<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/NCT03764813</url>
  </required_header>
  <id_info>
    <org_study_id>22139/18ID:1916</org_study_id>
    <nct_id>NCT03764813</nct_id>
  </id_info>
  <brief_title>Cord Blood Transfusion In Preterm Neonates (CB-TrIP)</brief_title>
  <acronym>CB-TrIP</acronym>
  <official_title>Fetal Hemoglobin Levels and Umbilical Cord or Adult Blood RBC Transfusions in Preterm Neonates.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</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>
      Repeated transfusions have been associated with very poor outcome of preterm infants. Fetal&#xD;
      hemoglobin (HbF) and adult Hb (HbA) have different affinity for oxygen. The high level of&#xD;
      adult Hb may contribute to exacerbating the oxidative damage responsible for prematurity&#xD;
      diseases. The investigators hypothesized that transfusing red blood cells (RBC) obtained from&#xD;
      allogeneic cord blood (CB) of healthy full-term babies (which contains almost exclusively&#xD;
      HbF) may prevent the non-physiological decrease of HbF in premature neonates, likewise&#xD;
      protecting them from oxygen radical diseases. Cord blood transfusion in preterms - CB TRIP -&#xD;
      is a monocentric prospective nonrandomized study aimed to monitor HbF levels in preterm&#xD;
      neonates receiving RBC transfusions from either umbilical blood of full-term healthy babies&#xD;
      (CB-RBC) and/or from adult donors (A-RBC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preterm neonates enrolled in this study are monitored for the level of HbF on capillary blood&#xD;
      samples, from birth to the week 32 of postmenstrual age (PMA). To fulfill the RBC transfusion&#xD;
      requirements, RBC concentrates obtained from umbilical blood of full-term healthy babies are&#xD;
      utilized, if available; otherwise, RBC concentrates from adult donors are assigned. For every&#xD;
      week of PMA, neonates undergo a minimum of three HbF determinations, and the median values&#xD;
      are considered.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 5, 2018</start_date>
  <completion_date type="Actual">August 2, 2019</completion_date>
  <primary_completion_date type="Actual">August 2, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Median Percentage of HbF at 32 Weeks of Post Menstrual Age</measure>
    <time_frame>From study entry to the completion of postmenstrual age of 32 weeks</time_frame>
    <description>The HbF level was determined by high-performance liquid chromatography and was expressed as percentage of total Hb, calculated as the sum of fetal and adult Hb, according to the formula: HbF= [HbF/ (FHbA1 + HbA2 + HbF)]. HbF.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Post-transfusion Hematocrit (Htc) Change</measure>
    <time_frame>From enrollment to last HbF assessment occurring at 36 weeks, discharge or death</time_frame>
    <description>Change from baseline of Htc observed after either adult-RBC or cord-RBC transfusions. To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intervals Between Transfusions</measure>
    <time_frame>From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death</time_frame>
    <description>Number of days between two consecutive transfusions.To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Percentage of HbF at Last Assessment</measure>
    <time_frame>From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death</time_frame>
    <description>Median percentage of HbF at last HbF assessment. The last HbF measure was obtained at the completion of the 36 week of age, discharge or death.</description>
  </secondary_outcome>
  <enrollment type="Actual">25</enrollment>
  <condition>Premature Infant Disease</condition>
  <condition>Transfusion Related Complication</condition>
  <condition>Fetal Hemoglobin</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      80-100 microL of capillary blood for HbF assessment&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The CB TRIP trial enrolls preterm neonates born before the 30th week of gestation and/or&#xD;
        neonates with birth weight &lt;1000 grams, admitted to the NICU of Policlinico Gemelli, and&#xD;
        candidate to receive one or more RBC transfusions. These characteristics (birth &lt;28 weeks&#xD;
        of gestation and birth weight &lt;1000 grams) identify a very fragile population, with&#xD;
        significant early mortality and morbidity and high risk for lifelong invalidating&#xD;
        consequences.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        preterm neonates born at PMA ≤30 weeks and/or with birth weight ≤1000 g born at the&#xD;
        delivery room of Fondazione Policlinico Universitario A. Gemelli candidate to receive one&#xD;
        or more RBC unit transfusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        One or more of the following criteria Maternal-fetal immunization Hydrops fetalis Major&#xD;
