<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/NCT02987764</url>
  </required_header>
  <id_info>
    <org_study_id>15-001134</org_study_id>
    <nct_id>NCT02987764</nct_id>
  </id_info>
  <brief_title>Cord Milking Impacts Neurodevelopmental Outcomes in Very Low Birth Weight Infants</brief_title>
  <acronym>Cordmilking</acronym>
  <official_title>Neurodevelopmental Outcomes of Cord Milking in Preterm Infants: Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Premature birth is a major risk factor for perinatal brain damage and cerebral palsy (CP)&#xD;
      with 47% of all CP cases occurring in infants with birth weight less than 2500 g. CP has&#xD;
      life-long neurological consequences that affect quality of life for the patient. In the last&#xD;
      2 decades, improvements in neonatal intensive care have improved survival of VLBW infants&#xD;
      significantly. This increased survival of VLBW infants poses new challenges towards&#xD;
      developing novel treatments and interventions to decrease neurodevelopmental impairment and&#xD;
      CP. While it is common for extremely preterm infant to survive at 23 weeks of gestation, the&#xD;
      neurologic consequences range from learning difficulties and cognitive defects to severe&#xD;
      disability and cerebral palsy. Currently prenatal neuroprotective agents such as&#xD;
      corticosteroids are utilized whenever a preterm birth is anticipated. However, there are no&#xD;
      proven postnatal interventions to prevent brain damage and cerebral palsy in VLBW infants.&#xD;
&#xD;
      Many recent studies show that delaying umbilical cord clamping (DCC) may improve hemodynamic&#xD;
      stability and decrease intraventricular hemorrhage (IVH) in preterm infants. A decrease in&#xD;
      incidence of IVH has a conceivable prospective benefit of decreasing brain injury and&#xD;
      improving long-term outcomes. Based on these findings, the American College of Obstetricians&#xD;
      and Gynecologist and American Academy of Pediatrics endorse that DCC may benefit the preterm&#xD;
      infants. However, these recommendations have not been adopted by most obstetricians in USA.&#xD;
      The main concern regarding the practice of DCC is the care delay in initiating resuscitation&#xD;
      and providing the needed care to this vulnerable population.&#xD;
&#xD;
      Therefore, as an alternative to DCC, method of cord milking (CM) has been developed to&#xD;
      provide cord blood transfusion to premature infants. CM offers a more practical alternative&#xD;
      to delayed cord clamping that may provide the same benefits without the need to delay&#xD;
      resuscitation. However, there are very few studies of CM in VLBW infants and there is no&#xD;
      evidence demonstrating long-term neurological outcomes and CP after CM.&#xD;
&#xD;
      The investigators hypothesize that cord milking in VLBW infants will result in improving&#xD;
      cerebral oxygenation, function and result in improved long-term neurodevelopmental outcomes&#xD;
      at 2 years of post-menstrual age. Premature infants born at less than or equal to 32 weeks&#xD;
      gestation age will receive cord milking after cutting versus standard care of immediate cord&#xD;
      clamping.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Aims&#xD;
&#xD;
      To Measure:&#xD;
&#xD;
        1. Cerebral oxygenation and function (aEEG abnormalities) in first 24 hours of life&#xD;
&#xD;
        2. Neurodevelopmental outcomes at 18 - 24 months PMA Secondary Aims&#xD;
&#xD;
      1. Assessment of Improved transition: Delivery room resuscitation, Apgar scores, acidosis&#xD;
      from cord gas or first hour blood gas 2. Neurological injury assessment: IVH/PVIH/PVL on head&#xD;
      ultrasound on day #3-5 and day #7-14, and at 36 wk PMA, MRI at 36 wk CGA 3. CVS response:&#xD;
      Blood pressure and ionotropic support in first 3-5 days 4. Hematological assessment:&#xD;
      Hemoglobin, Hematocrit of admission, and first 72 hours of life, need for phototherapy and&#xD;
      highest bilirubin level in first 7 days, blood transfusions needed till 36 wk PMA 5.&#xD;
      Gastrointestinal protection: Necrotizing enterocolitis till 36 wk PMA In this pilot study, we&#xD;
      plan to enroll 15 VLBW infants in each group (n=30) from Mattel Children's Hospital and Santa&#xD;
      Monica Hospital labor and delivery. Data pertaining to primary and secondary aims will be&#xD;
      obtained from EMR. Follow up utilizing Bayley's scores of infant development (BSID III) will&#xD;
      be scheduled at 18-22 months PMA&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Subject recruitment and enrollment was low throughout the three years the study was active.&#xD;
  </why_stopped>
  <start_date>May 2016</start_date>
  <completion_date type="Actual">May 15, 2018</completion_date>
  <primary_completion_date type="Actual">May 15, 2018</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>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measure Cerebral oxygenation and function</measure>
