. Present use of IVIG exceeds mere antibody replacement and extends to the treatment of autoimmune and inflammatory conditions. In fact, more than 75% of IVIG use in the U.S. today is for the treatment of inflammatory conditions, where proposed mechanisms include reduction of pro-inflammatory cytokine and adhesion molecule expression, superantigen neutralization, restoration of glucocorticoid responsiveness, and blockade of complement fragment deposition. It is plausible that IVIG could benefit neonates after cardiac surgery not only via restoration of humoral opsonization capacity, but also as a modulator of innate immunity and SIRS. According to this model, tissue injury, CPB, and shock trigger SIRS, leading to hypogammaglobulinemia and resultant increased susceptibility to inflammatory dysregulation which might be ameliorated via administration of IVIG.

In an adult study, IVIG failed to benefit postoperative cardiac patients with severe SIRS. However, the dose of IVIG given was relatively small compared with that typically given for autoimmune and inflammatory conditions. Neonates and infants may be more susceptible to the harmful effects of acquired hypogammaglobulinemia than adults as they may be unable to generate adequate quantities of antibodies in response to pathogens, relying mainly on maternal Igs until around the 4th to 6th month of life. In addition, they display an exaggerated inflammatory response to CPB as compared with older children and adults, so they might stand to benefit more from IVIG as an immunomodulator.

Because of the increased vulnerability to acquired infection and other morbidities in the setting of hypogammaglobulinemia as result of enhanced SIRS and immune dysfunction, it is feasible that normalization of IgG concentration in the neonatal and infant population may improve clinical outcomes via restoration of the humoral immune system, modulation of the innate immune system, and restoration of intravascular oncotic pressure. The appropriate IgG level threshold for treatment and optimal plasma IgG level to target after administration of IVIG are presently unknown.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Intravenous Immunoglobulin for Early Prevention of Cardiopulmonary Bypass Induced Hypogammaglobulinemia in Infants and Neonates

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IVIG Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose and will be administered per hospital standards for IVIG administration.	Drug: IVIG Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care. Other Names: Gamunex
Placebo Comparator: Normal Saline Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. This infusion will be administered as if the subject is receiving IVIG according to hospital policy.	Other: Placebo If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight. Other Names: Normal Saline

Arm

Intervention/Treatment

Experimental: IVIG

Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose and will be administered per hospital standards for IVIG administration.

Drug: IVIG

Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.

Other Names:

Gamunex

Placebo Comparator: Normal Saline

Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. This infusion will be administered as if the subject is receiving IVIG according to hospital policy.

Other: Placebo

If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.

Other Names:

Normal Saline

Outcome Measures

Primary Outcome Measures

Post-Operative Infections [until Hospital Discharge, an average of 30 days]
The primary endpoint of this study is incidence of post-operative infections through hospital discharge
Post-operative Infection [within 1 week of surgery]
Any positive culture or treatment for culture negative sepsis within 1 week of surgery
Blood Stream Infection [until Hospital Discharge, an average of 30 days]
Any positive blood culture during the post-operative period until hospital discharge
Blood Stream Infection Within 1 Week of Surgery [7 days]