        congenital malformations associated or not with genetic syndromes Previous transfusions&#xD;
        Hemorrhage at birth Congenital infections (such as infections from TORCH complex) Out-born&#xD;
        infants The health care team deems it inappropriate to approach the infant's family for&#xD;
        informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luciana Teofili, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione Policlinico Agostino Gemelli IRCCS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario A. Gemelli IRCCS</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario A.Gemelli IRCCS</name>
      <address>
        <city>Rome</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Bianchi M, Papacci P, Valentini CG, Barbagallo O, Vento G, Teofili L. Umbilical cord blood as a source for red-blood-cell transfusion in neonatology: a systematic review. Vox Sang. 2018 Nov;113(8):713-725. doi: 10.1111/vox.12720. Epub 2018 Oct 16.</citation>
    <PMID>30328121</PMID>
  </reference>
  <reference>
    <citation>Bianchi M, Giannantonio C, Spartano S, Fioretti M, Landini A, Molisso A, Tesfagabir GM, Tornesello A, Barbagallo O, Valentini CG, Vento G, Zini G, Romagnoli C, Papacci P, Teofili L. Allogeneic umbilical cord blood red cell concentrates: an innovative blood product for transfusion therapy of preterm infants. Neonatology. 2015;107(2):81-6. doi: 10.1159/000368296. Epub 2014 Nov 15.</citation>
    <PMID>25401961</PMID>
  </reference>
  <reference>
    <citation>Stutchfield CJ, Jain A, Odd D, Williams C, Markham R. Foetal haemoglobin, blood transfusion, and retinopathy of prematurity in very preterm infants: a pilot prospective cohort study. Eye (Lond). 2017 Oct;31(10):1451-1455. doi: 10.1038/eye.2017.76. Epub 2017 May 26.</citation>
    <PMID>28548651</PMID>
  </reference>
  <reference>
    <citation>dos Santos AM, Guinsburg R, de Almeida MF, Procianoy RS, Leone CR, Marba ST, Rugolo LM, Fiori HH, Lopes JM, Martinez FE; Brazilian Network on Neonatal Research. Red blood cell transfusions are independently associated with intra-hospital mortality in very low birth weight preterm infants. J Pediatr. 2011 Sep;159(3):371-376.e1-3. doi: 10.1016/j.jpeds.2011.02.040. Epub 2011 Apr 13.</citation>
    <PMID>21489555</PMID>
  </reference>
  <reference>
    <citation>Valieva OA, Strandjord TP, Mayock DE, Juul SE. Effects of transfusions in extremely low birth weight infants: a retrospective study. J Pediatr. 2009 Sep;155(3):331-37.e1. doi: 10.1016/j.jpeds.2009.02.026.</citation>
    <PMID>19732577</PMID>
  </reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <results_first_submitted>December 27, 2019</results_first_submitted>
  <results_first_submitted_qc>April 15, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 24, 2020</results_first_posted>
  <last_update_submitted>August 16, 2021</last_update_submitted>
  <last_update_submitted_qc>August 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</investigator_affiliation>
    <investigator_full_name>TEOFILI LUCIANA</investigator_full_name>
    <investigator_title>Medical Director of the UNICATT Cord Blood Bank</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infant, Premature, Diseases</mesh_term>
  </condition_browse>
  <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>April 2, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03764813/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Parents of neonates with birth weight &lt; 1000 gr and/or postmenstrual age &lt; 30 weeks consecutively admitted to the intensive neonatal unit of Fondazione Poiliclinico Gemelli IRCCS were informed about the study and asked to paricipate.</recruitment_details>
      <pre_assignment_details>Among 29 couples, 25 accepted to participate and overall 25 patients were enrolled.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Non Transfused</title>
          <description>Patient not receiving transfusions</description>
        </group>
        <group group_id="P2">
          <title>Cord-RBC Transfusions</title>
          <description>Patients receiving exclusively allogeneic top up transfusions obtained from healthy full term neonates.</description>
        </group>
        <group group_id="P3">
          <title>Adult-RBC Transfusion</title>
          <description>Patients receiving exclusively standard RBC transfusions from adult donors</description>
        </group>
        <group group_id="P4">
          <title>Cord- and Adult-RBC Transfusions</title>
          <description>Patients receiving both types of transfusions</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>From Enrollment to the Age of 32 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14">Patients receiving no transfusions before the age of 32 weeks</participants>
                <participants group_id="P2" count="3">Patients receiving only cord-RBC transfusions before the age of 32 weeks</participants>
