Pharmacy and Poisons Board
Protocol No: ECCT/17/07/01 Date of Protocol: 27-06-2017
Study Title:

Antibiotics for Children with Severe Diarrhea Trial
Study Objectives:

 

 

PRIMARY OBJECTIVES

  1. To compare all-cause mortality rates in the 90 days following an episode of high risk diarrhea without dysentery among children 2 to 23 months of age in low resource settings randomized to receive a 3-day course of azithromycin or placebo.
  2. To compare the average change in linear growth (∆LAZ) in the 90 days following an episode of high risk diarrhea without dysentery among children 2 to 23 months of age in low resource settings randomized to receive a 3-day course of azithromycin or placebo.

                       

SECONDARY OBJECTIVES

  1. To compare changes in markers of acute malnutrition (∆MUAC and ∆WLZ) in the 90 days following an episode of high-risk diarrhea without dysentery among children 2 to 23 months of age in low resource settings randomized to receive a 3-day course of azithromycin or placebo.
  2. To evaluate (as determined by verbal autopsy) cause-specific mortality rates across randomization arms in the 90 days following an episode of high risk diarrhea without dysentery among children 2 to 23 months of age in low resource settings randomized to receive a 3-day course of azithromycin or placebo.
  3. To compare the proportion of strains of E.coli, isolated from stool samples, resistant to selected antibiotics at enrolment among the study population. Since children entering later into the trial are coming from the same communities, they can serve as a comparator group indicative of the community level of resistance.
  4. To compare the proportion of strains of Streptococcus pneumonia (S. pneumoniae), isolated from nasopharyngeal swabs, resistant to selected antibiotics at DAY 90 and DAY 180 in a randomly selected sub-sample of children enrolled in the study and their child household contacts (children under five years of age living in the same household under the care of the same primary caregiver).
Laymans Summary:

In some parts of Africa and Asia, children under 2 years of age who have had diarrhea may continue to have health problems and grow more slowly than children without diarrhea. The usual treatment of diarrhea includes oral rehydration solution (ORS), zinc, and feeding advice. Medicines to fight the germs that cause diarrhea (called antibiotics) are only recommended for children with suspected cholera or when there is blood in the child’s stool. Some experts think that there may be other types of diarrhea that could benefit from an antibiotic. The purpose of this study is to find out if children treated with the antibiotic azithromycin for three days will recover from their diarrhea faster and grow better. We plan to enroll 11,500 children from 7 different countries in this study and approximately 1,644 children in Kenya.
Abstract of Study:

Diarrhea remains a leading cause of death in children, and the majority of diarrhea deaths occur in children under 2 years of age living in sub-Saharan Africa and Asia. Three of the four leading infectious causes of diarrhea are potentially treatable with antimicrobial agents and antimicrobials have demonstrated a mortality benefit in certain high-risk children. The purpose of this double-blind placebo-controlled clinical trial is to determine the efficacy of an antibiotic in reducing risk of death and malnutrition in children less than two years of age with diarrhea and dehydration or malnutrition. A total of eleven thousand five hundred children will be enrolled from 7 study sites (Kenya, Mali, Malawi, Tanzania, Bangladesh, India, and Pakistan) and randomized to a three-day course of azithromycin or placebo. Children will be followed to determine risk of death and linear growth faltering (a marker of chronic malnutrition) in the 90-days after study enrollment. Stool (or rectal swabs) will be collected from all children at enrollment and 90-days and nasopharyngeal swabs will be collected from a subset of children and a sibling in their household. Infections identified from stool and nasopharyngeal swabs will be used to evaluate the impact of the antibiotics on enteric and nasopharyngeal pathogens and antimicrobial resistance. Children enrolled in this sub-study will also be followed and provide samples 3 months after the 90-day visit to determine the long-term impact of the antibiotics on potential antimicrobial resistance. The Kenya Medical Research Institute/University of Washington (KEMRI/UW) team will collaborate with investigators at all field sites for data analysis, but is primarily responsible for research conducted at the Kenya sites under guidance from the World Health Organization (WHO) study coordinators.