<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/NCT02221219</url>
  </required_header>
  <id_info>
    <org_study_id>HD070792</org_study_id>
    <secondary_id>R01HD070792</secondary_id>
    <nct_id>NCT02221219</nct_id>
  </id_info>
  <brief_title>Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury</brief_title>
  <official_title>Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hong Huang</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) are brain lesions&#xD;
      that commonly occur in preterm infants and are well-recognized major contributors to&#xD;
      long-term brain injury and related disabilities later in life. Despite its prevalence, long&#xD;
      term consequences, and enormous medical and social costs, mechanisms of IVH and optimal&#xD;
      strategies to prevent or treat its occurrence are poorly defined, especially for extremely&#xD;
      premature infants. Only one medical therapy, prophylactic indomethacin during the first 3&#xD;
      days of life, has been shown to prevent or decrease the severity of IVH in preterm infants,&#xD;
      but its use is limited by toxic side effects and debatable effects on long-term outcomes.&#xD;
      Several small studies and case reports suggest that delayed umbilical cord-clamping (DCC) may&#xD;
      also decrease the incidence of IVH in premature infants, but thus far these trials have&#xD;
      indomethacin treatment mixed within their cord clamping protocols. The investigators are&#xD;
      conducting a randomized, blinded investigation of 4 treatment groups: 1) Control (no&#xD;
      intervention); 2) DCC alone; 3) Prophylactic indomethacin alone; 4) Combination of&#xD;
      DCC/indomethacin, with respect to survival, IVH or PVL incidence and severity,&#xD;
      neurodevelopmental outcomes, and relevant mechanistic effects. With the steady rise in&#xD;
      extreme prematurity births and clear links of IVH to long-term disabilities there is a need&#xD;
      to improve care for these patients. This multi- disciplinary project addresses an important&#xD;
      medical problem for an understudied patient population, where the current practice has clear&#xD;
      limitations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will compare efficacy and safety of prophylactic indomethacin, DCC, and&#xD;
      their combination, in affecting the incidence and severity of IVH/PVL in infants &lt;30wks&#xD;
      gestational age (primary outcome measure of 'fraction of survivors with no severe IVH or PVL'&#xD;
      among the 4 groups), and longer term neurocognitive function. Other secondary endpoints and&#xD;
      investigations include mechanistic effects of prophylactic indomethacin, DCC, and their&#xD;
      combination (blood volume/circulatory status, inflammatory stress, progenitor cells) as well&#xD;
      as defining relationships between clinical outcomes and mechanistic measurements among&#xD;
      treatment groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">August 28, 2021</completion_date>
  <primary_completion_date type="Actual">October 27, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL</measure>
    <time_frame>within first 60 days of life</time_frame>
    <description>determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Acute Kidney Injury</measure>
    <time_frame>first 60 days of life</time_frame>
    <description>measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Hematological Status</measure>
    <time_frame>first 60 days of life</time_frame>
    <description>hematocrit, ferritin, hemoglobin at various times during NICU stay</description>
  </other_outcome>
  <other_outcome>
    <measure>Inflammatory Stress</measure>
    <time_frame>first 60 days of life</time_frame>
    <description>measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay</description>
  </other_outcome>
  <other_outcome>
    <measure>Circulating Progenitor Cell Subpopulations</measure>
    <time_frame>first 60 days of life</time_frame>
    <description>measures of several progenitor cell subtypes in blood during the NICU stay</description>
  </other_outcome>
  <other_outcome>
    <measure>Neurocognitive Assessments at Post-NICU Followup</measure>
    <time_frame>up to 24 months of corrected gestational age</time_frame>
    <description>standardized neurocognitive assessments done at NICU graduate clinic.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">256</enrollment>
  <condition>Intraventricular Hemorrhage</condition>
  <condition>Periventricular Leukomalacia</condition>
  <condition>Brain Injury</condition>
  <condition>Renal Injury</condition>
  <arm_group>
    <arm_group_label>immediate cord clamp &amp; placebo IV solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>delay cord clamp &amp; placebo IV solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>immediate cord clamp &amp; indomethacin IV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>indomethacin iv &amp; delayed cord clamp</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indomethacin</intervention_name>
    <description>indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants</description>
    <arm_group_label>immediate cord clamp &amp; indomethacin IV</arm_group_label>
    <arm_group_label>indomethacin iv &amp; delayed cord clamp</arm_group_label>
    <other_name>indocin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>delay in umbilical cord clamp at birth</intervention_name>
    <description>provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)</description>
    <arm_group_label>delay cord clamp &amp; placebo IV solution</arm_group_label>
    <arm_group_label>indomethacin iv &amp; delayed cord clamp</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo infusion</intervention_name>
    <description>saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)</description>
    <arm_group_label>delay cord clamp &amp; placebo IV solution</arm_group_label>
    <arm_group_label>immediate cord clamp &amp; placebo IV solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>immediate cord clamp at birth</intervention_name>
    <description>no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
    <arm_group_label>immediate cord clamp &amp; indomethacin IV</arm_group_label>
    <arm_group_label>immediate cord clamp &amp; placebo IV solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pregnant women admitted &gt;24weeks and &lt;30weeks gestational age,&#xD;
&#xD;
          -  in-hospital birth (allowing for cord clamp randomization)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  preterm infant &lt;24weeks or &gt;30weeks at birth&#xD;
&#xD;
