<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/NCT03808051</url>
  </required_header>
  <id_info>
    <org_study_id>NL67770.058.18</org_study_id>
    <nct_id>NCT03808051</nct_id>
  </id_info>
  <brief_title>Aeration, Breathing, Clamping Study 3</brief_title>
  <acronym>ABC3</acronym>
  <official_title>Physiological-based Cord Clamping in Very Preterm Infants: a Multicentre Randomised Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Erasmus Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical Research Foundation, The Netherlands</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Leiden University Medical Center</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>
      Delayed cord clamping (DCC) in preterm infants results in a decrease in mortality and a trend&#xD;
      towards fewer intraventricular haemorrhages. However, preterm infants needing immediate&#xD;
      interventions for stabilisation or resuscitation were generally clamped immediately and&#xD;
      excluded from trials, while these infants might benefit the most of DCC.&#xD;
&#xD;
      Studies in preterm lambs demonstrated that delaying cord clamping beyond ventilation onset&#xD;
      resulted in more stable hemodynamic transition. This approach was called 'physiological-based&#xD;
      cord clamping' (PBCC). The hypothesis of this study is that PBCC in preterm infants at birth&#xD;
      will lead to an increase in intact survival when compared to standard care.&#xD;
&#xD;
      This study is a multicentre randomised controlled, parallel design, superiority trial,&#xD;
      including preterm infants less than 30 weeks of gestation. The intervention is PBCC:&#xD;
      stabilisation of the infant with the umbilical cord intact and only clamp the cord when the&#xD;
      infant is stable. Stable is defined as the establishment of heart rate greater than 100 bpm&#xD;
      and oxygen saturation above 85% while using supplemental oxygen lower than 40%. In the&#xD;
      control group cord clamping will be performed time-based: infants are clamped first (at 30-60&#xD;
      seconds if the clinical condition allows) and then moved to the resuscitation table for&#xD;
      further stabilisation.&#xD;
&#xD;
      The primary outcome will be intact survival at NICU discharge, defined as survival without&#xD;
      cerebral injury (intraventricular haemorrhage ≥ grade 2 and/or periventricular leukomalacia ≥&#xD;
      grade 2 and/or periventricular venous infarction) and/or necrotizing enterocolitis (Bell&#xD;
      stage ≥ 2).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 25, 2019</start_date>
  <completion_date type="Anticipated">May 15, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 15, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intact survival at NICU discharge</measure>
    <time_frame>From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.</time_frame>
    <description>Intact survival is defined as survival without major cerebral injury (IVH ≥ grade 2 and/or PVL ≥ grade 2 and/or periventricular venous infarction) and/or NEC ≥ Bell stage 2.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of treatment failure</measure>
    <time_frame>From birth until one hour of age.</time_frame>
    <description>Treatment failure defined as the number of participants in which abortion of prescribed procedure (intervention or control) occurred and the reasons for abortion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short-term neonatal outcomes</measure>
    <time_frame>From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.</time_frame>
    <description>Incidence of prematurity related morbidities during hospital stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short-term maternal outcomes</measure>
    <time_frame>From date of randomization until five days after intervention.</time_frame>
    <description>Incidence of postpartum haemorrhage (&gt; 1000 ml) and surgical site infection after caesarean section.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurodevelopmental outcome (Cognitive) at 2 years corrected age</measure>
    <time_frame>Assesment at two years corrected age.</time_frame>
    <description>Neurodevelopmental outcome assessed at 2 years corrected age by the standardized Bayley Scales of Infant Development III (BSID-III-NL), resulting in the Mental Developmental Index. A score of less than 85 (1 SD below the mean of 100) is considered as delayed development.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurodevelopmental outcome (Motor) at 2 years corrected age</measure>
    <time_frame>Assesment at two years corrected age.</time_frame>
    <description>Neurodevelopmental outcome assessed at 2 years corrected age by the standardized Bayley Scales of Infant Development III (BSID-III-NL), resulting in the Performance Developmental Index. A score of less than 85 (1 SD below the mean of 100) is considered as delayed development.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome at 2 years corrected age</measure>
    <time_frame>Assesment at two years corrected age.</time_frame>
    <description>The proportion of participants with cerebral palsy, the proportion of participants with hearing loss requiring hearing aids and the proportion of participants with blindness.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Parental perception and appreciation of stabilisation at birth</measure>
    <time_frame>Sent within 1 week after birth.</time_frame>
    <description>Questionnaire sent to parents concerning the perception and appreciation of the approach during birth and the perinatal stabilisation of the infant.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">689</enrollment>
