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| Name | Class |
|---|---|
| Center for Public Health Kinetics | OTHER |
| Muhimbili University of Health and Allied Sciences | OTHER |
| Boston Children's Hospital | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zinc-20 | Active Comparator | Zinc tablets, 20 mg per day |
|
| Zinc-10 | Experimental | Zinc tablets, 10 mg per day |
|
| Zinc-05 | Experimental | Zinc tablets, 5 mg per day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zinc tablets, 20 mg per day | Dietary Supplement | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion with long duration of diarrhoea | Diarrhoea continuing beyond five days | Measured daily for 15 days |
| Continuation of diarrhoea symptoms | Total number of loose or watery stools after enrolment | Measured daily for 15 days |
| Proportion of children vomiting after zinc treatment | Vomiting within 30 minutes of administration of zinc tablet | Measured daily for 15 days |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of children experiencing serious adverse events (SAEs) | Serious adverse events (life-threatening or requiring hospitalization) | Measured until 60 days |
| Proportion with intermediate duration of diarrhoea |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rajiv Bahl, MBBS | World Health Organization | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Public Health Kinetics | New Delhi | India | ||||
| Muhimbili University of Health and Allied Sciences |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38238656 | Derived | Kisenge R, Dhingra U, Rees CA, Liu E, Dutta A, Saikat D, Dhingra P, Somji S, Sudfeld C, Simon J, Ashorn P, Sazawal S, Duggan CP, Manji K. Risk factors for moderate acute malnutrition among children with acute diarrhoea in India and Tanzania: a secondary analysis of data from a randomized trial. BMC Pediatr. 2024 Jan 19;24(1):56. doi: 10.1186/s12887-024-04551-2. | |
| 32966722 |
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The exact mechanism of data sharing has not yet been decided among the researchers. But the study is funded by an Organization (Bill & Melinda Gates Foundation) that requires data sharing.
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| ID | Term |
|---|---|
| D003967 | Diarrhea |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D015032 | Zinc |
| ID | Term |
|---|---|
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D028561 | Transition Elements |
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All participants will get dispersible zinc tablets that, contain either 20 mg, 10 mg, or 5 mg of zinc. All tablets look and taste the same. Randomization and tablet package labelling was done in Geneva, and no-one at the trial sites knows the actual zinc content of tablets packaged for each participant number.
| Zinc tablets, 10 mg per day | Dietary Supplement | 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 |
|
| Zinc tablets, 5 mg per day | Dietary Supplement | 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 |
|
Diarrhoea continuing beyond three days
| Measured daily for 15 days |
| Proportion of guardians with positive attitude towards treatment | 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. | Day 15 |
| Treatment adherence | Mean number of tablets consumed by the study child during the 14 day treatment period. | Measured daily for 15 days |
| Mean serum plasma zinc concentration at Days 1, 3, 7, 15, 21 and 30 | Mean serum plasma zinc concentration at Days 1, 3, 7, 15, 21 and 30 | Days 1, 3, 7, 15, 21 and 30 |
| Illness symptoms between day 15 and 60 after the treatment | 2-week period prevalence and number of days with diarrhoea, fever, or respiratory symptoms | Days 30, 45, 60 |
| Dar es Salaam |
| Tanzania |
| Dhingra U, Kisenge R, Sudfeld CR, Dhingra P, Somji S, Dutta A, Bakari M, Deb S, Devi P, Liu E, Chauhan A, Kumar J, Semwal OP, Aboud S, Bahl R, Ashorn P, Simon J, Duggan CP, Sazawal S, Manji K. Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial. N Engl J Med. 2020 Sep 24;383(13):1231-1241. doi: 10.1056/NEJMoa1915905. |
| 31206083 | Derived | Somji SS, Dhingra P, Dhingra U, Dutta A, Devi P, Kumar J, Deb S, Semwal OP, Sazawal S, Manji K, Kisenge R, Bakari M, Aboud S, Liu E, Sudfeld C, Duggan CP, Ashorn P, Bahl R, Simon JL. Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania. BMJ Paediatr Open. 2019 Apr 24;3(1):e000460. doi: 10.1136/bmjpo-2019-000460. eCollection 2019. |
| D008670 |
| Metals |