<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/NCT02971566</url>
  </required_header>
  <id_info>
    <org_study_id>SO-2016-AREDF</org_study_id>
    <nct_id>NCT02971566</nct_id>
  </id_info>
  <brief_title>Splanchnic Oxygenation Response to Enteral Feeds in Preterm Infants With Abnormal Antenatal Doppler.</brief_title>
  <acronym>AREDF-SO</acronym>
  <official_title>Splanchnic Oxygenation and Perfusion Response to Enteral Feeds in Preterm Infants With Abnormal Antenatal Doppler: Pattern Assessment and Correlation With Feeding Intolerance</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Antenatal absent or reversed end-diastolic flow (AREDF) velocity through the umbilical&#xD;
      arteries places preterm infants at significant risk for developing gastrointestinal&#xD;
      complications, such as feeding intolerance, necrotizing enterocolitis or spontaneous&#xD;
      intestinal perforation. Due to the fear of the aforementioned conditions, the establishment&#xD;
      of adequate enteral feeds is frequently hampered in this population. Previous postnatal&#xD;
      Doppler studies have shown that AREDF preterm infants who later developed feeding intolerance&#xD;
      have a decreased blood flow velocity in the superior mesenteric artery in response to the&#xD;
      first enteral feed; to date, however, it is not known whether this hemodynamic impairment&#xD;
      persists over time, or if it is associated with reduced splanchnic oxygenation and perfusion,&#xD;
      monitored by Near-infrared spectroscopy (NIRS).&#xD;
&#xD;
      This observational prospective study aims:&#xD;
&#xD;
        -  to assess the patterns of abdominal oxygenation and perfusion in response to enteral&#xD;
           feeds in AREDF preterm infants at different phases of enteral feeding establishment;&#xD;
&#xD;
        -  to evaluate a possible correlation with the development of gastrointestinal&#xD;
           complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intrauterine growth restriction (IUGR) is a major cause of perinatal morbidity and mortality.&#xD;
      Severe IUGR is often due to impaired placental circulation, with absent or reversed&#xD;
      end-diastolic flow (AREDF) velocity through the umbilical arteries. Fetuses with AREDF adapt&#xD;
      to chronic hypoxia by undergoing a blood flow redistribution, which favors cerebral perfusion&#xD;
      at the expense of the mesenteric district. The resulting hypoxic-ischemic injury of the&#xD;
      intestinal mucosa represents a major risk factor for the post-natal development of&#xD;
      gastrointestinal complications, such as necrotizing enterocolitis (NEC), spontaneous&#xD;
      intestinal perforation (SIP) and feeding intolerance (FI). Due to the fear of the&#xD;
      aforementioned conditions, the establishment of adequate enteral feeding in AREDF preterm&#xD;
      infants is often difficult; hence, the identification of infants at highest risk for GI&#xD;
      complications could aid their delicate nutritional management.&#xD;
&#xD;
      Postnatal Doppler studies have shown a decreased blood flow velocity in the superior&#xD;
      mesenteric artery in response to the first enteral feed in AREDF preterm infants who later&#xD;
      developed feeding intolerance. A similar Doppler impairment and lower values of splanchnic&#xD;
      oxygenation at feeding introduction have been described in non-IUGR preterm infants with&#xD;
      later GI complications. To date, however, it is not known whether the impaired mesenteric&#xD;
      blood flow observed after the first feed in high-risk AREDF infants persists over time, or if&#xD;
      it correlates with reduced splanchnic oxygenation and perfusion.&#xD;
&#xD;
      This observational prospective study aims:&#xD;
&#xD;
        -  to assess the patterns of abdominal oxygenation and perfusion in response to enteral&#xD;
           feeds in AREDF preterm infants at different phases of enteral feeding establishment;&#xD;
&#xD;
        -  to evaluate a possible correlation with the development of gastrointestinal&#xD;
           complications.&#xD;
&#xD;
      Infants admitted to the Neonatal Intensive Care Unit (NICU) are consecutively enrolled in the&#xD;
      study if fulfilling the following criteria: gestational age ≤34 weeks, stable clinical&#xD;
      conditions, documented evidence of antenatal umbilical Doppler impairment.&#xD;
&#xD;
      Exclusion criteria are:&#xD;
&#xD;
        -  Enteral feeding prior to the enrollment&#xD;
&#xD;
        -  Major congenital abnormalities (including congenital heart diseases, gastroschisis,&#xD;
           exomphalos)&#xD;
&#xD;
        -  Hemodynamic instability, hypotension, patent ductus arteriosus, anemia, sepsis or other&#xD;
           infections at time of NIRS monitoring&#xD;
&#xD;
      Written, informed consent to participate in the study is obtained from the parents/legal&#xD;
      guardians of each infant before enrollment.&#xD;
&#xD;
      Enrolled infants undergo a continuous monitoring of splanchnic oxygenation (SrSO2) at enteral&#xD;
      feeding introduction (15 ml/kg/die volumes administered within the first 48 hours of life)&#xD;
      and full enteral feeding (FEF) achievement (enteral intake ≥150 ml/kg/die) from 30' before to&#xD;
      3 h after feed administration by means of INVOS 5100 oximeter (Somanetics Corporation, Troy,&#xD;
      MI, USA).&#xD;
&#xD;
      A simultaneous monitoring of peripheral oxygen saturation (SpO2) is be performed in order to&#xD;
      calculate splanchnic fractional oxygen extraction (SFOE) ratio ([SpO2-SrSO2]/SpO2). SrSO2&#xD;
      values recorded during hypoxic episodes (SpO2 &lt;85%) are excluded from statistical analysis.&#xD;
&#xD;
      GI complications are defined as NEC stage ≥2, SIP and/or FI (enteral feeding withholding ≥1&#xD;
      day because of suggestive clinical signs). Enrolled infants are retrospectively divided into&#xD;
      two groups: lack (group 1) vs. development (group 2) of GI complications.&#xD;
&#xD;
      Data are analyzed using IBM SPSS Statistic version 20.0.0 (IBM Corporation, IBM Corporation&#xD;
