<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/NCT03748914</url>
  </required_header>
  <id_info>
    <org_study_id>30-450 ex 17/18</org_study_id>
    <secondary_id>U1111-1223-3280</secondary_id>
    <nct_id>NCT03748914</nct_id>
  </id_info>
  <brief_title>C-UCM and Cerebral Oxygenation and Perfusion</brief_title>
  <official_title>The Influence of Cut-umbilical Cord Milking (C-UCM) on the Cerebral Oxygenation and Perfusion of Preterm and Term Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Graz</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>
      In this randomized controlled Pilot study the effects of cut-umbilical cord milking on&#xD;
      cerebral oxygenation and perfusion measured via near-infrared spectroscopy (NIRS) and the&#xD;
      effects on stroke volume (SV) and cardiac output (CO) also measured non-invasively in term&#xD;
      and preterm infants are evaluated for the first 15 minutes after birth and compared to a&#xD;
      control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      The transition to life after birth is a complex physiological process where the neonate has&#xD;
      to establish sufficient ventilation and changes from intra-uterine circulation to&#xD;
      extra-uterine circulation take place. During these processes the neonate has to provide the&#xD;
      brain with adequate perfusion and oxygen delivery to maintain normal cerebral tissue&#xD;
      oxygenation and activity. Instability of cerebral perfusion and oxygenation may be associated&#xD;
      with brain damage in preterm infants. The concept of C-UCM may substitute the adverse effects&#xD;
      of immediate cord clamping by supplying additional placental blood to the infant, which is&#xD;
      mostly performed during caesarean section or in the critically ill neonate.&#xD;
&#xD;
      In this randomized controlled Pilot study the effects of cut-umbilical cord milking on&#xD;
      cerebral oxygenation and perfusion measured via near-infrared spectroscopy (NIRS) and the&#xD;
      effects on stroke volume (SV) and cardiac output (CO) also measured non-invasively in term&#xD;
      and preterm infants are evaluated for the first 15 minutes after birth and compared to a&#xD;
      control group.&#xD;
&#xD;
      Aim&#xD;
&#xD;
      The aim of the study is to analyse whether C-UCM in preterm and term infants results in an&#xD;
      improvement of cerebral oxygenation and perfusion during immediate neonatal transition&#xD;
      measured with NIRS.&#xD;
&#xD;
      Hypotheses&#xD;
&#xD;
      Infants undergoing C-UCM after birth compared to infants without C-UCM show differences in&#xD;
      cerebral oxygenation and perfusion in the first 15 min after birth.&#xD;
&#xD;
      Hypothesis I: C-UCM and cerebral blood volume (CBV) In infants with C-UCM there is more CBV&#xD;
      decrease immediately after birth, compared to infants without C-UCM, due to improved cerebral&#xD;
      oxygen delivery.&#xD;
&#xD;
      Hypothesis II: C-UCM and cerebral regional oxygen saturation (crSO2) Infants with C-UCM have&#xD;
      higher crSO2 values during immediate neonatal transition, compared to infants without C-UCM,&#xD;
      again due to improved cerebral oxygen delivery.&#xD;
&#xD;
      Hypothesis III: C-UCM and stroke volume (SV) In infants with C-UCM the SV at 15 minutes after&#xD;
      birth is higher, compared to infants without C-UCM&#xD;
&#xD;
      Hypothesis IV: C-UCM and cardiac output (CO) In infants with C-UCM the CO at 15 minutes after&#xD;
      birth is higher, compared to infants without C-UCM.&#xD;
&#xD;
      Hypothesis V: C-UCM and mean arterial blood pressure (MABP) In infants with C-UCM the MABP at&#xD;
      5, 10 and 15 minutes after birth is higher, compared to infants without C-UCM.&#xD;
&#xD;
      Study population&#xD;
&#xD;
      Preterm infants Neonates with a gestational age ≥28 - 37 weeks delivered by caesarean section&#xD;
      at the Department of Obstetrics and Gynaecology, Medical University of Graz, will be enrolled&#xD;
      into the study, provided written informed consent is obtained from parents prior to birth.&#xD;
      Neonates with severe congenital malformations will be excluded.&#xD;
&#xD;
      Term Infants Neonates with a gestational age ≥37 weeks delivered by caesarean section at the&#xD;
      Department of Obstetrics and Gynaecology, Medical University of Graz, will be enrolled into&#xD;
      the study, provided written informed consent is obtained from parents prior to birth.&#xD;
      Neonates with severe congenital malformations will be excluded.&#xD;
&#xD;
      Study design&#xD;
&#xD;
      The present study is designed as a randomized controlled pilot trial. As there have not been&#xD;
      prior human studies investigating C-UCM regarding the outcome measures cerebral oxygenation&#xD;
      and perfusion, a randomized controlled pilot study is the appropriate first step to be able&#xD;
      to calculate sample size for a bigger trial.&#xD;
&#xD;
      Sample Size&#xD;
&#xD;
      Sample size calculations were not performed, since there are no data from previous human&#xD;
      studies available, and this pilot study needs to be conducted to generate data for the sample&#xD;
      size calculation of a consecutive main study. For this pilot study a sample size of 80&#xD;
      infants (20 subjects in the intervention group of preterm infants, 20 subjects in the&#xD;
      intervention group of term infants, 20 subjects in each of the two control groups) is&#xD;
      arbitrary designated.&#xD;
&#xD;
      Procedure&#xD;
&#xD;
      The medical history focussing on any pathologic findings during pregnancy and delivery will&#xD;
      be collected and stored anonymously.&#xD;
&#xD;
      After delivery of the neonate via caesarean section, in the intervention group the umbilical&#xD;
      cord will be clamped within 30 seconds and cut long at least 30 cm by the obstetrician. The&#xD;
      neonate is then placed under an overhead heater by the midwife. There, the umbilical cord&#xD;
      must be untwisted and held in a vertical position. It is milked once by the neonatologist&#xD;
      towards the baby at a speed of approximately 10 cm/s and then clamped 3 cm from the umbilicus&#xD;
      by one member of the clinical team. In contrast, in the control group the umbilical cord is&#xD;
      cut according to the standard procedure and no C-UCM is performed. The further treatment&#xD;
