<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/NCT04423016</url>
  </required_header>
  <id_info>
    <org_study_id>NEO-TOHRx</org_study_id>
    <nct_id>NCT04423016</nct_id>
  </id_info>
  <brief_title>Transitional Cerebrovascular Reactivity in Very Preterm Infants</brief_title>
  <official_title>Clinical Determinants of Cerebrovascular Reactivity in Very Preterm Infants During the Transitional Period</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS Azienda Ospedaliero-Universitaria di Bologna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS Azienda Ospedaliero-Universitaria di Bologna</source>
  <oversight_info>
    <has_dmc>No</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>
      The transitional period, defined as the first 72 hours after preterm birth, is often&#xD;
      characterized by a significant hemodynamic instability and may also be associated with an&#xD;
      impairment of cerebral autoregulation, with relevant clinical implications. The moving&#xD;
      correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx,&#xD;
      has been previously proposed as a marker of cerebrovascular reactivity and provides an&#xD;
      indirect estimation of cerebral autoregulation in preterm infants.&#xD;
&#xD;
      This study aims to evaluate whether different antenatal, perinatal and postnatal factors may&#xD;
      influence cerebrovascular reactivity in very preterm infants during the transitional period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The transitional period, defined as the first 72 hours after preterm birth, is often&#xD;
      characterized by a significant hemodynamic instability and may also be associated with an&#xD;
      impairment of cerebral autoregulation, with relevant clinical implications. The moving&#xD;
      correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx,&#xD;
      has been previously proposed as a marker of cerebrovascular reactivity and provides an&#xD;
      indirect estimation of cerebral autoregulation in preterm infants.&#xD;
&#xD;
      This prospective observational study aims to evaluate whether different antenatal, perinatal,&#xD;
      and postnatal factors may influence cerebrovascular reactivity in very preterm infants during&#xD;
      the transitional period.&#xD;
&#xD;
      Infants &lt;32 weeks' gestation are enrolled within 12h from birth. A simultaneous monitoring of&#xD;
      cerebral oxygenation (CrSO2) by near-infrared spectroscopy and of heart rate (HR) by pulse&#xD;
      oximetry and electrical velocimetry is performed continuously over the first 72h.&#xD;
&#xD;
      The moving correlation coefficient between CrSO2 and HR is calculated using the ICM+ software&#xD;
      (Cambridge Enterprise Ltd) using 5-min, 30-point epochs. Time periods with evidence of major&#xD;
      artefacts, or with a missing data proportion &gt;50% are excluded from this calculation.&#xD;
      Positive TOHRx values will be interpreted as markers of impaired autoregulation.&#xD;
&#xD;
      A screening echocardiogram is routinely performed at the time of enrollment and repeated 6-12&#xD;
      hourly in the presence of a patent ductus arteriosus (PDA) or 12-24 hourly if there is no&#xD;
      evidence of PDA. Based on echocardiographic features, the ductal status is classified as&#xD;
      follows: no evidence of PDA, restrictive PDA (restrictive shunt pattern and left atrium to&#xD;
      aortic root ratio [LA:Ao] ratio &lt;1.5), hemodynamically significant PDA (pulsatile shunt&#xD;
      pattern, LA:Ao ratio ≥1.5 or presence of reversed end-diastolic flow either in the descending&#xD;
      aorta or in the anterior cerebral artery).&#xD;
&#xD;
      A concomitant cerebral ultrasound scan, aimed at evaluating brain parenchyma and the&#xD;
      occurrence of prematurity-related complications, such as intraventricular hemorrhage, is also&#xD;
      performed.&#xD;
&#xD;
      During the study period, the following antenatal and neonatal data are tracked down on a&#xD;
      specific case report form: gestational age (GA); birth weight (BW); non-invasive blood&#xD;
      pressure; antenatal steroids (complete course vs. incomplete course or not given); evidence&#xD;
      of reversed end-diastolic flow at antenatal umbilical Doppler (uREDF) (present vs. absent);&#xD;
      ventilatory status over the first 72 hours of life (mechanical ventilation, continuous&#xD;
      positive airway pressure [CPAP], nasal cannulas or self-ventilating in air [SVIA]);&#xD;