      Armonk, New York, United States). Clinical characteristics in the study groups are compared&#xD;
      by Mann-Whitney U test for continuous variables and chi-square test for categorical&#xD;
      variables. Mann-Whitney U test is used to compare abdominal SrSO2 and FSOE patterns in&#xD;
      response to feeds between groups 1 and 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">October 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Increase/reduction of SrSO2 after enteral feeds</measure>
    <time_frame>3.5 hours</time_frame>
    <description>Increase/reduction of SrSO2 values in response to enteral feeds in infants who have developed gastrointestinal complications during their hospitalization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Increase/reduction of FSOE after enteral feeds</measure>
    <time_frame>3.5 hours</time_frame>
    <description>Increase/reduction of SrSO2 values in response to enteral feeds in infants who have developed gastrointestinal complications during their hospitalization.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">20</enrollment>
  <condition>Placental Insufficiency</condition>
  <condition>NEC - Necrotizing Enterocolitis</condition>
  <condition>Newborn, Premature</condition>
  <condition>Feeding Disorder Neonatal</condition>
  <arm_group>
    <arm_group_label>Gastrointestinal complications</arm_group_label>
    <description>Development of one ore more of the following gastrointestinal complications:&#xD;
necrotizing enterocolitis (stage ≥2)&#xD;
spontaneous intestinal perforation&#xD;
feeding intolerance, defined as enteral feeding withholding ≥1 day because of suggestive clinical signs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>no evidence of gastrointestinal complications during the hospitalization</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        20 preterm infants admitted to the Neonatal Intensive Care Unit of Sant'Orsola-Malpighi&#xD;
        University Hospital and fulfilling the inclusion criteria are going to be enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  gestational age ≤34 weeks&#xD;
&#xD;
          -  stable clinical conditions&#xD;
&#xD;
          -  documented evidence of antenatal umbilical Doppler impairment&#xD;
&#xD;
          -  written informed consent obtained from parents/guardians&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Enteral feeding prior to the enrollment&#xD;
&#xD;
          -  Major congenital abnormalities (including congenital heart diseases, gastroschisis,&#xD;
             exomphalos)&#xD;
&#xD;
          -  Hemodynamic instability, hypotension, patent ductus arteriosus, anemia, sepsis or&#xD;
             other infections at time of NIRS monitoring&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>2 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luigi T Corvaglia, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS Azienda Ospedaliero-Universitaria di Bologna</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Neonatal Intensive Care Unit of the S.Orsola-Malpighi Hospital</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Kempley S, Gupta N, Linsell L, Dorling J, McCormick K, Mannix P, Juszczak E, Brocklehurst P, Leaf A; ADEPT Trial Collaborative Group. Feeding infants below 29 weeks' gestation with abnormal antenatal Doppler: analysis from a randomised trial. Arch Dis Child Fetal Neonatal Ed. 2014 Jan;99(1):F6-F11. doi: 10.1136/archdischild-2013-304393. Epub 2013 Aug 23.</citation>
    <PMID>23973795</PMID>
  </reference>
  <reference>
    <citation>Bora R, Mukhopadhyay K, Saxena AK, Jain V, Narang A. Prediction of feed intolerance and necrotizing enterocolitis in neonates with absent end diastolic flow in umbilical artery and the correlation of feed intolerance with postnatal superior mesenteric artery flow. J Matern Fetal Neonatal Med. 2009 Nov;22(11):1092-6. doi: 10.3109/14767050903029600.</citation>
    <PMID>19900051</PMID>
  </reference>
  <reference>
    <citation>Kempley ST, Gamsu HR, Vyas S, Nicolaides K. Effects of intrauterine growth retardation on postnatal visceral and cerebral blood flow velocity. Arch Dis Child. 1991 Oct;66(10 Spec No):1115-8. doi: 10.1136/adc.66.10_spec_no.1115.</citation>
    <PMID>1750758</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 19, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>November 22, 2016</last_update_submitted>
  <last_update_submitted_qc>November 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 23, 2016</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, University of Bologna (Italy)</investigator_title>
  </responsible_party>
  <keyword>feeding intolerance</keyword>
  <keyword>preterm infants</keyword>
  <keyword>near infrared spectroscopy</keyword>
  <keyword>abnormal antenatal Doppler</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enterocolitis</mesh_term>
    <mesh_term>Enterocolitis, Necrotizing</mesh_term>
    <mesh_term>Placental Insufficiency</mesh_term>
    <mesh_term>Feeding and Eating Disorders</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/NCT02971566
org study id: SO-2016-AREDF
nct id: NCT02971566
lead sponsor: 
has dmc: No
Antenatal absent or reversed end-diastolic flow (AREDF) velocity through the umbilical
      arteries places preterm infants at significant risk for developing gastrointestinal
      complications, such as feeding intolerance, necrotizing enterocolitis or spontaneous
      intestinal perforation. Due to the fear of the aforementioned conditions, the establishment
      of adequate enteral feeds is frequently hampered in this population. Previous postnatal
      Doppler studies have shown that AREDF preterm infants who later developed feeding intolerance
      have a decreased blood flow velocity in the superior mesenteric artery in response to the
      first enteral feed; to date, however, it is not known whether this hemodynamic impairment
      persists over time, or if it is associated with reduced splanchnic oxygenation and perfusion,
      monitored by Near-infrared spectroscopy (NIRS).