      procedure is the same in both groups.&#xD;
&#xD;
      A NIRS transducer will be placed on the newborn's left forehead, and fixed with a modified&#xD;
      neonatal CPAP cap or gauze bandage by a scientific staff member without disturbing routine&#xD;
      medical care. Furthermore, a pulse oximeter sensor will be attached on the right wrist or&#xD;
      palm to monitor preductal oxygen saturation by pulse oximetry (SpO2) and heart rate (HR).&#xD;
      Moreover 4 electrodes are fixed on the skin for the non-invasive cardiac output monitoring&#xD;
      (NICOM) to evaluate SV and CO. All the measurements will be performed within the first 15&#xD;
      minutes after birth.&#xD;
&#xD;
      Intervention The pneumatic cuff for the oscillometric measurements of the arterial blood&#xD;
      pressure will be placed around the left upper arm (or alternatively on the left lower leg) at&#xD;
      5, 10 and 15 minutes after birth. A capillary blood gas check 15 minutes after birth will be&#xD;
      performed in all the patients; However infants in need for respiratory support during&#xD;
      postnatal stabilisation receive this blood gas check routinely. Moreover, rectal temperature&#xD;
      will be measured at 15 minutes after birth.&#xD;
&#xD;
      A stopwatch is started at delivery, the time points of umbilical cord clamping, C-UCM in the&#xD;
      intervention group, establishment of NIRS measurement, establishment of SpO2 measurement, and&#xD;
      blood drawing for the gas check will be noted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2018</start_date>
  <completion_date type="Actual">November 18, 2019</completion_date>
  <primary_completion_date type="Actual">November 18, 2019</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>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral blood volume</measure>
    <time_frame>within the first 15 minutes after birth.</time_frame>
    <description>Changes in CBV (ml/100g brain)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cerebral tissue oxygenation index</measure>
    <time_frame>within the first 15 minutes after birth</time_frame>
    <description>Changes in cTOI (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral oxygen saturation</measure>
    <time_frame>within the first 15 minutes after birth</time_frame>
    <description>Changes in SpO2 (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>within the first 15 minutes after birth</time_frame>
    <description>Changes in HR (beats per minute)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke volume</measure>
    <time_frame>within the first 15 minutes after birth</time_frame>
    <description>Changes in SV (ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac output</measure>
    <time_frame>within the first 15 minutes after birth</time_frame>
    <description>Changes in CO (l/min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean arterial blood pressure</measure>
    <time_frame>within the first 15 minutes after birth</time_frame>
    <description>Changes in MABP (mmHg)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Preterm Infant</condition>
  <condition>Term Infant</condition>
  <condition>Transition</condition>
  <arm_group>
    <arm_group_label>Intervention Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Milking the cut umbilical cord once towards the Infant at a speed of 10cm/second.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The umbilical cord is cut according to the standard procedure and no C-UCM is performed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intervention Group</intervention_name>
    <description>After delivery of the neonate via caesarean section the umbilical cord will be clamped within 30 seconds and cut long at least 30 cm by the obstetrician. The neonate is then placed under an overhead heater by the midwife. There, the umbilical cord must be untwisted and held in a vertical position. It is milked once by the neonatologist towards the baby at a speed of approximately 10 cm/s and then clamped 3 cm from the umbilicus by one member of the clinical team.</description>
    <arm_group_label>Intervention Group</arm_group_label>
    <other_name>Cut umbilical cord milking (C-UCM)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control Group</intervention_name>
    <description>The umbilical cord is cut according to the standard procedure and no C-UCM is performed.</description>
    <arm_group_label>Control Group</arm_group_label>
    <other_name>Standard care</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Neonates with a gestational age ≥28 weeks&#xD;
&#xD;
          -  Delivered by caesarean section&#xD;
&#xD;
          -  Decision to conduct full life support&#xD;
&#xD;
          -  Written informed consent prior to birth&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neonates with a gestational age &lt;28 weeks&#xD;
&#xD;
          -  No decision to conduct full life support&#xD;
&#xD;
          -  No written informed consent&#xD;
&#xD;
          -  Severe congenital malformations&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Minute</minimum_age>
    <maximum_age>15 Minutes</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Berndt Urlesberger, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Neonatology, Medical University of Graz</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dep. of Pediatrics, Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <state>Styria</state>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>November 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>March 15, 2021</last_update_submitted>
  <last_update_submitted_qc>March 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</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>June 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03748914/Prot_SAP_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/NCT03748914
org study id: 30-450 ex 17/18
secondary id: U1111-1223-3280
nct id: NCT03748914
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this randomized controlled Pilot study the effects of cut-umbilical cord milking on
      cerebral oxygenation and perfusion measured via near-infrared spectroscopy (NIRS) and the
      effects on stroke volume (SV) and cardiac output (CO) also measured non-invasively in term
      and preterm infants are evaluated for the first 15 minutes after birth and compared to a
      control group.
Background