      surfactant administration; development of IVH over the first 72 hours of life; ongoing&#xD;
      inotropes (dopamine, dobutamine or both).&#xD;
&#xD;
      The correlation between antenatal, perinatal, and postnatal clinical variables and TOHRx is&#xD;
      going to be evaluated using generalized linear mixed models or generalized estimating&#xD;
      equations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 21, 2018</start_date>
  <completion_date type="Actual">July 3, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between TOHRx and gestational age</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Correlation between TOHRx and gestational age</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between TOHRx and antenatal steroids administration</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Correlation between TOHRx and antenatal steroids administration (full course vs. incomplete course or not given)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between TOHRx and antenatal Doppler status</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Correlation between TOHRx and antenatal Doppler status (normal or abnormal)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between TOHRx and ductal status</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Correlation between TOHRx and ductal status (hemodynamically significant, restrictive or closed)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between TOHRx and respiratory support</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Correlation between TOHRx and respiratory support modality (mechanical ventilation, CPAP, nasal cannulas or self-ventilating in air)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between TOHRx and inotropes</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Correlation between TOHRx and inotropes administration (dopamine; dobutamine; dopamine and dobutamine)</description>
  </primary_outcome>
  <enrollment type="Actual">72</enrollment>
  <condition>Cerebral Autoregulation</condition>
  <condition>Preterm Birth</condition>
  <condition>Premature Infant Disease</condition>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Near Infrared Spectroscopy monitoring</intervention_name>
    <description>Non-invasive continuous monitoring of cerebral oxygenation</description>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Electrical velocimetry and pulse oximetry</intervention_name>
    <description>Non-invasive continuous monitoring of cerebral oxygenation</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Preterm infants &lt;32 weeks' gestation during the transitional period (0-72 hours of life)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  gestational age &lt;32 weeks' gestation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  major congenital malformations&#xD;
&#xD;
          -  congenital heart disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>3 Days</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Luigi Corvaglia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>S. Orsola-Malpighi University Hospital, Bologna, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sant'Orsola-Malpighi University Hospital</name>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>July 26, 2021</last_update_submitted>
  <last_update_submitted_qc>July 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS Azienda Ospedaliero-Universitaria di Bologna</investigator_affiliation>
    <investigator_full_name>Luigi Corvaglia</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>cerebral autoregulation</keyword>
  <keyword>cerebrovascular reactivity</keyword>
  <keyword>preterm infants</keyword>
  <keyword>transitional period</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Infant, Premature, Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04423016
org study id: NEO-TOHRx
nct id: NCT04423016
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The transitional period, defined as the first 72 hours after preterm birth, is often
      characterized by a significant hemodynamic instability and may also be associated with an
      impairment of cerebral autoregulation, with relevant clinical implications. The moving
      correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx,
      has been previously proposed as a marker of cerebrovascular reactivity and provides an
      indirect estimation of cerebral autoregulation in preterm infants.

