<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/NCT03771534</url>
  </required_header>
  <id_info>
    <org_study_id>1000060514</org_study_id>
    <nct_id>NCT03771534</nct_id>
  </id_info>
  <brief_title>Acute Maternal Hyperoxygenation for Fetal Transposition of the Great Arteries (TGA)</brief_title>
  <official_title>Transposition of the Great Arteries: Prenatal Anatomical and Hemodynamic Findings Associated With Perinatal Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Hospital for Sick Children</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This prospective study will examine whether transient maternal hyperoxygenation is useful as&#xD;
      a diagnostic test to more accurately detect TGA patients with poor vs. good neonatal&#xD;
      intra-cardiac mixing of blood, based on the in-utero response to oxygen exposure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective pilot study to examine whether transient maternal hyperoxygenation is&#xD;
      useful as a diagnostic test to more accurately detect TGA patients with poor vs. good&#xD;
      neonatal intracardiac mixing of blood, based on the in-utero response to oxygen exposure.&#xD;
      Acute maternal oxygen administration will transiently increase the fetal oxygen levels to&#xD;
      those reached at birth with spontaneous breathing, thus simulating conditions that will&#xD;
      naturally occur at the time of birth. Echocardiogram and MRI will be used to examine the&#xD;
      effects on the fetal circulation. The prenatal findings will then be compared to the neonatal&#xD;
      presentation.&#xD;
&#xD;
      The investigators postulate that conditions that predispose newborns to acute neonatal&#xD;
      compromise will be detectable and distinguishable prior to birth by echocardiography, MRI, or&#xD;
      by combining the findings of both exams.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 20, 2018</start_date>
  <completion_date type="Anticipated">March 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fetal intracardiac/ductal shunting measured by echocardiogram flow patterns and MRI fluximetry</measure>
    <time_frame>Outcome measure obtained during hyperoxygenation while undergoing echocardiography and MRI</time_frame>
    <description>Characterize effects of maternal hyperoxygenation on fetal intracardiac shunting measured using MRI fluximetry (ml/min/m2) of AAo, DA, SVC, IVC, UV, and DA.&#xD;
Ductal shunting measured using echo measurements of atrial septal morphology (2D; 4D) and foramen flow (color; 4D flow) of FO diameter and septal excursion. Ductus arteriosus flow (color and Doppler): minimal diameter, reversed end-diastolic flow, systolic peak flow, forward-reverse flow ratio, flow restriction.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fetal pulmonary blood flow measured by MRI fluximetry</measure>
    <time_frame>Outcome measure obtained during hyperoxygenation while undergoing echocardiography and MRI</time_frame>
    <description>Characterize effects of maternal hyperoxygenation on fetal pulmonary blood flow using MRI fluximetry (ml/min/m2) measures of Main PA, RPA and LPA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neonatal outcomes</measure>
    <time_frame>Intrauterine demise to hospital discharge, or up to 1 year of age if pulmonary hypertension exists</time_frame>
    <description>As measure of patient morbidity, a composite score of 10 variables will be used, assigning a value of 1 for each event that occurred 1) respiratory distress syndrome requiring surfactant; 2) cardiopulmonary resuscitation requiring chest compressions; 3) cerebral vascular injury (intra-ventricular or -parenchymal hemorrhage, ischemic stroke); 4) necrotizing enterocolitis; 5) need of ECMO; 6) infections associated with health care (bloodstream, surgical site, and urinary tract infection); 7) unplanned re-intubation; 8) re-operation for residual cardiac lesions; 9) interventional catheterization for residual cardiac lesions; and 10) unplanned intensive care readmission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fetal cerebral perfusion</measure>
    <time_frame>Outcome measure obtained during maternal hyperoxygenation while undergoing echocardiography and MRI</time_frame>
    <description>Effects of maternal hyperoxygenation on fetal cerebral perfusion measured by change in cDO2 (mL/min/m2) and cVO2 (mL/min/m2)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>TGA - Transposition of Great Arteries</condition>
