Diarrhea
Conditions
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.
Interventions
DIETARY_SUPPLEMENTZinc 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
DIETARY_SUPPLEMENTZinc 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
DIETARY_SUPPLEMENTZinc 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
Sponsors
Center for Public Health Kinetics
Muhimbili University of Health and Allied Sciences
Boston Children's Hospital
Ayesha De Costa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
6 Months to 59 Months
Healthy volunteers
No
Inclusion criteria
* 6 to 59 completed months of age * 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 * Likely to stay within the study area for the next 2 months * Written informed consent from caretaker
Exclusion criteria
* Presence of severe acute malnutrition (WHZ\<-3 or oedema) * Presence of severe dehydration that cannot be corrected in 4 to 6 hours * Signs of severe pneumonia (WHO definition of pneumonia with danger signs), sepsis, rapid diagnostic test (RDT) -confirmed malaria or other severe illness * Previously or currently enrolled in the study * Currently enrolled in another study * Other child currently enrolled in the study in the same household * Not intending to remain in study area for the duration of the study * Parents refuse participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Treatment adherence | Measured daily for 15 days | Mean number of tablets consumed by the study child during the 14 day treatment period. |
| Proportion of children experiencing serious adverse events (SAEs) | Measured until 60 days | Serious adverse events (life-threatening or requiring hospitalization) |
| 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 |
| 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 |
| 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. |
Countries
India, Tanzania
Outcome results
None listed