<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04452188</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00175086</org_study_id>
    <secondary_id>5UL1TR002240-05</secondary_id>
    <nct_id>NCT04452188</nct_id>
  </id_info>
  <brief_title>Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period</brief_title>
  <acronym>T-NOX</acronym>
  <official_title>Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period (T-NOX)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial is studying the use of different levels of oxygen exposure during and&#xD;
      after cardiopulmonary bypass in eligible infants to learn about its safety during heart&#xD;
      surgery.&#xD;
&#xD;
      In addition to having the various doses of oxygen, patients that participate will also have&#xD;
      blood samples, ultrasounds of the head, and brain wave patterns monitored.&#xD;
&#xD;
      The hypotheses of this trial are:&#xD;
&#xD;
        -  that there will be no difference with regards to adverse events between the infants in&#xD;
           the normoxia group compared to the infants in the standard of care group&#xD;
&#xD;
        -  there will be a significant difference in the measured partial pressure of oxygen (PaO2)&#xD;
           values between the two treatment groups.&#xD;
&#xD;
        -  the use of normoxia during cardiopulmonary bypass and in the immediate post-operative&#xD;
           period will result in clinically significant decrease in oxidative stress as measured by&#xD;
           thiobarbituric acid reactive substances (TBARS) after cardiac surgery&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 18, 2021</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Actual">April 20, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Systemic oxidative stress based on thiobarbituric acid reactive substances (TBARS)</measure>
    <time_frame>Up to 24 hours following surgery</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of observed adverse events between the two groups</measure>
    <time_frame>30 days after surgery</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative length of stay</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>Calculated as number of days in the hospital after surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Days alive and out of the intensive care unit (ICU) at 30 days after surgery</measure>
    <time_frame>30 days after surgery</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite outcome of major adverse events</measure>
    <time_frame>30 days after surgery</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Global rank score</measure>
    <time_frame>30 days after surgery</time_frame>
    <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.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Hypoplastic Left Heart Syndrome</condition>
  <condition>Total Anomalous Pulmonary Venous Return</condition>
  <condition>Truncus Arteriosus</condition>
  <condition>Pulmonary Atresia With Ventricular Septal Defect</condition>
  <condition>Transposition of the Great Arteries</condition>
  <condition>Double Outlet Right Ventricle, Subpulmonary VSD</condition>
  <condition>Tetralogy of Fallot</condition>
  <condition>Double Outlet Right Ventricle With Subaortic Ventricular Septal Defect and Pulmonary Stenosis</condition>
  <condition>Cardiopulmonary Bypass</condition>
  <arm_group>
    <arm_group_label>Normoxia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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&#xD;
Post-bypass, goal of PaO2 &lt;100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Normoxia (with controlled re-oxygenation)</intervention_name>
    <description>Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator.&#xD;
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:&#xD;
Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)&#xD;
Two ventricle patients (PaO2: 60-100 and oxygen saturation &gt;92%)</description>
    <arm_group_label>Normoxia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of care ventilation</intervention_name>
    <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.</description>
    <arm_group_label>Standard of care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age less than 30 days of age at time of surgery with need for cardiopulmonary bypass&#xD;
             with cardioplegic arrest (with or without deep hypothermic circulatory arrest)&#xD;
&#xD;
          -  Diagnosis with cyanosis at baseline (pre-operative PaO2 of less than 50mmHG) due to:&#xD;
&#xD;
               -  Complete admixture lesion (example: hypoplastic left heart syndrome, total&#xD;
                  anomalous pulmonary venous return, truncus arteriosus, pulmonary atresia with&#xD;
                  VSD)&#xD;
&#xD;
               -  Transposition physiology (example: D-Transposition of the great arteries or&#xD;
                  Double outlet right ventricle with subpulmonary VSD)&#xD;
&#xD;
               -  Right-to-left shunt (example: Tetralogy of Fallot, double outlet right ventricle&#xD;
                  with subaortic VSD and pulmonary stenosis)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Corrected gestation at time of surgery less than 37 weeks&#xD;
&#xD;
          -  Prior cardiac arrest&#xD;
&#xD;
          -  Current or prior history of extracorporeal membrane oxygenation (ECMO) support&#xD;
&#xD;
          -  Current or prior history of needing renal replacement therapy with dialysis&#xD;
&#xD;
          -  Prior cardiac surgery requiring cardiopulmonary bypass&#xD;
&#xD;
          -  Diagnosis of Ebstein's Anomaly&#xD;
&#xD;
          -  Known genetic syndrome other than Trisomy 21 or DiGeorge Syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>29 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nathaniel Sznycer-Taub, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Nathaniel Sznycer-Taub</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Open heart surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scimitar Syndrome</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
    <mesh_term>Heart Septal Defects</mesh_term>
    <mesh_term>Tetralogy of Fallot</mesh_term>
    <mesh_term>Hypoplastic Left Heart Syndrome</mesh_term>
    <mesh_term>Heart Septal Defects, Ventricular</mesh_term>
    <mesh_term>Transposition of Great Vessels</mesh_term>
    <mesh_term>Pulmonary Valve Stenosis</mesh_term>
    <mesh_term>Pulmonary Atresia</mesh_term>
    <mesh_term>Double Outlet Right Ventricle</mesh_term>
    <mesh_term>Truncus Arteriosus, Persistent</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 25, 2023</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT04452188/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04452188
org study id: HUM00175086
secondary id: 5UL1TR002240-05
nct id: NCT04452188
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Systemic oxidative stress based on thiobarbituric acid reactive substances (TBARS)
time frame: Up to 24 hours following surgery
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.
measure: Rate of observed adverse events between the two groups
time frame: 30 days after surgery
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.
measure: Post-operative length of stay
time frame: 30 days after surgery
description: Calculated as number of days in the hospital after surgery.
measure: Days alive and out of the intensive care unit (ICU) at 30 days after surgery
time frame: 30 days after surgery
measure: Composite outcome of major adverse events
time frame: 30 days after surgery
measure: Global rank score
time frame: 30 days after surgery
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.
arm group label: Normoxia
arm group type: Experimental
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 group label: Standard of care
arm group type: Active Comparator
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: Normoxia (with controlled re-oxygenation)
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%)
arm group label: Normoxia
intervention type: Other
intervention name: Standard of care ventilation
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.
arm group label: Standard of care
criteria: 
gender: All
minimum age: N/A
maximum age: 29 Days
healthy volunteers: No
last name: Nathaniel Sznycer-Taub, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Nathaniel Sznycer-Taub
investigator title: Assistant Professor of Pediatrics
mesh term: Scimitar Syndrome
mesh term: Heart Diseases
mesh term: Heart Defects, Congenital
mesh term: Heart Septal Defects
mesh term: Tetralogy of Fallot
mesh term: Hypoplastic Left Heart Syndrome
mesh term: Heart Septal Defects, Ventricular
mesh term: Transposition of Great Vessels
mesh term: Pulmonary Valve Stenosis
mesh term: Pulmonary Atresia
mesh term: Double Outlet Right Ventricle
mesh term: Truncus Arteriosus, Persistent
sharing ipd: No
provided document: 