<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/NCT03019367</url>
  </required_header>
  <id_info>
    <org_study_id>PREMOD2</org_study_id>
    <secondary_id>1R01HD088646-01A1</secondary_id>
    <nct_id>NCT03019367</nct_id>
  </id_info>
  <brief_title>Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2</brief_title>
  <acronym>PREMOD2</acronym>
  <official_title>Premature Infants Receiving Milking or Delayed Cord Clamping: Randomized Controlled Multicenter Non-inferiority Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sharp HealthCare</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sharp Mary Birch Hospital for Women &amp; Newborns</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Loma Linda University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Providence Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College Cork</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Ulm</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Christiana Care Health Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sharp Grossmont Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Mississippi Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>PIH Health Good Samaritan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, Irvine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cook County Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St. Louis University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>LAC+USC Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sharp HealthCare</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 study is being done to find out whether umbilical cord milking (UCM) is at least as good&#xD;
      as or better than delayed cord clamping (DCC) to reduce bleeding in the brain or prevent&#xD;
      death in premature newborns. The investigators will study short and long term outcomes of&#xD;
      infants delivered before 32 weeks gestation that receive either UCM or DCC.&#xD;
&#xD;
      * The trial was stopped by the DSMB for safety in the small strata. They subsequently allowed&#xD;
      for continuation of the trial in infants 29-32+6 wk GA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim 1. Compare the incidence of severe intraventricular hemorrhage (IVH) and/or death in&#xD;
      premature newborns &lt;33 weeks gestational age (GA) delivered by C/S receiving UCM to those&#xD;
      receiving DCC.&#xD;
&#xD;
      Hypothesis1: First demonstrate infants in the UCM group are not inferior to the DCC group&#xD;
      (reject H10).&#xD;
&#xD;
      Hypothesis2: If H1 is true, demonstrate lower incidence of severe IVH and/or death in UCM&#xD;
      infants compared to DCC.&#xD;
&#xD;
      Aim 2. Compare the safety and efficacy profiles of premature newborns &lt;33 weeks GA delivered&#xD;
      by C/S receiving UCM vs. DCC during their hospitalization.&#xD;
&#xD;
      Hypothesis3: UCM group will have a decreased need for resuscitation interventions with no&#xD;
      differences in bilirubin or polycythemia compared to DCC.&#xD;
&#xD;
      Hypothesis4: UCM group will have improved blood pressures in the first 24 hours of life&#xD;
      compared to DCC.&#xD;
&#xD;
      Aim 3 (exploratory). To compare the outcomes of premature newborns &lt;33 weeks GA delivered by&#xD;
      C/S (Cesarean section) (from Aims 1 and 2) with those born by V/D (vaginal delivery)&#xD;
      receiving UCM or DCC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 6, 2017</start_date>
  <completion_date type="Actual">September 16, 2022</completion_date>
  <primary_completion_date type="Actual">September 16, 2022</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>Prevention</primary_purpose>
    <masking>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>It is not possible to blind the delivering obstetrician, however all other caregivers will be blinded. The procedure will be documented as &quot;placental transfusion&quot; in the delivery summary or admission-progress notes and all study assessments whether primary (head US) or secondary (neurodevelopmental exams) will be performed by blinded team members.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of severe IVH or death</measure>
    <time_frame>Through study completion at death or discharge, up to 6 months corrected gestational age (CGA)</time_frame>
    <description>Severe intraventricular hemorrhage of grade 3 or 4 or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All Grade IVH</measure>
    <time_frame>Through study completion at discharge, up to 6 months corrected gestational age (CGA)</time_frame>
    <description>Any intraventricular hemorrhage (grades 1-4)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe IVH (Grade 3 or 4)</measure>
    <time_frame>Through study completion at discharge, up to 6 months corrected gestational age (CGA)</time_frame>
    <description>Severe intraventricular hemorrhage (bleeding in the brain parenchyma and/or ventricular dilation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin/Hematocrit at 4 hours</measure>
    <time_frame>4 +/- 2 hours of life</time_frame>
    <description>hemoglobin/hematocrit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Severe IVH or death in infants &lt;28 weeks gestation</measure>
    <time_frame>Through study completion at discharge, up to 6 months corrected gestational age (CGA)</time_frame>
    <description>Severe intraventricular hemorrhage (grade 3 or 4) in infants born under 28 weeks gestational age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delivery room interventions</measure>
    <time_frame>In the first 10 minutes of life</time_frame>
