Trial Outcomes & Findings for Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period (NCT NCT04452188)

NCT ID: NCT04452188

Last Updated: 2024-06-18

Results Overview

Oxidative stress (OS) reflects an imbalance between the production and accumulation of reactive oxygen species. Oxidation of lipids leads to the generation of lipid peroxides which can be detected as Thiobarbituric acid reactive substances (TBARS). Thus, levels of serum TBARS were assessed in participants as indicators of OS. TBARS levels were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline pre-operative sample and described as a fold-of-change from baseline. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as TBARS level at each PO time point / TBARS at baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 29 participants
• Primary outcome timeframe: Up to 24 hours following surgery
• Results posted on: 2024-06-18

Participant Flow

Participant milestones

Measure	Normoxia On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Overall Study STARTED	15	14
Overall Study COMPLETED	15	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period

Baseline characteristics by cohort

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.	Total n=29 Participants Total of all reporting groups
Age, Continuous	5 days n=5 Participants	5 days n=7 Participants	5 days n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 hours following surgery

Oxidative stress (OS) reflects an imbalance between the production and accumulation of reactive oxygen species. Oxidation of lipids leads to the generation of lipid peroxides which can be detected as Thiobarbituric acid reactive substances (TBARS). Thus, levels of serum TBARS were assessed in participants as indicators of OS.

TBARS levels were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline pre-operative sample and described as a fold-of-change from baseline. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as TBARS level at each PO time point / TBARS at baseline.

The mean values of the fold of change from baseline between the two groups at each PO time-point were compared.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS) 2 hours Post-Op (PO)	1.21 Fold Change from Baseline Standard Deviation 0.26	1.93 Fold Change from Baseline Standard Deviation 0.63
Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS) 6 hours PO	1.09 Fold Change from Baseline Standard Deviation 0.25	1.77 Fold Change from Baseline Standard Deviation 0.7
Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS) 24 hours PO	0.96 Fold Change from Baseline Standard Deviation 0.16	1.41 Fold Change from Baseline Standard Deviation 0.29

PRIMARY outcome

Timeframe: 30 days after surgery

Population: A patient can have more than one of the outcomes listed.

The count of each of the adverse events within 30 days after the index cardiac surgery, listed here: mortality, cardiac arrest, need for mechanical circulatory support, seizures (clinical or subclinical based on EEG), and need for dialysis is presented below.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Rate of Observed Adverse Events Between the Two Groups Need for Mechanical Circulatory Support	1 Participants	3 Participants
Rate of Observed Adverse Events Between the Two Groups Cardiac Arrest	1 Participants	2 Participants
Rate of Observed Adverse Events Between the Two Groups Mortality	1 Participants	1 Participants
Rate of Observed Adverse Events Between the Two Groups Need for dialysis	1 Participants	1 Participants
Rate of Observed Adverse Events Between the Two Groups Seizure	2 Participants	1 Participants

PRIMARY outcome

Timeframe: 30 days after surgery

Calculated as number of days in the hospital after surgery.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Post-operative Length of Stay	15 Days Interval 9.0 to 21.0	15.5 Days Interval 10.0 to 21.0

PRIMARY outcome

Timeframe: 30 days after surgery

This composite measure reflects the number of days alive and not admitted to the ICU. Non-survivors at day 30 were considered to have no ICU-free days.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Days Alive and Out of the Intensive Care Unit (ICU) at 30 Days After Surgery	22 days Interval 19.0 to 26.0	22.5 days Interval 9.0 to 26.0

PRIMARY outcome

Timeframe: 30 days after surgery

The composite endpoint assessed in this study combines in-hospital mortality, cardiac arrest, ECMO, seizures, and dialysis and reflects the number of participants affected by one or more of these outcomes.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Composite Outcome of Major Adverse Events	3 Participants	3 Participants

PRIMARY outcome

Timeframe: 30 days after surgery

Per NCT03229538, a composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. For this endpoint, each randomized patient will be assigned a rank based upon their most-severe outcome. Rank of 91= Post-operative length of stay > 90 days, 92= Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93= Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94= Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95= Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96= Heart transplant (during hospitalization); 97= Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days. A lower score means a better outcome.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Global Rank Score	15 score on a scale Interval 10.0 to 20.0	17 score on a scale Interval 10.0 to 80.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 hours after surgery

