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

This study has been completed.
Sponsor:
Collaborators:
Tribhuvan University, Nepal
Statens Serum Institut
All India Institute of Medical Sciences, New Delhi
IRD, Epidemiologie et Prevention, Montpelier, France
Society for Applied Studies
Information provided by:
Centre For International Health
ClinicalTrials.gov Identifier:
NCT00148733
First received: September 6, 2005
Last updated: June 17, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Pneumonia
Drug: Zinc
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Community- and Health Facility-based Intervention With Zinc as Adjuvant Therapy for Pneumonia to Enhance Child Health and Nutrition

Resource links provided by NLM:


Further study details as provided by Centre For International Health:

Primary Outcome Measures:
  • Risk of treatment failure and the duration of illness. For those with severe pneumonia: length of hospital stay. [ Time Frame: Within 2 weeks after enrollment ] [ Designated as safety issue: No ]
    Enrolled children will be followed and given zinc or placebo for 14 days.

  • Non-injury clinic visits and hospital admissions after treatment has been initiated [ Time Frame: Within 2 weeks after enrollment ] [ Designated as safety issue: No ]
  • Active and passive morbidity surveillance for six months after the 14-day supplementation period is completed [ Time Frame: six months ] [ Designated as safety issue: No ]
  • Difference in growth and thymic size between the treatment groups measured at three and six months after the zinc supplementation [ Time Frame: six months ] [ Designated as safety issue: No ]
  • Adverse effects [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Vomiting, regurgitation, pain in abdomen for 15 minutes after zinc or placebo administration.


Secondary Outcome Measures:
  • Whether the following are modifiers for the above-mentioned effect of zinc given during pneumonia: i. severe inflammation, reflected in: high fever and/or elevated plasma C-reactive protein (CRP) concentration [ Time Frame: Within 2 weeks after enrollment ] [ Designated as safety issue: No ]
  • The efficacy of zinc according to breast feeding status and in different age categories [ Time Frame: Within 2 weeks after enrollment ] [ Designated as safety issue: No ]
  • The efficacy of zinc in malnourished and non-malnourished children [ Time Frame: Within 2 weeks after enrollment ] [ Designated as safety issue: No ]
    We will compare the efficacy of zinc in those that are stunted, wasted or underweight with those who are not.

  • Will presence of a RNA virus modify the effect of zinc [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    We will compare the efficacy of zinc according to virus detected in nasopharyngeal secretions

  • Folate, cobalamin and vitamin D status of the enrolled children [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    And whether or not these vitamins predict treatment failure and duration of illness.


Enrollment: 2628
Study Start Date: January 2004
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Zinc
Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months
Other Name: Produced by Nutriset, Malaunay, France
Placebo Comparator: Placebo
Placebo
Drug: Zinc
Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months
Other Name: Produced by Nutriset, Malaunay, France

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

Ages Eligible for Study:   2 Months to 3 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00148733

Locations
Nepal
Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan
Bhaktapur, Nepal, P.O.Box 40
Sponsors and Collaborators
Centre For International Health
Tribhuvan University, Nepal
Statens Serum Institut
All India Institute of Medical Sciences, New Delhi
IRD, Epidemiologie et Prevention, Montpelier, France
Society for Applied Studies
Investigators
Study Director: Tor A Strand, MD PhD Centre for International Health, University of Bergen, 5021 Bergen, Norway
Study Chair: Halvor Sommerfelt, MD PhD Centre for International Health, University of Bergen, 5021 Bergen, Norway
Study Director: Prakash S Shrestha, MD Professor Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj
Study Chair: Ramesh K Adhikari, MD Dean Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj
Principal Investigator: Palle Valentiner-Branth, MD PhD Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tor A Strand, MD, PhD, ProfessorII, University of Bergen
ClinicalTrials.gov Identifier: NCT00148733     History of Changes
Other Study ID Numbers: 003740, 003740(Eur. Comm. INCO), NUFU PRO 36/2002
Study First Received: September 6, 2005
Last Updated: June 17, 2011
Health Authority: Norway:National Committee for Medical and Health Research Ethics

Keywords provided by Centre For International Health:
Child
pneumonia
Zinc
clinical trial
Nepal
nutrition
therapeutic

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Zinc
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 25, 2014