    <description>Resuscitation interventions including positive pressure ventilation, continuous positive airway pressure, intubation, chest compressions and medications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressures in the first 24 hours of life</measure>
    <time_frame>In the first 24 hours of life</time_frame>
    <description>Blood pressure on admission, 6, 12, 18 and 24 hours of life</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1201</enrollment>
  <condition>Intraventricular Haemorrhage Neonatal</condition>
  <condition>Death; Neonatal</condition>
  <arm_group>
    <arm_group_label>Umbilical cord milking UCM</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Milking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed cord clamping DCC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Delayed clamping of the umbilical cord for at least 60 seconds.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Umbilical cord milking UCM</intervention_name>
    <description>At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before it is clamped. This procedure infuses a placental transfusion of blood into the preterm neonate and can be done in 15-20 seconds.</description>
    <arm_group_label>Umbilical cord milking UCM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Delayed cord clamping DCC</intervention_name>
    <description>At delivery, delayed cord clamping will be performed by having the delivering obstetrician delay clamping of the umbilical cord for at least 60 seconds.</description>
    <arm_group_label>Delayed cord clamping DCC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  23 to 32 +6 Gestational age (currently enrolling 29 to 32+6 weeks)&#xD;
&#xD;
          -  Multiples without Twin-to-twin Transfusion Syndrome (TTTS)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Congenital anomalies&#xD;
&#xD;
          -  Major cardiac defects&#xD;
&#xD;
          -  Placental abruption or previa with hemorrhage&#xD;
&#xD;
          -  Cord prolapse&#xD;
&#xD;
          -  Hydrops&#xD;
&#xD;
          -  Bleeding Accreta&#xD;
&#xD;
          -  Monochorionic multiples with evidence of TTTS&#xD;
&#xD;
          -  Fetal or maternal risk (i.e. compromise)&#xD;
&#xD;
          -  Parents declined study&#xD;
&#xD;
          -  Unlikely to return for 2 yr Follow Up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>23 Weeks</minimum_age>
    <maximum_age>33 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anup C Katheria, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sharp HealthCare</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-0004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loma Linda Medical Center</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92350</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LAC+USC Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PIH Health Good Samaritan Hospital</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Grossmont Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>91942</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Mary Birch Hospital for Women and Newborns</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John H. Stroger, Jr. Hospital of Cook County</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence St. Vincent Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97225-6603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee-Womens Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Governors of University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2R3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of ULM</name>
      <address>
        <city>Ulm</city>
        <state>Baden-Wurttemberg</state>
        <zip>89075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cork University Maternity Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.premod2.org</url>
    <description>Website for trial</description>
  </link>
  <link>
    <url>https://clinicaltrials.gov/show/NCT03145142</url>
    <description>NIRS Sub-study PREMOD2</description>
  </link>
  <link>
    <url>http://clinicaltrials.gov/show/nct03476980</url>
    <description>Followup Study-PREMOD2</description>
  </link>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sharp HealthCare</investigator_affiliation>
    <investigator_full_name>Anup Katheria, M.D.</investigator_full_name>
    <investigator_title>Director of Neonatal Research Institute</investigator_title>
  </responsible_party>
  <keyword>Premature infants</keyword>
  <keyword>Umbilical cord milking</keyword>
  <keyword>Delayed cord clamping</keyword>
  <keyword>Intraventricular Hemorrhage</keyword>
  <keyword>Death</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be made available per NICHD requirements (National Institute of Child Health and Human Development).</ipd_description>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>2 years after primary publication</ipd_time_frame>
    <ipd_access_criteria>An archived dataset with documentation will be made available for additional uses by outside investigators, in collaboration with the study investigators. We will work with NICHD program staff to develop a broad data sharing plan over time.</ipd_access_criteria>
  </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/NCT03019367
org study id: PREMOD2
secondary id: 1R01HD088646-01A1
nct id: NCT03019367
lead sponsor: 
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has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is being done to find out whether umbilical cord milking (UCM) is at least as good
      as or better than delayed cord clamping (DCC) to reduce bleeding in the brain or prevent
      death in premature newborns. The investigators will study short and long term outcomes of
      infants delivered before 32 weeks gestation that receive either UCM or DCC.

