Zinc Dosing Trial - Does Dose Reduction Reduce Side Effects But Retain Efficacy in Diarrhoea Management (ZTDT)

Ayesha De Costa

Status: Completed

Conditions: Diarrhea

Treatments: Dietary Supplement: Zinc tablets, 5 mg per day; Dietary Supplement: Zinc tablets, 10 mg per day; Dietary Supplement: Zinc tablets, 20 mg per day

Study type: Interventional

Funder types: Other

Identifiers

NCT03078842

ERC.0002738

Details and patient eligibility

About

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.

Enrollment: 4,500 patients

Sex: All

Ages: 6 to 59 months old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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4,500 participants in 3 patient groups

Zinc-20

Active Comparator group

Description:

Zinc tablets, 20 mg per day

Treatment:

Dietary Supplement: Zinc tablets, 20 mg per day

Zinc-10

Experimental group

Description:

Zinc tablets, 10 mg per day

Treatment:

Dietary Supplement: Zinc tablets, 10 mg per day

Zinc-05

Experimental group

Description:

Zinc tablets, 5 mg per day

Treatment:

Dietary Supplement: Zinc tablets, 5 mg per day