<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/NCT04424667</url>
  </required_header>
  <id_info>
    <org_study_id>Neo-HTST</org_study_id>
    <nct_id>NCT04424667</nct_id>
  </id_info>
  <brief_title>Clinical Impact of Donor Milk Pasteurized by HTST Treatment in Preterm Infants</brief_title>
  <official_title>Clinical and Economic Impact of Supplementation With Donor Milk Pasteurized by HTST Method Versus Holder Method in Extremely Birth Weight Preterm Infants. Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Carmen Rosa Pallas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Universitario 12 de Octubre</source>
  <oversight_info>
    <has_dmc>No</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>
      Randomized double-blind clinical trial to compare the incidence of microbiological proven&#xD;
      late onset sepsis in extremely preterm infants (&lt;1000 grams) that are supplemented with donor&#xD;
      milk pasteurized by High Temperature Short Time (HTST) method versus the Holder method.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Donor milk pasteurized by an innovative High Temperature Short Time (HTST) system (patented&#xD;
      by researchers) retains more immune and trophic compounds than pasteurized milk by&#xD;
      traditional Holder method. These compounds are related to the protection conferred by breast&#xD;
      milk against nosocomial sepsis and necrotizing enterocolitis in preterm infants, so it would&#xD;
      be of interest to study if there is a clinical benefit in these patients when health&#xD;
      professionals are supplementing with donor milk pasteurized by both methods.&#xD;
&#xD;
      The purpose of this study is to compare the incidence of microbiological proven late onset&#xD;
      sepsis in newborns under 1000 grams that in the first 28 days of life need to be supplemented&#xD;
      with donor milk pasteurized by HTST method versus the Holder method.&#xD;
&#xD;
      This is a randomized double-blind clinical trial with parallel assignment. A total of 305&#xD;
      premature babies with a birth weight of less than 1000 grams will be recruited, admitted to&#xD;
      the Neonatology Services of the Hospital 12 de Octubre and the Hospital de La Paz and meet&#xD;
      the inclusion criteria. Half of the patients will be supplemented exclusively with donor milk&#xD;
      pasteurized by the HTST system and the other half with pasteurized milk by the Holder method.&#xD;
      Linear generalized models will be used for longitudinal data analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 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>
    <intervention_model_description>Parallel assignment</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Microbiological proven late onset sepsis rate</measure>
    <time_frame>From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks</time_frame>
    <description>Incidence of Microbiological proven late onset sepsis expressed as a percentage</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Central line associated bloodstream infections (CLABSI) rate</measure>
    <time_frame>From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks</time_frame>
    <description>Number of CLABSI events per 1000 catheter-days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Necrotizing enterocolitis (NEC) and/or microbiological proven late onset sepsis rate</measure>
    <time_frame>From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks</time_frame>
    <description>Incidence of NEC nad late onset sepsis as a percentage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality rate</measure>
    <time_frame>From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks</time_frame>
    <description>Percentage of preterm infant died during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen supplementation</measure>
    <time_frame>Assessed up to 24 weeks</time_frame>
    <description>Percentage of infants with respiratory assistance with fraction of inspired oxygen greater than 0.21 at 36 weeks postmenstrual age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage 3-5 Retinopathy</measure>
    <time_frame>From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks</time_frame>
    <description>Percentage of infants diagnosed with retinopathy by the ophthalmologist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth velocity</measure>
    <time_frame>Assessed up to 24 weeks</time_frame>
    <description>Growth calculated as the weight gain in g/kg/day</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">211</enrollment>
  <condition>Late-Onset Neonatal Sepsis</condition>
  <arm_group>
    <arm_group_label>Holder pasteurization</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Donor milk pasteurized by Holder method (62.5ºC, 30 minutes)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HTST pasteurization</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Donor milk pasteurized by High Temperature Short Time (HTST) method (72ºC, 15 seconds)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>donor milk</intervention_name>
    <description>pasteurized donor milk</description>
    <arm_group_label>HTST pasteurization</arm_group_label>
    <arm_group_label>Holder pasteurization</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (all criteria are necessary) :&#xD;
&#xD;
          -  Infants weighing 1000 grams or less at birth&#xD;
&#xD;
          -  Infants born or transferred before the third day of life to the participating centers&#xD;
&#xD;
          -  Start enteral feeding in the first week of life&#xD;
&#xD;
