<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/NCT02226263</url>
  </required_header>
  <id_info>
    <org_study_id>R-2010-1002-12</org_study_id>
    <nct_id>NCT02226263</nct_id>
  </id_info>
  <brief_title>Severe Necrotizing Enterocolitis in Preterm Newborns &lt;1500g Using Probiotics</brief_title>
  <acronym>EPP</acronym>
  <official_title>Incidence of Severe Necrotizing Enterocolitis in Preterm Newborns &lt;1500g Using Probiotics Lactobacillus Boucardii.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Coordinación de Investigación en Salud, Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Coordinación de Investigación en Salud, Mexico</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to know the effects of probiotics on the incidence of&#xD;
      Necrotizing Enterocolitis (NEC) in preterm infants less than 1500 g.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators performed a clinical, randomized, double-blind trial in preterm infants&#xD;
      &lt;1500g from March 1, 2010 to February 28, 2012. Group A received enteral stimulation trophic&#xD;
      five days and later increments 20ml/k/day of breast milk or formula for premature; the group&#xD;
      B apart from the above the probiotic Lactobacillus acidophilus (boucardii strain) 1 X109&#xD;
      colonic forming unit (CFU)/ day for 4 weeks was added. Gastric tolerance, evolution, reason&#xD;
      for discharge, and the development of Necrotizing enterocolitis was monitored. The diagnosis&#xD;
      of Necrotizing enterocolitis was made by the treating physician according to Bell's criteria&#xD;
      and was blinded to group assignments.The formulas were prepared by one of the investigators&#xD;
      according to the group each patient was assigned. Using sterile technique, the probiotic with&#xD;
      1x109 (CFU) Lactobacillus acidophilus (boucardii strain) was added at a dose of 125 mg/&#xD;
      kg/dose twice daily for 4 weeks to fresh supplement breast milk or formula for preterm&#xD;
      infants. In case of control group only breast milk or formula for preterm infants was used.&#xD;
&#xD;
      All formulas were labeled for each patient and were delivered to the nurse in charge of&#xD;
      infant feeding at 9:00 and 21:00 h.&#xD;
&#xD;
      Characteristics of Sample size and statistical analysis:&#xD;
&#xD;
      Sample size showed that the investigators needed 190 total preterm infants, based on the&#xD;
      expected 50% decrease in the incidence of severe necrotizing enterocolitis in preterm&#xD;
      neonates who received probiotics compared with control group with α 0.05 and β 0.20.&#xD;
      Student´s t test or Mann Whitney U test were performed for mean differences regarding the&#xD;
      general characteristics in the two study groups, Chi square or Fisher´s test for differences&#xD;
      in proportions for mortality and complications between groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2010</start_date>
  <completion_date type="Actual">February 2012</completion_date>
  <primary_completion_date type="Actual">February 2012</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of severe necrotizing enterocolitis in preterm newborns &lt;1500g</measure>
    <time_frame>23 month</time_frame>
    <description>Group A received enteral stimulation trophic five days and later increments 20ml/k/day of breast milk or formula for premature; the group B apart from the above the probiotic Lactobacillus boucardii 1 X109 (CFU) / day for 4 weeks was added.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse effects with probiotic use in preterm newborns &lt;1500g.</measure>
    <time_frame>23 month</time_frame>
    <description>The amount of food was increased slowly if tolerated according to the Clinical Practice Guidelines for enteral feeding preterm in our hospital, enteral feeding was interrupted if there was any sign of intolerance such as vomiting, presence of bile or blood content by probe orogastric, bloating, or bloody stools which were assessed and recorded daily.Our primary outcome was the presence of severe necrotizing enterocolitis (NEC) monitored by the Bell´s criteria; secondarily we evaluated the presence of sepsis diagnosed with clinical signs of systemic inflammatory response and positive blood culture.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Diagnosis the Necrotizing Enterocolitis (NEC)</measure>
    <time_frame>23 month</time_frame>
    <description>Our primary outcome was the presence of severe (NEC) monitored by the Bell´s criteria; secondarily we evaluated the presence of sepsis diagnosed with clinical signs of systemic inflammatory response and positive blood culture,</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Infectious Diseases</condition>
  <arm_group>
