Clinical trial NCT00148733: CHIZAP: Community- and Health Facility-Based Intervention With Zinc as Adjuvant Therapy for Childhood Pneumonia
Official title: Community- and Health Facility-based Intervention With Zinc as Adjuvant Therapy for Pneumonia to Enhance Child Health and Nutrition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pneumonia
Keywords: Child
pneumonia
Zinc
clinical trial
Nepal
nutrition
therapeutic
Lead sponsor: Centre For International Health
Sponsor class: OTHER
Collaborators: name: Tribhuvan University, Nepal
name: Statens Serum Institut
name: All India Institute of Medical Sciences
name: IRD, Epidemiologie et Prevention, Montpelier, France
name: Society for Applied Studies
First posted: 2005-09-08
Enrollment: 2628
Sex: ALL
Minimum age (years): 2
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Risk of Treatment Failure.
timeFrame: Within 2 weeks after enrollment
measure: Non-injury Clinic Visits and Hospital Admissions After Treatment Has Been Initiated
timeFrame: Within 2 weeks after enrollment
measure: Active and Passive Morbidity Surveillance for Six Months After the 14-day Supplementation Period is Completed
timeFrame: six months
measure: Difference in Growth and Thymic Size Between the Treatment Groups Measured at Three and Six Months After the Zinc Supplementation
timeFrame: six months
measure: Adverse Effects
timeFrame: 14 days
Secondary outcomes:
measure: Effect Modifiers for the Effect of Zinc Given During Pneumonia
timeFrame: Within 2 weeks after enrollment
measure: The Efficacy of Zinc According to Breast Feeding Status and in Different Age Categories
timeFrame: Within 2 weeks after enrollment
measure: The Efficacy of Zinc in Malnourished and Non-malnourished Children
timeFrame: Within 2 weeks after enrollment
measure: Will Presence of a RNA Virus Modify the Effect of Zinc
timeFrame: 14 days
measure: Folate, Cobalamin and Vitamin D Status of the Enrolled Children
timeFrame: 14 days
Other outcomes:
Locations:
city: Bhaktapur
country: Nepal
facility: Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan
Study officials:
affiliation: Centre for International Health, University of Bergen, 5021 Bergen, Norway
name: Tor A Strand, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for International Health, University of Bergen, 5021 Bergen, Norway
name: Halvor Sommerfelt, MD PhD
role: STUDY_DIRECTOR
affiliation: Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj
name: Prakash S Shrestha, MD Professor
role: STUDY_DIRECTOR
affiliation: Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj
name: Ramesh K Adhikari, MD Dean
role: STUDY_CHAIR
affiliation: Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark
name: Palle Valentiner-Branth, MD PhD
role: PRINCIPAL_INVESTIGATOR
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