    <time_frame>First 24 hours of life</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Apgar Scores</measure>
    <time_frame>1 and 5 minutes</time_frame>
    <description>Basic score to measure the newborn status. From 0 to 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological injury assessment</measure>
    <time_frame>Days 3-5 and at 36 weeks postmenstrual age</time_frame>
    <description>Head ultrasound on day #3-5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological injury assessment</measure>
    <time_frame>weeks postmenstrual age</time_frame>
    <description>MRI at 36 wk CGA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematological assessment</measure>
    <time_frame>First 72 hours of life</time_frame>
    <description>Hematocrit of admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal protection</measure>
    <time_frame>36 weeks postmenstrual age</time_frame>
    <description>Necrotizing enterocolitis till 36 wk PMA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure Neurodevelopmental impairment</measure>
    <time_frame>18-24 months postmenstrual age</time_frame>
    <description>Outcome assessments will be conducted by physicians or nurse practitioners or occupation therapist specializing in neonatal follow-up examination using Bayley Scales of Infant Development III</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Very Low Birth Weight Infant</condition>
  <arm_group>
    <arm_group_label>Cord Milking</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The research team member will untwist the cord, and hold it in a vertical position. The cord will then be milked twice towards the abdominal insertion of the cord. The cord will be cut 1 inch above the abdominal wall. After milking for exact measurement of the cord will be obtained.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observational</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Observational infants will receive usual care with immediate cord clamping by the delivering obstetrician. The time of cord clamping will be recorded for both groups using a timer.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>cord milking</intervention_name>
    <description>For infants in the cord milking group, the cord will be clamped at the longest distance possible and neonatal team will bring the infant to the resuscitation table for further care. The clinical care will be provided by the clinicians taking care of the infant. The research team will be trained and be responsible for requesting the obstetrician in advance to provide the maximum length of umbilical cord.</description>
    <arm_group_label>Cord Milking</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Expected delivery at &lt;32 week GA.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Prenatal diagnosis of chromosomal or severe congenital malformations such as&#xD;
             cyanotic congenital heart disease 2. Cord accidents such as ruptured Vasa Previa&#xD;
             results in fetal blood loss, need for urgent delivery, placental abruption and cord&#xD;
             prolapse 3. considered non-viable by attending neonatologist or obstetrician 4.&#xD;
             Consent not granted&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>32 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mattel Children's Hospital UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>October 10, 2018</last_update_submitted>
  <last_update_submitted_qc>October 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Meena Garg, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Premature</keyword>
  <keyword>Birth weight</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Birth Weight</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/NCT02987764
org study id: 15-001134
nct id: NCT02987764
lead sponsor: 
has dmc: No
Premature birth is a major risk factor for perinatal brain damage and cerebral palsy (CP)
      with 47% of all CP cases occurring in infants with birth weight less than 2500 g. CP has
      life-long neurological consequences that affect quality of life for the patient. In the last
      2 decades, improvements in neonatal intensive care have improved survival of VLBW infants
      significantly. This increased survival of VLBW infants poses new challenges towards
      developing novel treatments and interventions to decrease neurodevelopmental impairment and
      CP. While it is common for extremely preterm infant to survive at 23 weeks of gestation, the
      neurologic consequences range from learning difficulties and cognitive defects to severe
      disability and cerebral palsy. Currently prenatal neuroprotective agents such as
      corticosteroids are utilized whenever a preterm birth is anticipated. However, there are no
      proven postnatal interventions to prevent brain damage and cerebral palsy in VLBW infants.

