A Phase 2/3 interventional study of Zinc in Pneumonia, sponsored by Centre For International Health. Completed at 1 site in Nepal. Open to participants aged 2 Months to 3 Years. Per ClinicalTrials.gov, last updated 2022-03-16.
Sponsored by Centre For International Health · Phase 2/3, Interventional, and Treatment
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.
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.
2,072 studies on the registry are indexed under Pneumonia; 286 are open to participants now.
This study's enrollment of 2,628 is above the median of 107 across 1,263 interventional studies indexed under Pneumonia.
Browse Pneumonia studies →Centre For International Health is the lead sponsor of 12 studies on the registry; none are open to participants now.
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Severe pneumonia: Child presenting with cough or difficult breathing and chest indrawing , but without any of the following danger signs:
Exclusion Criteria:
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
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
Also known as: Produced by Nutriset, Malaunay, France
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
Time frame: Within 2 weeks after enrollment
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.
Time frame: Within 2 weeks after enrollment
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
Time frame: six months
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
Time frame: six months
Adverse Effects
Vomiting, regurgitation, pain in abdomen for 15 minutes after zinc or placebo administration.
Time frame: 14 days
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
Time frame: Within 2 weeks after enrollment
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
Time frame: Within 2 weeks after enrollment
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.
Time frame: Within 2 weeks after enrollment
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
Time frame: 14 days
Folate, Cobalamin and Vitamin D Status of the Enrolled Children
And whether or not these vitamins predict treatment failure and duration of illness.
Time frame: 14 days
| Milestone | Zinc | Placebo |
|---|---|---|
| Started | 1314 | 1314 |
| Completed | 1300 | 1299 |
| Not completed | 14 | 15 |
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
| participants | Zinc | Placebo |
|---|---|---|
| Risk of Treatment Failure. | 267 | 253 |
We will measure to what extent the intervention can reduce the number of severe events.
Results for this outcome have not been posted.
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
Results for this outcome have not been posted.
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
Results for this outcome have not been posted.
Vomiting, regurgitation, pain in abdomen for 15 minutes after zinc or placebo administration.
Results for this outcome have not been posted.
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
Results for this outcome have not been posted.
We will measure to what extent breastfeeding status modifies the effect of zinc on pneumonia
Results for this outcome have not been posted.
We will compare the efficacy of zinc in those that are stunted, wasted or underweight with those who are not.
Results for this outcome have not been posted.
We will compare the efficacy of zinc according to virus detected in nasopharyngeal secretions
Results for this outcome have not been posted.
And whether or not these vitamins predict treatment failure and duration of illness.
Results for this outcome have not been posted.
Collected over 14 days, while zinc or placebo were given. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Zinc | — | 0/1,314 (0%) | 181/1,314 (13.8%) |
| Placebo | — | 0/1,314 (0%) | 53/1,314 (4%) |
| Event | Zinc | Placebo |
|---|---|---|
| RegurgitationGastrointestinal disorders | 181/1314 | 53/1314 |
| Age, Continuous(months) | Zinc | Placebo | Total |
|---|---|---|---|
| Mean | 7.3 ± 7.4 | 7.2 ± 7.2 | 7.2 ± 7.3 |
| Sex: Female, Male(Participants) | Zinc | Placebo | Total |
|---|---|---|---|
| Female | 575 | 576 | 1151 |
| Male | 739 | 738 | 1477 |
Plan to share: No
The record gives a start of Jan 2004, a primary completion of Jan 2008 and a completion of Jan 2008. It does not say whether these dates are actual or estimated.
Results were first posted in Feb 2015, 7 years 1 month after primary completion.
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This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Zinc
Centre For International Health