  <condition>Preterm Infant</condition>
  <condition>Birth, Preterm</condition>
  <arm_group>
    <arm_group_label>Physiological-based cord clamping</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Stabilisation of the infant is performed while the cord is intact and the cord will be clamped after the infant is cardiopulmonary stable. Stable is defined as the establishment of heart rate greater than 100 bpm and oxygen saturation above 85% while using supplemental oxygen lower than 40%. The maximum cord clamping time is 10 minutes and prior to cord clamping a trial of weaning from PPV to CPAP is performed. With the exception that the infant is stabilised close to the mother and the cord is clamped later, the infant will receive standard resuscitation interventions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Time-based cord clamping</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Infants are clamped first and then moved to the standard resuscitation table for further treatment and intervention needed for cardiopulmonary stabilisation. Clamping is time based and performed immediately or delayed at 30-60 seconds, depending on the clinical condition of the infant. Uterotonic drugs are administered immediately after cord clamping.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Physiological-based cord clamping</intervention_name>
    <description>See Arm description.</description>
    <arm_group_label>Physiological-based cord clamping</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Time-based cord clamping</intervention_name>
    <description>See Arm description.</description>
    <arm_group_label>Time-based cord clamping</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants born at a gestational age below 30 weeks in a participating centre.&#xD;
&#xD;
          -  Parental consent (see 9.2).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A potential subject who meets any of the following criteria will be excluded from&#xD;
        participation in this study:&#xD;
&#xD;
          -  Significant congenital malformations influencing cardiopulmonary transition.&#xD;
&#xD;
          -  Signs of acute placental abruption.&#xD;
&#xD;
          -  Anterior placenta praevia or invasive placentation (accreta/percreta).&#xD;
&#xD;
          -  Birth by emergency caesarean section (ordered to be executed within 15 minutes).&#xD;
&#xD;
          -  Maternal general anaesthesia during caesarean section.&#xD;
&#xD;
          -  Twin gestation with signs of Twin Transfusion Syndrome or Twin Anaemia Polycythemia&#xD;
             Syndrome not treated with fetoscopic laser treatment.&#xD;
&#xD;
          -  Multiple pregnancy &gt; 2 (triplets or higher order).&#xD;
&#xD;
          -  Decision documented to give palliative neonatal care.&#xD;
&#xD;
        In case of twin delivery by caesarean section it is not possible to perform PBCC in both&#xD;
        infants. Both infants will be included: the first infant will receive standard treatment&#xD;
        and the second infant will be randomised to either PBCC or standard treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>29 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arjan B Te Pas, Prof</last_name>
    <role>Study Chair</role>
    <affiliation>Leiden University Medical Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ronny Knol, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Erasmus Medical Centre Rotterdam</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Amsterdam University Medical Centre, location AMC</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam University Medical Centre, location VU</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Centre Groningen</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Centre</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maastricht University Medical Centre</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboud University Medical Centre</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus Medical Centre - Sophia Children's Hospital</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Centre Utrecht</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maxima Medical Centre</name>
      <address>
        <city>Veldhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala Clinics Zwolle</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 1, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>May 9, 2023</last_update_submitted>
  <last_update_submitted_qc>May 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
    <investigator_full_name>PasABte</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Preterm infant</keyword>
  <keyword>Cord clamping</keyword>
  <keyword>Resuscitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03808051
org study id: NL67770.058.18
nct id: NCT03808051
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Delayed cord clamping (DCC) in preterm infants results in a decrease in mortality and a trend
      towards fewer intraventricular haemorrhages. However, preterm infants needing immediate
      interventions for stabilisation or resuscitation were generally clamped immediately and
      excluded from trials, while these infants might benefit the most of DCC.

      Studies in preterm lambs demonstrated that delaying cord clamping beyond ventilation onset
      resulted in more stable hemodynamic transition. This approach was called 'physiological-based
      cord clamping' (PBCC). The hypothesis of this study is that PBCC in preterm infants at birth
      will lead to an increase in intact survival when compared to standard care.

