| Primary | Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS) | 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. | | Posted | | Mean | Standard Deviation | Fold Change from Baseline | | Up to 24 hours following surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
| | OG001 | 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. |
| | | Title | Denominators | Categories |
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| 2 hours Post-Op (PO) | | | Title | Measurements |
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| - OG0001.21± 0.26
- OG0011.93± 0.63
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| | 6 hours PO | | |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| Each participant's post-operative samples were normalized to their baseline sample and described as a fold-of-change from baseline. | t-test, 2 sided | | <0.01 | To provide a more conservative estimate of significance, the Hochberg sequential procedure was used for adjustment of multiple comparisons in the serum biomarker data including the primary outcome. | | | | | | | | | | | | | Equivalence | Prior studies suggest a 25-50% reduction in oxidative stress in normoxia relative to supra-physiologic oxygen. A 20% difference was considered clinically meaningful, and a sample size of 42 total participants was anticipated to achieve at least 80% power with a two-sided 5% significance level. However, an interim analysis recommended by the DSMB after enrollment of 29 patients revealed a significant difference in the primary outcome between the groups, and enrollment was thus stopped. |
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| Primary | Rate of Observed Adverse Events Between the Two Groups | 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. | A patient can have more than one of the outcomes listed. | Posted | | Count of Participants | | Participants | | 30 days after surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
| | OG001 | 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. |
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| Primary | Post-operative Length of Stay | Calculated as number of days in the hospital after surgery. | | Posted | | Median | Inter-Quartile Range | Days | | 30 days after surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
| | OG001 | 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. |
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| Primary | Days Alive and Out of the Intensive Care Unit (ICU) at 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. | | Posted | | Median | Inter-Quartile Range | days | | 30 days after surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
| | OG001 | 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. |
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| Primary | Composite Outcome of Major Adverse Events | 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. | | Posted | | Count of Participants | | Participants | | 30 days after surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
| | OG001 | 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. |
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| Primary | Global Rank Score | 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. | | Posted | | Median | Inter-Quartile Range | score on a scale | | 30 days after surgery | | | | ID | Title | Description |
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| OG000 | 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 participant's physiology:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
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| Other Pre-specified | Systemic Oxidative Stress Based on Protein Carbonyl Levels 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. | | Posted | | Mean | Standard Deviation | Fold Change from Baseline | | Up to 24 hours after surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
|
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| Other Pre-specified | Systemic Oxidative Stress Based on Total Antioxidant Capacity (TAC) | 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. | | Posted | | Mean | Standard Deviation | Fold Change from Baseline | | Up to 24 hours after surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
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| Other Pre-specified | Systemic Oxidative Stress Based on 8-Isoprostane Levels 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. | | Posted | | Mean | Standard Deviation | Fold Change from Baseline | | Up to 24 hours after surgery | | | | ID | Title | Description |
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| OG000 | 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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
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