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

Cardiopulmonary Bypass Clinical Trial

— T-NOX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04452188
• Other study ID #: HUM00175086
• Secondary ID: 5UL1TR002240-05
• Status: Completed
• Phase: N/A
• Start date: January 18, 2021
• Est. completion date: April 20, 2023

Study information

• Verified date: May 2024
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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, participants 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: April 20, 2023
• Est. primary completion date: April 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 29 Days

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• 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%)
• 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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
University of Michigan	National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Up to 24 hours after surgery
Other	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.	Up to 24 hours after surgery
Other	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.	Up to 24 hours after surgery
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.	Up to 24 hours following surgery
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.	30 days after surgery
Primary	Post-operative Length of Stay	Calculated as number of days in the hospital after surgery.	30 days after surgery
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.	30 days after surgery
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.	30 days after surgery
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.	30 days after surgery