<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/NCT02185196</url>
  </required_header>
  <id_info>
    <org_study_id>PR-13088</org_study_id>
    <nct_id>NCT02185196</nct_id>
  </id_info>
  <brief_title>Vitamin-D Supplementation: Impact on Severe Pneumonia Among Under-five Children</brief_title>
  <acronym>Vitamin-D</acronym>
  <official_title>Vitamin D Supplementation: Impact on Severe Pneumonia Among Under-five Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Centre for Diarrhoeal Disease Research, Bangladesh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>International Centre for Diarrhoeal Disease Research, Bangladesh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
        -  Burden: Pneumonia is the leading cause of morbidity and mortality in under-five&#xD;
           children, particularly in developing countries.&#xD;
&#xD;
        -  Knowledge gap: Although many studies have reported an association between vitamin D&#xD;
           deficiency and pneumonia, there is lack in information on its therapeutic impact, i.e.&#xD;
           the impact of vitamin D supplementation in the management of childhood pneumonia.&#xD;
&#xD;
        -  Relevance: Vitamin D plays an important role in modulating the innate immune response&#xD;
           against infections. We, therefore, propose to conduct this study to assess the impact of&#xD;
           vitamin D supplementation, in addition to standard antibiotic and supportive therapy, on&#xD;
           the outcome of severe childhood pneumonia.&#xD;
&#xD;
      Hypothesis: The investigators hypothesise that in the management of hospitalized severe&#xD;
      pneumonia in under-five children, vitamin D3 supplementation, as an adjunct to the standard&#xD;
      antibiotic and other supportive therapy, will hasten recover from severe pneumonia and may&#xD;
      thereby shorten duration of severe pneumonia and also reduce the risk of new episode of&#xD;
      pneumonia.&#xD;
&#xD;
      Objectives: The objective of the investigators study is to assess the clinical benefit of&#xD;
      oral supplementation of vitamin D3, in addition to standard antibiotic and other supportive&#xD;
      therapy, to hospitalised, under-five children with severe pneumonia.&#xD;
&#xD;
      Methods: This would be a randomised, double blind, controlled clinical trial (RCT). Children&#xD;
      of either sex, aged 3-59 months, attending the Dhaka Hospital of icddr,b, with clinically&#xD;
      diagnosed severe pneumonia will comprise the study population. Eligible children will be&#xD;
      allotted a sequential study number, which will have been previously assigned to vitamin D or&#xD;
      placebo in accordance with the randomisation. The study staff and mothers/ caregivers of the&#xD;
      children will be blinded as to whether vitamin D3 or placebo has been added to their child's&#xD;
      diet. Infants aged 3-5 months will receive breast milk and/or infant formula, and those 6&#xD;
      months or older will receive &quot;Milk Suji&quot; as a complementary food. Vitamin D3 supplementation&#xD;
      will be given on five consecutive days, from the day of enrolment in addition to standard&#xD;
      antibiotic and other supportive therapy.&#xD;
&#xD;
      Outcome measures/variables:&#xD;
&#xD;
      Primary outcome measure will be time to resolution of severe pneumonia.&#xD;
&#xD;
      Secondary outcome measures will be duration of hospitalization, fever, tachypnoea, chest in&#xD;
      drawing, hypoxia, lethargy and inability to feed during hospital stay and as well as new&#xD;
      episode of pneumonia after discharge.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis to be tested:&#xD;
&#xD;
      In a hypothesis testing research proposal, briefly mention the hypothesis to be tested and&#xD;
      provide the scientific basis of the hypothesis, critically examining the observations leading&#xD;
      to the formulation of the hypothesis.&#xD;
&#xD;
      Does this research proposal involve testing of hypothesis: 0 No 1 Yes (describe below)&#xD;
&#xD;
      The investigators hypothesise that supplementation of vitamin D3 (Cholecalciferol), in&#xD;
      addition to standard antibiotic and other supportive therapy in the management of under-five&#xD;
      children with severe pneumonia will significantly shorten the duration of severity of&#xD;
      pneumonia and thereby reduce hospital stay and also reduce the risk of new episode of&#xD;
      pneumonia.&#xD;
&#xD;
      Specific Objectives:&#xD;
&#xD;
      Objective: To assess the clinical benefit of oral vitamin D3 supplementation, in addition to&#xD;
      standard antibiotic and other supportive therapy, in the management of hospitalised,&#xD;
      under-five children with severe pneumonia.&#xD;
&#xD;
      Primary objective: To compare the duration of severe pneumonia of children in the two study&#xD;
      groups receiving the standard therapy (appropriate antibiotic and other supportive therapy)&#xD;