    <arm_group_label>probiotics Lactobacillus acidophilus boucardii strain.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lactobacillus acidophilus boucardii strain was added at a dose of 125 mg/ kg/dose twice daily for 4 weeks .The probiotic presentation used was powder in an envelope with 160mg (Carnot ® Laboratories), scientific products, Mexico, (Registration Number 274M91SSA). This was stored in a dry place at room temperature, avoiding sunlight.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>probiotics Lactobacillus acidophilus boucardii</intervention_name>
    <description>Using sterile technique, the probiotic with 1x109 [CFU] Lactobacillus acidophilus boucardii strain was added at a dose of 125 mg/ kg/dose twice daily for 4 weeks to fresh supplement breast milk or formula for preterm infants.</description>
    <arm_group_label>probiotics Lactobacillus acidophilus boucardii strain.</arm_group_label>
    <other_name>Gastric tolerance, characteristics of discharges, evolution, reason for discharge, and the development of NEC was monitored.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  We studied 150 preterm newborns &lt;1500gr who were recruited on the day that began&#xD;
             enteral feeding according to the decision of the treating physician.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Preterm infants &gt; 1500g with Apgar score &lt;6 at 5 minutes, gastrointestinal&#xD;
             malformations, fetopathies, patent ductus arteriosis with hemodynamic decompensation,&#xD;
             asphyxia, and NEC suspected as classified by Bell were excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>27 Weeks</minimum_age>
    <maximum_age>34 Weeks</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guadalupe Gómez, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad de Guanajuato</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto Mexicano del seguro social</name>
      <address>
        <city>Leon</city>
        <state>Guanajuato</state>
        <zip>37000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>August 25, 2014</last_update_submitted>
  <last_update_submitted_qc>August 25, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 27, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Coordinación de Investigación en Salud, Mexico</investigator_affiliation>
    <investigator_full_name>Guadalupe Gómez Rodríguez</investigator_full_name>
    <investigator_title>neonatologist</investigator_title>
  </responsible_party>
  <keyword>Necrotizing enterocolitis</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Preterm newborns</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Infections</mesh_term>
    <mesh_term>Enterocolitis</mesh_term>
    <mesh_term>Enterocolitis, Necrotizing</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>October 15, 2015</submitted>
    <returned>November 17, 2015</returned>
    <submitted>January 22, 2016</submitted>
    <returned>February 18, 2016</returned>
    <submitted>March 1, 2016</submitted>
    <returned>March 30, 2016</returned>
    <submitted>December 23, 2016</submitted>
    <returned>February 15, 2017</returned>
    <submitted>September 14, 2017</submitted>
    <returned>April 6, 2018</returned>
    <submitted>September 2, 2022</submitted>
    <returned>July 25, 2023</returned>
  </pending_results>
  <!-- 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/NCT02226263
org study id: R-2010-1002-12
nct id: NCT02226263
lead sponsor: 
has dmc: No
The purpose of this study is to know the effects of probiotics on the incidence of
      Necrotizing Enterocolitis (NEC) in preterm infants less than 1500 g.
The investigators performed a clinical, randomized, double-blind trial in preterm infants
      <1500g from March 1, 2010 to February 28, 2012. Group A received enteral stimulation trophic
      five days and later increments 20ml/k/day of breast milk or formula for premature; the group
      B apart from the above the probiotic Lactobacillus acidophilus (boucardii strain) 1 X109
      colonic forming unit (CFU)/ day for 4 weeks was added. Gastric tolerance, evolution, reason
      for discharge, and the development of Necrotizing enterocolitis was monitored. The diagnosis
      of Necrotizing enterocolitis was made by the treating physician according to Bell's criteria
      and was blinded to group assignments.The formulas were prepared by one of the investigators
      according to the group each patient was assigned. Using sterile technique, the probiotic with
      1x109 (CFU) Lactobacillus acidophilus (boucardii strain) was added at a dose of 125 mg/
      kg/dose twice daily for 4 weeks to fresh supplement breast milk or formula for preterm
      infants. In case of control group only breast milk or formula for preterm infants was used.

