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

Primary Purpose

Hypoplastic Left Heart Syndrome, Total Anomalous Pulmonary Venous Return, Truncus Arteriosus

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Normoxia (with controlled re-oxygenation)
Standard of care ventilation
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoplastic Left Heart Syndrome focused on measuring Open heart surgery

Eligibility Criteria

undefined - 29 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Michigan

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Normoxia

Standard of care

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.
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.
Post-operative length of stay
Calculated as number of days in the hospital after surgery.
Days alive and out of the intensive care unit (ICU) at 30 days after surgery
Composite outcome of major adverse events
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.

Secondary Outcome Measures

Full Information

First Posted
June 22, 2020
Last Updated
June 30, 2023
Sponsor
University of Michigan
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT04452188
Brief Title
Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period
Acronym
T-NOX
Official Title
Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period (T-NOX)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 18, 2021 (Actual)
Primary Completion Date
April 20, 2023 (Actual)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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, 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Open heart surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normoxia
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard of care
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Other
Intervention Name(s)
Normoxia (with controlled re-oxygenation)
Intervention Description
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%)
Intervention Type
Other
Intervention Name(s)
Standard of care ventilation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Systemic oxidative stress based on thiobarbituric acid reactive substances (TBARS)
Description
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.
Time Frame
Up to 24 hours following surgery
Title
Rate of observed adverse events between the two groups
Description
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.
Time Frame
30 days after surgery
Title
Post-operative length of stay
Description
Calculated as number of days in the hospital after surgery.
Time Frame
30 days after surgery
Title
Days alive and out of the intensive care unit (ICU) at 30 days after surgery
Time Frame
30 days after surgery
Title
Composite outcome of major adverse events
Time Frame
30 days after surgery
Title
Global rank score
Description
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.
Time Frame
30 days after surgery

10. Eligibility

Sex
All
Maximum Age & Unit of Time
29 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nathaniel Sznycer-Taub, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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