      * The trial was stopped by the DSMB for safety in the small strata. They subsequently allowed
      for continuation of the trial in infants 29-32+6 wk GA.
Aim 1. Compare the incidence of severe intraventricular hemorrhage (IVH) and/or death in
      premature newborns <33 weeks gestational age (GA) delivered by C/S receiving UCM to those
      receiving DCC.

      Hypothesis1: First demonstrate infants in the UCM group are not inferior to the DCC group
      (reject H10).

      Hypothesis2: If H1 is true, demonstrate lower incidence of severe IVH and/or death in UCM
      infants compared to DCC.

      Aim 2. Compare the safety and efficacy profiles of premature newborns <33 weeks GA delivered
      by C/S receiving UCM vs. DCC during their hospitalization.

      Hypothesis3: UCM group will have a decreased need for resuscitation interventions with no
      differences in bilirubin or polycythemia compared to DCC.

      Hypothesis4: UCM group will have improved blood pressures in the first 24 hours of life
      compared to DCC.

      Aim 3 (exploratory). To compare the outcomes of premature newborns <33 weeks GA delivered by
      C/S (Cesarean section) (from Aims 1 and 2) with those born by V/D (vaginal delivery)
      receiving UCM or DCC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
masking description: It is not possible to blind the delivering obstetrician, however all other caregivers will be blinded. The procedure will be documented as "placental transfusion" in the delivery summary or admission-progress notes and all study assessments whether primary (head US) or secondary (neurodevelopmental exams) will be performed by blinded team members.
measure: Incidence of severe IVH or death
time frame: Through study completion at death or discharge, up to 6 months corrected gestational age (CGA)
description: Severe intraventricular hemorrhage of grade 3 or 4 or death
measure: All Grade IVH
time frame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
description: Any intraventricular hemorrhage (grades 1-4)
measure: Severe IVH (Grade 3 or 4)
time frame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
description: Severe intraventricular hemorrhage (bleeding in the brain parenchyma and/or ventricular dilation)
measure: Hemoglobin/Hematocrit at 4 hours
time frame: 4 +/- 2 hours of life
description: hemoglobin/hematocrit
measure: Incidence of Severe IVH or death in infants <28 weeks gestation
time frame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
description: Severe intraventricular hemorrhage (grade 3 or 4) in infants born under 28 weeks gestational age
measure: Delivery room interventions
time frame: In the first 10 minutes of life
description: Resuscitation interventions including positive pressure ventilation, continuous positive airway pressure, intubation, chest compressions and medications
measure: Blood pressures in the first 24 hours of life
time frame: In the first 24 hours of life
description: Blood pressure on admission, 6, 12, 18 and 24 hours of life
arm group label: Umbilical cord milking UCM
arm group type: Active Comparator
description: Milking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds.
arm group label: Delayed cord clamping DCC
arm group type: Active Comparator
description: Delayed clamping of the umbilical cord for at least 60 seconds.
intervention type: Procedure
intervention name: Umbilical cord milking UCM
description: At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before it is clamped. This procedure infuses a placental transfusion of blood into the preterm neonate and can be done in 15-20 seconds.
arm group label: Umbilical cord milking UCM
intervention type: Procedure
intervention name: Delayed cord clamping DCC
description: At delivery, delayed cord clamping will be performed by having the delivering obstetrician delay clamping of the umbilical cord for at least 60 seconds.
arm group label: Delayed cord clamping DCC
criteria: 
gender: All
minimum age: 23 Weeks
maximum age: 33 Weeks
healthy volunteers: No
last name: Anup C Katheria, MD
role: Principal Investigator
affiliation: Sharp HealthCare
facility: 
facility: 
facility: 
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country: Canada
country: Germany
country: Ireland
country: United States
url: http://www.premod2.org
description: Website for trial
url: https://clinicaltrials.gov/show/NCT03145142
description: NIRS Sub-study PREMOD2
url: http://clinicaltrials.gov/show/nct03476980
description: Followup Study-PREMOD2
responsible party type: Principal Investigator
investigator affiliation: Sharp HealthCare
investigator full name: Anup Katheria, M.D.
investigator title: Director of Neonatal Research Institute
mesh term: Premature Birth
mesh term: Hemorrhage
sharing ipd: Yes
ipd description: Data will be made available per NICHD requirements (National Institute of Child Health and Human Development).
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: 2 years after primary publication
ipd access criteria: An archived dataset with documentation will be made available for additional uses by outside investigators, in collaboration with the study investigators. We will work with NICHD program staff to develop a broad data sharing plan over time.