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

• ClinicalTrials.gov Identifier: NCT04452188
• Recruitment Status: Active, not recruiting
• First Posted: June 30, 2020
• Last Update Posted: July 5, 2023
• Sponsor: University of Michigan
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Nathaniel Sznycer-Taub, University of Michigan

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

Condition or disease	Intervention/treatment	Phase
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	Other: Normoxia (with controlled re-oxygenation); Other: Standard of care ventilation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period (T-NOX)
• Actual Study Start Date: January 18, 2021
• Actual Primary Completion Date: April 20, 2023
• Estimated Study Completion Date: August 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	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 patient's physiology: Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%); Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
Active Comparator: 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	Other: 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.

Outcome Measures

Primary Outcome Measures :

1. Systemic oxidative stress based on thiobarbituric acid reactive substances (TBARS) [ Time Frame: Up to 24 hours following surgery ]
   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.
2. Rate of observed adverse events between the two groups [ Time Frame: 30 days after surgery ]
   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.
3. Post-operative length of stay [ Time Frame: 30 days after surgery ]
   Calculated as number of days in the hospital after surgery.
4. Days alive and out of the intensive care unit (ICU) at 30 days after surgery [ Time Frame: 30 days after surgery ]
5. Composite outcome of major adverse events [ Time Frame: 30 days after surgery ]
6. Global rank score [ Time Frame: 30 days after surgery ]
   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.

Eligibility Criteria

• Ages Eligible for Study: up to 29 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

National Institutes of Health (NIH)

Investigators

• Principal Investigator: Nathaniel Sznycer-Taub, MD; University of Michigan

  Study Documents (Full-Text)

Documents provided by Nathaniel Sznycer-Taub, University of Michigan:

Informed Consent Form  [PDF] January 25, 2023

More Information

• Responsible Party: Nathaniel Sznycer-Taub, Assistant Professor of Pediatrics, University of Michigan
• ClinicalTrials.gov Identifier: NCT04452188
• Other Study ID Numbers: HUM00175086; 5UL1TR002240-05 ( U.S. NIH Grant/Contract )
• First Posted: June 30, 2020
• Last Update Posted: July 5, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Nathaniel Sznycer-Taub, University of Michigan:

Open heart surgery

Additional relevant MeSH terms:

Scimitar Syndrome; Heart Diseases; Heart Defects, Congenital; Heart Septal Defects; Tetralogy of Fallot; Hypoplastic Left Heart Syndrome; Heart Septal Defects, Ventricular; Transposition of Great Vessels; Pulmonary Valve Stenosis; Pulmonary Atresia; Double Outlet Right Ventricle; Truncus Arteriosus, Persistent; Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Heart Valve Diseases; Ventricular Outflow Obstruction; Vascular Malformations; Aortopulmonary Septal Defect; Lung Diseases; Respiratory Tract Diseases; Respiratory System Abnormalities; Vascular Diseases