          -  Receive any amount of donor milk in the first 28 days of life&#xD;
&#xD;
          -  Informed consent signed by parents or legal guardians&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Language barrier&#xD;
&#xD;
          -  Infants with chromosomopathies&#xD;
&#xD;
          -  Infants with major congenital malformations&#xD;
&#xD;
          -  Infants with severe asphyxiation (cord pH or first arterial pH &lt;7)&#xD;
&#xD;
          -  Infants included in another clinical trial that modifies nutritional management&#xD;
&#xD;
          -  Infants who previously fed with formula&#xD;
&#xD;
        Post-randomization exclusion criteria:&#xD;
&#xD;
        - Randomized infant who do not fulfill inclusion criteria&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>28 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carmen Rosa Pallas Alonso</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Universitario 12 de Octubre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitario 12 de Octubre</investigator_affiliation>
    <investigator_full_name>Carmen Rosa Pallas</investigator_full_name>
    <investigator_title>Head of Neonatology Service, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>neonatal sepsis</keyword>
  <keyword>extremely low birth weight infant</keyword>
  <keyword>donor milk</keyword>
  <keyword>HTST pasteurization</keyword>
  <keyword>Holder pasteurization</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neonatal Sepsis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04424667
org study id: Neo-HTST
nct id: NCT04424667
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Randomized double-blind clinical trial to compare the incidence of microbiological proven
      late onset sepsis in extremely preterm infants (<1000 grams) that are supplemented with donor
      milk pasteurized by High Temperature Short Time (HTST) method versus the Holder method.
Donor milk pasteurized by an innovative High Temperature Short Time (HTST) system (patented
      by researchers) retains more immune and trophic compounds than pasteurized milk by
      traditional Holder method. These compounds are related to the protection conferred by breast
      milk against nosocomial sepsis and necrotizing enterocolitis in preterm infants, so it would
      be of interest to study if there is a clinical benefit in these patients when health
      professionals are supplementing with donor milk pasteurized by both methods.

      The purpose of this study is to compare the incidence of microbiological proven late onset
      sepsis in newborns under 1000 grams that in the first 28 days of life need to be supplemented
      with donor milk pasteurized by HTST method versus the Holder method.

      This is a randomized double-blind clinical trial with parallel assignment. A total of 305
      premature babies with a birth weight of less than 1000 grams will be recruited, admitted to
      the Neonatology Services of the Hospital 12 de Octubre and the Hospital de La Paz and meet
      the inclusion criteria. Half of the patients will be supplemented exclusively with donor milk
      pasteurized by the HTST system and the other half with pasteurized milk by the Holder method.
      Linear generalized models will be used for longitudinal data analysis.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Microbiological proven late onset sepsis rate
time frame: From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks
description: Incidence of Microbiological proven late onset sepsis expressed as a percentage
measure: Central line associated bloodstream infections (CLABSI) rate
time frame: From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks
description: Number of CLABSI events per 1000 catheter-days
measure: Necrotizing enterocolitis (NEC) and/or microbiological proven late onset sepsis rate
time frame: From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks
description: Incidence of NEC nad late onset sepsis as a percentage
measure: Mortality rate
time frame: From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks
description: Percentage of preterm infant died during the study
measure: Oxygen supplementation
time frame: Assessed up to 24 weeks
description: Percentage of infants with respiratory assistance with fraction of inspired oxygen greater than 0.21 at 36 weeks postmenstrual age
measure: Stage 3-5 Retinopathy
time frame: From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks
description: Percentage of infants diagnosed with retinopathy by the ophthalmologist
measure: Growth velocity
time frame: Assessed up to 24 weeks
description: Growth calculated as the weight gain in g/kg/day
arm group label: Holder pasteurization
arm group type: Active Comparator
description: Donor milk pasteurized by Holder method (62.5ºC, 30 minutes)
arm group label: HTST pasteurization
arm group type: Experimental
description: Donor milk pasteurized by High Temperature Short Time (HTST) method (72ºC, 15 seconds)
intervention type: Other
intervention name: donor milk
description: pasteurized donor milk
arm group label: HTST pasteurization
arm group label: Holder pasteurization
criteria: 
gender: All
minimum age: N/A
maximum age: 28 Days
healthy volunteers: No
last name: Carmen Rosa Pallas Alonso
role: Study Chair
affiliation: Hospital Universitario 12 de Octubre
facility: 
facility: 
country: Spain
responsible party type: Sponsor-Investigator
investigator affiliation: Hospital Universitario 12 de Octubre
investigator full name: Carmen Rosa Pallas
investigator title: Head of Neonatology Service, MD, PhD
mesh term: Neonatal Sepsis
sharing ipd: No