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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04452188
Recruitment Status : Not yet recruiting
First Posted : June 30, 2020
Last Update Posted : September 9, 2020
Information provided by (Responsible Party):
Nathaniel Sznycer-Taub, University of Michigan

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 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)
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

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:

  1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
  2. 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.

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.

Information from the National Library of Medicine

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04452188

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Contact: Adriana Batazzi 734-763-3140
Contact: Nathaniel Sznycer-Taub, MD 734-764-5176

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United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Contact: Adriana Batazzi    734-763-3140   
Sponsors and Collaborators
University of Michigan
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Principal Investigator: Nathaniel Sznycer-Taub, MD University of Michigan
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Responsible Party: Nathaniel Sznycer-Taub, Assistant Professor of Pediatrics, University of Michigan Identifier: NCT04452188    
Other Study ID Numbers: HUM00175086
First Posted: June 30, 2020    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Scimitar Syndrome
Heart Diseases
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
Cardiovascular Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Congenital Abnormalities
Heart Valve Diseases
Ventricular Outflow Obstruction
Vascular Malformations
Lung Diseases
Respiratory Tract Diseases
Respiratory System Abnormalities
Vascular Diseases