                <participants group_id="P3" count="4">Patients receiving only adult-RBC transfusions before the age of 32 weeks</participants>
                <participants group_id="P4" count="4">Patients receiving both adult-RBC and cord-RBCs before the age of 32 weeks</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death before the age of 32 weeks</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>From Enrollment to the Last HbF Test</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13">Patients receiving no transfusions before last HbF test (occurring at 36 weeks,discharge or death)</participants>
                <participants group_id="P2" count="3">Patients receiving only cord-RBCs before last HbF test (occurring at 36 wks,discharge or death)</participants>
                <participants group_id="P3" count="4">Patients receiving only adult-RBC before last HbF test (occurring at 36 wks,discharge or death)</participants>
                <participants group_id="P4" count="5">Patients receiving both cord and adult-RBCs before the last HbFtest(age of 36 wk,discharge or death)</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="5"/>
              </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>
      <population>These data refer to all patients enrolled in the study, grouped according types of transfusions received (if any) until the completion of the age of 36 weeks, discharge or death.</population>
      <group_list>
        <group group_id="B1">
          <title>Non-Transfused</title>
          <description>13 patients not receiving transfusions.</description>
        </group>
        <group group_id="B2">
          <title>Only Cord-RBC</title>
          <description>3 patients receiving exclusively cord-RBC transfusions</description>
        </group>
        <group group_id="B3">
          <title>Only Adult-RBC</title>
          <description>4 patients receiving exclusively adult-RBC transfusions</description>
        </group>
        <group group_id="B4">
          <title>Cord- and Adult-RBC</title>
          <description>5 patients receiving both adult-RBC and cord-RBC transfusions</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="13"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="25"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>HbF measures</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="224"/>
            <count group_id="B2" value="46"/>
            <count group_id="B3" value="68"/>
            <count group_id="B4" value="140"/>
            <count group_id="B5" value="478"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Gestational age at birth (weeks)</description>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="13"/>
                <count group_id="B2" value="3"/>
                <count group_id="B3" value="4"/>
                <count group_id="B4" value="5"/>
                <count group_id="B5" value="25"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>HbF measures</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="224"/>
                <count group_id="B2" value="46"/>
                <count group_id="B3" value="68"/>
                <count group_id="B4" value="140"/>
                <count group_id="B5" value="478"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.0" lower_limit="29.0" upper_limit="30.4"/>
                    <measurement group_id="B2" value="29.3" lower_limit="24" upper_limit="29.3"/>
                    <measurement group_id="B3" value="28.5" lower_limit="26.4" upper_limit="29.4"/>
                    <measurement group_id="B4" value="26.4" lower_limit="25.2" upper_limit="28.3"/>
                    <measurement group_id="B5" value="29.4" lower_limit="27.1" upper_limit="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="13"/>
                <count group_id="B2" value="3"/>
                <count group_id="B3" value="4"/>
                <count group_id="B4" value="5"/>
                <count group_id="B5" value="25"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>HbF measures</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="224"/>
                <count group_id="B2" value="46"/>
                <count group_id="B3" value="68"/>
                <count group_id="B4" value="140"/>
                <count group_id="B5" value="478"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="0"/>
                <count group_id="B2" value="0"/>
                <count group_id="B3" value="0"/>
                <count group_id="B4" value="0"/>
                <count group_id="B5" value="0"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>HbF measures</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="224"/>
                <count group_id="B2" value="46"/>
                <count group_id="B3" value="68"/>
                <count group_id="B4" value="140"/>