          -  maternal risks identified by obstetrician&#xD;
&#xD;
          -  fetal risks identified by obstetrician&#xD;
&#xD;
          -  any congenital abnormality of newborn infant&#xD;
&#xD;
          -  placental abruption/placental previa&#xD;
&#xD;
          -  delivery less than 2hrs from consenting to study participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>24 Weeks</minimum_age>
    <maximum_age>30 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vicki Whitehead, RN</last_name>
    <role>Study Director</role>
    <affiliation>UK Section of Neonatology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Bauer, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UK Department of Pediatrics</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hong Huang, MD-PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Kentucky Section of Neonatology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kentucky Childrens Hospital Neonatal Intensive Care Unit</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <results_first_submitted>November 13, 2020</results_first_submitted>
  <results_first_submitted_qc>November 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 8, 2020</results_first_posted>
  <last_update_submitted>October 28, 2021</last_update_submitted>
  <last_update_submitted_qc>October 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Hong Huang</investigator_full_name>
    <investigator_title>Research Protocol Manager/Clinical/UKHC</investigator_title>
  </responsible_party>
  <keyword>infant</keyword>
  <keyword>brain injury</keyword>
  <keyword>renal</keyword>
  <keyword>indomethacin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Leukomalacia, Periventricular</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Indomethacin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 15, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT02221219/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Immediate Cord Clamp &amp; Placebo IV Solution</title>
          <description>This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
        </group>
        <group group_id="P2">
          <title>Delay Cord Clamp &amp; Placebo IV Solution</title>
          <description>A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)</description>
        </group>
        <group group_id="P3">
          <title>Immediate Cord Clamp &amp; Indomethacin IV</title>
          <description>Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
        </group>
        <group group_id="P4">
          <title>Indomethacin iv &amp; Delayed Cord Clamp</title>
          <description>A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="87"/>
                <participants group_id="P3" count="41"/>
                <participants group_id="P4" count="92"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="87"/>
                <participants group_id="P3" count="41"/>
                <participants group_id="P4" count="92"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Immediate Cord Clamp &amp; Placebo IV Solution</title>
          <description>This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
        </group>
        <group group_id="B2">
          <title>Delay Cord Clamp &amp; Placebo IV Solution</title>
          <description>A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)</description>
        </group>
        <group group_id="B3">
          <title>Immediate Cord Clamp &amp; Indomethacin IV</title>
          <description>Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
        </group>
        <group group_id="B4">
          <title>Indomethacin iv &amp; Delayed Cord Clamp</title>
          <description>A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="36"/>
            <count group_id="B2" value="87"/>
            <count group_id="B3" value="41"/>
            <count group_id="B4" value="92"/>
            <count group_id="B5" value="256"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.2" spread="1.8"/>
                    <measurement group_id="B2" value="26.6" spread="2.0"/>
                    <measurement group_id="B3" value="26.6" spread="1.8"/>
                    <measurement group_id="B4" value="26.4" spread="1.8"/>
                    <measurement group_id="B5" value="26.5" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="47"/>
                    <measurement group_id="B5" value="132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="45"/>
                    <measurement group_id="B5" value="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="84"/>
                    <measurement group_id="B3" value="39"/>
                    <measurement group_id="B4" value="90"/>
                    <measurement group_id="B5" value="245"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="74"/>
                    <measurement group_id="B3" value="36"/>
                    <measurement group_id="B4" value="76"/>
                    <measurement group_id="B5" value="213"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="87"/>
                    <measurement group_id="B3" value="41"/>
                    <measurement group_id="B4" value="92"/>
                    <measurement group_id="B5" value="256"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Birth Weight</title>
          <units>grams</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="797.2" spread="267.4"/>
                    <measurement group_id="B2" value="935.1" spread="295.0"/>
                    <measurement group_id="B3" value="902.4" spread="369.8"/>
                    <measurement group_id="B4" value="916.8" spread="254.8"/>
                    <measurement group_id="B5" value="903.9" spread="291.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL</title>
        <description>determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age</description>
        <time_frame>within first 60 days of life</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Immediate Cord Clamp &amp; Placebo IV Solution</title>
            <description>This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
          </group>
          <group group_id="O2">
            <title>Delay Cord Clamp &amp; Placebo IV Solution</title>
            <description>A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)</description>
          </group>
          <group group_id="O3">
            <title>Immediate Cord Clamp &amp; Indomethacin IV</title>
            <description>Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
          </group>
          <group group_id="O4">
            <title>Indomethacin iv &amp; Delayed Cord Clamp</title>