Secondary Outcome Measures

Post-operative Plasma Albumin [up to 48 hours post CPB]
Plasma albumin will be assessed at 24 and 48 hours.
Fluid Overload Variables [0-24 hours post-CPB]
The following fluid overload variables will be assessed in milliliters per kilogram at 0-24 hours post-cardiopulmonary bypass: blood product and albumin administration, chest tube output, urine output, peritoneal dialysis output, net fluid balance, and percent fluid overload. The total output the subject's produce (urine, chest tube, peritoneal drainage, etc.) will be subtracted from the total input (medications, blood products, albumin administration, etc) to determine the total fluid intake in milliliters. This total number will then be divided by the subject's weight in kilograms to determine the fluid overload in mL/kg.
Post-operative Inotrope Score [first 48 hours post-CPB]
The average admit, 12 hour, 24 hour, and 48 hour post-operative inotrope score will be calculated excluding Milrinone. To calculate the inotrope score the following formula was used: (Epinephrine/Norepinephrine dose in mcg/kg/min x 100) + (Dopamine dose in mcg/kg/min x 1) + (Phenylephrine dose in mcg/kg/min x 10) + (Vasopressin dose unit/kg/hr x 60/10000). The higher the inotrope score the more cardiac support the subject requires. There is not a "normal" scale or range used for this calculation.
Respiratory Variables [until Hospital Discharge, an average of 30 days]
Alive, ventilator free days will be recorded at hospital discharge.
Hospital Discharge [Approximately 1 month]
From admit post-operative to the Pediatric cardiac intensive care unit until discharge from the hospital in days.
Plasma Immunoglobulins [5 days post-op]
Plasma Immunoglobulin levels will be checked pre-operatively, 12 hours post-op and 5 days post-op
Interferon-gamma Plasma Cytokine Levels [Pre-operative to 48 hours post-operative]
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Immunoglobulin Concentration in Chest Tube Drainage [24 hours post-op]
Immunoglobulin concentration will be measured from chest tube every 4 hours for first 12 hours post-operative and then 24 hours post-operative.
Mortality [Approximately 1 month]
Incidence of mortality from admit to Pediatric cardiac intensive care unit post-operatively until hospital discharge .
Intensive Care Unit Length of Stay [1 month]
The length of stay in the pediatric cardiac intensive care unit from admit post-operative until either discharge home, discharge to another unit/hospital/care facility, or death. This value is calculated in hours. Admit post-operative is recorded as hour 0.
Fluid Overload Variables [0-48 hours post-CPB]
The following fluid overload variables will be assessed at 0-24 hours, 25-48 hours, and 0-48 hours post-cardiopulmonary bypass: blood product and albumin administration, chest tube output, urine output, peritoneal dialysis output, net fluid balance, and percent fluid overload.The total output the subject's produce (urine, chest tube, peritoneal drainage, etc.) will be subtracted from the total input (medications, blood products, albumin administration, etc) to determine the total fluid intake in milliliters. This total number will then be divided by the subject's weight in kilograms to determine the fluid overload in mL/kg.
Respiratory Variables [until extubation, an average of 2 days]
Time until first extubation in hours
Respiratory Variables [until extubation, an average of 2 days]
Total time duration of post-operative length of mechanical ventilation until hospital discharge
Interleukin-10 Plasma Cytokine Levels [pre-operative through 48 hours post-operative]
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Interleukin-12p70 Plasma Cytokine Levels [pre-operative through 48 hours post-operative]
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Interleukin-1b Plasma Cytokine Levels [pre-operative through 48 hours post-operative]
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Interleukin-6 Plasma Cytokine Levels [pre-operative through 48 hours post-operative]
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Interleukin-8 Plasma Cytokine Levels [pre-operative through 48 hours post-operative]
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Tumor Necrosis Factor Plasma Cytokine Levels [pre-operative through 48 hours post-operative]
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Immunoglobulin Concentration in Peritoneal Dialysis Drainage [24 hours post-op]
Immunoglobulin concentration will be measured from chest tube and peritoneal drain every 4 hours for first 12 hours post-operative and 24 hours post-operative.
Serum Creatinine [48 hours]
Pre-operative and 48 hour post-operative maximum creatinine recorded.
Lactic Acid [pre-operative through 24 hours post-operative]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 6 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Infants <6 months old
Successfully weaned off cardiopulmonary bypass after cardiac surgery

Exclusion Criteria:

Requirement of extra corporeal membrane oxygenation in the operating room
Known immune deficiency
Current Do Not Resuscitate or limitation of care order
Current enrollment in another interventional clinical study
Refusal of parental consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's of Alabama	Birmingham	Alabama	United States	35233

Sponsors and Collaborators

University of Alabama at Birmingham
Grifols Biologicals, LLC

Investigators

Principal Investigator: Jeffrey Alten, MD, University of Alabama at Birmingham Pediatric Cardiac Critical Care

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jeffrey Alten, MD, Principal Investigator, University of Alabama at Birmingham

ClinicalTrials.gov Identifier:

NCT02043379

Other Study ID Numbers:

F13114002
F13114002

First Posted:

Jan 23, 2014

Last Update Posted:

Apr 13, 2017

Last Verified:

Mar 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Keywords provided by Jeffrey Alten, MD, Principal Investigator, University of Alabama at Birmingham

congenital heart disease

Cardiopulmonary Bypass

Hypogammaglobulinemia

Additional relevant MeSH terms:

Heart Diseases

Heart Defects, Congenital

Agammaglobulinemia

Immunoglobulins, Intravenous

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Period Title: Overall Study
STARTED	30	20
COMPLETED	30	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	IVIG	Normal Saline	Total
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.	Total of all reporting groups
Overall Participants	30	20	50
Age (Count of Participants)
<=18 years	30 100%	20 100%	50 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	9	47	11.5
Sex: Female, Male (Count of Participants)
Female	14 46.7%	8 40%	22 44%
Male	16 53.3%	12 60%	28 56%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 26.7%	2 10%	10 20%
White	22 73.3%	18 90%	40 80%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kilograms) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kilograms]	3.45	3.85	3.51
Gestational Age (weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [weeks]	38	38.5	38
STAT category (participants) [Number]
1	3 10%	0 0%	3 6%
2	2 6.7%	5 25%	7 14%
3	7 23.3%	8 40%	15 30%
4	12 40%	4 20%	16 32%
5	6 20%	3 15%	9 18%
Cardiopulmonyar bypass time (minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [minutes]	105.5	91.5	97.5
Aortic cross clamp time (minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [minutes]	52	56	53.5
Intubated Pre-operatively (subjects) [Number]
Yes	5	5	10
No	25	15	40

Outcome Measures

1. Primary Outcome

Title	Post-Operative Infections
Description	The primary endpoint of this study is incidence of post-operative infections through hospital discharge
Time Frame	until Hospital Discharge, an average of 30 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Yes	9	6
No	21	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	We used alpha level of 0.05 and power of 0.8 to calculate the sample size necessary to detect a meaningful clinical difference for our primary endpoint.

Statistical Test of Hypothesis	p-Value	1
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	Post-operative Infection
Description	Any positive culture or treatment for culture negative sepsis within 1 week of surgery
Time Frame	within 1 week of surgery

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Yes	5	3
No	25	17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	1
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Chi-squared
	Comments

3. Primary Outcome

Title	Blood Stream Infection
Description	Any positive blood culture during the post-operative period until hospital discharge
Time Frame	until Hospital Discharge, an average of 30 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Yes	5	1
No	25	19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.38
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Chi-squared
	Comments

4. Primary Outcome

Title	Blood Stream Infection Within 1 Week of Surgery
Description
Time Frame	7 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Yes	3	0
No	27	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.26
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Post-operative Plasma Albumin
Description	Plasma albumin will be assessed at 24 and 48 hours.
Time Frame	up to 48 hours post CPB

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
24 hour post-op	3.7 (0.74)	4.1 (0.67)
48 hour post-op	3.3 (0.57)	3.6 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-CPB albumin
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.42
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hour post CPB albumin
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.06
	Comments	a p-value of <0.05 represents the threshold for test signficance
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Fluid Overload Variables
Description	The following fluid overload variables will be assessed in milliliters per kilogram at 0-24 hours post-cardiopulmonary bypass: blood product and albumin administration, chest tube output, urine output, peritoneal dialysis output, net fluid balance, and percent fluid overload. The total output the subject's produce (urine, chest tube, peritoneal drainage, etc.) will be subtracted from the total input (medications, blood products, albumin administration, etc) to determine the total fluid intake in milliliters. This total number will then be divided by the subject's weight in kilograms to determine the fluid overload in mL/kg.
Time Frame	0-24 hours post-CPB

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Median (Inter-Quartile Range) [mililiters/kilogram]	30	58.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.52
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Post-operative Inotrope Score
Description	The average admit, 12 hour, 24 hour, and 48 hour post-operative inotrope score will be calculated excluding Milrinone. To calculate the inotrope score the following formula was used: (Epinephrine/Norepinephrine dose in mcg/kg/min x 100) + (Dopamine dose in mcg/kg/min x 1) + (Phenylephrine dose in mcg/kg/min x 10) + (Vasopressin dose unit/kg/hr x 60/10000). The higher the inotrope score the more cardiac support the subject requires. There is not a "normal" scale or range used for this calculation.
Time Frame	first 48 hours post-CPB

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Admit	5	4.5
12 hr post-op	5.3	5.3
24 hr post-op	5.3	5.8
48 hr post-op	6.8	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	Admit Inotrope Score
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.81
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hours post-operative inotrope score
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.82
	Comments	a p value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hours post-operative inotrope score
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.9
	Comments	a p value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hours post-operative inotrope score
	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	a p-value of <0.05 represents the threshold for statistical signficance
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Respiratory Variables
Description	Alive, ventilator free days will be recorded at hospital discharge.
Time Frame	until Hospital Discharge, an average of 30 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Median (Inter-Quartile Range) [days]	24.7	25.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.49
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Hospital Discharge
Description	From admit post-operative to the Pediatric cardiac intensive care unit until discharge from the hospital in days.
Time Frame	Approximately 1 month