                <count group_id="B5" value="478"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Birth weight</title>
          <description>Weight at birth</description>
          <units>grams</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="13"/>
                <count group_id="B2" value="3"/>
                <count group_id="B3" value="4"/>
                <count group_id="B4" value="5"/>
                <count group_id="B5" value="25"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>HbF measures</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="224"/>
                <count group_id="B2" value="46"/>
                <count group_id="B3" value="68"/>
                <count group_id="B4" value="140"/>
                <count group_id="B5" value="478"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1285" lower_limit="1070" upper_limit="1340"/>
                    <measurement group_id="B2" value="710" lower_limit="700" upper_limit="710"/>
                    <measurement group_id="B3" value="1070" lower_limit="548" upper_limit="1445"/>
                    <measurement group_id="B4" value="930" lower_limit="565" upper_limit="949"/>
                    <measurement group_id="B5" value="1030" lower_limit="750" upper_limit="1317"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hb at birth</title>
          <description>Hemoglobin at birth (g/dL)</description>
          <units>g/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="13"/>
                <count group_id="B2" value="3"/>
                <count group_id="B3" value="4"/>
                <count group_id="B4" value="5"/>
                <count group_id="B5" value="25"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>HbF measures</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="B1" value="224"/>
                <count group_id="B2" value="46"/>
                <count group_id="B3" value="68"/>
                <count group_id="B4" value="140"/>
                <count group_id="B5" value="478"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.3" lower_limit="14.6" upper_limit="18.0"/>
                    <measurement group_id="B2" value="16.3" lower_limit="12.7" upper_limit="16.3"/>
                    <measurement group_id="B3" value="14.9" lower_limit="11.9" upper_limit="16.0"/>
                    <measurement group_id="B4" value="14.2" lower_limit="13.5" upper_limit="17.3"/>
                    <measurement group_id="B5" value="15.4" lower_limit="13.9" upper_limit="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Median Percentage of HbF at 32 Weeks of Post Menstrual Age</title>
        <description>The HbF level was determined by high-performance liquid chromatography and was expressed as percentage of total Hb, calculated as the sum of fetal and adult Hb, according to the formula: HbF= [HbF/ (FHbA1 + HbA2 + HbF)]. HbF.</description>
        <time_frame>From study entry to the completion of postmenstrual age of 32 weeks</time_frame>
        <population>The overall amount of 264 HbF results were included in the analysis. HbF was expressed as percentage of total Hb (i.e. HbF+HbA1+HbA2)</population>
        <group_list>
          <group group_id="O1">
            <title>Non-transfused</title>
            <description>127 HbF measures obtained from 13 preterm neonates surviving until the completion of postmenstrual age of 32 weeks without receiving transfusions</description>
          </group>
          <group group_id="O2">
            <title>Only Cord-RBC</title>
            <description>19 HbF measures obtained from 2 preterm neonates surviving until the completion of postmenstrual age of 32 weeks,receiving only cord-RBC transfusions</description>
          </group>
          <group group_id="O3">
            <title>Only adult_RBC</title>
            <description>33 HbF measures obtained from 3 preterm neonates surviving until the completion of postmenstrual age of 32 weeks,receiving only adult-RBC transfusions</description>
          </group>
          <group group_id="O4">
            <title>Both Cord-RBC and adult_RBC</title>
            <description>85 HbF measures obtained from 5 preterm neonates surviving until the completion of postmenstrual age of 32 weeks,receiving both cord-RBC and adult-RBC transfusions</description>
          </group>
        </group_list>
        <measure>
          <title>Median Percentage of HbF at 32 Weeks of Post Menstrual Age</title>
          <description>The HbF level was determined by high-performance liquid chromatography and was expressed as percentage of total Hb, calculated as the sum of fetal and adult Hb, according to the formula: HbF= [HbF/ (FHbA1 + HbA2 + HbF)]. HbF.</description>
          <population>The overall amount of 264 HbF results were included in the analysis. HbF was expressed as percentage of total Hb (i.e. HbF+HbA1+HbA2)</population>