      This observational prospective study aims:

        -  to assess the patterns of abdominal oxygenation and perfusion in response to enteral
           feeds in AREDF preterm infants at different phases of enteral feeding establishment;

        -  to evaluate a possible correlation with the development of gastrointestinal
           complications.
Intrauterine growth restriction (IUGR) is a major cause of perinatal morbidity and mortality.
      Severe IUGR is often due to impaired placental circulation, with absent or reversed
      end-diastolic flow (AREDF) velocity through the umbilical arteries. Fetuses with AREDF adapt
      to chronic hypoxia by undergoing a blood flow redistribution, which favors cerebral perfusion
      at the expense of the mesenteric district. The resulting hypoxic-ischemic injury of the
      intestinal mucosa represents a major risk factor for the post-natal development of
      gastrointestinal complications, such as necrotizing enterocolitis (NEC), spontaneous
      intestinal perforation (SIP) and feeding intolerance (FI). Due to the fear of the
      aforementioned conditions, the establishment of adequate enteral feeding in AREDF preterm
      infants is often difficult; hence, the identification of infants at highest risk for GI
      complications could aid their delicate nutritional management.

      Postnatal Doppler studies have shown a decreased blood flow velocity in the superior
      mesenteric artery in response to the first enteral feed in AREDF preterm infants who later
      developed feeding intolerance. A similar Doppler impairment and lower values of splanchnic
      oxygenation at feeding introduction have been described in non-IUGR preterm infants with
      later GI complications. To date, however, it is not known whether the impaired mesenteric
      blood flow observed after the first feed in high-risk AREDF infants persists over time, or if
      it correlates with reduced splanchnic oxygenation and perfusion.

      This observational prospective study aims:

        -  to assess the patterns of abdominal oxygenation and perfusion in response to enteral
           feeds in AREDF preterm infants at different phases of enteral feeding establishment;

        -  to evaluate a possible correlation with the development of gastrointestinal
           complications.

      Infants admitted to the Neonatal Intensive Care Unit (NICU) are consecutively enrolled in the
      study if fulfilling the following criteria: gestational age ≤34 weeks, stable clinical
      conditions, documented evidence of antenatal umbilical Doppler impairment.