            <description>A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL</title>
          <description>determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age</description>
          <units>percent of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="87"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.2"/>
                    <measurement group_id="O2" value="14.9"/>
                    <measurement group_id="O3" value="17.1"/>
                    <measurement group_id="O4" value="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Acute Kidney Injury</title>
        <description>measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population).</description>
        <time_frame>first 60 days of life</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Immediate Cord Clamp &amp; Placebo IV Solution</title>
            <description>This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
          </group>
          <group group_id="O2">
            <title>Delay Cord Clamp &amp; Placebo IV Solution</title>
            <description>A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)</description>
          </group>
          <group group_id="O3">
            <title>Immediate Cord Clamp &amp; Indomethacin IV</title>
            <description>Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
          </group>
          <group group_id="O4">
            <title>Indomethacin iv &amp; Delayed Cord Clamp</title>
            <description>A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Acute Kidney Injury</title>
          <description>measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population).</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="87"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No acute kidney injury</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="48"/>
                    <measurement group_id="O3" value="23"/>
                    <measurement group_id="O4" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1 Acute Kidney Injury</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="27"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2 Acute Kidney Injury</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 Acute Kidney Injury</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Acute Kidney Injury</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hematological Status</title>
        <description>hematocrit, ferritin, hemoglobin at various times during NICU stay</description>
        <time_frame>first 60 days of life</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Inflammatory Stress</title>
        <description>measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay</description>
        <time_frame>first 60 days of life</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Circulating Progenitor Cell Subpopulations</title>
        <description>measures of several progenitor cell subtypes in blood during the NICU stay</description>
        <time_frame>first 60 days of life</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Neurocognitive Assessments at Post-NICU Followup</title>
        <description>standardized neurocognitive assessments done at NICU graduate clinic.</description>
        <time_frame>up to 24 months of corrected gestational age</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>First 60 days of life.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Immediate Cord Clamp &amp; Placebo IV Solution</title>
          <description>This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
        </group>
        <group group_id="E2">
          <title>Delay Cord Clamp &amp; Placebo IV Solution</title>
          <description>A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)&#xD;
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)</description>
        </group>
        <group group_id="E3">
          <title>Immediate Cord Clamp &amp; Indomethacin IV</title>
          <description>Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
immediate cord clamp at birth: no delay in umbilical cord clamp; &lt;10sec (recorded in delivery note)</description>
        </group>
        <group group_id="E4">
          <title>Indomethacin iv &amp; Delayed Cord Clamp</title>
          <description>A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.&#xD;
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants&#xD;
delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="87"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="87"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Septic Shock</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="87"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Necrotizing Enterocolitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="87"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Bowel Perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="87"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Multiorgan Failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="87"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>CMV</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="87"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Extreme Prematurity</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="36"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="87"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Free Air in Abdomen</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="87"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="87"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="87"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Research Protocol Manager/Clinical/UKHC</name_or_title>
      <organization>University of Kentucky</organization>
      <phone>(859) 257-1000</phone>
      <email>hong.huang@uky.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02221219
org study id: HD070792
secondary id: R01HD070792
nct id: NCT02221219
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) are brain lesions
      that commonly occur in preterm infants and are well-recognized major contributors to
      long-term brain injury and related disabilities later in life. Despite its prevalence, long
      term consequences, and enormous medical and social costs, mechanisms of IVH and optimal
      strategies to prevent or treat its occurrence are poorly defined, especially for extremely
      premature infants. Only one medical therapy, prophylactic indomethacin during the first 3
      days of life, has been shown to prevent or decrease the severity of IVH in preterm infants,
      but its use is limited by toxic side effects and debatable effects on long-term outcomes.