          <units>percentage of total Hb</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>HbF values</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>HbF values</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="127"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="33"/>
                <count group_id="O4" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.2" lower_limit="91.9" upper_limit="93.9"/>
                    <measurement group_id="O2" value="90.8" lower_limit="85.7" upper_limit="93.7"/>
                    <measurement group_id="O3" value="58.0" lower_limit="51.0" upper_limit="93.5"/>
                    <measurement group_id="O4" value="69.0" lower_limit="47.3" upper_limit="93.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Group comparison is carried out among HbF values grouped according to the transfusion regimen (only cord blood transfusions, only adult transfusions, both cord and adult transfusions).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post-transfusion Hematocrit (Htc) Change</title>
        <description>Change from baseline of Htc observed after either adult-RBC or cord-RBC transfusions. To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.</description>
        <time_frame>From enrollment to last HbF assessment occurring at 36 weeks, discharge or death</time_frame>
        <population>Eight patients received 13 cord-RBC units and 9 patients received 18 adult-RBC units. Change of hematocrit value after each transfusion was recorded.</population>
        <group_list>
          <group group_id="O1">
            <title>Cord-RBC Transfusions</title>
            <description>top up transfusions obtained from cord blood of healthy full term neonates.</description>
          </group>
          <group group_id="O2">
            <title>Adult-RBC Transfusions</title>
            <description>top up transfusions obtained from adult blood donors</description>
          </group>
        </group_list>
        <measure>
          <title>Post-transfusion Hematocrit (Htc) Change</title>
          <description>Change from baseline of Htc observed after either adult-RBC or cord-RBC transfusions. To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.</description>
          <population>Eight patients received 13 cord-RBC units and 9 patients received 18 adult-RBC units. Change of hematocrit value after each transfusion was recorded.</population>
          <units>percentage of total volume</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>number of transfusions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>number of transfusions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" lower_limit="6.5" upper_limit="12.0"/>
                    <measurement group_id="O2" value="11.5" lower_limit="7.7" upper_limit="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0.165</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intervals Between Transfusions</title>
        <description>Number of days between two consecutive transfusions.To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.</description>
        <time_frame>From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death</time_frame>
        <population>Eight patients received a total number of 13 cord-RBC trasfusions and 9 patients received a total number of 18 adult -RBC transfusions. The intervals between two consecutive transfusions was recorded for each type of RBC unit.</population>
        <group_list>
          <group group_id="O1">
            <title>Cord-RBC Transfusions</title>
            <description>top up transfusions obtained from cord blood of healthy full term neonates.</description>
          </group>
          <group group_id="O2">
            <title>Adult-RBC Transfusions</title>
            <description>top up transfusions obtained from adult blood donors</description>
          </group>
        </group_list>
        <measure>
          <title>Intervals Between Transfusions</title>
          <description>Number of days between two consecutive transfusions.To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.</description>
          <population>Eight patients received a total number of 13 cord-RBC trasfusions and 9 patients received a total number of 18 adult -RBC transfusions. The intervals between two consecutive transfusions was recorded for each type of RBC unit.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>number of transfusions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>number of transfusions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="5.0" upper_limit="18.5"/>
                    <measurement group_id="O2" value="7.0" lower_limit="3.0" upper_limit="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0.537</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Percentage of HbF at Last Assessment</title>
        <description>Median percentage of HbF at last HbF assessment. The last HbF measure was obtained at the completion of the 36 week of age, discharge or death.</description>
