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PneumoniaPhase 2/3NCT00148733

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

A Phase 2/3 study testing Zinc in people with Pneumonia, run by Centre For International Health at 1 site in Nepal.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 months to 3 years
Conditions the study is for
Pneumonia
What is being tested?
Zinc
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
2,628 participants
Where
1 siteNepal
Study dates
Jan 2004to Jan 2008
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 months to 3 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

Nepal1 site
  • Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan

    Bhaktapur, P.O.Box 40

Other trials in Nepal

About this study

Official title: Community- and Health Facility-based Intervention With Zinc as Adjuvant Therapy for Pneumonia to Enhance Child Health and Nutrition

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.

Read the 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.

Conditions
Pneumonia
Being tested
Zinc
Keywords
Child, pneumonia, Zinc, clinical trial, Nepal, nutrition, therapeutic
Medical subject headings
Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZincDrug

    Also called Produced by Nutriset, Malaunay, France

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

Study groups in NCT00148733
Study groupRoleWhat they receive
ZincExperimentalZinc sulphate 10 or 20 mg (elemental zinc) per day. Intervention and placebo given perorally mixed with approximately 5 mL of breastmilk or clean water
Receives: Drug: Zinc
PlaceboPlacebo comparatorPlacebo
Receives: Drug: Zinc

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Risk of Treatment Failure.

    Enrolled children will be followed and given zinc or placebo for 14 days. We will compare the proportion with treatment failure (i.e. lack of improvement within 3 days) between the two groups

    Measured: Within 2 weeks after enrollment

  2. Non-injury Clinic Visits and Hospital Admissions After Treatment Has Been Initiated

    We will measure to what extent the intervention can reduce the number of severe events.

    Measured: Within 2 weeks after enrollment

  3. Active and Passive Morbidity Surveillance for Six Months After the 14-day Supplementation Period is Completed

    We will measure to what extent short term zinc administration has an impact on growth and morbidity for up to 6 months after end of supplementation

    Measured: six months

  4. Difference in Growth and Thymic Size Between the Treatment Groups Measured at Three and Six Months After the Zinc Supplementation

    Thymus size will be measured using ultrasonography and compared between the two groups. at two occasions 2.5 and 6 months after end of supplementation

    Measured: six months

  5. Adverse Effects

    Vomiting, regurgitation, pain in abdomen for 15 minutes after zinc or placebo administration.

    Measured: 14 days

Secondary outcomes (5)
  1. Effect Modifiers for the Effect of Zinc Given During Pneumonia

    We will also measure of there are factors at baseline that modifies the effect of zinc. 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

    Measured: Within 2 weeks after enrollment

  2. The Efficacy of Zinc According to Breast Feeding Status and in Different Age Categories

    We will measure to what extent breastfeeding status modifies the effect of zinc on pneumonia

    Measured: Within 2 weeks after enrollment

  3. The Efficacy of Zinc in Malnourished and Non-malnourished Children

    We will compare the efficacy of zinc in those that are stunted, wasted or underweight with those who are not.

    Measured: Within 2 weeks after enrollment

  4. Will Presence of a RNA Virus Modify the Effect of Zinc

    We will compare the efficacy of zinc according to virus detected in nasopharyngeal secretions

    Measured: 14 days

  5. Folate, Cobalamin and Vitamin D Status of the Enrolled Children

    And whether or not these vitamins predict treatment failure and duration of illness.

    Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2005 (estimated)
  2. Study startJan 2004
  3. Primary completionJan 2008
  4. Study completionJan 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
2,628 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00148733
Sponsor's protocol ID
003740
Other IDs
003740(Eur. Comm. INCO), NUFU PRO 36/2002
Status last verified
Mar 2022
First submitted
6 Sep 2005
Last updated
16 Mar 2022
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr. 1999 Dec;135(6):689-97. doi: 10.1016/s0022-3476(99)70086-7.

    PubMed 10586170
  • Bates CJ, Prentice A. Breast milk as a source of vitamins, essential minerals and trace elements. Pharmacol Ther. 1994 Apr-May;62(1-2):193-220. doi: 10.1016/0163-7258(94)90011-6.

    PubMed 7991643
  • Walsh CT, Sandstead HH, Prasad AS, Newberne PM, Fraker PJ. Zinc: health effects and research priorities for the 1990s. Environ Health Perspect. 1994 Jun;102 Suppl 2(Suppl 2):5-46. doi: 10.1289/ehp.941025.

    PubMed 7925188
  • Strand TA, Chandyo RK, Bahl R, Sharma PR, Adhikari RK, Bhandari N, Ulvik RJ, Molbak K, Bhan MK, Sommerfelt H. Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children. Pediatrics. 2002 May;109(5):898-903. doi: 10.1542/peds.109.5.898.

    PubMed 11986453
  • Bates CJ, Evans PH, Dardenne M, Prentice A, Lunn PG, Northrop-Clewes CA, Hoare S, Cole TJ, Horan SJ, Longman SC, et al. A trial of zinc supplementation in young rural Gambian children. Br J Nutr. 1993 Jan;69(1):243-55. doi: 10.1079/bjn19930026.

    PubMed 8457531
  • Black RE. Therapeutic and preventive effects of zinc on serious childhood infectious diseases in developing countries. Am J Clin Nutr. 1998 Aug;68(2 Suppl):476S-479S. doi: 10.1093/ajcn/68.2.476S.

    PubMed 9701163
  • 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.

    PubMed 9651405
  • Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ. 2002 Jun 8;324(7350):1358. doi: 10.1136/bmj.324.7350.1358.

    PubMed 12052800
  • Hambidge KM, Krebs NF, Miller L. Evaluation of zinc metabolism with use of stable-isotope techniques: implications for the assessment of zinc status. Am J Clin Nutr. 1998 Aug;68(2 Suppl):410S-413S. doi: 10.1093/ajcn/68.2.410S.

    PubMed 9701153
  • Chai F, Truong-Tran AQ, Ho LH, Zalewski PD. Regulation of caspase activation and apoptosis by cellular zinc fluxes and zinc deprivation: A review. Immunol Cell Biol. 1999 Jun;77(3):272-8. doi: 10.1046/j.1440-1711.1999.00825.x.

    PubMed 10361260
  • Truong-Tran AQ, Carter J, Ruffin R, Zalewski PD. New insights into the role of zinc in the respiratory epithelium. Immunol Cell Biol. 2001 Apr;79(2):170-7. doi: 10.1046/j.1440-1711.2001.00986.x.

    PubMed 11264713
  • Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug;68(2 Suppl):447S-463S. doi: 10.1093/ajcn/68.2.447S.

    PubMed 9701160
  • Lira PI, Ashworth A, Morris SS. Effect of zinc supplementation on the morbidity, immune function, and growth of low-birth-weight, full-term infants in northeast Brazil. Am J Clin Nutr. 1998 Aug;68(2 Suppl):418S-424S. doi: 10.1093/ajcn/68.2.418S.

    PubMed 9701155
  • Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Pediatrics. 2002 Jun;109(6):e86. doi: 10.1542/peds.109.6.e86.

    PubMed 12042580
  • Brooks WA, Yunus M, Santosham M, Wahed MA, Nahar K, Yeasmin S, Black RE. Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Lancet. 2004 May 22;363(9422):1683-8. doi: 10.1016/S0140-6736(04)16252-1.

    PubMed 15158629

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Zinc in people with Pneumonia, run by Centre For International Health at 1 site in Nepal.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Risk of Treatment Failure. (time frame: Within 2 weeks after enrollment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00148733, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2022.

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