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

Diarrhea Clinical Trial

— ZTDT  

Official title:

Establishing the Optimal Dose of Therapeutic Zinc Supplementation for the Treatment of Acute Diarrhea in Under Five Children - a Dose Response Trial in a South Asian and a Sub-Saharan African Setting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03078842
• Other study ID #: ERC.0002738
• Status: Completed
• Phase: N/A
• Start date: January 23, 2017
• Est. completion date: February 1, 2020

Study information

• Verified date: October 2020
• Source: World Health Organization
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4500
• Est. completion date: February 1, 2020
• Est. primary completion date: February 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 59 Months

Eligibility

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

Related Conditions & MeSH terms

• Diarrhea

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
India	Centre for Public Health Kinetics	New Delhi
Tanzania	Muhimbili University of Health and Allied Sciences	Dar es Salaam

Sponsors (4)

Lead Sponsor	Collaborator
Ayesha De Costa	Boston Children's Hospital, Center for Public Health Kinetics, Muhimbili University of Health and Allied Sciences

Countries where clinical trial is conducted

India,  Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion with long duration of diarrhoea	Diarrhoea continuing beyond five days	Measured daily for 15 days
Primary	Continuation of diarrhoea symptoms	Total number of loose or watery stools after enrolment	Measured daily for 15 days
Primary	Proportion of children vomiting after zinc treatment	Vomiting within 30 minutes of administration of zinc tablet	Measured daily for 15 days
Secondary	Proportion of children experiencing serious adverse events (SAEs)	Serious adverse events (life-threatening or requiring hospitalization)	Measured until 60 days
Secondary	Proportion with intermediate duration of diarrhoea	Diarrhoea continuing beyond three days	Measured daily for 15 days
Secondary	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
Secondary	Treatment adherence	Mean number of tablets consumed by the study child during the 14 day treatment period.	Measured daily for 15 days
Secondary	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
Secondary	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