      Several small studies and case reports suggest that delayed umbilical cord-clamping (DCC) may
      also decrease the incidence of IVH in premature infants, but thus far these trials have
      indomethacin treatment mixed within their cord clamping protocols. The investigators are
      conducting a randomized, blinded investigation of 4 treatment groups: 1) Control (no
      intervention); 2) DCC alone; 3) Prophylactic indomethacin alone; 4) Combination of
      DCC/indomethacin, with respect to survival, IVH or PVL incidence and severity,
      neurodevelopmental outcomes, and relevant mechanistic effects. With the steady rise in
      extreme prematurity births and clear links of IVH to long-term disabilities there is a need
      to improve care for these patients. This multi- disciplinary project addresses an important
      medical problem for an understudied patient population, where the current practice has clear
      limitations.
The investigators will compare efficacy and safety of prophylactic indomethacin, DCC, and
      their combination, in affecting the incidence and severity of IVH/PVL in infants <30wks
      gestational age (primary outcome measure of 'fraction of survivors with no severe IVH or PVL'
      among the 4 groups), and longer term neurocognitive function. Other secondary endpoints and
      investigations include mechanistic effects of prophylactic indomethacin, DCC, and their
      combination (blood volume/circulatory status, inflammatory stress, progenitor cells) as well
      as defining relationships between clinical outcomes and mechanistic measurements among
      treatment groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL
time frame: within first 60 days of life
description: determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age
measure: Number of Participants With Acute Kidney Injury
time frame: first 60 days of life
description: measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population).
measure: Hematological Status
time frame: first 60 days of life
description: hematocrit, ferritin, hemoglobin at various times during NICU stay
measure: Inflammatory Stress
time frame: first 60 days of life
description: measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay
measure: Circulating Progenitor Cell Subpopulations
time frame: first 60 days of life
description: measures of several progenitor cell subtypes in blood during the NICU stay
measure: Neurocognitive Assessments at Post-NICU Followup
time frame: up to 24 months of corrected gestational age
description: standardized neurocognitive assessments done at NICU graduate clinic.
arm group label: immediate cord clamp & placebo IV solution
arm group type: Placebo Comparator
description: This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
arm group label: delay cord clamp & placebo IV solution
arm group type: Experimental
description: A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
arm group label: immediate cord clamp & indomethacin IV
arm group type: Active Comparator
description: Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
arm group label: indomethacin iv & delayed cord clamp
arm group type: Experimental
description: A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
intervention type: Drug
intervention name: Indomethacin
description: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
arm group label: immediate cord clamp & indomethacin IV
arm group label: indomethacin iv & delayed cord clamp
other name: indocin
intervention type: Procedure
intervention name: delay in umbilical cord clamp at birth
description: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)
arm group label: delay cord clamp & placebo IV solution
arm group label: indomethacin iv & delayed cord clamp
intervention type: Drug
intervention name: placebo infusion
description: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
arm group label: delay cord clamp & placebo IV solution
arm group label: immediate cord clamp & placebo IV solution
intervention type: Procedure
intervention name: immediate cord clamp at birth
description: no delay in umbilical cord clamp; <10sec (recorded in delivery note)
arm group label: immediate cord clamp & indomethacin IV
arm group label: immediate cord clamp & placebo IV solution
criteria: 
gender: All
minimum age: 24 Weeks
maximum age: 30 Weeks
healthy volunteers: No
last name: Vicki Whitehead, RN
role: Study Director
affiliation: UK Section of Neonatology
last name: John Bauer, PhD
role: Principal Investigator
affiliation: UK Department of Pediatrics
last name: Hong Huang, MD-PhD
role: Study Director
affiliation: University of Kentucky Section of Neonatology
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Hong Huang
investigator title: Research Protocol Manager/Clinical/UKHC
mesh term: Brain Injuries
mesh term: Leukomalacia, Periventricular
mesh term: Hemorrhage
mesh term: Wounds and Injuries
mesh term: Indomethacin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 