        <time_frame>From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death</time_frame>
        <population>Data recorded in all patient enetering the study were included in the analysis. Patients were grouped according to the type of RBC receved.</population>
        <group_list>
          <group group_id="O1">
            <title>Non Transfused</title>
            <description>Patient not receiving transfusions</description>
          </group>
          <group group_id="O2">
            <title>Cord-RBC Transfusions</title>
            <description>Patients receiving exclusively allogeneic top up transfusions obtained from healthy full term neonates.</description>
          </group>
          <group group_id="O3">
            <title>Adult-RBC Transfusion</title>
            <description>Patients receiving exclusively standard RBC transfusions from adult donors</description>
          </group>
          <group group_id="O4">
            <title>Cord- and Adult-RBC Transfusions</title>
            <description>Patients receiving both types of transfusions</description>
          </group>
        </group_list>
        <measure>
          <title>Median Percentage of HbF at Last Assessment</title>
          <description>Median percentage of HbF at last HbF assessment. The last HbF measure was obtained at the completion of the 36 week of age, discharge or death.</description>
          <population>Data recorded in all patient enetering the study were included in the analysis. Patients were grouped according to the type of RBC receved.</population>
          <units>% HbF</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>median HbF (%)</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>median HbF (%)</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="224"/>
                <count group_id="O2" value="46"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.3" lower_limit="91.0" upper_limit="93.4"/>
                    <measurement group_id="O2" value="90.6" lower_limit="85.6" upper_limit="93.6"/>
                    <measurement group_id="O3" value="53.6" lower_limit="48.8" upper_limit="92.7"/>
                    <measurement group_id="O4" value="62.0" lower_limit="47.4" upper_limit="92.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Group comparison is carried out among HbF values grouped according to the transfusion regimen (only cord blood transfusions, only adult transfusions, both cord and adult transfusions).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From enrollment to postmenstrual age of 36 weeks.</time_frame>
      <desc>All cause mortality</desc>
      <group_list>
        <group group_id="E1">
          <title>Non-transfused</title>
          <description>13 preterm neonates non receiving transfusions</description>
        </group>
        <group group_id="E2">
          <title>Only Cord-TBC</title>
          <description>3 neonates receiving only cord-RBC</description>
        </group>
        <group group_id="E3">
          <title>Only Adult-RBC</title>
          <description>4 neonates receiving only adult-RBC</description>
        </group>
        <group group_id="E4">
          <title>Both Cord- and Adult-RBC</title>
          <description>5 neonates receiving both RBC types</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="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinopathy stage II-III</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Necrotizing enterocolitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>documented infections</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </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>luciana teofilili medical director of the UNICATT cord blood bank</name_or_title>
      <organization>Fondazione Policlinico Gemelli IRCCS</organization>
      <phone>39 06 30154180</phone>
      <email>luciana.teofili@unicatt.it</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/NCT03764813
org study id: 22139/18ID:1916
nct id: NCT03764813
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Repeated transfusions have been associated with very poor outcome of preterm infants. Fetal
      hemoglobin (HbF) and adult Hb (HbA) have different affinity for oxygen. The high level of
      adult Hb may contribute to exacerbating the oxidative damage responsible for prematurity
      diseases. The investigators hypothesized that transfusing red blood cells (RBC) obtained from
      allogeneic cord blood (CB) of healthy full-term babies (which contains almost exclusively
      HbF) may prevent the non-physiological decrease of HbF in premature neonates, likewise
      protecting them from oxygen radical diseases. Cord blood transfusion in preterms - CB TRIP -
      is a monocentric prospective nonrandomized study aimed to monitor HbF levels in preterm
      neonates receiving RBC transfusions from either umbilical blood of full-term healthy babies
      (CB-RBC) and/or from adult donors (A-RBC).
