<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/NCT04440670</url>
  </required_header>
  <id_info>
    <org_study_id>Guang dong W C H</org_study_id>
    <nct_id>NCT04440670</nct_id>
  </id_info>
  <brief_title>Effect of Autologous Cord Blood Mononuclear Cells for Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates</brief_title>
  <official_title>Effect of Autologous Cord Blood Mononuclear Cells for Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates: a Placebo-controlled Randomized Multicenter Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guangdong Women and Children Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Foshan Chancheng Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Foshan Women and Children Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hexian Memorial Affiliated Hospital of Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Heyuan Women and Children Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dongguan Women and Children Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangzhou Huadu Women and Children Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The fifth Affiliated Hospital of Guangzhou Medcial University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangdong Cord Blood Bank</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dongguang People Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Guangdong Women and Children Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is the first and largest randomized, controlled, blinded trial that evaluates the&#xD;
      efficacy of autologous cord blood mononuclear cells infusion as a prevention therapy for BPD.&#xD;
      The results of this trial will provide valuable clinical evidence for recommendations on the&#xD;
      management of BPD in extremely preterm infants. In this prospective, randomized controlled&#xD;
      double-blind multi-center clinical trial, 200 preterm neonates less than 28 weeks are&#xD;
      randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion&#xD;
      (5×107cells/kg) or placebo ( normal saline) within 24 hours after birth in a 1:1 ratio using&#xD;
      a central randomization system. The primary outcome is survival without bronchopulmonary&#xD;
      dysplasia at 36 weeks of postmenstrual age or discharge home. The secondary outcomes will&#xD;
      include mortality rate, other common preterm complication rate, respiratory support duration,&#xD;
      the length and cost of hospitalization and long term outcomes after two years follow up post&#xD;
      infusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design and settings:&#xD;
&#xD;
      This present study will be a randomized, placebo-controlled, double-blinded, multi-center&#xD;
      trial to be conducted at 14 medical centers in tertiary hospitals with Neonatal Intensive&#xD;
      Care Unit that were selected by the expert committee. A total of 200 neonates fulfilling the&#xD;
      eligibility criteria will be enrolled. Subsequently, the participants will be randomly&#xD;
      divided into two groups (ACBMNC infusion group and control (placebo) group ) in a ratio of&#xD;
      1:1.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Primary objective： The primary objective of this trial is to evaluate the efficacy of ACBMNC&#xD;
      infusion in preventing bronchopulmonary dysplasia at 36 weeks of postmenstrual age or&#xD;
      discharge home in extremely preterm infants.&#xD;
&#xD;
      Secondary objectives：&#xD;
&#xD;
        -  To compare the mortality rate at 36 weeks of postmenstrual age.&#xD;
&#xD;
        -  To compare the rate of other common preterm complications included intraventricular&#xD;
           hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP),&#xD;
           respiratory distress syndrome (RDS), ventilation-associated pneumonia (VAP), hypoxic&#xD;
           ischemic encephalopathy (HIE), late onset sepsis (LOS) and anemia.To compare the&#xD;
           duration of mechanical ventilation and oxygen therapy in two groups&#xD;
&#xD;
        -  To determine re-intubation rate and time return to BW&#xD;
&#xD;
        -  To compare the duration of antibiotic usage&#xD;
&#xD;
        -  To determine the long term outcomes after two years follow up&#xD;
&#xD;
      Participants:&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
      Infants fulfilling all the following inclusion criteria will be enrolled in this trial: 1.&#xD;
      born at study hospital; 2. singleton birth; 3. less than 28 weeks GA 4.Signed informed&#xD;
      consent obtained; 5. had available umbilical cord blood (UCB).&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
      Those infants are excluded if they were 1. with severe congenital abnormalities; 2.with&#xD;
      maternal clinical chorioamnionitis 3. the mother was positive for hepatitis B (HBsAg and/or&#xD;
      HBeAg) or C virus (anti-HCV), syphilis, HIV (anti-HIV-1 and -2) or IgM against&#xD;
      cytomegalovirus, rubella, toxoplasma and herpes simplex virus.&#xD;
&#xD;
      Trial treatment methods:&#xD;
&#xD;
      Soon after the preterm infant was deliveried, written consent was signed by the parents, and&#xD;
      autologous cord blood infusion was applied to the baby in addition to routine pulmonary&#xD;
      surfactant replacement, and mechanical ventilation support as indicated. Those assigned to&#xD;
      the ACBMNC group received an infusion of ACBMNC with 24 h after birth. Those in control group&#xD;
      received an infusion of a placebo solution which is normal saline with the same volume. Cell&#xD;