      Many recent studies show that delaying umbilical cord clamping (DCC) may improve hemodynamic
      stability and decrease intraventricular hemorrhage (IVH) in preterm infants. A decrease in
      incidence of IVH has a conceivable prospective benefit of decreasing brain injury and
      improving long-term outcomes. Based on these findings, the American College of Obstetricians
      and Gynecologist and American Academy of Pediatrics endorse that DCC may benefit the preterm
      infants. However, these recommendations have not been adopted by most obstetricians in USA.
      The main concern regarding the practice of DCC is the care delay in initiating resuscitation
      and providing the needed care to this vulnerable population.

      Therefore, as an alternative to DCC, method of cord milking (CM) has been developed to
      provide cord blood transfusion to premature infants. CM offers a more practical alternative
      to delayed cord clamping that may provide the same benefits without the need to delay
      resuscitation. However, there are very few studies of CM in VLBW infants and there is no
      evidence demonstrating long-term neurological outcomes and CP after CM.

      The investigators hypothesize that cord milking in VLBW infants will result in improving
      cerebral oxygenation, function and result in improved long-term neurodevelopmental outcomes
      at 2 years of post-menstrual age. Premature infants born at less than or equal to 32 weeks
      gestation age will receive cord milking after cutting versus standard care of immediate cord
      clamping.
Primary Aims

      To Measure:

        1. Cerebral oxygenation and function (aEEG abnormalities) in first 24 hours of life

        2. Neurodevelopmental outcomes at 18 - 24 months PMA Secondary Aims

      1. Assessment of Improved transition: Delivery room resuscitation, Apgar scores, acidosis
      from cord gas or first hour blood gas 2. Neurological injury assessment: IVH/PVIH/PVL on head
      ultrasound on day #3-5 and day #7-14, and at 36 wk PMA, MRI at 36 wk CGA 3. CVS response:
      Blood pressure and ionotropic support in first 3-5 days 4. Hematological assessment:
      Hemoglobin, Hematocrit of admission, and first 72 hours of life, need for phototherapy and
      highest bilirubin level in first 7 days, blood transfusions needed till 36 wk PMA 5.
      Gastrointestinal protection: Necrotizing enterocolitis till 36 wk PMA In this pilot study, we
      plan to enroll 15 VLBW infants in each group (n=30) from Mattel Children's Hospital and Santa
      Monica Hospital labor and delivery. Data pertaining to primary and secondary aims will be
      obtained from EMR. Follow up utilizing Bayley's scores of infant development (BSID III) will
      be scheduled at 18-22 months PMA
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Measure Cerebral oxygenation and function
time frame: First 24 hours of life
measure: Apgar Scores
time frame: 1 and 5 minutes
description: Basic score to measure the newborn status. From 0 to 10.
measure: Neurological injury assessment
time frame: Days 3-5 and at 36 weeks postmenstrual age
description: Head ultrasound on day #3-5
measure: Neurological injury assessment
time frame: weeks postmenstrual age
description: MRI at 36 wk CGA
measure: Hematological assessment
time frame: First 72 hours of life
description: Hematocrit of admission
measure: Gastrointestinal protection
time frame: 36 weeks postmenstrual age
description: Necrotizing enterocolitis till 36 wk PMA
measure: Measure Neurodevelopmental impairment
time frame: 18-24 months postmenstrual age
description: Outcome assessments will be conducted by physicians or nurse practitioners or occupation therapist specializing in neonatal follow-up examination using Bayley Scales of Infant Development III
arm group label: Cord Milking
arm group type: Experimental
description: The research team member will untwist the cord, and hold it in a vertical position. The cord will then be milked twice towards the abdominal insertion of the cord. The cord will be cut 1 inch above the abdominal wall. After milking for exact measurement of the cord will be obtained.
arm group label: Observational
arm group type: No Intervention
description: Observational infants will receive usual care with immediate cord clamping by the delivering obstetrician. The time of cord clamping will be recorded for both groups using a timer.
intervention type: Other
intervention name: cord milking
description: For infants in the cord milking group, the cord will be clamped at the longest distance possible and neonatal team will bring the infant to the resuscitation table for further care. The clinical care will be provided by the clinicians taking care of the infant. The research team will be trained and be responsible for requesting the obstetrician in advance to provide the maximum length of umbilical cord.
arm group label: Cord Milking
criteria: 
gender: All
minimum age: N/A
maximum age: 32 Weeks
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Meena Garg, MD
investigator title: Principal Investigator
mesh term: Birth Weight
sharing ipd: No