      The transition to life after birth is a complex physiological process where the neonate has
      to establish sufficient ventilation and changes from intra-uterine circulation to
      extra-uterine circulation take place. During these processes the neonate has to provide the
      brain with adequate perfusion and oxygen delivery to maintain normal cerebral tissue
      oxygenation and activity. Instability of cerebral perfusion and oxygenation may be associated
      with brain damage in preterm infants. The concept of C-UCM may substitute the adverse effects
      of immediate cord clamping by supplying additional placental blood to the infant, which is
      mostly performed during caesarean section or in the critically ill neonate.

      In this randomized controlled Pilot study the effects of cut-umbilical cord milking on
      cerebral oxygenation and perfusion measured via near-infrared spectroscopy (NIRS) and the
      effects on stroke volume (SV) and cardiac output (CO) also measured non-invasively in term
      and preterm infants are evaluated for the first 15 minutes after birth and compared to a
      control group.

      Aim

      The aim of the study is to analyse whether C-UCM in preterm and term infants results in an
      improvement of cerebral oxygenation and perfusion during immediate neonatal transition
      measured with NIRS.

      Hypotheses

      Infants undergoing C-UCM after birth compared to infants without C-UCM show differences in
      cerebral oxygenation and perfusion in the first 15 min after birth.

      Hypothesis I: C-UCM and cerebral blood volume (CBV) In infants with C-UCM there is more CBV
      decrease immediately after birth, compared to infants without C-UCM, due to improved cerebral
      oxygen delivery.

      Hypothesis II: C-UCM and cerebral regional oxygen saturation (crSO2) Infants with C-UCM have
      higher crSO2 values during immediate neonatal transition, compared to infants without C-UCM,
      again due to improved cerebral oxygen delivery.

      Hypothesis III: C-UCM and stroke volume (SV) In infants with C-UCM the SV at 15 minutes after
      birth is higher, compared to infants without C-UCM

      Hypothesis IV: C-UCM and cardiac output (CO) In infants with C-UCM the CO at 15 minutes after
      birth is higher, compared to infants without C-UCM.

      Hypothesis V: C-UCM and mean arterial blood pressure (MABP) In infants with C-UCM the MABP at
      5, 10 and 15 minutes after birth is higher, compared to infants without C-UCM.

      Study population

      Preterm infants Neonates with a gestational age ≥28 - 37 weeks delivered by caesarean section
      at the Department of Obstetrics and Gynaecology, Medical University of Graz, will be enrolled
      into the study, provided written informed consent is obtained from parents prior to birth.
      Neonates with severe congenital malformations will be excluded.

      Term Infants Neonates with a gestational age ≥37 weeks delivered by caesarean section at the
      Department of Obstetrics and Gynaecology, Medical University of Graz, will be enrolled into
      the study, provided written informed consent is obtained from parents prior to birth.
      Neonates with severe congenital malformations will be excluded.

