MORDOR II Burkina Faso: Longitudinal Trial
Condition: Child Growth; Diversity of Microbiome; Child Mortality; Resistance Bacterial
Intervention: Azithromycin; Placebo
Intervention description: Zithromax® for oral suspension is supplied in bottles containing azithromycin dehydrate powder equivalent to 1200mg per bottle and the following inactive ingredients: sucrose; tribasic anhydrous sodium phosphate; hydroxypropyl cellulose; xanthan gum; FD&C Red #40; and flavoring including spray dried artificial cherry, crème de vanilla, and banana. After constitution, a 5mL suspension contains 200mg of azithromycin.; Oral suspension of placebo for azithromycin
Intervention MeSH terms: Azithromycin
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Individually randomized placebo-controlled trail of azithromycin vs. placebo to establish the efficacy and safety of azithromycin.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Quadruple: (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 500.0
Sex: All
Minimum age: 8 Days
Maximum age: 59 Months
Healthy volunteers: Accepts Healthy Volunteers
Keywords: azithromycin; mass drug administration; childhood mortality

Summary:

      Globally, childhood mortality has shown a promising downward trend in recent years, however,
      many sub-Saharan countries still have relatively high child mortality rates. In previous
      studies within Niger, Tanzania, and Malawi, mass azithromycin treatment to children aged 1-59
      months old effectively reduced all-cause childhood mortality. A similar study will be
      conducted in Burkina Faso to replicate the results of mass azithromycin treatment.

      The investigators propose an individually randomized placebo-controlled trial alongside the
      MORDOR II Burkina Faso trial to evaluate the effect of a single dose of azithromycin (20
      mg/kg) on potential mediators of the effect of azithromycin on all-cause mortality. Many
      questions surround the mechanism behind azithromycin's effect on reducing childhood
      mortality. Further questions exist regarding antibiotic resistance and how mass antibiotic
      administration can impact intestinal microflora. The goal of this study is to demonstrate the
      changes in the gut microbiome after antibiotic administration and to measure the growth of
      children after receiving a single dose of azithromycin. Additionally we will measure
      resistance markers, inflammatory markers, and IgA-bound bacteria. We hypothesize that a
      single dose of azithromycin will lead to a significant increase in child growth and that the
      gut microbiome will be significantly different in children who received azithromycin compared
      to those who received placebo.

      Objectives:

        1. . To determine the effect of a single dose of azithromycin for children aged 8 days-59
           months on longitudinal changes in the intestinal microbiome over a 6-month period. We
           hypothesize that a single dose of azithromycin will result in a significant difference
           in the intestinal microbiome within the treatment group compared to the placebo group
           after a 6-month period within children ages 8 days-59 months.

        2. . To determine the effect of a single dose of azithromycin for children aged 8 days-59
           months on child growth over a 6-month period. We hypothesize that a single dose of
           azithromycin will increase child growth over a 6-month period in children aged 8 days-59
           months.

        3. . To determine the effect of a single dose of azithromycin for children aged 8 days to
           59 months on the presence of macrolide genetic resistance determinants within the first
           two weeks post-treatment. The investigators hypothesize that a single dose of
           azithromycin will increase the presence of macrolide resistance determinants over a 2
           week period in children aged 8 days to 59 months.

      The study will be conducted in Nouna Town in northwestern Burkina Faso.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Between 8 days and 59 months old

          -  Primary residence within catchment area of study site

          -  Available for full 6 month study

          -  No known allergy to macrolides/azalides

          -  Appropriate written informed consent from at least one parent or guardian

          -  Able to feed orally

        Exclusion Criteria:

          -  <8 days old or >59 months

          -  Primary residence outside catchment area of study site

          -  Not available for full 6 month study

          -  Known allergy to macrolides/azalides

          -  No written informed consent from at least one parent or guardian

          -  Unable to feed orally