  <arm_group>
    <arm_group_label>Oxygen gas</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10-15 L/min of oxygen by face mask for up to 45 minutes for the MRI and up to 30 minutes for the echocardiogram.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxygen gas</intervention_name>
    <description>Brief maternal administration of 65-70% O2 via a face mask during the last trimester</description>
    <arm_group_label>Oxygen gas</arm_group_label>
    <other_name>Praxair</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fetus with simple TGA +/- small VSD&#xD;
&#xD;
          -  Intention of active postnatal management after birth&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fetus with complex form of TGA&#xD;
&#xD;
          -  Significant fetal arrhythmia&#xD;
&#xD;
          -  Major non-cardiac lesions&#xD;
&#xD;
          -  Maternal contraindications for fetal MRI&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edgar Jaeggi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Hospital for Sick Children, Toronto</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Edgar Jaeggi, MD</last_name>
    <phone>+1(416)813-7500</phone>
    <phone_ext>207466</phone_ext>
    <email>edgar.jaeggi@sickkids.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mika Saito, MD</last_name>
    <phone>+1(416)813-7500</phone>
    <phone_ext>201527</phone_ext>
    <email>mika.saito@sickkids.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Hospital For Sick Children</name>
      <address>
        <city>Toronto</city>
        <zip>M5G1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edgar Jaeggi, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Mika Saito, MD</last_name>
    </contact_backup>
    <investigator>
      <last_name>Edgar Jaeggi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mike Seed, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mika Saito, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Sun L, Macgowan CK, Portnoy S, Sled JG, Yoo SJ, Grosse-Wortmann L, Jaeggi E, Kingdom J, Seed M. New advances in fetal cardiovascular magnetic resonance imaging for quantifying the distribution of blood flow and oxygen transport: Potential applications in fetal cardiovascular disease diagnosis and therapy. Echocardiography. 2017 Dec;34(12):1799-1803. doi: 10.1111/echo.13760.</citation>
    <PMID>29287129</PMID>
  </reference>
  <reference>
    <citation>Porayette P, Madathil S, Sun L, Jaeggi E, Grosse-Wortmann L, Yoo SJ, Hickey E, Miller SP, Macgowan CK, Seed M. MRI reveals hemodynamic changes with acute maternal hyperoxygenation in human fetuses with and without congenital heart disease. Prenat Diagn. 2016 Mar;36(3):274-81. doi: 10.1002/pd.4762. Epub 2016 Feb 9.</citation>
    <PMID>26701792</PMID>
  </reference>
  <reference>
    <citation>Sun L, Macgowan CK, Sled JG, Yoo SJ, Manlhiot C, Porayette P, Grosse-Wortmann L, Jaeggi E, McCrindle BW, Kingdom J, Hickey E, Miller S, Seed M. Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation. 2015 Apr 14;131(15):1313-23. doi: 10.1161/CIRCULATIONAHA.114.013051. Epub 2015 Mar 11.</citation>
    <PMID>25762062</PMID>
  </reference>
  <reference>
    <citation>Porayette P, van Amerom JF, Yoo SJ, Jaeggi E, Macgowan CK, Seed M. MRI shows limited mixing between systemic and pulmonary circulations in foetal transposition of the great arteries: a potential cause of in utero pulmonary vascular disease. Cardiol Young. 2015 Apr;25(4):737-44. doi: 10.1017/S1047951114000870. Epub 2014 Jun 16.</citation>
    <PMID>24932863</PMID>
  </reference>
  <reference>
    <citation>Prsa M, Sun L, van Amerom J, Yoo SJ, Grosse-Wortmann L, Jaeggi E, Macgowan C, Seed M. Reference ranges of blood flow in the major vessels of the normal human fetal circulation at term by phase-contrast magnetic resonance imaging. Circ Cardiovasc Imaging. 2014 Jul;7(4):663-70. doi: 10.1161/CIRCIMAGING.113.001859. Epub 2014 May 29.</citation>
    <PMID>24874055</PMID>
  </reference>
  <reference>
    <citation>Mawad W, Chaturvedi RR, Ryan G, Jaeggi E. Percutaneous Fetal Atrial Balloon Septoplasty for Simple Transposition of the Great Arteries With an Intact Atrial Septum. Can J Cardiol. 2018 Mar;34(3):342.e9-342.e11. doi: 10.1016/j.cjca.2017.12.010. Epub 2017 Dec 15.</citation>
    <PMID>29398177</PMID>
  </reference>
  <reference>
