CHIZAP: Community- and Health Facility-Based Intervention With Zinc as Adjuvant Therapy for Childhood Pneumonia

Centre For International Health

Status and phase: Completed; Phase 3; Phase 2

Conditions: Pneumonia

Treatments: Drug: Zinc

Study type: Interventional

Funder types: Other

Identifiers

NCT00148733

003740

NUFU PRO 36/2002 (Other Grant/Funding Number)

003740(Eur. Comm. INCO) (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,628 patients

Sex: All

Ages: 2 months to 3 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pneumonia: Child presenting with cough or difficult breathing and elevated respiratory rate.

• Severe pneumonia: Child presenting with cough or difficult breathing and chest indrawing , but without any of the following danger signs:

  • not able to drink/breastfeed,
  • vomit everything,
  • has had convulsions,
  • is lethargic or unconscious.

• Must be able to take Zinc

Exclusion criteria

• The child requires special care for severe illness other than pneumonia
• Severe malnutrition defined as being < 70% National Center for Health Statistics (NCHS) median weight for height
• Presence of congenital heart disease
• Documented tuberculosis
• Any antibiotic treatment during the last 48 hours
• The child was enrolled less than 6 months ago
• Presence of dysentery
• Cough for more than 14 days

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,628 participants in 2 patient groups, including a placebo group

Zinc

Experimental group

Description:

Zinc sulphate 10 or 20 mg (elemental zinc) per day. Intervention and placebo given perorally mixed with approximately 5 mL of breastmilk or clean water

Treatment:

Drug: Zinc

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Zinc