      This study is a multicentre randomised controlled, parallel design, superiority trial,
      including preterm infants less than 30 weeks of gestation. The intervention is PBCC:
      stabilisation of the infant with the umbilical cord intact and only clamp the cord when the
      infant is stable. Stable is defined as the establishment of heart rate greater than 100 bpm
      and oxygen saturation above 85% while using supplemental oxygen lower than 40%. In the
      control group cord clamping will be performed time-based: infants are clamped first (at 30-60
      seconds if the clinical condition allows) and then moved to the resuscitation table for
      further stabilisation.

      The primary outcome will be intact survival at NICU discharge, defined as survival without
      cerebral injury (intraventricular haemorrhage ≥ grade 2 and/or periventricular leukomalacia ≥
      grade 2 and/or periventricular venous infarction) and/or necrotizing enterocolitis (Bell
      stage ≥ 2).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Intact survival at NICU discharge
time frame: From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.
description: Intact survival is defined as survival without major cerebral injury (IVH ≥ grade 2 and/or PVL ≥ grade 2 and/or periventricular venous infarction) and/or NEC ≥ Bell stage 2.
measure: Rate of treatment failure
time frame: From birth until one hour of age.
description: Treatment failure defined as the number of participants in which abortion of prescribed procedure (intervention or control) occurred and the reasons for abortion.
measure: Short-term neonatal outcomes
time frame: From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.
description: Incidence of prematurity related morbidities during hospital stay.
measure: Short-term maternal outcomes
time frame: From date of randomization until five days after intervention.
description: Incidence of postpartum haemorrhage (> 1000 ml) and surgical site infection after caesarean section.
measure: Neurodevelopmental outcome (Cognitive) at 2 years corrected age
time frame: Assesment at two years corrected age.
description: Neurodevelopmental outcome assessed at 2 years corrected age by the standardized Bayley Scales of Infant Development III (BSID-III-NL), resulting in the Mental Developmental Index. A score of less than 85 (1 SD below the mean of 100) is considered as delayed development.
measure: Neurodevelopmental outcome (Motor) at 2 years corrected age
time frame: Assesment at two years corrected age.
description: Neurodevelopmental outcome assessed at 2 years corrected age by the standardized Bayley Scales of Infant Development III (BSID-III-NL), resulting in the Performance Developmental Index. A score of less than 85 (1 SD below the mean of 100) is considered as delayed development.
measure: Functional outcome at 2 years corrected age
time frame: Assesment at two years corrected age.
description: The proportion of participants with cerebral palsy, the proportion of participants with hearing loss requiring hearing aids and the proportion of participants with blindness.
measure: Parental perception and appreciation of stabilisation at birth
time frame: Sent within 1 week after birth.
description: Questionnaire sent to parents concerning the perception and appreciation of the approach during birth and the perinatal stabilisation of the infant.
arm group label: Physiological-based cord clamping
arm group type: Experimental
description: Stabilisation of the infant is performed while the cord is intact and the cord will be clamped after the infant is cardiopulmonary stable. Stable is defined as the establishment of heart rate greater than 100 bpm and oxygen saturation above 85% while using supplemental oxygen lower than 40%. The maximum cord clamping time is 10 minutes and prior to cord clamping a trial of weaning from PPV to CPAP is performed. With the exception that the infant is stabilised close to the mother and the cord is clamped later, the infant will receive standard resuscitation interventions.
arm group label: Time-based cord clamping
arm group type: Active Comparator
description: Infants are clamped first and then moved to the standard resuscitation table for further treatment and intervention needed for cardiopulmonary stabilisation. Clamping is time based and performed immediately or delayed at 30-60 seconds, depending on the clinical condition of the infant. Uterotonic drugs are administered immediately after cord clamping.
intervention type: Procedure
intervention name: Physiological-based cord clamping
description: See Arm description.
arm group label: Physiological-based cord clamping
intervention type: Procedure
intervention name: Time-based cord clamping
description: See Arm description.
arm group label: Time-based cord clamping
criteria: 
gender: All
minimum age: N/A
maximum age: 29 Weeks
healthy volunteers: No
last name: Arjan B Te Pas, Prof
role: Study Chair
affiliation: Leiden University Medical Centre
last name: Ronny Knol, MD
role: Principal Investigator
affiliation: Erasmus Medical Centre Rotterdam
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Leiden University Medical Center
investigator full name: PasABte
investigator title: Principal Investigator
mesh term: Premature Birth
sharing ipd: Undecided