    <citation>Jaeggi E, Renaud C, Ryan G, Chaturvedi R. Intrauterine therapy for structural congenital heart disease: Contemporary results and Canadian experience. Trends Cardiovasc Med. 2016 Oct;26(7):639-46. doi: 10.1016/j.tcm.2016.04.006. Epub 2016 Apr 22.</citation>
    <PMID>27234352</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>October 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>April 8, 2021</last_update_submitted>
  <last_update_submitted_qc>April 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Edgar Jaeggi</investigator_full_name>
    <investigator_title>Principal Investigator, Head of Fetal Cardiology</investigator_title>
  </responsible_party>
  <keyword>maternal hyperoxygenation</keyword>
  <keyword>fetal echocardiography</keyword>
  <keyword>fetal MRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Transposition of Great Vessels</mesh_term>
    <mesh_term>Situs Inversus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03771534/Prot_SAP_002.pdf</document_url>
    </provided_document>
    <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>November 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03771534/ICF_003.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/NCT03771534
org study id: 1000060514
nct id: NCT03771534
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This prospective study will examine whether transient maternal hyperoxygenation is useful as
      a diagnostic test to more accurately detect TGA patients with poor vs. good neonatal
      intra-cardiac mixing of blood, based on the in-utero response to oxygen exposure.
This is a prospective pilot study to examine whether transient maternal hyperoxygenation is
      useful as a diagnostic test to more accurately detect TGA patients with poor vs. good
      neonatal intracardiac mixing of blood, based on the in-utero response to oxygen exposure.
      Acute maternal oxygen administration will transiently increase the fetal oxygen levels to
      those reached at birth with spontaneous breathing, thus simulating conditions that will
      naturally occur at the time of birth. Echocardiogram and MRI will be used to examine the
      effects on the fetal circulation. The prenatal findings will then be compared to the neonatal
      presentation.

      The investigators postulate that conditions that predispose newborns to acute neonatal
      compromise will be detectable and distinguishable prior to birth by echocardiography, MRI, or
      by combining the findings of both exams.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Fetal intracardiac/ductal shunting measured by echocardiogram flow patterns and MRI fluximetry
time frame: Outcome measure obtained during hyperoxygenation while undergoing echocardiography and MRI
description: Characterize effects of maternal hyperoxygenation on fetal intracardiac shunting measured using MRI fluximetry (ml/min/m2) of AAo, DA, SVC, IVC, UV, and DA.
Ductal shunting measured using echo measurements of atrial septal morphology (2D; 4D) and foramen flow (color; 4D flow) of FO diameter and septal excursion. Ductus arteriosus flow (color and Doppler): minimal diameter, reversed end-diastolic flow, systolic peak flow, forward-reverse flow ratio, flow restriction.
measure: Fetal pulmonary blood flow measured by MRI fluximetry
time frame: Outcome measure obtained during hyperoxygenation while undergoing echocardiography and MRI
description: Characterize effects of maternal hyperoxygenation on fetal pulmonary blood flow using MRI fluximetry (ml/min/m2) measures of Main PA, RPA and LPA
measure: Neonatal outcomes
time frame: Intrauterine demise to hospital discharge, or up to 1 year of age if pulmonary hypertension exists
description: As measure of patient morbidity, a composite score of 10 variables will be used, assigning a value of 1 for each event that occurred 1) respiratory distress syndrome requiring surfactant; 2) cardiopulmonary resuscitation requiring chest compressions; 3) cerebral vascular injury (intra-ventricular or -parenchymal hemorrhage, ischemic stroke); 4) necrotizing enterocolitis; 5) need of ECMO; 6) infections associated with health care (bloodstream, surgical site, and urinary tract infection); 7) unplanned re-intubation; 8) re-operation for residual cardiac lesions; 9) interventional catheterization for residual cardiac lesions; and 10) unplanned intensive care readmission.