      All formulas were labeled for each patient and were delivered to the nurse in charge of
      infant feeding at 9:00 and 21:00 h.

      Characteristics of Sample size and statistical analysis:

      Sample size showed that the investigators needed 190 total preterm infants, based on the
      expected 50% decrease in the incidence of severe necrotizing enterocolitis in preterm
      neonates who received probiotics compared with control group with α 0.05 and β 0.20.
      Student´s t test or Mann Whitney U test were performed for mean differences regarding the
      general characteristics in the two study groups, Chi square or Fisher´s test for differences
      in proportions for mortality and complications between groups.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Incidence of severe necrotizing enterocolitis in preterm newborns <1500g
time frame: 23 month
description: Group A received enteral stimulation trophic five days and later increments 20ml/k/day of breast milk or formula for premature; the group B apart from the above the probiotic Lactobacillus boucardii 1 X109 (CFU) / day for 4 weeks was added.
measure: Adverse effects with probiotic use in preterm newborns <1500g.
time frame: 23 month
description: The amount of food was increased slowly if tolerated according to the Clinical Practice Guidelines for enteral feeding preterm in our hospital, enteral feeding was interrupted if there was any sign of intolerance such as vomiting, presence of bile or blood content by probe orogastric, bloating, or bloody stools which were assessed and recorded daily.Our primary outcome was the presence of severe necrotizing enterocolitis (NEC) monitored by the Bell´s criteria; secondarily we evaluated the presence of sepsis diagnosed with clinical signs of systemic inflammatory response and positive blood culture.
measure: Diagnosis the Necrotizing Enterocolitis (NEC)
time frame: 23 month
description: Our primary outcome was the presence of severe (NEC) monitored by the Bell´s criteria; secondarily we evaluated the presence of sepsis diagnosed with clinical signs of systemic inflammatory response and positive blood culture,
arm group label: probiotics Lactobacillus acidophilus boucardii strain.
arm group type: Experimental
description: Lactobacillus acidophilus boucardii strain was added at a dose of 125 mg/ kg/dose twice daily for 4 weeks .The probiotic presentation used was powder in an envelope with 160mg (Carnot ® Laboratories), scientific products, Mexico, (Registration Number 274M91SSA). This was stored in a dry place at room temperature, avoiding sunlight.
intervention type: Dietary Supplement
intervention name: probiotics Lactobacillus acidophilus boucardii
description: Using sterile technique, the probiotic with 1x109 [CFU] Lactobacillus acidophilus boucardii strain was added at a dose of 125 mg/ kg/dose twice daily for 4 weeks to fresh supplement breast milk or formula for preterm infants.
arm group label: probiotics Lactobacillus acidophilus boucardii strain.
other name: Gastric tolerance, characteristics of discharges, evolution, reason for discharge, and the development of NEC was monitored.
criteria: 
gender: All
minimum age: 27 Weeks
maximum age: 34 Weeks
healthy volunteers: Accepts Healthy Volunteers
last name: Guadalupe Gómez, M.D.
role: Principal Investigator
affiliation: Universidad de Guanajuato
facility: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: Coordinación de Investigación en Salud, Mexico
investigator full name: Guadalupe Gómez Rodríguez
investigator title: neonatologist
mesh term: Communicable Diseases
mesh term: Infections
mesh term: Enterocolitis
mesh term: Enterocolitis, Necrotizing
submitted: October 15, 2015
returned: November 17, 2015
submitted: January 22, 2016
returned: February 18, 2016
submitted: March 1, 2016
returned: March 30, 2016
submitted: December 23, 2016
returned: February 15, 2017
submitted: September 14, 2017
returned: April 6, 2018
submitted: September 2, 2022
returned: July 25, 2023