      with those receiving vitamin D supplementation in addition to the standard therapy.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        -  To compare the duration of hospitalization, fever, tachypnoea, chest in drawing,&#xD;
           hypoxia, lethargy and inability to feed during hospital stay, in under-five children in&#xD;
           the two study groups, as mentioned under the primary aim.&#xD;
&#xD;
        -  To compare the recurrence of new episode of pneumonia over the next 6 months after&#xD;
           discharge from hospital in the two study groups.&#xD;
&#xD;
        -  To identify the optimum safety dose of vitamin D3 for different groups of under-five&#xD;
           children.&#xD;
&#xD;
        -  In severe pneumonia patient who also have acute watery diarrhoea we will assess the&#xD;
           indirect absorption of vitamin D by measuring serum vitamin D level and will also assess&#xD;
           the clinical outcome in the subgroup.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</primary_completion_date>
  <phase>Phase 1</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time taken for recovery from severe pneumonia</measure>
    <time_frame>12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time taken for normalisation of temperature</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time taken for normalisation of respiratory rate</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time taken for recovery from chest in drawing</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time taken for oxygen saturation to normalise</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time taken for normalization of mental status</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time taken for normalization of child feeding</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of study children who will develop new episode of pneumonia during the follow up period</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">197</enrollment>
  <condition>Pneumonia</condition>
  <arm_group>
    <arm_group_label>Vitamin D3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3, Doses form: 20,000 IU vitamin D3 in children &lt;6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Miglyol-oil</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>20,000 IU Miglyol-oil in children &lt;6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3</intervention_name>
    <description>20,000 IU vitamin D3 in children &lt;6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days</description>
    <arm_group_label>Vitamin D3</arm_group_label>
    <other_name>Vigantol-oil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>20,000 IU Miglyol-oil in children &lt;6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days</description>
    <arm_group_label>Miglyol-oil</arm_group_label>
    <other_name>Miglyol Oil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children of either sex aged 3 - 59 months, with a clinical diagnosis of severe&#xD;
             pneumonia with or without diarrhea.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known case of hypercalcaemia or allergy to vitamin D, as determined by history or&#xD;
             previous medical records.&#xD;
&#xD;
          2. Congenital Heart disease, evidenced by clinical exam or past medical records.&#xD;
&#xD;
          3. Renal or hepatic insufficiency, evidenced by clinical exams or past medical records.&#xD;
&#xD;
          4. Known case of tuberculosis, evidenced by medical records&#xD;
&#xD;
          5. Known case of asthma, evidenced by history and clinical exam findings.&#xD;
&#xD;
          6. Critically ill children requiring ICU care, such as those with septic shock or cardiac&#xD;
             arrest or apnoea.&#xD;
&#xD;
          7. Received vitamin D or calcium supplementation within the last 4 weeks before current&#xD;
             admission, as evidenced by history or medical prescription.&#xD;
&#xD;
          8. Any children diagnosed as hypernatraemia during the main phase of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Months</minimum_age>
    <maximum_age>59 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fahmida Chowdhury, MBBS, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>International Centre for Diarrhoeal Disease Research, Bangladesh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh</name>
      <address>
        <city>Dhaka</city>
        <zip>1212</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bangladesh</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>June 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>August 5, 2019</last_update_submitted>
  <last_update_submitted_qc>August 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vitamin D,</keyword>
  <keyword>Severe pneumonia,</keyword>
  <keyword>Under-five children,</keyword>
  <keyword>Randomised</keyword>
  <keyword>Controlled</keyword>
  <keyword>Trial (RCT)</keyword>
  <keyword>Morbidity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02185196
org study id: PR-13088
nct id: NCT02185196
lead sponsor: 
collaborator: 
has dmc: Yes
Background:

        -  Burden: Pneumonia is the leading cause of morbidity and mortality in under-five
           children, particularly in developing countries.

        -  Knowledge gap: Although many studies have reported an association between vitamin D
           deficiency and pneumonia, there is lack in information on its therapeutic impact, i.e.
           the impact of vitamin D supplementation in the management of childhood pneumonia.

        -  Relevance: Vitamin D plays an important role in modulating the innate immune response
           against infections. We, therefore, propose to conduct this study to assess the impact of
           vitamin D supplementation, in addition to standard antibiotic and supportive therapy, on
           the outcome of severe childhood pneumonia.

      Hypothesis: The investigators hypothesise that in the management of hospitalized severe
      pneumonia in under-five children, vitamin D3 supplementation, as an adjunct to the standard
      antibiotic and other supportive therapy, will hasten recover from severe pneumonia and may
      thereby shorten duration of severe pneumonia and also reduce the risk of new episode of
      pneumonia.

      Objectives: The objective of the investigators study is to assess the clinical benefit of
      oral supplementation of vitamin D3, in addition to standard antibiotic and other supportive
      therapy, to hospitalised, under-five children with severe pneumonia.

      Methods: This would be a randomised, double blind, controlled clinical trial (RCT). Children
      of either sex, aged 3-59 months, attending the Dhaka Hospital of icddr,b, with clinically
      diagnosed severe pneumonia will comprise the study population. Eligible children will be
      allotted a sequential study number, which will have been previously assigned to vitamin D or
      placebo in accordance with the randomisation. The study staff and mothers/ caregivers of the
      children will be blinded as to whether vitamin D3 or placebo has been added to their child's
      diet. Infants aged 3-5 months will receive breast milk and/or infant formula, and those 6
      months or older will receive "Milk Suji" as a complementary food. Vitamin D3 supplementation
      will be given on five consecutive days, from the day of enrolment in addition to standard
      antibiotic and other supportive therapy.

      Outcome measures/variables:

      Primary outcome measure will be time to resolution of severe pneumonia.

      Secondary outcome measures will be duration of hospitalization, fever, tachypnoea, chest in
      drawing, hypoxia, lethargy and inability to feed during hospital stay and as well as new
      episode of pneumonia after discharge.
Hypothesis to be tested:

      In a hypothesis testing research proposal, briefly mention the hypothesis to be tested and
      provide the scientific basis of the hypothesis, critically examining the observations leading
      to the formulation of the hypothesis.

      Does this research proposal involve testing of hypothesis: 0 No 1 Yes (describe below)

      The investigators hypothesise that supplementation of vitamin D3 (Cholecalciferol), in
      addition to standard antibiotic and other supportive therapy in the management of under-five
      children with severe pneumonia will significantly shorten the duration of severity of
      pneumonia and thereby reduce hospital stay and also reduce the risk of new episode of
      pneumonia.

      Specific Objectives:

      Objective: To assess the clinical benefit of oral vitamin D3 supplementation, in addition to
      standard antibiotic and other supportive therapy, in the management of hospitalised,
      under-five children with severe pneumonia.

      Primary objective: To compare the duration of severe pneumonia of children in the two study
      groups receiving the standard therapy (appropriate antibiotic and other supportive therapy)
      with those receiving vitamin D supplementation in addition to the standard therapy.

      Secondary objectives:

        -  To compare the duration of hospitalization, fever, tachypnoea, chest in drawing,
           hypoxia, lethargy and inability to feed during hospital stay, in under-five children in
           the two study groups, as mentioned under the primary aim.

        -  To compare the recurrence of new episode of pneumonia over the next 6 months after
           discharge from hospital in the two study groups.

        -  To identify the optimum safety dose of vitamin D3 for different groups of under-five
           children.

        -  In severe pneumonia patient who also have acute watery diarrhoea we will assess the
           indirect absorption of vitamin D by measuring serum vitamin D level and will also assess
           the clinical outcome in the subgroup.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time taken for recovery from severe pneumonia
time frame: 12 months
measure: Duration of hospitalization
time frame: 12 months
measure: Time taken for normalisation of temperature
time frame: 12 months
measure: Time taken for normalisation of respiratory rate
time frame: 12 months
measure: Time taken for recovery from chest in drawing
time frame: 12 months
measure: Time taken for oxygen saturation to normalise
time frame: 12 months
measure: Time taken for normalization of mental status
time frame: 12 months
measure: Time taken for normalization of child feeding
time frame: 12 months
measure: Proportion of study children who will develop new episode of pneumonia during the follow up period
time frame: 12 months
arm group label: Vitamin D3
arm group type: Active Comparator
description: Vitamin D3, Doses form: 20,000 IU vitamin D3 in children <6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days.
arm group label: Miglyol-oil
arm group type: Placebo Comparator
description: 20,000 IU Miglyol-oil in children <6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days.
intervention type: Drug
intervention name: Vitamin D3
description: 20,000 IU vitamin D3 in children <6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days
arm group label: Vitamin D3
other name: Vigantol-oil
intervention type: Drug
intervention name: Placebo
description: 20,000 IU Miglyol-oil in children <6 months, 50,000 IU in children 6-12 months and 1,00,000 IU in children 13-59 months of age on first day and thereafter 10,000 IU for next 4 days
arm group label: Miglyol-oil
other name: Miglyol Oil
criteria: 
gender: All
minimum age: 3 Months
maximum age: 59 Months
healthy volunteers: No
last name: Fahmida Chowdhury, MBBS, MPH
role: Principal Investigator
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
facility: 
country: Bangladesh
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Vitamin D
mesh term: Cholecalciferol