Preterm neonates enrolled in this study are monitored for the level of HbF on capillary blood
      samples, from birth to the week 32 of postmenstrual age (PMA). To fulfill the RBC transfusion
      requirements, RBC concentrates obtained from umbilical blood of full-term healthy babies are
      utilized, if available; otherwise, RBC concentrates from adult donors are assigned. For every
      week of PMA, neonates undergo a minimum of three HbF determinations, and the median values
      are considered.
observational model: Cohort
time perspective: Prospective
measure: Median Percentage of HbF at 32 Weeks of Post Menstrual Age
time frame: From study entry to the completion of postmenstrual age of 32 weeks
description: The HbF level was determined by high-performance liquid chromatography and was expressed as percentage of total Hb, calculated as the sum of fetal and adult Hb, according to the formula: HbF= [HbF/ (FHbA1 + HbA2 + HbF)]. HbF.
measure: Post-transfusion Hematocrit (Htc) Change
time frame: From enrollment to last HbF assessment occurring at 36 weeks, discharge or death
description: Change from baseline of Htc observed after either adult-RBC or cord-RBC transfusions. To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.
measure: Intervals Between Transfusions
time frame: From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death
description: Number of days between two consecutive transfusions.To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.
measure: Median Percentage of HbF at Last Assessment
time frame: From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death
description: Median percentage of HbF at last HbF assessment. The last HbF measure was obtained at the completion of the 36 week of age, discharge or death.
80-100 microL of capillary blood for HbF assessment
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Luciana Teofili, MD, PhD
role: Principal Investigator
affiliation: Fondazione Policlinico Agostino Gemelli IRCCS
facility: 
facility: 
country: Italy
citation: Bianchi M, Papacci P, Valentini CG, Barbagallo O, Vento G, Teofili L. Umbilical cord blood as a source for red-blood-cell transfusion in neonatology: a systematic review. Vox Sang. 2018 Nov;113(8):713-725. doi: 10.1111/vox.12720. Epub 2018 Oct 16.
PMID: 30328121
citation: Bianchi M, Giannantonio C, Spartano S, Fioretti M, Landini A, Molisso A, Tesfagabir GM, Tornesello A, Barbagallo O, Valentini CG, Vento G, Zini G, Romagnoli C, Papacci P, Teofili L. Allogeneic umbilical cord blood red cell concentrates: an innovative blood product for transfusion therapy of preterm infants. Neonatology. 2015;107(2):81-6. doi: 10.1159/000368296. Epub 2014 Nov 15.
PMID: 25401961
citation: Stutchfield CJ, Jain A, Odd D, Williams C, Markham R. Foetal haemoglobin, blood transfusion, and retinopathy of prematurity in very preterm infants: a pilot prospective cohort study. Eye (Lond). 2017 Oct;31(10):1451-1455. doi: 10.1038/eye.2017.76. Epub 2017 May 26.
PMID: 28548651
citation: dos Santos AM, Guinsburg R, de Almeida MF, Procianoy RS, Leone CR, Marba ST, Rugolo LM, Fiori HH, Lopes JM, Martinez FE; Brazilian Network on Neonatal Research. Red blood cell transfusions are independently associated with intra-hospital mortality in very low birth weight preterm infants. J Pediatr. 2011 Sep;159(3):371-376.e1-3. doi: 10.1016/j.jpeds.2011.02.040. Epub 2011 Apr 13.
PMID: 21489555
citation: Valieva OA, Strandjord TP, Mayock DE, Juul SE. Effects of transfusions in extremely low birth weight infants: a retrospective study. J Pediatr. 2009 Sep;155(3):331-37.e1. doi: 10.1016/j.jpeds.2009.02.026.
PMID: 19732577
responsible party type: Principal Investigator
investigator affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
investigator full name: TEOFILI LUCIANA
investigator title: Medical Director of the UNICATT Cord Blood Bank
mesh term: Infant, Premature, Diseases
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 