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Median (Inter-Quartile Range) [days]	22	22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.79
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Plasma Immunoglobulins
Description	Plasma Immunoglobulin levels will be checked pre-operatively, 12 hours post-op and 5 days post-op
Time Frame	5 days post-op

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative serum IgG level	487 (226.1)	414 (230.5)
12 hour post-operative serum IgG level	496 (183)	569 (272)
Post-operative day 3 serum IgG level	837 (243)	508 (215.4)
Post-operative day 5 serum IgG level	839 (213)	585 (212.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative IgG level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.32
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hours post-operative IgG level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.36
	Comments	a p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	post-operative day 3 (72 hours) IgG level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	<0.01
	Comments	p-value of <0.05 represents the threshold for statistical signficance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	post-operative day 5 (120 hours) IgG level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	<0.01
	Comments	p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Secondary Outcome

Title	Interferon-gamma Plasma Cytokine Levels
Description	Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time Frame	Pre-operative to 48 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	2.2	3.5
0 hour post-op	2.6	6
4 hour post-op	2.8	6.1
12 hour post-op	2.8	6.3
24 hour post-op	2	5.6
48 hour post-op	2.2	3.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.60
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.06
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.06
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hours post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.33
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hours post-operative
	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	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hours post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.83
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Secondary Outcome

Title	Immunoglobulin Concentration in Chest Tube Drainage
Description	Immunoglobulin concentration will be measured from chest tube every 4 hours for first 12 hours post-operative and then 24 hours post-operative.
Time Frame	24 hours post-op

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
0 hr post-op	50.9	62.2
4 hr post-op	154.3	161.3
8 hr post-op	195.2	227.6
12 hr post-op	233.5	226.8
24 hr post-op	614.2	268.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour levels
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.27
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.34
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	8 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.14
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.13
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.02
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Mortality
Description	Incidence of mortality from admit to Pediatric cardiac intensive care unit post-operatively until hospital discharge .
Time Frame	Approximately 1 month

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Yes	3	2
No	27	18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	1
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Chi-squared
	Comments

14. Secondary Outcome

Title	Intensive Care Unit Length of Stay
Description	The length of stay in the pediatric cardiac intensive care unit from admit post-operative until either discharge home, discharge to another unit/hospital/care facility, or death. This value is calculated in hours. Admit post-operative is recorded as hour 0.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Median (Inter-Quartile Range) [hours]	357.9	189.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.4
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	Fluid Overload Variables
Description	The following fluid overload variables will be assessed at 0-24 hours, 25-48 hours, and 0-48 hours post-cardiopulmonary bypass: blood product and albumin administration, chest tube output, urine output, peritoneal dialysis output, net fluid balance, and percent fluid overload.The total output the subject's produce (urine, chest tube, peritoneal drainage, etc.) will be subtracted from the total input (medications, blood products, albumin administration, etc) to determine the total fluid intake in milliliters. This total number will then be divided by the subject's weight in kilograms to determine the fluid overload in mL/kg.
Time Frame	0-48 hours post-CPB

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
0-24 hours post-CPB	30	58.1
25-48 hours post-CPB	7.4	34.9
0-48 hours post-CPB	46.6	77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0-48 hours post-CPB
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.09
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0-24 hours post CPB
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.52
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

16. Secondary Outcome

Title	Respiratory Variables
Description	Time until first extubation in hours
Time Frame	until extubation, an average of 2 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Median (Inter-Quartile Range) [hours]	46	43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.72
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

17. Secondary Outcome

Title	Respiratory Variables
Description	Total time duration of post-operative length of mechanical ventilation until hospital discharge
Time Frame	until extubation, an average of 2 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Median (Inter-Quartile Range) [hours]	62.1	59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.63
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

18. Secondary Outcome

Title	Interleukin-10 Plasma Cytokine Levels
Description	Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time Frame	pre-operative through 48 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	1.4	1.8
0 hour post-operative	54.4	124
4 hour post-operative	10.1	20.1
12 hour post-operative	4.7	10.2
24 hour post-operative	1.8	4
48 hour post-operatiave	1.1	2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.41
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.34
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.47
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.42
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.82
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hour post-operative
	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	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

19. Secondary Outcome

Title	Interleukin-12p70 Plasma Cytokine Levels
Description	Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time Frame	pre-operative through 48 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	0.2	0.2
0 hour post-operative	0.2	0.6
4 hour post-operative	0.4	0.5
12 hour post-operative	0.5	1
24 hour post-operative	0.3	0.7
48 hour post-operatiave	0.2	0.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.28
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.37
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.42
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.31
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.38
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.4
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

