Vitamin-D Supplementation: Impact on Severe Pneumonia Among Under-five Children
Condition: Pneumonia
MeSH terms: Pneumonia
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Vitamin D3; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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; 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
Other intervention name(s): Vigantol-oil; Miglyol Oil
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Vitamin D,; Severe pneumonia,; Under-five children,; Randomised; Controlled; Trial (RCT); Morbidity