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

NCT ID: NCT00148733

Last Updated: 2022-03-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

2628 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2008-01-31

Brief Summary

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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

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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.

Conditions

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Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Zinc

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

Group Type EXPERIMENTAL

Zinc

Intervention Type DRUG

Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Zinc

Intervention Type DRUG

Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months

Interventions

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Zinc

Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months

Intervention Type DRUG

Other Intervention Names

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Produced by Nutriset, Malaunay, France

Eligibility Criteria

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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
Minimum Eligible Age

2 Months

Maximum Eligible Age

3 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tribhuvan University, Nepal

OTHER

Sponsor Role collaborator

Statens Serum Institut

OTHER

Sponsor Role collaborator

All India Institute of Medical Sciences

OTHER

Sponsor Role collaborator

IRD, Epidemiologie et Prevention, Montpelier, France

UNKNOWN

Sponsor Role collaborator

Society for Applied Studies

OTHER

Sponsor Role collaborator

Centre For International Health

OTHER

Sponsor Role lead

Responsible Party

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Tor A. Strand

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tor A Strand, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for International Health, University of Bergen, 5021 Bergen, Norway

Halvor Sommerfelt, MD PhD

Role: STUDY_DIRECTOR

Centre for International Health, University of Bergen, 5021 Bergen, Norway

Prakash S Shrestha, MD Professor

Role: STUDY_DIRECTOR

Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj

Ramesh K Adhikari, MD Dean

Role: STUDY_CHAIR

Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj

Palle Valentiner-Branth, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark

Locations

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Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan

Bhaktapur, , Nepal

Site Status

Countries

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Nepal

References

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Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998 Jul;102(1 Pt 1):1-5. doi: 10.1542/peds.102.1.1.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Haugen J, Chandyo RK, Brokstad KA, Mathisen M, Ulak M, Basnet S, Valentiner-Branth P, Strand TA. Cytokine Concentrations in Plasma from Children with Severe and Non-Severe Community Acquired Pneumonia. PLoS One. 2015 Sep 25;10(9):e0138978. doi: 10.1371/journal.pone.0138978. eCollection 2015.

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Valentiner-Branth P, Shrestha PS, Chandyo RK, Mathisen M, Basnet S, Bhandari N, Adhikari RK, Sommerfelt H, Strand TA. A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal. Am J Clin Nutr. 2010 Jun;91(6):1667-74. doi: 10.3945/ajcn.2009.28907. Epub 2010 Apr 7.

Reference Type DERIVED
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Other Identifiers

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003740(Eur. Comm. INCO)

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NUFU PRO 36/2002

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

003740

Identifier Type: -

Identifier Source: org_study_id

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