20. Secondary Outcome

Title	Interleukin-1b Plasma Cytokine Levels
Description	Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time Frame	pre-operative through 48 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	0.2	0.2
0 hour post-operative	0.3	0.4
4 hour post-operative	0.3	0.5
12 hour post-operative	0.3	0.3
24 hour post-operative	0.3	0.5
48 hour post-operatiave	0.3	0.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.1
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.12
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.51
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.27
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.88
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.38
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

21. Secondary Outcome

Title	Interleukin-6 Plasma Cytokine Levels
Description	Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time Frame	pre-operative through 48 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	2.1	3.3
0 hour post-operative	10.3	17.3
4 hour post-operative	32.6	52.4
12 hour post-operative	43.6	49.8
24 hour post-operative	26.3	40.8
48 hour post-operatiave	15.8	15.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.35
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.39
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.58
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.36
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.61
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.38
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

22. Secondary Outcome

Title	Interleukin-8 Plasma Cytokine Levels
Description	Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time Frame	pre-operative through 48 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	18.7	17.7
0 hour post-operative	76.5	163
4 hour post-operative	116.5	147.5
12 hour post-operative	67.1	90
24 hour post-operative	47.7	46
48 hour post-operatiave	33.6	38.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.1
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.02
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.34
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.35
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.67
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.47
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

23. Secondary Outcome

Title	Tumor Necrosis Factor Plasma Cytokine Levels
Description	Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time Frame	pre-operative through 48 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	2.3	2.9
0 hour post-operative	2.9	4.3
4 hour post-operative	3.7	5.3
12 hour post-operative	3.1	4.1
24 hour post-operative	2.9	3.8
48 hour post-operatiave	2.4	3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.46
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour post-operative
	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	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.14
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.82
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.9
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	48 hour post-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.78
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	Wilcoxon (Mann-Whitney)
	Comments

24. Secondary Outcome

Title	Immunoglobulin Concentration in Peritoneal Dialysis Drainage
Description	Immunoglobulin concentration will be measured from chest tube and peritoneal drain every 4 hours for first 12 hours post-operative and 24 hours post-operative.
Time Frame	24 hours post-op

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
0 hr post-op	33.1	101.6
4 hr post-op	136.2	201.6
8 hr post-op	279.8	221.2
12 hr post-op	387.33	300.1
24 hr post-op	1613.9	366.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	0 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.37
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	4 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.47
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	8 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.47
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	12 hour level
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.79
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour level
	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	A p-value of <0.05 represents the threshold for statistical significance.
	Method	Wilcoxon (Mann-Whitney)
	Comments

25. Secondary Outcome

Title	Serum Creatinine
Description	Pre-operative and 48 hour post-operative maximum creatinine recorded.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	0.4 (0.15)	0.4 (0.17)
Max	0.8 (0.28)	0.7 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.43
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	max
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.68
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	t-test, 2 sided
	Comments

26. Secondary Outcome

Title	Lactic Acid
Description
Time Frame	pre-operative through 24 hours post-operative

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	IVIG	Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.	Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Measure Participants	30	20
Pre-operative	1.3 (0.65)	1.4 (0.75)
24 hour maximum	5.7 (4)	5.4 (4.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	pre-operative
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation.

Statistical Test of Hypothesis	p-Value	0.87
	Comments	A p-value of <0.05 represents the threshold for statistical significance.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVIG, Normal Saline
	Comments	24 hour post-operative max
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculations were not performed on this statistical calculation

Statistical Test of Hypothesis	p-Value	0.79
	Comments	A p-value of <0.05 represents the threshold for statistical significance
	Method	t-test, 2 sided
	Comments

Adverse Events

	IVIG		Normal Saline
Time Frame
Adverse Event Reporting Description

Arm/Group Title	IVIG		Normal Saline
Arm/Group Description	Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose. IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.		Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug. Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IVIG		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	IVIG		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Jeffrey Alten, MD
Organization	UAB Pediatric Cardiac Critical Care Medicine
Phone	(205) 975-3123
Email	jalten@peds.uab.edu

Responsible Party:

Jeffrey Alten, MD, Principal Investigator, University of Alabama at Birmingham

ClinicalTrials.gov Identifier:

NCT02043379

Other Study ID Numbers:

F13114002
F13114002

First Posted:

Jan 23, 2014

Last Update Posted:

Apr 13, 2017

Last Verified:

Mar 1, 2017