      This study aims to evaluate whether different antenatal, perinatal and postnatal factors may
      influence cerebrovascular reactivity in very preterm infants during the transitional period.
The transitional period, defined as the first 72 hours after preterm birth, is often
      characterized by a significant hemodynamic instability and may also be associated with an
      impairment of cerebral autoregulation, with relevant clinical implications. The moving
      correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx,
      has been previously proposed as a marker of cerebrovascular reactivity and provides an
      indirect estimation of cerebral autoregulation in preterm infants.

      This prospective observational study aims to evaluate whether different antenatal, perinatal,
      and postnatal factors may influence cerebrovascular reactivity in very preterm infants during
      the transitional period.

      Infants <32 weeks' gestation are enrolled within 12h from birth. A simultaneous monitoring of
      cerebral oxygenation (CrSO2) by near-infrared spectroscopy and of heart rate (HR) by pulse
      oximetry and electrical velocimetry is performed continuously over the first 72h.

      The moving correlation coefficient between CrSO2 and HR is calculated using the ICM+ software
      (Cambridge Enterprise Ltd) using 5-min, 30-point epochs. Time periods with evidence of major
      artefacts, or with a missing data proportion >50% are excluded from this calculation.
      Positive TOHRx values will be interpreted as markers of impaired autoregulation.

      A screening echocardiogram is routinely performed at the time of enrollment and repeated 6-12
      hourly in the presence of a patent ductus arteriosus (PDA) or 12-24 hourly if there is no
      evidence of PDA. Based on echocardiographic features, the ductal status is classified as
      follows: no evidence of PDA, restrictive PDA (restrictive shunt pattern and left atrium to
      aortic root ratio [LA:Ao] ratio <1.5), hemodynamically significant PDA (pulsatile shunt
      pattern, LA:Ao ratio ≥1.5 or presence of reversed end-diastolic flow either in the descending
      aorta or in the anterior cerebral artery).

      A concomitant cerebral ultrasound scan, aimed at evaluating brain parenchyma and the
      occurrence of prematurity-related complications, such as intraventricular hemorrhage, is also
      performed.

      During the study period, the following antenatal and neonatal data are tracked down on a
      specific case report form: gestational age (GA); birth weight (BW); non-invasive blood
      pressure; antenatal steroids (complete course vs. incomplete course or not given); evidence
      of reversed end-diastolic flow at antenatal umbilical Doppler (uREDF) (present vs. absent);
      ventilatory status over the first 72 hours of life (mechanical ventilation, continuous
      positive airway pressure [CPAP], nasal cannulas or self-ventilating in air [SVIA]);
      surfactant administration; development of IVH over the first 72 hours of life; ongoing
      inotropes (dopamine, dobutamine or both).

      The correlation between antenatal, perinatal, and postnatal clinical variables and TOHRx is
      going to be evaluated using generalized linear mixed models or generalized estimating
      equations.
observational model: Cohort
time perspective: Prospective
measure: Correlation between TOHRx and gestational age
time frame: 0-72 hours
description: Correlation between TOHRx and gestational age
measure: Correlation between TOHRx and antenatal steroids administration
time frame: 0-72 hours
description: Correlation between TOHRx and antenatal steroids administration (full course vs. incomplete course or not given)
measure: Correlation between TOHRx and antenatal Doppler status
time frame: 0-72 hours
description: Correlation between TOHRx and antenatal Doppler status (normal or abnormal)
measure: Correlation between TOHRx and ductal status
time frame: 0-72 hours
description: Correlation between TOHRx and ductal status (hemodynamically significant, restrictive or closed)
measure: Correlation between TOHRx and respiratory support
time frame: 0-72 hours
description: Correlation between TOHRx and respiratory support modality (mechanical ventilation, CPAP, nasal cannulas or self-ventilating in air)
measure: Correlation between TOHRx and inotropes
time frame: 0-72 hours
description: Correlation between TOHRx and inotropes administration (dopamine; dobutamine; dopamine and dobutamine)
intervention type: Device
intervention name: Near Infrared Spectroscopy monitoring
description: Non-invasive continuous monitoring of cerebral oxygenation
intervention type: Device
intervention name: Electrical velocimetry and pulse oximetry
description: Non-invasive continuous monitoring of cerebral oxygenation
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 3 Days
last name: Luigi Corvaglia, MD
role: Principal Investigator
affiliation: S. Orsola-Malpighi University Hospital, Bologna, Italy
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
investigator full name: Luigi Corvaglia
investigator title: Associate Professor
mesh term: Premature Birth
mesh term: Infant, Premature, Diseases
sharing ipd: No