CHIZAP: Community- and Health Facility-Based Intervention With Zinc as Adjuvant Therapy for Childhood Pneumonia
Condition: Pneumonia
MeSH terms: Pneumonia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of the study described is to measure the degree with which zinc given as adjunct
      therapy to standard antibiotic treatment during childhood pneumonia reduces the risk of
      treatment failure and the duration of the illness.
    

Detailed description: 
      Hypothesis: Zinc deficiency is a major public health problem in developing counties. Poor
      zinc status is associated with stunted growth and reduced resistance to infections. Several
      in vitro experiments and in vivo studies in animals and humans have demonstrated detrimental
      effects of zinc depletion on almost all facets of the immune system. The epithelial linings
      in the gut and in the respiratory tract are important for the resistance to infections and
      continuous cell division is required for proper function of these barriers. Zinc is crucial
      for cellular division and for the maintenance of organs with cells with a rapid turnover,
      including epithelial cells. Clinical trials in children in developing countries have
      demonstrated improved growth and reduced prevalence of diarrhea and respiratory tract
      infections following zinc supplementation. Furthermore, zinc has a well-documented
      therapeutic effect when given during acute or persistent diarrhea. The effect of zinc may be
      explained by correction of a deficiency state and/or by a pharmacological, as yet poorly
      described, action.

      Due to the promising results from previous studies, WHO are now supporting large clinical
      trials in Nepal, India and Tanzania to assess whether routine zinc supplementation reduces
      mortality in early childhood. If the results of these trials show a mortality reduction,
      routine zinc supplementation or zinc dense foods may be promoted. However, while the first
      approach is logistically difficult and expensive, the second approach is difficult because
      zinc dense foods and foods with low phytic acid content are expensive and not readily
      available. Moreover, both approaches may be perceived to be incompatible with the current
      breast-feeding recommendations for the youngest children in most developing countries.

      There is limited information on zinc as adjunct therapy for pneumonia. A recent
      hospital-based study in young children with severe pneumonia, showed that the zinc group had
      a faster recovery, resulting in a shortening of stay in hospital of one day. However, this
      study was small and no community based study has been conducted so far. Whether zinc has an
      effect during respiratory infections has to be assessed in studies with larger sample sizes
      in children with less severe disease and should be repeated in children with more severe
      disease. Short-term zinc administration during infections may become an alternative or an
      addition to long-term supplementation or promotion of zinc dense foods. Furthermore,
      therapeutic administration of zinc will not interfere with the current breast-feeding
      recommendations.

      Hypothesis: Zinc as adjunct therapy for pneumonia may lead to faster recovery. Furthermore,
      long-term beneficial effects may include improved immuno-nutritional status measured by
      thymus size, less morbidity and improved growth.

      Comparison: Duration of illness, risk of treatment failure, for those with severe pneumonia:
      length of hospital stay. Number of non-injury clinic visits and hospitalizations during the
      intervention with Zinc and an in a 6 month period after enrolment. Growth assessed by
      anthropometry and thymus size assessed by ultrasonography. Explore the efficacy of zinc in
      etiology-sub groups including those defined by nutritional status, inflammation, fever,
      gender, breastfeeding status and viral etiology.
    

Intervention name(s): Zinc
Intervention type(s): Drug
Intervention description(s): Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months
Other intervention name(s): Produced by Nutriset, Malaunay, France
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Child; pneumonia; Zinc; clinical trial; Nepal; nutrition; therapeutic