ZTDT: Zinc Dosing Trial - Does Dose Reduction Reduce Side Effects But Retain Efficacy in Diarrhoea Management
Study Details
Study Description
Brief Summary
Diarrhoea continues to be a major cause of child deaths. Current treatment of acute watery diarrhoea includes oral rehydration solution (ORS), zinc and continued feeding. The use of zinc is based on a number of studies that showed that zinc reduces the duration and severity of diarrhoea. The recommended dose of zinc in 6-59 month old children is 20mg/day for 10-14 days. This dose is associated with an increased risk of vomiting. No dosing studies are available to determine the optimal dose of zinc, which while maintaining the benefits also has a low risk of vomiting.
The investigators will conduct a double-blind randomized controlled trial of three doses of zinc (20mg/day, 10mg/day and 5mg/day) in two settings - one in Sub-Saharan Africa and the other in South Asia. The study population will be 4500 children with diarrhoea of less than 72 hours duration who are aged 6-59 months. They will be recruited from outpatient health facilities. All enrolled children will receive ORS and continued feeding as recommended by the World Health Organization. Those allocated to the standard zinc dose will receive an oral dispersible tablet with 20mg zinc daily for 14 days. Those allocated to lower dose zinc will receive identical tablets with either 10mg or 5mg zinc daily for 14 days. Enrolled children will be followed by until recovery from diarrhoea or 15 days after enrolment, whichever is later. In addition, study children will be assessed again at thirty (30), forty-five (45), and sixty (60) days to estimate impact on post illness outcomes. Primary outcomes will be mean duration of diarrhoea, proportion of episodes that last longer than 5 days, mean number of stools and proportion of children with vomiting.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Zinc-20 Zinc tablets, 20 mg per day |
Dietary Supplement: Zinc tablets, 20 mg per day
Participants will receive rehydration, dietary counseling, and 1 tablet per day for 14 days of zinc-tablets, each of which contains 20 mg of zinc
|
| Experimental: Zinc-10 Zinc tablets, 10 mg per day |
Dietary Supplement: Zinc tablets, 10 mg per day
Participants will receive rehydration, dietary counseling, and 1 tablet per day for 14 days of zinc-tablets, each of which contains 10 mg of zinc
|
| Experimental: Zinc-05 Zinc tablets, 5 mg per day |
Dietary Supplement: Zinc tablets, 5 mg per day
Participants will receive rehydration, dietary counseling, and 1 tablet per day for 14 days of zinc-tablets, each of which contains 5 mg of zinc
|
Outcome Measures
Primary Outcome Measures
- Proportion with long duration of diarrhoea [Measured daily for 15 days]
Diarrhoea continuing beyond five days
- Continuation of diarrhoea symptoms [Measured daily for 15 days]
Total number of loose or watery stools after enrolment
- Proportion of children vomiting after zinc treatment [Measured daily for 15 days]
Vomiting within 30 minutes of administration of zinc tablet
Secondary Outcome Measures
- Proportion of children experiencing serious adverse events (SAEs) [Measured until 60 days]
Serious adverse events (life-threatening or requiring hospitalization)
- Proportion with intermediate duration of diarrhoea [Measured daily for 15 days]
Diarrhoea continuing beyond three days
- Proportion of guardians with positive attitude towards treatment [Day 15]
The guardians will be asked if was easy to administer the treatment, if they think the child liked the treatment, if they saw any changes in the children after the treatment and if they would recommend this treatment to their friends' children.
- Treatment adherence [Measured daily for 15 days]
Mean number of tablets consumed by the study child during the 14 day treatment period.
- Mean serum plasma zinc concentration at Days 1, 3, 7, 15, 21 and 30 [Days 1, 3, 7, 15, 21 and 30]
Mean serum plasma zinc concentration at Days 1, 3, 7, 15, 21 and 30
- Illness symptoms between day 15 and 60 after the treatment [Days 30, 45, 60]
2-week period prevalence and number of days with diarrhoea, fever, or respiratory symptoms
Eligibility Criteria
Criteria
Inclusion Criteria:
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6 to 59 completed months of age
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Acute diarrhoea of less than 3 days at the time of screening or dysentery, defined as visible blood in the stool, of less than 3 days at the time of screening
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Likely to stay within the study area for the next 2 months
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Written informed consent from caretaker
Exclusion Criteria:
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Presence of severe acute malnutrition (WHZ<-3 or oedema)
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Presence of severe dehydration that cannot be corrected in 4 to 6 hours
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Signs of severe pneumonia (WHO definition of pneumonia with danger signs), sepsis, rapid diagnostic test (RDT) -confirmed malaria or other severe illness
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Previously or currently enrolled in the study
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Currently enrolled in another study
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Other child currently enrolled in the study in the same household
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Not intending to remain in study area for the duration of the study
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Parents refuse participation in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre for Public Health Kinetics | New Delhi | India | ||
| 2 | Muhimbili University of Health and Allied Sciences | Dar es Salaam | Tanzania |
Sponsors and Collaborators
- Ayesha De Costa
- Center for Public Health Kinetics
- Muhimbili University of Health and Allied Sciences
- Boston Children's Hospital
Investigators
- Study Director: Rajiv Bahl, MBBS, World Health Organization
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ERC.0002738