      Study design

      The present study is designed as a randomized controlled pilot trial. As there have not been
      prior human studies investigating C-UCM regarding the outcome measures cerebral oxygenation
      and perfusion, a randomized controlled pilot study is the appropriate first step to be able
      to calculate sample size for a bigger trial.

      Sample Size

      Sample size calculations were not performed, since there are no data from previous human
      studies available, and this pilot study needs to be conducted to generate data for the sample
      size calculation of a consecutive main study. For this pilot study a sample size of 80
      infants (20 subjects in the intervention group of preterm infants, 20 subjects in the
      intervention group of term infants, 20 subjects in each of the two control groups) is
      arbitrary designated.

      Procedure

      The medical history focussing on any pathologic findings during pregnancy and delivery will
      be collected and stored anonymously.

      After delivery of the neonate via caesarean section, in the intervention group the umbilical
      cord will be clamped within 30 seconds and cut long at least 30 cm by the obstetrician. The
      neonate is then placed under an overhead heater by the midwife. There, the umbilical cord
      must be untwisted and held in a vertical position. It is milked once by the neonatologist
      towards the baby at a speed of approximately 10 cm/s and then clamped 3 cm from the umbilicus
      by one member of the clinical team. In contrast, in the control group the umbilical cord is
      cut according to the standard procedure and no C-UCM is performed. The further treatment
      procedure is the same in both groups.

      A NIRS transducer will be placed on the newborn's left forehead, and fixed with a modified
      neonatal CPAP cap or gauze bandage by a scientific staff member without disturbing routine
      medical care. Furthermore, a pulse oximeter sensor will be attached on the right wrist or
      palm to monitor preductal oxygen saturation by pulse oximetry (SpO2) and heart rate (HR).
      Moreover 4 electrodes are fixed on the skin for the non-invasive cardiac output monitoring
      (NICOM) to evaluate SV and CO. All the measurements will be performed within the first 15
      minutes after birth.

      Intervention The pneumatic cuff for the oscillometric measurements of the arterial blood
      pressure will be placed around the left upper arm (or alternatively on the left lower leg) at
      5, 10 and 15 minutes after birth. A capillary blood gas check 15 minutes after birth will be
      performed in all the patients; However infants in need for respiratory support during
      postnatal stabilisation receive this blood gas check routinely. Moreover, rectal temperature
      will be measured at 15 minutes after birth.

      A stopwatch is started at delivery, the time points of umbilical cord clamping, C-UCM in the
      intervention group, establishment of NIRS measurement, establishment of SpO2 measurement, and
      blood drawing for the gas check will be noted.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
measure: Cerebral blood volume
time frame: within the first 15 minutes after birth.
description: Changes in CBV (ml/100g brain)
measure: Cerebral tissue oxygenation index
time frame: within the first 15 minutes after birth
description: Changes in cTOI (%)
measure: Peripheral oxygen saturation
time frame: within the first 15 minutes after birth
description: Changes in SpO2 (%)
measure: Heart rate
time frame: within the first 15 minutes after birth
description: Changes in HR (beats per minute)
measure: Stroke volume
time frame: within the first 15 minutes after birth
description: Changes in SV (ml)
measure: Cardiac output
time frame: within the first 15 minutes after birth
description: Changes in CO (l/min)
measure: Mean arterial blood pressure
time frame: within the first 15 minutes after birth
description: Changes in MABP (mmHg)
arm group label: Intervention Group
arm group type: Experimental
description: Milking the cut umbilical cord once towards the Infant at a speed of 10cm/second.
arm group label: Control Group
arm group type: Active Comparator
description: The umbilical cord is cut according to the standard procedure and no C-UCM is performed.
intervention type: Other
intervention name: Intervention Group
description: After delivery of the neonate via caesarean section the umbilical cord will be clamped within 30 seconds and cut long at least 30 cm by the obstetrician. The neonate is then placed under an overhead heater by the midwife. There, the umbilical cord must be untwisted and held in a vertical position. It is milked once by the neonatologist towards the baby at a speed of approximately 10 cm/s and then clamped 3 cm from the umbilicus by one member of the clinical team.
arm group label: Intervention Group
other name: Cut umbilical cord milking (C-UCM)
intervention type: Other
intervention name: Control Group
description: The umbilical cord is cut according to the standard procedure and no C-UCM is performed.
arm group label: Control Group
other name: Standard care
criteria: 
gender: All
minimum age: 1 Minute
maximum age: 15 Minutes
healthy volunteers: Accepts Healthy Volunteers
last name: Berndt Urlesberger, Professor
role: Principal Investigator
affiliation: Division of Neonatology, Medical University of Graz
facility: 
country: Austria
responsible party type: Sponsor
mesh term: Premature Birth
sharing ipd: No
provided document: 