      dose for all patients was targeted at 5×107 cells per kilogram.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 20, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>In this prospective, randomized controlled double-blind multi-center clinical trial, 200 preterm neonates less than 28 weeks are randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg) or placebo ( normal saline) within 24 hours after birth in a 1:1 ratio using a central randomization system.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>A hospital ethics committee reviewed the study data during the trials. None of them were involved in the study or aware of the treatment-group assignments of the infants. Only nurses and physicians staff conducted the infusion were aware of the treatment assignment, and these individuals had no contact with the staff who collected and analyzed the patients data. The parents are not aware of the assignment. This study is double-blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>frequency of bronchopulmonary dysplasia</measure>
    <time_frame>36 weeks of postmenstrual age or discharge home whichever comes first.</time_frame>
    <description>The frequency of bronchopulmonary dysplasia at 36 weeks of postmenstrual age or discharge home whichever comes first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>36 weeks of postmenstrual age or the discharge</time_frame>
    <description>The mortality rate.&#xD;
Incidence of other preterm complications including intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), respiratory distress syndrome (RDS), ventilation-associated pneumonia (VAP), late onset sepsis (LOS) and anemia .&#xD;
Duration of hospitalization.&#xD;
Duration of mechanical ventilation and oxygen therapy&#xD;
The frequency of re-intubation.&#xD;
The time (days) return to BW.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>BPD</condition>
  <arm_group>
    <arm_group_label>ACBMNC infusion group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Those assigned to the ACBMNC group will receive intravenous autologous cord blood mononuclear cells infusion within 24 h after birth. Cell dose for all patients was targeted at 5×107 cells per kilogram.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Those in control group will receive an infusion of a placebo solution which is normal saline with the same volume.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>autologous cord blood mononuclear cells</intervention_name>
    <description>preterm neonates less than 28 weeks are assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg) within 24 hours after birth</description>
    <arm_group_label>ACBMNC infusion group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>normal saline</intervention_name>
    <description>preterm neonates less than 28 weeks are assigned to receive normal saline within 24 hours after birth</description>
    <arm_group_label>control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Infants fulfilling all the following inclusion criteria will be enrolled in this trial: 1.&#xD;
        born at study hospital; 2. singleton birth; 3. less than 28 weeks GA 4.Signed informed&#xD;
        consent obtained; 5. had available umbilical cord blood (UCB).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Those infants are excluded if they were 1. with severe congenital abnormalities; 2.with&#xD;
        maternal clinical chorioamnionitis 3. the mother was positive for hepatitis B (HBsAg and/or&#xD;
        HBeAg) or C virus (anti-HCV), syphilis, HIV (anti-HIV-1 and -2) or IgM against&#xD;
        cytomegalovirus, rubella, toxoplasma and herpes simplex virus.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Weeks</minimum_age>
    <maximum_age>28 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jie Yang</last_name>
    <role>Study Chair</role>
    <affiliation>Guangdong Women and Children Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>zhuxiao Ren, MD</last_name>
    <phone>+8613538984634</phone>
    <email>renzhx1990@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ren Xuejun</name>
      <address>
        <city>Dongguan</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ren Xuejun, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jie Yang</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>511442</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jie Yang, PHD</last_name>
      <phone>39151777</phone>
      <phone_ext>020</phone_ext>
      <email>jieyang@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>November 15, 2021</last_update_submitted>
  <last_update_submitted_qc>November 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Guangdong Women and Children Hospital</investigator_affiliation>
    <investigator_full_name>yang jie</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Autologous cord blood mononuclear cells</keyword>
  <keyword>bronchopulmonary dysplasia</keyword>
  <keyword>extremely preterm neonates</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>public</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>all time</ipd_time_frame>
    <ipd_access_criteria>all</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04440670
org study id: Guang dong W C H
nct id: NCT04440670
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is the first and largest randomized, controlled, blinded trial that evaluates the
      efficacy of autologous cord blood mononuclear cells infusion as a prevention therapy for BPD.
      The results of this trial will provide valuable clinical evidence for recommendations on the
      management of BPD in extremely preterm infants. In this prospective, randomized controlled
      double-blind multi-center clinical trial, 200 preterm neonates less than 28 weeks are
      randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion
      (5×107cells/kg) or placebo ( normal saline) within 24 hours after birth in a 1:1 ratio using
      a central randomization system. The primary outcome is survival without bronchopulmonary
      dysplasia at 36 weeks of postmenstrual age or discharge home. The secondary outcomes will
      include mortality rate, other common preterm complication rate, respiratory support duration,
      the length and cost of hospitalization and long term outcomes after two years follow up post
      infusion.
Study design and settings:

      This present study will be a randomized, placebo-controlled, double-blinded, multi-center
      trial to be conducted at 14 medical centers in tertiary hospitals with Neonatal Intensive
      Care Unit that were selected by the expert committee. A total of 200 neonates fulfilling the
      eligibility criteria will be enrolled. Subsequently, the participants will be randomly
      divided into two groups (ACBMNC infusion group and control (placebo) group ) in a ratio of
      1:1.

      Objectives:

      Primary objective： The primary objective of this trial is to evaluate the efficacy of ACBMNC
      infusion in preventing bronchopulmonary dysplasia at 36 weeks of postmenstrual age or
      discharge home in extremely preterm infants.

      Secondary objectives：

        -  To compare the mortality rate at 36 weeks of postmenstrual age.

        -  To compare the rate of other common preterm complications included intraventricular
           hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP),
           respiratory distress syndrome (RDS), ventilation-associated pneumonia (VAP), hypoxic
           ischemic encephalopathy (HIE), late onset sepsis (LOS) and anemia.To compare the
           duration of mechanical ventilation and oxygen therapy in two groups

        -  To determine re-intubation rate and time return to BW

        -  To compare the duration of antibiotic usage

        -  To determine the long term outcomes after two years follow up

      Participants:

      Inclusion criteria:

      Infants fulfilling all the following inclusion criteria will be enrolled in this trial: 1.
      born at study hospital; 2. singleton birth; 3. less than 28 weeks GA 4.Signed informed
      consent obtained; 5. had available umbilical cord blood (UCB).

      Exclusion criteria:

      Those infants are excluded if they were 1. with severe congenital abnormalities; 2.with
      maternal clinical chorioamnionitis 3. the mother was positive for hepatitis B (HBsAg and/or
      HBeAg) or C virus (anti-HCV), syphilis, HIV (anti-HIV-1 and -2) or IgM against
      cytomegalovirus, rubella, toxoplasma and herpes simplex virus.

      Trial treatment methods:

      Soon after the preterm infant was deliveried, written consent was signed by the parents, and
      autologous cord blood infusion was applied to the baby in addition to routine pulmonary
      surfactant replacement, and mechanical ventilation support as indicated. Those assigned to
      the ACBMNC group received an infusion of ACBMNC with 24 h after birth. Those in control group
      received an infusion of a placebo solution which is normal saline with the same volume. Cell
      dose for all patients was targeted at 5×107 cells per kilogram.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: In this prospective, randomized controlled double-blind multi-center clinical trial, 200 preterm neonates less than 28 weeks are randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg) or placebo ( normal saline) within 24 hours after birth in a 1:1 ratio using a central randomization system.
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: A hospital ethics committee reviewed the study data during the trials. None of them were involved in the study or aware of the treatment-group assignments of the infants. Only nurses and physicians staff conducted the infusion were aware of the treatment assignment, and these individuals had no contact with the staff who collected and analyzed the patients data. The parents are not aware of the assignment. This study is double-blinded.
measure: frequency of bronchopulmonary dysplasia
time frame: 36 weeks of postmenstrual age or discharge home whichever comes first.
description: The frequency of bronchopulmonary dysplasia at 36 weeks of postmenstrual age or discharge home whichever comes first.
measure: mortality
time frame: 36 weeks of postmenstrual age or the discharge
description: The mortality rate.
Incidence of other preterm complications including intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), respiratory distress syndrome (RDS), ventilation-associated pneumonia (VAP), late onset sepsis (LOS) and anemia .
Duration of hospitalization.
Duration of mechanical ventilation and oxygen therapy
The frequency of re-intubation.
The time (days) return to BW.
arm group label: ACBMNC infusion group
arm group type: Experimental
description: Those assigned to the ACBMNC group will receive intravenous autologous cord blood mononuclear cells infusion within 24 h after birth. Cell dose for all patients was targeted at 5×107 cells per kilogram.
arm group label: control group
arm group type: Placebo Comparator
description: Those in control group will receive an infusion of a placebo solution which is normal saline with the same volume.
intervention type: Biological
intervention name: autologous cord blood mononuclear cells
description: preterm neonates less than 28 weeks are assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg) within 24 hours after birth
arm group label: ACBMNC infusion group
intervention type: Biological
intervention name: normal saline
description: preterm neonates less than 28 weeks are assigned to receive normal saline within 24 hours after birth
arm group label: control group
criteria: 
gender: All
minimum age: 0 Weeks
maximum age: 28 Weeks
healthy volunteers: No
last name: Jie Yang
role: Study Chair
affiliation: Guangdong Women and Children Hospital
last name: zhuxiao Ren, MD
phone: +8613538984634
email: renzhx1990@163.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Guangdong Women and Children Hospital
investigator full name: yang jie
investigator title: Professor
mesh term: Bronchopulmonary Dysplasia
sharing ipd: Yes
ipd description: public
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: all time
ipd access criteria: all