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

Study Overview
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Brief Summary
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This clinical trial is studying the use of different levels of oxygen exposure during and after cardiopulmonary bypass in eligible infants to learn about its safety during heart surgery. In addition to having the various doses of oxygen, patients that participate will also have blood samples, ultrasounds of the head, and brain wave patterns monitored. The hypotheses of this trial are: that there will be no difference with regards to adverse events between the infants in the normoxia group compared to the infants in the standard of care group there will be a significant difference in the measured partial pressure of oxygen (PaO2) values between the two treatment groups. the use of normoxia during cardiopulmonary bypass and in the immediate post-operative period will result in clinically significant decrease in oxidative stress as measured by thiobarbituric acid reactive substances (TBARS) after cardiac surgery

Official Title
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Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period (T-NOX)

Conditions
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Hypoplastic Left Heart Syndrome, Total Anomalous Pulmonary Venous Return, Truncus Arteriosus, Pulmonary Atresia With Ventricular Septal Defect, Transposition of the Great Arteries, Double Outlet Right Ventricle, Subpulmonary VSD, Tetralogy of Fallot, Double Outlet Right Ventricle With Subaortic Ventricular Septal Defect and Pulmonary Stenosis, Cardiopulmonary Bypass

Intervention / Treatment
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* Other: Normoxia (with controlled re-oxygenation)
* Other: Standard of care ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age less than 30 days of age at time of surgery with need for cardiopulmonary bypass with cardioplegic arrest (with or without deep hypothermic circulatory arrest) Diagnosis with cyanosis at baseline (pre-operative PaO2 of less than 50mmHG) due to: Complete admixture lesion (example: hypoplastic left heart syndrome, total anomalous pulmonary venous return, truncus arteriosus, pulmonary atresia with VSD) Transposition physiology (example: D-Transposition of the great arteries or Double outlet right ventricle with subpulmonary VSD) Right-to-left shunt (example: Tetralogy of Fallot, double outlet right ventricle with subaortic VSD and pulmonary stenosis) Exclusion Criteria: Corrected gestation at time of surgery less than 37 weeks Prior cardiac arrest Current or prior history of extracorporeal membrane oxygenation (ECMO) support Current or prior history of needing renal replacement therapy with dialysis Prior cardiac surgery requiring cardiopulmonary bypass Diagnosis of Ebstein's Anomaly Known genetic syndrome other than Trisomy 21 or DiGeorge Syndrome

Ages Eligible for Study
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Maximum Age: 29 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normoxia<br>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. | Other: Normoxia (with controlled re-oxygenation)<br>* 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%)<br>|
| Active Comparator: Standard of care<br>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 | Other: Standard of care ventilation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic oxidative stress based on thiobarbituric acid reactive substances (TBARS) | This will be assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). An analysis of co-variance will be used incorporating all available data to model the outcome with an adjustment for pre-operative baseline. The model will compare the mean values (and 95% confidence intervals) between the two groups at each time-point. | Up to 24 hours following surgery | 
| Rate of observed adverse events between the two groups | The composite with any of the following outcomes within 30 days after the index cardiac surgery: mortality, cardiac arrest, need for mechanical circulatory support, seizures (clinical or subclinical based on EEG), and need for dialysis. These will be compared between both treatment groups using Chi-square test or Fisher's exact test as appropriate. | 30 days after surgery | 
| Post-operative length of stay | Calculated as number of days in the hospital after surgery. | 30 days after surgery | 
| Days alive and out of the intensive care unit (ICU) at 30 days after surgery |  | 30 days after surgery | 
| Composite outcome of major adverse events |  | 30 days after surgery | 
| Global rank score | Scores will be calculated based on a pre-specified ranking of outcomes: mortality, cardiac arrest, extracorporeal membrane oxygenation (ECMO), seizures, and dialysis. This study will also explore the inclusion of other clinical endpoints in both the global rank score and composite outcome, as well as different ranking strategies. | 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open heart surgery