Protein carbonyls are generated upon oxidation of proteins and are a marker of oxidative stress. Serum protein carbonyl contents were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline sample and described as a fold-of-change from baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as Protein Carbonyl level at each PO time point / Protein Carbonyl at baseline.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Systemic Oxidative Stress Based on Protein Carbonyl Levels After Surgery 2 hours PO	0.87 Fold Change from Baseline Standard Deviation 0.25	1.3 Fold Change from Baseline Standard Deviation 0.35
Systemic Oxidative Stress Based on Protein Carbonyl Levels After Surgery 6 hours PO	0.95 Fold Change from Baseline Standard Deviation 0.3	1.6 Fold Change from Baseline Standard Deviation 0.47
Systemic Oxidative Stress Based on Protein Carbonyl Levels After Surgery 24 hours PO	0.86 Fold Change from Baseline Standard Deviation 0.2	1.7 Fold Change from Baseline Standard Deviation 0.76

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 hours after surgery

TAC assays measure serum antioxidants in biological samples. Therefore, lower values reflect depletion of antioxidants in the setting of oxidative stress. Serum TAC was assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline sample and described as a fold-of-change from baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as TAC level at each PO time point / TAC at baseline.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Systemic Oxidative Stress Based on Total Antioxidant Capacity (TAC) 2 hours PO	1.3 Fold Change from Baseline Standard Deviation 0.38	0.79 Fold Change from Baseline Standard Deviation 0.27
Systemic Oxidative Stress Based on Total Antioxidant Capacity (TAC) 6 hours PO	1.4 Fold Change from Baseline Standard Deviation 0.42	0.87 Fold Change from Baseline Standard Deviation 0.33
Systemic Oxidative Stress Based on Total Antioxidant Capacity (TAC) 24 hours PO	1.4 Fold Change from Baseline Standard Deviation 0.46	0.88 Fold Change from Baseline Standard Deviation 0.23

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 hours after surgery

8-isoprostane is a stable oxidative stress marker formed by non-enzymatic perioxidation of lipids. Serum levels of 8-isoprostane were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline sample and described as a fold-of-change from baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as 8-isoprostane level at each PO time point / 8-isoprostane at baseline.

Outcome measures

Measure	Normoxia n=15 Participants On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 Participants Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Systemic Oxidative Stress Based on 8-Isoprostane Levels After Surgery 2 hour post-operative (PO)	0.52 Fold Change from Baseline Standard Deviation 0.41	0.89 Fold Change from Baseline Standard Deviation 0.52
Systemic Oxidative Stress Based on 8-Isoprostane Levels After Surgery 6 hours PO	0.60 Fold Change from Baseline Standard Deviation 0.50	1.0 Fold Change from Baseline Standard Deviation 0.69
Systemic Oxidative Stress Based on 8-Isoprostane Levels After Surgery 24 hours PO	0.44 Fold Change from Baseline Standard Deviation 0.37	1.1 Fold Change from Baseline Standard Deviation 1.4

Adverse Events

Normoxia

Serious events: 3 serious events

Other events: 7 other events

Deaths: 1 deaths

Standard of Care

Serious events: 3 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Measure	Normoxia n=15 participants at risk On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 participants at risk Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Cardiac disorders Cardiac arrest requiring CPR and medications	6.7% 1/15 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.	14.3% 2/14 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.
Cardiac disorders Cardiopulmonary insufficiency requiring ECMO	6.7% 1/15 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.	21.4% 3/14 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.
Nervous system disorders Seizures	13.3% 2/15 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.	7.1% 1/14 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.
Renal and urinary disorders Need for dialysis	6.7% 1/15 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.	7.1% 1/14 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.

Other adverse events

Measure	Normoxia n=15 participants at risk On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op. Normoxia (with controlled re-oxygenation): Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the patient's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)	Standard of Care n=14 participants at risk Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice Standard of care ventilation: As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.
Cardiac disorders Post-op Arrhythmias requiring treatment	46.7% 7/15 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.	21.4% 3/14 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.
Nervous system disorders Post-up Stroke	0.00% 0/15 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.	7.1% 1/14 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.
Nervous system disorders Post-op Hemorrhage	13.3% 2/15 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.	7.1% 1/14 • From time of surgery to 30 days post-operation Because all of these neonates had just undergone surgery and have many kinds of complications, the IRB approved our collection of a limited set of adverse events. All collected adverse events are shown here.

Additional Information

Dr. Nathaniel Sznycer-Taub

The University of Michigan Health System

Phone: 734-936-8993

Email: nsznycer@umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place