      Exclusion criteria are:

        -  Enteral feeding prior to the enrollment

        -  Major congenital abnormalities (including congenital heart diseases, gastroschisis,
           exomphalos)

        -  Hemodynamic instability, hypotension, patent ductus arteriosus, anemia, sepsis or other
           infections at time of NIRS monitoring

      Written, informed consent to participate in the study is obtained from the parents/legal
      guardians of each infant before enrollment.

      Enrolled infants undergo a continuous monitoring of splanchnic oxygenation (SrSO2) at enteral
      feeding introduction (15 ml/kg/die volumes administered within the first 48 hours of life)
      and full enteral feeding (FEF) achievement (enteral intake ≥150 ml/kg/die) from 30' before to
      3 h after feed administration by means of INVOS 5100 oximeter (Somanetics Corporation, Troy,
      MI, USA).

      A simultaneous monitoring of peripheral oxygen saturation (SpO2) is be performed in order to
      calculate splanchnic fractional oxygen extraction (SFOE) ratio ([SpO2-SrSO2]/SpO2). SrSO2
      values recorded during hypoxic episodes (SpO2 <85%) are excluded from statistical analysis.

      GI complications are defined as NEC stage ≥2, SIP and/or FI (enteral feeding withholding ≥1
      day because of suggestive clinical signs). Enrolled infants are retrospectively divided into
      two groups: lack (group 1) vs. development (group 2) of GI complications.

      Data are analyzed using IBM SPSS Statistic version 20.0.0 (IBM Corporation, IBM Corporation
      Armonk, New York, United States). Clinical characteristics in the study groups are compared
      by Mann-Whitney U test for continuous variables and chi-square test for categorical
      variables. Mann-Whitney U test is used to compare abdominal SrSO2 and FSOE patterns in
      response to feeds between groups 1 and 2.
observational model: Case-Control
time perspective: Prospective
measure: Increase/reduction of SrSO2 after enteral feeds
time frame: 3.5 hours
description: Increase/reduction of SrSO2 values in response to enteral feeds in infants who have developed gastrointestinal complications during their hospitalization.
measure: Increase/reduction of FSOE after enteral feeds
time frame: 3.5 hours
description: Increase/reduction of SrSO2 values in response to enteral feeds in infants who have developed gastrointestinal complications during their hospitalization.
arm group label: Gastrointestinal complications
description: Development of one ore more of the following gastrointestinal complications:
necrotizing enterocolitis (stage ≥2)
spontaneous intestinal perforation
feeding intolerance, defined as enteral feeding withholding ≥1 day because of suggestive clinical signs
arm group label: Controls
description: no evidence of gastrointestinal complications during the hospitalization
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 2 Months
healthy volunteers: No
last name: Luigi T Corvaglia, Prof
role: Principal Investigator
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
facility: 
country: Italy
citation: Kempley S, Gupta N, Linsell L, Dorling J, McCormick K, Mannix P, Juszczak E, Brocklehurst P, Leaf A; ADEPT Trial Collaborative Group. Feeding infants below 29 weeks' gestation with abnormal antenatal Doppler: analysis from a randomised trial. Arch Dis Child Fetal Neonatal Ed. 2014 Jan;99(1):F6-F11. doi: 10.1136/archdischild-2013-304393. Epub 2013 Aug 23.
PMID: 23973795
citation: Bora R, Mukhopadhyay K, Saxena AK, Jain V, Narang A. Prediction of feed intolerance and necrotizing enterocolitis in neonates with absent end diastolic flow in umbilical artery and the correlation of feed intolerance with postnatal superior mesenteric artery flow. J Matern Fetal Neonatal Med. 2009 Nov;22(11):1092-6. doi: 10.3109/14767050903029600.
PMID: 19900051
citation: Kempley ST, Gamsu HR, Vyas S, Nicolaides K. Effects of intrauterine growth retardation on postnatal visceral and cerebral blood flow velocity. Arch Dis Child. 1991 Oct;66(10 Spec No):1115-8. doi: 10.1136/adc.66.10_spec_no.1115.
PMID: 1750758
responsible party type: Principal Investigator
investigator affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
investigator full name: Luigi Corvaglia
investigator title: Associate Professor, University of Bologna (Italy)
mesh term: Enterocolitis
mesh term: Enterocolitis, Necrotizing
mesh term: Placental Insufficiency
mesh term: Feeding and Eating Disorders
sharing ipd: No