measure: Fetal cerebral perfusion
time frame: Outcome measure obtained during maternal hyperoxygenation while undergoing echocardiography and MRI
description: Effects of maternal hyperoxygenation on fetal cerebral perfusion measured by change in cDO2 (mL/min/m2) and cVO2 (mL/min/m2)
arm group label: Oxygen gas
arm group type: Experimental
description: 10-15 L/min of oxygen by face mask for up to 45 minutes for the MRI and up to 30 minutes for the echocardiogram.
intervention type: Drug
intervention name: Oxygen gas
description: Brief maternal administration of 65-70% O2 via a face mask during the last trimester
arm group label: Oxygen gas
other name: Praxair
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Edgar Jaeggi, MD
role: Principal Investigator
affiliation: The Hospital for Sick Children, Toronto
last name: Edgar Jaeggi, MD
phone: +1(416)813-7500
phone ext: 207466
email: edgar.jaeggi@sickkids.ca
last name: Mika Saito, MD
phone: +1(416)813-7500
phone ext: 201527
email: mika.saito@sickkids.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: Canada
citation: Sun L, Macgowan CK, Portnoy S, Sled JG, Yoo SJ, Grosse-Wortmann L, Jaeggi E, Kingdom J, Seed M. New advances in fetal cardiovascular magnetic resonance imaging for quantifying the distribution of blood flow and oxygen transport: Potential applications in fetal cardiovascular disease diagnosis and therapy. Echocardiography. 2017 Dec;34(12):1799-1803. doi: 10.1111/echo.13760.
PMID: 29287129
citation: Porayette P, Madathil S, Sun L, Jaeggi E, Grosse-Wortmann L, Yoo SJ, Hickey E, Miller SP, Macgowan CK, Seed M. MRI reveals hemodynamic changes with acute maternal hyperoxygenation in human fetuses with and without congenital heart disease. Prenat Diagn. 2016 Mar;36(3):274-81. doi: 10.1002/pd.4762. Epub 2016 Feb 9.
PMID: 26701792
citation: Sun L, Macgowan CK, Sled JG, Yoo SJ, Manlhiot C, Porayette P, Grosse-Wortmann L, Jaeggi E, McCrindle BW, Kingdom J, Hickey E, Miller S, Seed M. Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation. 2015 Apr 14;131(15):1313-23. doi: 10.1161/CIRCULATIONAHA.114.013051. Epub 2015 Mar 11.
PMID: 25762062
citation: Porayette P, van Amerom JF, Yoo SJ, Jaeggi E, Macgowan CK, Seed M. MRI shows limited mixing between systemic and pulmonary circulations in foetal transposition of the great arteries: a potential cause of in utero pulmonary vascular disease. Cardiol Young. 2015 Apr;25(4):737-44. doi: 10.1017/S1047951114000870. Epub 2014 Jun 16.
PMID: 24932863
citation: Prsa M, Sun L, van Amerom J, Yoo SJ, Grosse-Wortmann L, Jaeggi E, Macgowan C, Seed M. Reference ranges of blood flow in the major vessels of the normal human fetal circulation at term by phase-contrast magnetic resonance imaging. Circ Cardiovasc Imaging. 2014 Jul;7(4):663-70. doi: 10.1161/CIRCIMAGING.113.001859. Epub 2014 May 29.
PMID: 24874055
citation: Mawad W, Chaturvedi RR, Ryan G, Jaeggi E. Percutaneous Fetal Atrial Balloon Septoplasty for Simple Transposition of the Great Arteries With an Intact Atrial Septum. Can J Cardiol. 2018 Mar;34(3):342.e9-342.e11. doi: 10.1016/j.cjca.2017.12.010. Epub 2017 Dec 15.
PMID: 29398177
citation: Jaeggi E, Renaud C, Ryan G, Chaturvedi R. Intrauterine therapy for structural congenital heart disease: Contemporary results and Canadian experience. Trends Cardiovasc Med. 2016 Oct;26(7):639-46. doi: 10.1016/j.tcm.2016.04.006. Epub 2016 Apr 22.
PMID: 27234352
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Edgar Jaeggi
investigator title: Principal Investigator, Head of Fetal Cardiology
mesh term: Transposition of Great Vessels
mesh term: Situs Inversus
sharing ipd: No
provided document: 
provided document: 